Registration Dossier
Registration Dossier
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EC number: 203-576-3 | CAS number: 108-38-3
Endpoint summary
Administrative data
Description of key information
In repeated dose studies, the principle effects of xylenes were adaptive changes in the liver, organ weight and body weight changes. Inhalation studies in rodents have demonstrated a potential to cause ototoxicity.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 11 July 2019 to 23 January 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- The rat is a suitable rodent species for toxicity testing, acceptable to regulatory authorities and for which extensive background data are available.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 40 male and 40 female rats of the Crl:WI(Han) strain were supplied by Charles River (UK) Limited, Margate, Kent, CT9 4LT, England. The animals were 5 to 6 weeks of age on arrival and on examination were found to be healthy. After 12 days acclimatisation, they were re-examined and confirmed to be suitable for use. On the first day of dosing the males weighed 169 to 231 g and the females weighed 141 to 184 g.
Allocation to groups was performed using the Provantis stratified randomisation procedure based on individual body weights recorded on arrival. The cages were positioned in the battery using a specific cage-plan. Each animal was uniquely identified by a subcutaneously implanted micro-identification device. To aid identification, animals were tail marked with their own unique identification numbers using an indelible pen.
Animals were housed in groups up to five, by sex, in solid-floor cages with bedding provided. Bedding was changed as often as necessary to maintain hygiene.
The study room was illuminated to give a cycle of 12 hours light and 12 hours dark and was air-conditioned. The target ranges for temperature and humidity were 19 °C to 23 °C and 40 % to 70 %, respectively. Recorded values were within, or only marginally outside, these limits.
A pelleted diet, Teklad 2014C Rodent Maintenance Diet, supplied by Envigo RMS (UK) Limited, and mains tap water (in bottles) were freely available.
Certificates of analysis for diet and water are held centrally and retained within the Sequani archives. It was considered that none of the contaminants that were monitored was present at a level that might have prevented the study objective from being achieved. - Route of administration:
- oral: gavage
- Details on route of administration:
- Animals were dosed once daily for at least 90 days, by gavage using a rubber catheter and disposable syringe, at a constant dose volume of 4 mL/kg body weight, until necropsy. Individual doses were adjusted according to the most recent body weight.
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples were sent to the Principal Investigator, Dale Burton, at Covance, Eye, Suffolk, IP23 7PX, England for analysis (Covance reference number: WP50YW). The method of analysis used to analyse the dose formulation was validated in Covance Study Number TK45GM
- Duration of treatment / exposure:
- at least 90 days
- Frequency of treatment:
- once daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Group 1
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- Group 2
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- Group 3
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- Group 4
- No. of animals per sex per dose:
- 10 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- A total of 80 animals were used in this study, where animals were dosed once daily for at least 90 days, by gavage using a rubber cather and disposable syringe, at a constant dose volume of 4 mL/kg body weight, until necropsy. Individual doses were adjusted according to the most recent body weight.
- Observations and examinations performed and frequency:
- Clinical observations
- Animals were examined twice daily for mortality and mobility
- Detailed clinical examination once each week
- Animals were observed approx. 1 and 2 hours after dosing
- Following the onset of clinical signs, animals were observed at approximately 15 minutes and at one and around four hours after dosing and at the weekend they were observed either at one hour after dosing or at the end of the working day, whichever was sooner
Ophthalmoscopy
- Both eyes of all animals were examined before the start of treatment
Body weight
- All animals were weighed at the start of dosing and then weekly until necropsy
Food intake
- During the treatment period, the amount of food consumed by each cage of animals was recorded weekly until necropsy.
Behavioural observations
- All animals were observed once weekly, starting predose, for their behaviour both within their cage and then after placement in an open arena
Functional observation battery
- During Week 12/13, sensorimotor responses to visual, acoustic, tactile or proprioceptive stimuli, grip strength and motor activity were recorded for all animals on two occasions for each animal, one before dosing and the second after dosing on the same day - Sacrifice and pathology:
- Sacrifice
At the end of the treatment period, all animals were killed by exposure to carbon dioxide gas in a rising concentration, weighed and examined externally. The abdominal cavity was opened and the animals were exsanguinated from the caudal vena cava. The cranial and thoracic cavities were opened, a full internal examination was performed and all macroscopic abnormalities were recorded and retained.
Pathology
- macroscopic and microscopic pathology on:
Macroscopic and microscopic pathology on adrenal glands, pancreas, aorta, pituitary, bone marrow smear, prostate & seminal vesicles (incl. coagulating gland), brain (10 levels examined), rectum, caecum, salivary gland (submandibular), colon, sciatic nerve (LS and TS), duodenum, site of mammary gland, epididymides, skeletal muscle, eyes (incl. optic nerves), skin, femur & join (incl. Marrow), spinal cord (3 levels examined LS and TS), Harderian glands, spleen, heart, stomach, ileum, (incl. Peyer’s patch), submandibular lymph nodes, jejunum, testes, kidneys, thymus, lacrimal glands, thyroids (incl. parathyroids), larynx, trachea, liver, urinary bladder, lungs (incl. mainstem bronchi), uterus (incl. uterine cervix and oviducts), mesenteric lymph nodes, vagina, oesophagus, all gross lesions, and ovaries. - Other examinations:
- Clinical laboratory studies
- Blood sample collection: blood samples (1.5 mL) were taken under isoflurane anaesthesia from the sublingual vein of all animals on the day of necropsy (0.5 mL into EDTA for haematology; 0.5 mLinto 3.2% w/v aqueous trisodium citrate for coagulation; 0.5 mL into lithium heparin for blood chemistry).
1. Haematology:
Haemoglobin concentration (Hb), platelet count (plate), red blood cell count (RBC), total leucocyte count (WBC), packed cell volume (PCV), neutrophils (Neut), mean cell volume (MCV), lymphocytes (Lymph), mean cell haemoglobin (MCH), monocytes (Mono), mean cell haemoglobin concentration (MCHC), eosinophils (Eosin), mean platelet volume (MPV), basophils (Baso), mean corpuscular volume retics (MCHr), large unstained cells (LUC), platelet distribution width (PDW), reticulocytes (Retics), cellular haemoglobin retics (CHr), plateletcrit (PCT), red blood cell distribution width (RDW), absolute reticulocyte count (A Retic), haemoglobin distribution width (HDW), and cell morphology*)
(*blood smears were prepared and were examined when warranted by machine morphology flags. All parameters were measured on the ADVIA 120 haematology analyser)
2. Coagulation (measured on the ACL Elite Pro):
Prothrombin time (PT) and activated partial thromboplastin time (APTT)
3. Blood chemistry:
Urea, globulin (Glob), creatinine (Cluc), albumin/globulin ratio (A/G), glucose (Gluc), total bilirubin (BiliT), alkaline phosphatase (ALP), cholesterol (Chol), alanine aminotransferase (ALT), sodium (Na), aspartate aminotransferase (AST), chloride (Cl), bile acids (B.Acids), calcium (Ca), total protein (T.Prot), potassium (K), albumin (Alb), HDL cholesterol (HDL), and cholesterol (LDL).
Thyroid hormone assessment - blood sampling and analysis
Vaginal smears - taken by lavage, examined under light microscopy and the stage of oestrous cycle was determined by the type of cell present.but
Organ weights: the following organs were weighed after trimming of fat and other contiguous tissue (contralateral organs were weighed together):
Adrenal glands, prostate & seminal vesicls (incl. coagulating gland), brain, epididymides, spleen, heart, testes, kidneys, thymus, liver, thyroids (incl. parathyroids), ovaries, uterus (incl. uterine cervix), and pituitary - Statistics:
- Data were processed to give group mean values and standard deviations, where appropriate. Where the data allowed, the following methods were used for statistical analysis, comparing Groups 2, 3 and 4 against Group 1.
Depending on the nature of the data set that was to be analysed, appropriate tests were applied. Where parametric tests were appropriate they were preceded by a check for homogeneity of variance using the Levene test and, where available, the Shapiro-Wilks test for normality. If either of these two assumptions failed, a log transformation was applied before retesting. If the transformation failed, appropriate non-parametric tests were applied.
Probability values of less than 5 % were regarded as providing sufficient evidence to reject the null hypothesis and therefore statistical significance was identified at the p<0.05 level. For illustrative purposes, significance levels of p<0.01 and p<0.001 were also noted. - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Males and females given 1000 mg/kg/day showed decreased activity and unsteady gait from Days 19/18 of dosing onwards (from approximately 15 minutes after dosing persisting for up to four hours), respectively. The incidence of these clinical signs decreased with time and by Day 72 of dosing, only one male was showing decreased activity and abnormal gait and over Days 84 to 92 of dosing; at the most, eight out of ten females showed these signs after dosing.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no deaths during the study
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- For the first 3 weeks of dosing the body weights of males given 300 or 1000 mg/kg/day were very close to those of the Controls but by Week 4 it appeared that they were starting to diverge from the Controls and by Week 5 this was more pronounced. The Week 5 body weights of males given 300 or 1000 mg/kg/day were 5 % lower than those of the Controls and their body weight gains over Weeks 1 to 5 were 13 % and 15 % lower (p≤ 0.05). This separation of the growth curves continued such that by Week 14 males given 300 or 1000 mg/kg/day weighed 6 % and 11 % (p≤ 0.05), less than the Controls, with corresponding reductions in overall body weight gain compared with Controls of 12 % (p≤ 0.05) and 21 % (p≤ 0.01) over the duration of the study.
There was no effect on body weight for males given 100 mg/kg/day or for females. - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There was no adverse effect on food intake in either sex at any dose level. Although there were occasional weeks where the food intake of males given o-xylene was statistically significantly higher than that of the Controls, this clearly reflected an unusual pattern of variation in the Controls. Whereas Controls had some weeks of much lower food intake, male groups given o-xylene maintained a more consistent pattern of food intake overall.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- There were no ocular changes or abnormalities that were considered to be related to administration of o-xylene.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no effects on haematology or coagulation parameters that were considered to be test item related. Although a number of parameters showed statistically significant differences between Control and treated groups the differences were minor, not consistent between sexes, lacked a strict dose-response relationship or biological plausibility and so were considered to reflect normal biological variation or to be fortuitous. Mean cell haemoglobin concentration (MCHC) was negligibly (1 %), but statistically significantly lower (p≤ 0.05) in males given 1000 mg/kg/day than in Controls. However, as most values were within the historical range and there were no changes in the primary red cell variates (red blood cell count, haemoglobin concentration, packed cell volume), this trivial difference in this derived parameter was considered not to be meaningful. Group mean platelet count for males given 1000 mg/kg/day was marginally (11 %), but statistically significantly higher than in Controls (p≤ 0.05) and group mean mean platelet volume (MPV) for males given 300 or 1000 mg/kg/day (p≤ 0.05) and plateletcrit (PCT) for males given 1000 mg/kg/day (p≤ 0.01) were also statistically significantly higher than in Controls. Individual platelet counts were within the historical Control range. Although, MPV and PCT values for all animals, including the Controls were outside the historical range, based on the magnitude of differences, which was marginal to negligible, these findings were considered not to be test item related. Group mean neutrophil counts were statistically significantly (p≤ 0.05) higher for males given 300 or 1000 mg/kg/day, however, this was not dose-related, individual values were within historical Control values and as there were no effects on other white blood cell parameters, these differences were considered not to be test item related. Activated partial thromboplastin time (APTT) was marginally (around one second), but significantly (p≤ 0.05) lower, relative to Controls in all male groups given o-xylene. Prothrombin time was marginally (up to 1.5 seconds), but significantly (p≤ 0.05), lower in males given 300 or 1000 mg/kg/day. Since apparent differences in these clotting times were no greater at 1000 mg/kg/day than at 300 mg/kg/day, all individual values were within the historical Control range and, as an increase in these parameters would normally be sought for evidence of impairment of the intrinsic or extrinsic clotting pathways, these variations were considered not to be meaningful. Females given 1000 mg/kg/day had slightly higher red blood cell count (p≤ 0.05) and packed cell volume (p≤ 0.01) than Controls and a lower MCHC (p≤ 0.05). As decreases in primary red cell variates would be more of a concern, and as values remained within normal range, these variations are considered likely to be fortuitous. Group mean total white blood cell count in females given 1000 mg/kg/day was statistically significantly higher (p≤ 0.05) than in Controls as a result of an increase in lymphocyte count (p≤ 0.01). Therefore, as all individual values were well within historical Control ranges these differences are considered of no consequence. Group mean platelet distribution width (PDW) was statistically significantly higher (p≤ 0.01) for females given 1000 mg/kg/day and there was a non-dose related lowering in PCT (p≤ 0.05) for females given o-xylene when compared with Controls. However, as there was no difference in platelet count, these minor differences in these derived indices are considered not to be test item related.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Plasma albumin concentration in males and females given 1000 mg/kg/day was slightly higher than the Control means (p≤ 0.001), leading to increases in the albumin/globulin ratio for these animals (p≤ 0.01 for males and p≤ 0.001 for females). All of the individual albumin values were within the historical background ranges and this effect was considered to be non-adverse given that a reduction would more normally be sought as evidence of impaired hepatic protein synthesis or of reduced dietary protein intake. Statistically significant inter-group differences in globulin concentrations between females given test item and those given vehicle alone were due to unusually high (above the upper limit of the historical background range) individual values in the Control group. Other statistically significant inter-group differences were minor, not consistent between sexes or lacked a strict dose relationship and so were considered to either reflect normal biological variation or to be fortuitous. These are detailed below:
Plasma sodium was negligibly (<2 %), but significantly, (p≤ 0.01 to p≤ 0.001), higher in males given 300 or 1000 mg/kg/day than in Controls and plasma chloride was negligibly (<1 %), but significantly (p≤ 0.05) lower in males given 1000 mg/kg/day than in Controls. These trivial differences within the normal range were considered to be fortuitous. Males given 1000 mg/kg/day had a higher group mean alanine aminotransferase (ALT) activity (p≤ 0.05) than Controls, with five out of ten individual values above the historical background range. However, in the absence of degenerative pathology changes in the liver, this increased activity was considered to be non-adverse. The slight increase in plasma ALT in males given 1000 mg/kg/day may reflect the observed hepatic hypertrophy in this group. Glucose was lower in a non-dose related manner in males given o-xylene when compared with Controls (p≤ 0.01). Plasma urea was lower in a non-dose related manner for females given o-xylene (p≤ 0.05 to p≤ 0.01), relative to Controls. Cholesterol (p≤ 0.05) and high density lipoproteins (HDL) (p≤ 0.01) were higher in females given 1000 mg/kg/day than in Controls. These differences are considered likely to be entirely fortuitous as they either lacked a dose
relationship, were very minor in degree or, for urea, moved in the wrong direction for diagnostic evidence of renal dysfunction. - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- There were no effects on sensory reaction or grip strength elicited by o-xylene. During the weekly functional observations, in the open arena, males given 1000 mg/kg/day exhibited effects on arousal (hypoactivity or hyperactivity), unusual posture and abnormal gait. Twitches were observed in one male given 300 mg/kg/day and one male given 1000 mg/kg/day. Increased episodes of arousal in the arena and abnormal gait were observed between Days 21 to 63 and Days 21 to 56 of dosing, respectively. Excessive salivation in the arena was also noted between Days 14 and 70 of dosing for males given 300 or 1000 mg/kg/day, with incidence generally increasing with time. Excessive rearing was noted in a small number of males given 1000 mg/kg/day but this was also seen in one male given 100 mg/kg/day and one Control male and therefore considered not to be test item related. A few females given 300 or 1000 mg/kg/day salivated on removal from the cage between Days 14 to 42. Females given 1000 mg/kg/day also exhibited effects on arousal in the arena (both hyperactivity and hypoactivity), unusual flattened posture, abnormal gait and salivation. In addition, a small number of females exhibited twitching or excessive rearing. Although incidences generally increased with time similarly to the males, these effects were not seen after Day 77 of dosing. During the last week of treatment when the functional observations were performed before and after dosing three females given 1000 mg/kg/day had abnormal gait after dosing, that had not been seen before dosing. In males given 100, 300 or 1000 mg/kg/day o-xylene, movement counts and distance travelled were statistically significantly lower than in Controls (p≤ 0.05 to p≤ 0.01) during a number of post dose counting periods and this was, on occasions, accompanied by a statistically significant increase in time at rest (p≤ 0.05 to p≤ 0.01). There were fewer instances where there were similar statistically significant effects on movement in females and these effects were not dose-related.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight related liver weights for both sexes given 300 or 1000 mg/kg/day (p≤ 0.05 to p≤ 0.001) and females given 100 mg/kg/day (p≤ 0.05) were statistically significantly higher than Controls. Most of the individual relative liver weights for males and females given 1000 mg/kg/day were also above the upper limit of the historical background range. When adjusted for brain weight liver weight was 19 % heavier than Controls in males and 40 % heavier in females (p≤ 0.001) given 1000 mg/kg/day.
Body weight related kidney weights for both sexes given 300 or 1000 mg/kg/day (p≤ 0.01 to p≤ 0.001) and females given 100 mg/kg/day (p≤ 0.05) were statistically significantly higher than Controls. Most of the individual weights were within the historical background range. When adjusted for brain weight kidney weights for both sexes given 300 mg/kg/day were 15 % and 7 % respectively, heavier than those of Controls (p≤ 0.01) and 26 % and 17 % respectively, heavier at 1000 mg/kg/day (p≤ 0.001). Thyroid weights (relative to body weight or brain weight) of females given 1000 mg/kg/day were all heavier than those of Controls (p≤ 0.01 to p≤ 0.001), however, most of the individual weights were within the historical background range.
The adrenals (relative but not absolute weights), of males given 1000 mg/kg/day were 19 % heavier than those of Controls (p≤ 0.05). However, there were no macroscopic or microscopic findings in the adrenals and as all individual values were within the historical control range this increase in adrenal weight was considered not to be adverse. The remaining organ weight differences for relative brain, heart, testes and epididymis weights between Controls and males given up to 1000 mg/kg/day were considered to be due to the slight growth retardation which was evident by the reduced body weight gains over the duration of the study. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- A variety of spontaneous changes was noted in Control and animals given o-xylene with no indication of an effect of treatment. The spectrum of these findings is generally consistent with changes encountered in rats of this age kept under laboratory conditions.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Findings considered to be related to treatment were seen in the liver (hepatocellular hypertrophy) and thyroid (follicular cell hypertrophy) and in the kidneys (eosinophilic inclusions (hyaline droplets) in the tubular epithelium (males only)). Although there were indications of positive α2μ-globulin staining in 3/10 males given 1000 mg/kg/day, there was also minimal staining in 2/10 Controls, thus failing to conclusively indicate that the increased number of hyaline droplets was related to α2μ-globulin. Thus, the mechanism of the increased incidence/severity of hyaline droplets seen within the cortical tubules of male kidneys in this study remained unestablished. A variety of other spontaneous changes was noted in Control and treated animals with no indication of an effect of treatment. The spectrum of these findings is generally consistent with changes encountered in rats of this age kept under laboratory conditions.
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Thyroid Hormone Analysis
As samples were obtained at only a single timepoint, these findings represent only a snapshot of thyroid hormone levels. In addition, due to the relatively small group size (n=10), the analysis lacks sufficient statistical power. There was some variation in thyroid hormones within groups with no evidence of a consistent pattern of change elicited by o-xylene. There were no statistically significant inter-group differences for TSH that showed a clear dose response relationship and there were no statistically differences for triiodothyronine (T3) for either sex at any dose. T4 concentrations in females given 1000 mg/kg/day was actually slightly (25 %), but significantly, (p< 0.05) higher than that in Controls but within normal biological variability and, T4 in males given 1000 mg/kg/day was marginally (10 %) lower than in Controls, this difference did not attain statistical significance compared to Controls, nor did it show a dose response relationship. Any of the changes in circulating T4 concentrations
were considered to be within normal biological variability and likely due to the natural diurnal variation in thyroid hormone concentrations.
Oestrous cycles
There was no effect of o-xylene on the oestrous cycles; the data were variable with the majority of females in all groups being in dioestrus. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- clinical signs
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical signs
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 300 mg/kg bw/day (nominal)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- no
- Conclusions:
- In conclusion, when administered by gavage to the Han Wistar rat, once daily for at least 90 days, o-xylene was generally well tolerated in-life at 100 and 300 mg/kg/day with, at the latter dose, only a mild retardation of body weight gain in males and clinical signs being limited to some transient excessive salivation after dosing. However, more profound (decreased activity, unsteady gait, effects on arousal, unusual posture), but transient, clinical signs were apparent at 1000 mg/kg/day and a more marked retardation of body weight gains in males. Target organ pathology was restricted to rat specific adaptive responses consisting of hepatic centrilobular hypertrophy and secondary thyroid follicular hypertrophy consistent with enzyme induction and adverse renal tubular changes in males only likely reflecting proteinuria and inclusion of non α2μ-globulin proteins. Therefore, the No Observed Adverse Effect Level (NOAEL) was defined as 300 mg/kg/day o-xylene in the female rat because of the severity of clinical signs at 1000 mg/kg/day and as 100 mg/kg/day in the male rat, because of the incidence and severity of the renal changes. However, given the physiological differences between the male rat kidney and human, the observed tubular changes are unlikely to represent a hazard to man. Therefore, if the findings in the kidney are disregarded as being human relevant, the NOAEL for the male would be 300 mg/kg/day.
- Executive summary:
An OECD 408 rat study was conducted to assess the potential toxicity of o-xylene when administered by gavage to the rat once daily for at least 90 days. The test material, o-xylene (CAS 95-47 -6), was administered to male and female rats by oral gavage. Dose levels were 0, 100, 300, and 1000 mg/kg/day (Groups 1 through 4, respectively), with 10 animals/sex/group dosed daily for at least 90 days.The following were investigated: clinical observations, ophthalmoscopy, body weight, food intake, functional observation battery, haematology, blood chemistry, thyroid hormone analysis, organ weights, macroscopic and microscopic pathology.
There were no deaths during the study. Males and females given 1000 mg/kg/day showed decreased activity and unsteady gait from Days 19/18 of dosing onwards (persisting for up to 4 hours after dosing), respectively. The incidence of these clinical signs decreased with time and by Day 72 of dosing, only one male was showing decreased activity and abnormal gait. Over Days 84 to 92 of dosing at most eight out of ten females showed one or both of these signs after dosing. No effects on sensory reaction or grip strength were elicited by o-xylene. In open arena testing, males given 1000 mg/kg/day exhibited effects on arousal, unusual posture and abnormal gait. Twitches or extended rearing were also observed in a small number of individual males given 1000 mg/kg/day. Increased episodes of arousal in the arena and abnormal gait were observed between Days 21 to 70 and Days 21 to 56 of dosing, respectively. Excessive salivation in the arena was also noted between Days 14 and 70 of dosing for males given 300 or 1000 mg/kg/day, with incidence increasing with time. Females given 1000 mg/kg/day also exhibited effects on arousal in the arena, abnormal gait and salivation. Although incidences increased with time similarly to the males, these observations were not seen in either sex after Day 77 of dosing. Movement counts and distance travelled were reduced in males given 100, 300 or 1000 mg/kg/day and this was occasionally accompanied by an increased time at rest. Males given 300 or 1000 mg/kg/day gained less weight over the study than Controls with terminal body weights that were 6 % and 11 % respectively, lower than those of the Controls. There was no effect on body weight for females and no effect on food intake in either sex. There were slight increases in Thyroxine (T4) and no effect on thyroid stimulating hormone (TSH) or triiodothyronine (T3) levels at the end of the treatment period and no adverse effects on haematology, coagulation or blood chemistry parameters. Both sexes given 300 or 1000 mg/kg/day and females given 100 mg/kg/day had statistically significantly higher liver and kidney weights when compared with Controls. In addition, thyroid weights for females given 1000 mg/kg/day were also higher than Controls.
Histopathology findings considered to be related to o-xylene were seen in the liver (hepatocellular hypertrophy) and thyroid (follicular cell hypertrophy) in both sexes and, in the kidneys, eosinophilic inclusions (hyaline droplets) in the tubular epithelium (males only). Following α2μ-globulin staining of the kidneys, although positive staining was observed in 3/10 high dose males, minimal staining was also observed in 2/10 Controls. The precise content of the hyaline droplets observed at an increased incidence/severity of within the cortical tubules of male kidneys therefore remained unestablished. Given the physiological differences between the male rat kidney and human, these findings are considered unlikely to represent a hazard to man.
In conclusion, when administered by gavage to the Han Wistar rat, once daily for at least 90 days, o-xylene was generally well tolerated in-life at 100 and 300 mg/kg/day with, at the latter dose, only a mild retardation of body weight gain in males and clinical signs being limited to some transient excessive salivation after dosing. However, more profound (decreased activity, unsteady gait, effects on arousal, unusual posture), but transient, clinical signs were apparent at 1000 mg/kg/day and a more marked retardation of body weight gains in males. Target organ pathology was restricted to rat specific adaptive responses consisting of hepatic centrilobular hypertrophy and secondary thyroid follicular hypertrophy consistent with enzyme induction and adverse renal tubular changes in males only likely reflecting proteinuria and inclusion of non α2μ-globulin proteins. Therefore, the No Observed Adverse Effect Level (NOAEL) was defined as 300 mg/kg/day o-xylene in the female rat because of the severity of clinical signs at 1000 mg/kg/day and as 100 mg/kg/day in the male rat, because of the incidence and severity of the renal changes. However, given the physiological differences between the male rat kidney and human, the observed tubular changes are unlikely to represent a hazard to man. Therefore, if the findings in the kidney are disregarded as being human relevant, the NOAEL for the male would be 300 mg/kg/day.
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 11th April - 16th July 1986
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Remarks:
- There are no significant deviations which affected the quality or the integrity of the study or the interpretation of the results in the report.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
- Deviations:
- no
- Remarks:
- There are no significant deviations which affected the quality or the integrity of the study or the interpretation of the results in the report.
- Principles of method if other than guideline:
- The aim of this study was to evaluate the subchronic toxicity of m-xylene when administered to rats daily by oral gavage for at least 90 days.
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Test material name: m-xylene
- CAS number: 108-38-3
- State: clear colourless liquid
- Source: Fluka Chemical Corporation, Hauppauge, New York
- Sponsor: Dynamac Corporation
- Lot No.of test material: 259 211
- Expiration date of the lot/batch: not specified
- Purity: 99.1% (pure by GC-analysis)
- The test substance was analysed for identity and purity prior to study initiation and for purity after study termination.
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- During transit: stored frozen and protected from light
- Storage condition of formulated test material: room temperature
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: dosing preparations prepared using corn oil (vehicle) and were adjusted to 100% activity, based on a purity of 99% - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- No further details specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc.
- Total number of animals: 168 males and 168 females
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 46 days
- Weight at study initiation: males = 203.7-246.4g and females = 142.1 - 174.8g
- Housing: rats were uniquely identified by ear tags and cage cards and were housed individually in elevated wire-mesh cages
- Diet (e.g. ad libitum): commercial rodent diet (Purina Certified Rodent Chow® #5002)
- Water (e.g. ad libitum): acidified tap water
- Acclimation period: acclimated to laboratory conditions for approximately 2 weeks
DETAILS OF FOOD AND WATER QUALITY: Contaminant analysis for the rodent chow 5002 diet and water can be found in the 'attached background material'
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 70-77
- Humidity (%): 31-69
> temperature and relative humidity in the animal were recorded twice daily (with few exceptions)
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle was maintained daily via artificial illumination
IN-LIFE DATES: From: 11th April To: 14-16th July 1986 - Route of administration:
- oral: gavage
- Details on route of administration:
- The formulated test material was given to the animals by oral gavage. The dosing volume was 2.5 mL/kg
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
- Dosing solutions were prepared weekly.
- For each dose level, the amount of test material required was calculated and then weighed. It was transferred to a volumetric flask and then the vehicle, corn oil, was added to reach the final volume.
- The flask was capped and inverted by hand until thoroughly mixed.
- Groups and doses can be seen in Table 1 below. - Analytical verification of doses or concentrations:
- yes
- Remarks:
- Formulated test material was analysed for purity, stability and dose concentration.
- Details on analytical verification of doses or concentrations:
- Stability results reveal that there was a small amount of test material lost after 21 days of storage at 5°C.
All samples analysed were within the specific limits ± 10% of target concentration - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- Daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Group 1 (control) and Group 5 (baseline)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- Group 2
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Remarks:
- Group 3
- Dose / conc.:
- 800 mg/kg bw/day (nominal)
- Remarks:
- Group 4
- No. of animals per sex per dose:
- 20 animals/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Rationale for animal assignment : Sprague-Dawley rats were employed since they have historically been used in safety evaluation studies and were requested by the EPA
- Animal selection: following physical and ophthalmologic examinations, a total of 85 clinically acceptable rats of each sex were randomly allocated to 4 treatment groups using a computer weight randomisation program, each composed of 20 animals/sex/group and 5 animals/sex were assigned to the baseline group employed for pre-treatment bloodwork.
- Animals not selected were assigned to another study or discarded without necropsy.
- Baseline groups were used for pre-treatment bloodwork and later discarded without necropsy. - Positive control:
- No positive control was employed.
- Observations and examinations performed and frequency:
- - All rats were observed daily for clear signs of toxicity, beginning about one hour after dosing
- A cursory examination was performed during dosing
PHYSICAL EXAMINATIONS: Yes
- Time schedule: performed at initiation and weekly thereafter
MORIBUNDITY/MORTALITY CHECKS: Yes
- Time schedule: twice daily
INDIVIDUAL BODY WEIGHTS: Yes
- Time schedule for examinations: recorded during the randomisation procedure, at initiation and weekly thereafter
FOOD CONSUMPTION : Yes
- Food consumption for each animal determined: Yes, recorded weekly
FOOD EFFICIENCY: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Performed by a board-certified veterinary opthalmologist
- Time schedule for examinations: prior to treatment, Week 13
- Dose groups that were examined: all animals prior to treatment and the last 10 survivors per sex per group during Week 13
- Pupils of both eyes were dilated prior to examination using 1% Atropine Sulphate
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to study initiation, weeks 5-13
- Anaesthetic used for blood collection: Yes - samples were collected via the orbital sinus while under carbon dioxide anaesthesia
- Animals fasted: Yes, overnight
- How many animals: 5 animals/sex (Baseline group) prior to initiation and on the first 10 survivors/sex/group during weeks 5-13
- Parameters examined: please see Table 2 below
CLINICAL PATHOLOGY: Yes
- Time schedule for collection of blood: prior to study initiation, weeks 5-13
- Animals fasted: Yes - samples were collected via the orbital sinus while under carbon dioxide anaesthesia
- How many animals: 5 animals/sex (Baseline group) prior to initiation and on the first 10 survivors/sex/group during weeks 5-13
- Parameters examined: please see Table 3 below
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- For all animals that died during the study and all survivors that were sacrificed after 13 weeks of treatment and were given a complete gross necropsy. Please see Table 4 below.
- Euthanasia was exsanguination whilst under sodium pentoarbital anaesthesia.
- At the terminal sacrifice, five animals per sex from the control group and 10 animals per sex from each treated group were selected for electron microscopy, the results of which will be available in a separate report.
HISTOPATHOLOGY: Yes
- All preserved tissues from all animals were embedded in paraffin, sectioned, and stained with haemoxylin and eosin.
- The following tissues were examined microscopically:
(1) All tissues from control and high-dose animals and from all animals not surviving to termination.
(2) Gross lesions, lungs, liver and kidneys from all remaining animals. - Other examinations:
- ORGAN WEIGHTS
-The following organs were weighed for all terminally killed animals, except those selected for electron microscopy:
liver, kidneys, spleen, adrenal glands, brain with stem, heart, tested with epididymides, ovaries
TISSUE PRESERVATION
- Please see Table 5 below for all tissues that were preserved from each animal (when present) in 10% neutral buffered formalin. - Statistics:
- - Cumulative survival data were analysed using the National Centre Institute Package (Life Table Analysis).
- Trend analysis of survival was evaluated at the 5.0% one-tailed probability level.
- Body weights, food consumption, appropriate clinical pathology data and organ weight data were compared between the control and treated groups of the same sex
- Tests for homogeneity of variances and ANOVA were evaluated at the 5.0% two-tailed probability level.
- Control vs. treated group means were evaluated using Dunnett's t-test at the 5.0% two-tailed probability level.
- Data transformations were performed where variances were heterogenous, which are indicated in the tables with an appropriate superscript next to the control group mean. The list of these superscripts can be seen in Table 6 below.
- When an effect is referred to as 'significant', it means that there is a statistically significant difference between the control group and the specified treated group of the same sex - Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Urine stains were observed weekly in both sexes of Group 4 and thought to be possibly treatment-related.
Other common weekly signs observed were chromodacryorrhea and malocclusion, but these are not thought to be treatment-related.
Salivation was frequently observed in both sexes of Group 4 and only rarely in the other treated groups. It occurred just prior to dosing and the animals returned to normal by the one-hour post-dosing observations.
Other daily observations included hyperactivity, convulsions and epistaxis - they were only observed in the first three weeks of the study at a low frequency - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Males: there was a significantly higher mortality in Group 3 (5 males died), but there was not a significant trend.
Females: there was significant trend and a significantly higher mortality in Group 3 (5 females died) and Group 4 (4 females died).
Males and females: In the 19 unscheduled deaths, all but one of the animals had foreign material in the alveoli and were determined to be related to gavage dosing accidents rather than being related to the test material (please refer to the histopathological findings section). This may also relate to the lung lesions, mottled lungs and failure of the lungs to collapse seen in males and females of Groups 3 and 4. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The mean body weight gain over the course of the experiment was significantly decreased in Groups 3 and 4 for males and in Group 4 for females.
There was a clear relationship between dose and body weight reduction in both sexes.
The overall total mean body weights (Groups 1-4) were 15% and 8% lower than in the controls for males and females respectively. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Statistical analysis was employed at three intervals - Weeks 1-5, 6-9 and 10-13.
Food consumption was significantly reduced during Weeks 1-5 for Group 4 males and during Weeks 6-9 for Group 3 and 4 males.
Food consumption was comparable for all female groups at all three intervals. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Only two animals (one Group 1 male and one Group 3 male) showed abnormalities at the terminal examination and thus were judged to be unrelated to treatment.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The haemotocrit was significantly decreased in Group 4 females.
At Week 13, there were no significant changes to the haematology parameters in either sex. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Significant changes were observed at the Week 5 interval:
- Group 4 males - potassium was increased and total bilirubin was decreased.
- Group 4 females - cholesterol and calcium increased
- Group 3 and 4 females - potassium was increased.
There were fewer significant changes at Week 13:
- Group 4 males - alanine aminotransferase was increased
- Group 4 females - calcium and cholesterol was increased - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Group 4:
- the terminal body weights were significantly decreased in both sexes
- males - there were few significant changes in organ weights, however heart weight was decreased and relative brain and kidney weights were increased vs. control
- females - no significant changes in absolute or relative organ weights vs. control - Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were few gross lesions observed.
The most commonly seen gross lesions were mottled lungs and failure of the lungs to collapse.
These observations were most frequently observed in both sexes of Group 3 and 4, but were only found in the animals found dead during the experiment.
The other lesions observed were sporadic and showed no apparent dose relationship - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Several spontaneously-occurring incidental lesions were observed in animals at the terminal sacrifice, but were concluded to be not related to treatment.
In the 19 unscheduled deaths (males Group 2-4; females Group 3-4), all but one of the animals had foreign material in the alveoli and were determined to be related to gavage dosing accidents rather than related to the test material. - Histopathological findings: neoplastic:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- m-xylene
- Effect level:
- ca. 200 mg/kg bw/day (nominal)
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: It has been reported as NOEL in the report
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- m-xylene
- Effect level:
- ca. 100 mg/kg bw/day (nominal)
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: It was reported as NOEL in the report.
- Critical effects observed:
- not specified
- Conclusions:
- Based on the results of this study and following the assumption that the vehicle and/or test material aspiration were responsible for the deaths in the treated animals, the no-observed-adverse-effect level (NOAEL) of m-xylene was 100 mg/kg/day for males and 200 mg/kg/day for females.
- Executive summary:
The sub-chronic toxicity of m-xylene was investigated in this study on male and female Sprague-Dawley rats. The rats were acclimated for approximately 2 weeks and were 46 days of age at the start of the study. The rats underwent physical and ophthalmologic examinations prior to the test and then 85 clinically acceptable rats of each sex were assigned to treatment groups, each composed of 20 rats/sex plus 5 rats/sex used in the baseline haematology group. The rats were gavaged daily at each sex were tested at each dose daily for at least 90 days.
Dosing solutions were prepared weekly. For each dose level, the calculated amount of test substance, m-xylene, was weighed and transferred to a volumetric flask. The vehicle, corn oil, was added to achieve the final volume and then the flask was capped and inverted by hand until thoroughly mixed. M-xylene was administered to the rats daily via oral gavage at the following dose levels; 0, 100, 200 and 800 mg/kg/day (Groups 1 -4 respectively). The control group (Group 1) received the vehicle only and the Baseline group (Group 5 0 mg/m^3) were used for pre-treatment bloodwork and later discarded without necropsy. Several observations were recorded, including clinical signs, body weights, food consumption, opthalmologic examinations, organ weights and organ-to-body weight ratios, mortality, gross pathology, clinical chemistry and histopathology was recorded.
Mortality was found to be significantly increased in male Group 3 and female Group 3 and 4, however based on histopathology findings, it is thought that the cause of these deaths was most likely to be due to vehicle and/or compound aspiration. In the 19 unscheduled deaths seen in males (Group 2 -4) and females (Groups 3 -4), all but one of the animals had foreign material in the alveoli and were determined to be related to gavage dosing accidents rather than being related to the test material, which may also relate to the lung lesions, mottled lungs and failure of the lungs to collapse seen in males and females of Groups 3 and 4, which were only observed in the animals found dead. Salivation was frequently observed in both sexes of Group 4 and only rarely seen in the other treatment groups. Urine stains were also observed weekly in both sexes of Group 4 and thought to be possibly-treatment related. Other commonly observed clinical signs were chromodacryorrhea and malocclusion, but were not thought to be treatment-related. Food consumption was significantly reduced for males during Weeks 1-5 for Group 4 males and during Weeks 6-9 for Group 3 and 4 males. The results remained comparable throughout the study for female rats. Only two animals showed abnormalities in the ophthalmological examination and thus it was concluded to be unrelated to the treatment. Few clinical pathology parameters were significantly changed and all were observed in Group 4, except for one seen in female Group 3. Few significant changes were seen in absolute or relative organ weights, all of which were seen in Group 4 males, where heart weight was decreased and relative brain and kidney weights were increased.
The mean body weight change was significantly lower than controls for males in Group 3 (200 mg/kg bw/day) and Group 4 (800 mg/kg bw/day) and for females in Group 4 (800 mg/kg bw/day) (Table 10). The percentage difference in mean body weight change between the control and each dose group for males and females were calculated. The percentage difference for males was 9.5% and 25.1% for Group 3 and 4 males respectively and 15.4% for Group 4 females. Reduced absolute body weight of approximately >10% is generally considered to be a sign of general toxicity, therefore the dose-related reductions in Group 3 and 4 males and Group 4 females are considered to be adverse and are therefore have been listed as NOAELs, whilst they have been reported as NOELs in the report.
Based on the results of this study and following the assumption that the vehicle and/or test material aspiration was responsible for the deaths in the treated animals in groups 3 and 4, the no-observed-effect level (NOAEL) of m-xylene was 100 mg/kg/day for males and 200 mg/kg/day for females.
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 April - 23 July 1986
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- Protocol required bloodwork to be taken in Week 4 but was actually performed during Week 5. We consider that there are no significant deviations which affected the quality or the integrity of the study or the interpretation of the results in the report.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
- Deviations:
- yes
- Remarks:
- Protocol required bloodwork to be taken in Week 4 but was actually performed during Week 5. We consider that there are no significant deviations which affected the quality or the integrity of the study or the interpretation of the results in the report.
- Principles of method if other than guideline:
- The purpose of the study was to evaluate the subchronic toxicity of p-xylene when administered to Sprague-Dawley rats daily by oral gavage for at least 90 days.
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Test material: p-xylene
- CAS number: 106-42-3
-State: clear colorless liquid
- Source: Fluka Chemical Corporation, Hauppauge, New York (in three shipments - March 6, April 17, April 30 1986)
- Lot No.of test material: 235 855
- Expiration date of the lot/batch: not specified
- Purity: 99% (by GC-analysis)
> the test material was analysed for purity and identity prior to study initation and repeated at termination for purity only.
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- During transit: frozen and protected from light
- Storage condition of formulated test material: room temperature
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: dosing formulations were prepared using corn oil (vehicle) and were adjusted to 100% activity based on the purity - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- No further details specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Raleigh, North Carolina
-Total number of animals: 105 males and 105 females
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: 45 days
- Weight at study initiation: 199.1 - 257.8g (males) and 144.9-192.1g (females)
- Fasting period before study: not specified
- Housing: rats were uniquely identified by ear tags and cage cards and were housed individually in elevated wire-mesh cages
- Diet (e.g. ad libitum): commercial rodent diet (Purina Certified Rodent Chow ® #5002)
- Water (e.g. ad libitum): acidified tap water
- Acclimation period: approximately two weeks
DETAILS OF FOOD AND WATER QUALITY: Contaminant analysis for the rodent chow® 5002 diet and water are attached to the study report.
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71-78
- Humidity (%): 31-69
- Temperature and relative humidity in the animal room were recorded twice daily (with few exceptions)
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle
IN-LIFE DATES: From: 17th April To: 21st- 23rd July 1986 - Route of administration:
- oral: gavage
- Details on route of administration:
- The formulated test material was administered to the animals by oral gavage daily for 13 weeks; control animals recieved the vehicle only. The dosing volume was 2.5 mL/kg.
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
- Dosing solutions were prepared weekly.
- For each dose level, the amount of test material was calculated, weighed and then transferred to a volumetric flask.
- The vehicle, corn oil, was added to achieve the final volume, and then the flask was capped and inverted by hand until thoroughly mixed.
- Groups and doses can be seen in Table 1 below. - Analytical verification of doses or concentrations:
- yes
- Remarks:
- The formulated test material was analysed for purity, dose concentration and stability
- Details on analytical verification of doses or concentrations:
- Stability results revealed that there was a small amount of test material lost after 21 days of storage at 5°C.
All samples analysed were within the specific limits ± 10% of target concentration - Duration of treatment / exposure:
- 13 weeks (at least 90 days)
- Frequency of treatment:
- Daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Control (group 1) and Baseline (Group 5)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- Group 2
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Remarks:
- Group 3
- Dose / conc.:
- 800 mg/kg bw/day (nominal)
- Remarks:
- Group 4
- No. of animals per sex per dose:
- 20 animals/sex/group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Rationale for animal assignment : Sprague-Dawley rats were used since they have historically been employed in safety evaluation studies and were requested by the US EPA.
- Animal selection:Following physical and opthalmologic examinations, 85 clinically acceptable rats of each sex were assigned to treatment groups using a computer weight randomisation programme, each composed of 20 animals/sex/group and 5 animals/sex were assigned to the baseline group employed for pre-treatment bloodwork
- Animals not selected were assigned to another study or discarded without necropsy.
- The baseline groups were used for pretreatment bloodwork and later discarded without necropsy. - Positive control:
- No positive control was employed.
- Observations and examinations performed and frequency:
- -All rats were observed for overt signs of toxicity daily, beginning about one hour after completion of dosing
-A cursory exam was conducted during dosing
CAGE SIDE OBSERVATIONS: Yes
- Looking for clear signs of toxicity
- Time schedule: Daily starting one hour after completion of dosing
DETAILED CLINICAL OBSERVATIONS: Yes
- Complete physical examiniations
- Time schedule: at initiation and weekly thereafter
MORTALITY/MORBIDITY CHECKS: Yes
- Time schedule: twice daily
INDIVIDUAL BODY WEIGHT: Yes
- Time schedule for examinations: during the randomisation procedure, at initiation and weekly thereafter
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined Yes
- Time schedule: weekly
FOOD EFFICIENCY: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Performed by a board-certified veterinary opthalmologist. 1% Atropine Sulphate was used to dilate pupils of both eyes prior to examination.
- Time schedule for examinations: Prior to treatment and on the last 10 survivors per sex per group during Week 13
- Dose groups that were examined: all groups
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to study initiation, weeks 5-13
- Anaesthetic used for blood collection: Yes - samples were collected via the orbital sinus while under carbon dioxide anaesthesia
- Animals fasted: Yes, overnight
- How many animals: 5 animals/sex (Baseline group) prior to initiation and on the first 10 survivors/sex/group during weeks 5-13
- Parameters examined: please see Table 2 below
CLINICAL PATHOLOGY: Yes
- Samples were collected via the orbital sinus while under carbon dioxide anaesthesia
- Time schedule for collection of blood: prior to initiation and during weeks 5 and 13. (Protocol required bloodwork to be taken in Week 4 but was actually performed during Week 5).
- Animals fasted: yes overnight
- How many animals: Five animals per sex (baseline group) and the first 10 survivors per sex per group during week 5 and 13
- Parameters tested: please see Table 3 below
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- All animals that died during the course of the study and all survivors were sacrificed after 13 weeks of treatment and were given a complete gross necropsy. Please see Table 4 below.
- Euthanasia was exsanguination while under sodium pentoarbital anaesthesia.
- At the terminal sacrifice, five animals per sex from the control group and 10 animals per sex from each treated group were selected for electron microscopy, the results of which will be available in a separate report.
HISTOPATHOLOGY: Yes
- All preserved tissues from all animals were embedded in paraffin, sectioned, and stained with haemoxylin and eosin.
- The following tissues were examined microscopically:
(1) All tissues from control and high-dose animals and from all animals not surviving to termination.
(2) Gross leesions, lungs, liver and kidneys from all remaining animals. - Other examinations:
- ORGAN WEIGHTS
-The following organs were weighed for all terminally killed animalls, except those selected for electron microscopy:
liver, kidneys, spleen, adrenal glands, brain with stem, heart, tested with epididymides, ovaries
TISSUE PRESERVATION
- Please see Table 5 below for all tissues that were preserved from each animal (when present) in 10% neutral buffered formalin. - Statistics:
- - Cumulative survival data were analysed using the National Centre Institute Package (Life Table Analysis).
- Trend analysis of survival was evaluated at the 5.0% one-tailed probability level.
- Body weights, food consumption, appropriate clinical pathology data and organ weight data were compared between the control and treated groups of the same sex
- Tests for homogeneity of variances and ANOVA were evaluated at the 5.0% two-tailed probability level.
- Control vs. treated group means were evaluated using Dunnett's t-test at the 5.0% two-tailed probability level.
- Data transformations were performed where variances were heterogenous, which are indicated in the tables with an appropriate superscript next to the control group mean. The list of these superscripts can be seen in Table 6 below.
-When an effect is referred to as "significant", it means that there is a statistically significant difference between the control group and the specified treated group of the same sex - Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The most commonly observed weekly clinical signs were malocclusion, chromodacryorrhea, sores and salivation.
Only salivation showed a compound-related effect and was seen in both sexes in Group 4. Observed every week except the first week, generally just prior to dosing and then the animals returned to normal by the one-hour post-dosing observations.
Sores were mostly seen on the ears, most likely due to the ear tags (method of identification)
Daily observations included sensitivity to touch and salivation. The former had such a low incidence (observed twice during the study) that it was not considered important. Salivation, however, was observed frequently during every study week except the first, and it occurred only in Group 4 (both sexes). Generally, it was observed just prior to dosing and the animals were back to normal by the one-hour post-dosing observations. - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Males: a significant trend for increased mortality and in Group 4 there was a significantly higher mortality
Females: no significant differences in mortality and no significant trend
Intra-alveolar foreign material was found in the lungs of nearly all of the unscheduled deaths in males and females, and were determined to be associated with congestion and appeared secondary to vehicle and/or test material aspiration rather than being related to the test material (please refer to the histopathological findings section). - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The mean body weights of both sexes in Group 4 were lower than the other groups.
There was no significant difference in total body weight gain between the control and treated groups of either sex or a significant difference in mean body weights at Week 13. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption was generally highest in Group 4 of both sexes. Total food consumption was significantly increased in the Group 4 females during Weeks 10-13.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No ocular abnormalities were seen in any of the animals at the terminal examination
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No significant differences observed in any haematology parameters in the treated groups of either sex at Week 5.
The only significant difference at Week 13 was in segmented neutrophils, which were decreased in the Group 3 males. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Few significant differences were observed in any clinical chemistry parameters at week 5: all the Group 4 females showed increased levels of phosphorus, cholesterol and alanine aminotransferase.
At week 13, there were no significant changes seen in either sex. - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No significant differences were observed between the control and treated groups of either sex in any of the absolute or relative organ weights.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were few gross lesions observed at necropsy, which were infrequent and concluded to show no dose relationship.
In unscheduled deaths, mottled lungs and failure of lungs to collapse were seen more frequently than other types of lesions. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - In both treated and control animals, lesions were found in the kidneys and liver and included:
(1) kidneys - e.g. tubular regeneration, focal mononuclear cell infiltrates, interstitial fibrosis
(2) liver - e.g. mononuclear cell infiltrates, subacute inflammation, fatty change
-1 male in Group 3 and 3 males in Group 4 (all unscheduled deaths) - cytoplasmic hyaline inclusions were observed.
- The nature of these inclusions was unclear and they were not considered to be biologically significant, since they were not present in terminally sacrificed rats, they were observed with a low overall incidence and only seen in male rats.
- In nearly all of the unscheduled deaths, intra-alveolar foreign material was present in the lungs that was often accompanied by congestion and thus thought to be secondary to vehicle and/or test aspiration.
- Various incidental lesions were observed in all groups, which were not treatment-related.
- No specific compound-related histopathologic alterations were present in the tissues examined. - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 200 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other:
- Remarks:
- Although the report lists 200 mg/kg bw/day as a NOEL, the LOA XWG considers 200 mg/kg bw/day as a NOAEL based on significantly reduced M and F body weight at 800 m/kg bw/day (Table 1).
- Critical effects observed:
- not specified
- Conclusions:
- Based on the results of this study and the conclusion that vehicle and/or test material aspiration was the cause of all unscheduled deaths in the treated animals, the no-observed--adverse-effect-level (NOAEL) of p-xylene was determined to be 200 mg/kg/day.
- Executive summary:
This 90-day study was undertaken in order to evaluate the sub-chronic toxicity of the test substance, p-xylene (99% purity) in rats. Four doses were tested in this study: 0, 100, 200 and 800 mg/kg/day (Groups 1 -4 respectively) and Group 5 (0 mg/kg/day) was a baseline group that was used solely for pre-treatment bloodwork (animals assigned to this group were later discarded without necropsy). Physical and opthalmologic examinations were performed on male and female Sprague-Dawley rats used in this study. Twenty animals/sex were assigned to each dose group and were dosed daily for at least 90 days.
Dosing solutions were prepared weekly. For each dose level, the calculated amount of test substance, p-xylene, was weighed and transferred to a volumetric flask. The vehicle, corn oil, was added to achieve the final volume and then the flask was capped and inverted by hand until thoroughly mixed. . Several observations were recorded, including clinical signs, body weights, food consumption, opthalmologic examinations, organ weights and organ-to-body weight ratios, mortality, gross pathology, clinical chemistry and histopathology.
Results show that mortality was present in all treatment groups, but significantly increased with a significant trend in Group 4 males, whilst there were significant differences seen in the female groups. However based on histopathology findings, it is thought that the cause of these deaths was most likely to be due to vehicle and/or compound aspiration and are not treatment-related, since intra-alveolar foreign material was found in all of the unscheduled deaths in males and females. The most commonly observed clinical signs were malocclusion, chromodacryorrhea, sores and salivation. Salivation was increased in both sexes of Group 4. It was a sign observed weekly, generally just prior to dosing and then the animals returned to normal one-hour post-dosing. Sores were seen mostly on the ears and were most likely due to the ear tags (method of identification). There were no ocular abnormalities or significant differences seen in the haematology parameters, but there were a few significant differences identified in the clinical chemistry parameters in Group 4 females at Week 5, however these returned to normal levels at Week 13. Overall mean body weight across all treatment groups were slightly decreased, whilst food consumption was slightly increased in Group 4 males and females. In terms of histopathology, lesions were discovered in the liver and kidneys of control and treated animals and foreign material was found in the lungs of nearly all unscheduled deaths, often accompanied with congestion thus indicating it was secondary to vehicle and/or test material aspiration. Among the animals that died on test, mottled lungs and failure of the lungs to collapse were detected in males and females from groups 2 -4, however these lesions were considered to be unrelated to p-xylene exposure. No compound -related histopathologic alterations in the tissues examined.
The mean body weight change was significantly lower than controls for males and females in Group 4 (800 mg/kg bw/day) (Table 1). The percentage difference in mean body weight change between the control and each dose group for males and females were calculated. The percentage differences for males was 11.02% and 11.2% for females in Group 4. Reduced absolute body weight of approximately >10% is generally considered to be a sign of general toxicity. Although the report lists 200 mg/kg bw/day as a NOEL, LOA XMG considers the 200 mg/kg bw/day as a NOAEL based on significantly reduced male and female body weight at 800 mg/kg/day.
Based on the results of this study and the conclusion that vehicle and/or test substance aspiration was the cause of all unscheduled deaths in treated animals. The NOAEL of p-xylene was determined to be 200 mg/kg/day.
Referenceopen allclose all
Table 1. body weights (g) – group mean values
Sex: Male |
body weight (week number) |
|||||||
Group |
1 (#) |
2 |
3 |
4 |
5 |
6 |
7 |
|
Group 1 Control 0 mg/kg/day |
Mean |
192.5 |
232.3 |
265.9 |
292.1 |
315.6 |
335.4 |
349.1 |
SD |
11.1 |
14.9 |
17.6 |
19.8 |
22.2 |
24.8 |
25.5 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
- |
- |
- |
- |
- |
- |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
194.2 |
234.3 |
265.7 |
290.1 |
309.3 |
327.2 |
341.7 |
SD |
14.4 |
19.1 |
22.8 |
25.6 |
29.6 |
31.8 |
32.3 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
193.2 |
231.9 |
259.8 |
282.1 |
299.9 |
314.9 |
328.7 |
SD |
13.6 |
16.4 |
16.4 |
19.2 |
21.6 |
23.4 |
24.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
195.5 |
231.5 |
261.7 |
282.6 |
299.9 |
313.5 |
324.8 |
SD |
15.5 |
16.5 |
19.4 |
25.4 |
33.2 |
35.9 |
34.7 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
- |
- |
- |
- |
- |
- |
|
(#) – Williams, Anova & Dunnett
Table 1. body weights (g) – group mean values (Continued)
Sex: Male |
body weight (week number) |
|||||||
Group |
8 |
9 |
10 |
11 |
12 |
13 |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
362.8 |
375.6 |
388.1 |
397.1 |
404.6 |
413.2 |
420.2 |
SD |
27.6 |
29.8 |
31.5 |
32.7 |
32.4 |
32.5 |
35.2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
0 |
- |
- |
- |
- |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
354.8 |
366.2 |
378.4 |
388.5 |
396.4 |
405.3 |
414.3 |
SD |
33.6 |
36.1 |
37.4 |
36.5 |
37.3 |
38.4 |
39.8 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
342.0 |
352.3 |
360.9 |
371.0 |
377.8 |
386.5 |
393.8 |
SD |
25.0 |
27.4 |
29.7 |
32.5 |
32.1 |
34.5 |
33.0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
> 0.05 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
336.8 |
344.4 |
351.3 |
360.2 |
366.4 |
372.4 |
375.7 |
SD |
38.3 |
38.8 |
39.3 |
41.1 |
41.6 |
42.1 |
41.6 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
≤ 0.05 * |
|
(#) – Williams, Anova & Dunnett: * = p≤0.05
Table 1. body weights (g) – group mean values (Continued)
Sex: Female |
body weight (week number) |
|||||||
Group |
1 (#) |
2 |
3 |
4 |
5 |
6 |
7 |
|
Group 1 Control 0 mg/kg/day |
Mean |
160.4 |
178.4 |
189.5 |
199.4 |
210.1 |
220.3 |
224.5 |
SD |
14.8 |
14.6 |
13.9 |
15.3 |
15.4 |
15.5 |
15.1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
- |
- |
- |
- |
- |
- |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
159.4 |
177.1 |
186.8 |
198.9 |
208.8 |
216.4 |
221.2 |
SD |
10.8 |
12.5 |
13.6 |
13.8 |
12.3 |
12.4 |
14.7 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
161.7 |
178.8 |
189.6 |
199.5 |
208.8 |
217.1 |
223.7 |
SD |
13.0 |
16.1 |
15.4 |
17.3 |
15.0 |
17.2 |
18.5 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
160.4 |
181.9 |
192.3 |
205.2 |
214.5 |
224.3 |
226.6 |
SD |
13.0 |
15.0 |
16.5 |
18.9 |
20.1 |
21.6 |
23.3 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0 .05 |
- |
- |
- |
- |
- |
- |
|
(#) – Williams, Anova & Dunnett
Table 1. body weights (g) – group mean values (Continued)
Sex: Female |
body weight (week number) |
|||||||
Group |
8 |
9 |
10 |
11 |
12 |
13 |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
228.0 |
231.6 |
237.0 |
239.6 |
239.9 |
241.3 |
247.7 |
SD |
18.9 |
17.6 |
19.3 |
18.0 |
18.8 |
19.0 |
19.2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
227.4 |
232.5 |
236.7 |
239.2 |
240.2 |
244.0 |
246.7 |
SD |
13.7 |
10.1 |
12.1 |
13.7 |
14.5 |
12.2 |
13.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
225.3 |
232.5 |
234.6 |
238.1 |
239.0 |
241.5 |
245.2 |
SD |
18.9 |
10.1 |
21.2 |
21.0 |
22.3 |
21.1 |
23.8 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
231.3 |
238.5 |
241.2 |
242.2 |
244.4 |
249.4 |
249.0 |
SD |
21.5 |
21.8 |
22.1 |
23.1 |
23.4 |
23.7 |
25.9 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
Table 2. body weight gains (g) – group mean values
Sex: Male |
body weight (week number)
|
|||
Group |
1 to 5 (#) |
5 to 14 (#) |
1 to 14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
123.1 |
104.6 |
227.7 |
SD |
15.8 |
17.0 |
30.1 |
|
N |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
115.1 |
105.0 |
220.1 |
SD |
21.5 |
16.8 |
35.9 |
|
N |
10 |
10 |
10 |
|
Trend |
> 0.05 |
- |
> 0.05 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
106.7 |
93.9 |
200.6 |
SD |
15.1 |
18.0 |
30.3 |
|
N |
10 |
10 |
10 |
|
Trend |
≤ 0.05* |
> 0.05 |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
104.4 |
75.8 |
180.2 |
SD |
24.1 |
12.4 |
33.3 |
|
N |
10 |
10 |
10 |
|
Trend |
≤ 0.05* |
≤ 0.001*** |
≤0.01** |
|
(#) – Williams, Anova & Dunnett: *= p≤0.05, **= p≤ 0.01, ***=p≤ 0.001
Table 2. body weight gains (g) – group mean values (Continued)
Sex: Female |
body weight (week number)
|
|||
Group |
1 to 5 (#) |
5 to 14 (#) |
1 to 14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
49.7 |
37.6 |
87.3 |
SD |
3.6 |
5.9 |
5.7 |
|
N |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
49.3 |
38.0 |
87.3 |
SD |
6.1 |
5.8 |
9.9 |
|
N |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
47.1 |
36.4 |
83.5 |
SD |
7.2 |
10.4 |
14.4 |
|
N |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
54.1 |
34.5 |
88.6 |
SD |
8.4 |
8.8 |
14.0 |
|
N |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
Table 3. Food intake (g/animal/day) – group mean cage values
Sex: Male |
Food Intake Per Animal / Day (g) (Week Number) |
|||||||
Group |
1 to 2 (#) |
2 to 3 (#) |
3 to 4 (#) |
4 to 5 (#) |
5 to 6 (#) |
6 to 7 (#) |
7 to 8 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
22.2 |
22.8 |
22.1 |
21.4 |
20.5 |
19.7 |
19.5 |
SD |
1.4 |
0.8 |
0.8 |
1.5 |
1.1 |
1.3 |
1.2 |
|
N |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
22.9 |
22.8 |
21.6 |
21.1 |
20.7 |
20.7 |
20.7 |
SD |
1.1 |
1.6 |
1.0 |
1.4 |
0.6 |
0.3 |
0.3 |
|
N |
4 |
4 |
4 |
4 |
4 |
1 |
4 |
|
Trend |
- |
- |
- |
- |
- |
> 0.05 |
> 0.05 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
22.6 |
22.7 |
21.8 |
21.2 |
21.0 |
21.4 |
21.1 |
SD |
0.6 |
0.8 |
1.4 |
1.1 |
0.9 |
0.7 |
0.5 |
|
N |
4 |
4 |
4 |
4 |
4 |
4 |
1 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
22.1 |
24.3 |
22.6 |
22.4 |
22.3 |
22.0 |
21.5 |
SD |
1.3 |
2.4 |
2.3 |
3.1 |
2.9 |
1.4 |
1.6 |
|
N |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett: * = p≤0.05
Table 3. Food intake (g/animal/day) – group mean cage values (Continued)
Sex: Male |
Food Intake Per Animal / Day (g) (Week Number) |
|||||||
Group |
8 to 9 (#) |
9 to 10 (#) |
10 to 11 (#) |
11 to 12 (#) |
12 to 13 (#1) |
13 to 14 (#) |
1 to 14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
19.1 |
18.9 |
18.3 |
17.8 |
18.1 |
17.2 |
19.8 |
SD |
1.6 |
1.6 |
1.3 |
1.2 |
1.7 |
1.3 |
1.2 |
|
N |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
20.3 |
20.2 |
20.3 |
20.3 |
21.1 |
19.1 |
20.9 |
SD |
0.6 |
0.7 |
0.4 |
0.3 |
0.2 |
1.2 |
0.6 |
|
N |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Trend |
- |
- |
≤ 0.05* |
≤ 0.05* |
≤ 0.05* |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
20.6 |
20.3 |
20.7 |
20.5 |
20.0 |
19.0 |
21.0 |
SD |
1.0 |
0.9 |
0.6 |
0.6 |
0.3 |
0.4 |
0.6 |
|
N |
4 |
4 |
4 |
4 |
4 |
4 |
1 |
|
Trend |
> 0.05 |
- |
≤ 0.05* |
≤ 0.05* |
≤ 0.05* |
> 0.05 |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
21.3 |
20.6 |
20.9 |
21.5 |
21.3 |
19.7 |
21.7 |
SD |
1.6 |
1.8 |
2.1 |
2.9 |
2.4 |
2.4 |
2.0 |
|
N |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Trend |
≤ 0.05* |
> 0.05 |
≤ 0.05* |
≤ 0.05* |
≤ 0.05* |
≤ 0.05* |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: * = p≤0.05
(#1) – Shirley, Kruskal-Wallis & Steel: * = p≤0.05
Table 3. Food intake (g/animal/day) – group mean cage values (Continued)
Sex: Female |
Food Intake Per Animal / Day (g) (Week Number) |
|||||||
Group |
1 to 2 (#) |
2 to 3 (#) |
3 to 4 (#) |
4 to 5 (#) |
5 to 6 (#) |
6 to 7 (#) |
7 to 8 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
14.8 n |
14.3 n |
15.1 n |
15.1 n |
15.2 n |
14.1 n |
14.3 n |
SD |
1.4 |
0.2 |
0.5 |
0.7 |
0.6 |
0.6 |
0.6 |
|
N |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
14.3 n |
14.1 n |
14.6 n |
14.5 n |
14.6 n |
14.0 n |
14.2 n |
SD |
1.2 |
0.9 |
1.2 |
1.3 |
1.4 |
1.7 |
1.6 |
|
N |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
14.4 n |
14.5 n |
15.0 n |
15.1 n |
14.9 n |
14.2 n |
14.1 |
SD |
0.7 |
0.6 |
0.8 |
0.9 |
1.2 |
0.9 |
1.2 |
|
N |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
13.7 n |
15.4 n |
15.7 n |
15.3 n |
15.4 n |
14.6 n |
14.8 n |
SD |
0.0 |
0.6 |
0.5 |
0.5 |
0.6 |
0.2 |
0.2 |
|
N |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
(#) – Shirley, Kruskal-Wallis & Steel: n – inappropriate for statistics
Table 3. Food intake (g/animal/day) – group mean cage values (Continued)
Sex: Female |
Food Intake Per Animal / Day (g) (Week Number) |
|||||||
Group |
8 to 9 (#) |
9 to 10 (#) |
10 to 11 (#) |
11 to 12 (#) |
12 to 13 (#) |
13 to 14 (#) |
1 to 14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
13.9 n |
13.9 n |
13.3 n |
13.2 n |
13.6 n |
12.2 n |
14.1 n |
SD |
0.4 |
0.6 |
0.8 |
0.9 |
1.3 |
0.5 |
0.6 |
|
N |
2 |
2 |
2 |
2 |
22 |
2 |
2 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
13.8 n |
14.1 n |
13.2 n |
13.2 n |
12.9 n |
12.2 n |
13.8 n |
SD |
1.2 |
1.1 |
1.9 |
1.9 |
1.1 |
2.0 |
1.4 |
|
N |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
14.0 n |
14.0 n |
13.9 n |
13.7 n |
13.4 n |
12.6 n |
14.1 n |
SD |
1.0 |
1.1 |
1.1 |
1.5 |
1.4 |
1.2 |
1.0 |
|
N |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
14.6 n |
14.5 n |
14.0 n |
14.2 n |
13.2 n |
12.8 n |
14.5 n |
SD |
0.0 |
0.6 |
0.3 |
0.3 |
0.5 |
0.0 |
0.1 |
|
N |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
(#) – Shirley, Kruskal-Wallis & Steel: n – inappropriate for statistics
Table 4. Thyroid analysis – group mean values
Sex: Male |
Mean Total T3 (ng/mL) |
Mean Total T4 (ng/mL) |
Mean Total TSH (ng/mL) |
|
Group |
(#) |
(#) |
(#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
16.639 |
427.735 |
0.498 |
SD |
2.676 |
82.494 |
0.210 |
|
N |
10 |
10 |
10 |
|
Trend |
↑ |
↓ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
16.682 |
440.194 |
0.510 |
SD |
5.221 |
46.662 |
0.152 |
|
N |
9 |
9 |
9 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
19.031 |
437.204 |
0.555 |
SD |
5.116 |
89.539 |
0.192 |
|
N |
9 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
18.468 |
383.893 |
0.605 |
SD |
4.758 |
44.318 |
0.314 |
|
N |
9 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
(#1) – Shirley, Kruskal-Wallis & Steel
Table 4. Thyroid analysis – group mean values (Continued)
Sex: Male |
Mean Total T3 (ng/mL) |
Mean Total T4 (ng/mL) |
Mean Total TSH (ng/mL) |
|
Group |
(#) |
(#) |
(#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
17.233* |
277.065 |
0.673* |
SD |
5.928 |
37.594 |
0.303 |
|
N |
8 |
10 |
10 |
|
Trend |
↑ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
12.174 |
291.000 |
0.497 |
SD |
3.053 |
71.508 |
0.182 |
|
N |
8 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
14.009 |
296.776 |
0.421* |
SD |
3.301 |
59.956 |
0.066 |
|
N |
9 |
10 |
10 |
|
Trend |
- |
> 0.05 |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
19.130 |
346.589 |
0.595 |
SD |
6.317 |
56.001 |
0.209 |
|
N |
10 |
10 |
10 |
|
Trend |
> 0.05 |
≤ 0.05* |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: * = p≤ 0.05
(#1) – Williams, Anova & Dunnett(Log): * = p≤0.05
Table 5. Functional observation battery – rodents – key values
HOME CAGE |
ON REMOVAL FROM CAGE |
PERFORMANCE IN OPEN FIELD |
RESPONSE TO SENSORIMOTOR STIMULI |
|
Arousal upon openingcage 0 = normal 1 = increased 2 = decreased
Dispersion in cage 0 = normal 1 = closely bunched 2 = loosely bunched
Excessive vocalisation 0 = absent 1 = present
Fighting 0 = absent 1 = present
Stereotypical behaviour 0 = absent 1 = present
Aggressive behaviour 0 = absent 1 = present
Convulsions 0 = absent 1 = short 2 = sustained |
Reaction to handling 0 = normal 1 = no resistance 2 = vocalising 3 = tense 4 = squirming
Lacrimation 0 = normal 1 = excess at eyelid margin 2 = extends beyond margin
Salivation 0 = normal 1 = slight 2 = marked
Chromodacryorrhea 0 = absent 1 = present
Exophthalmos 0 = absent 1= present
|
Arousal in arena 0 = normal 1 = hyperactive 2 = hypoactive
Unusual posture 0 = absent 1 = hunched 2 = flattened
Abnormal gait 0 = absent 1 = slight 2 = marked
Convulsions arena 0 = absent 1 = slight 2 = marked
Tremors 0 = none 1 = intermittent 2 = constant
Twitches 0 = normal 1 = slight 2 = marked
Urination 0 = none 1 = present 2 = excess |
Defecation 0 = none 1 = present 2 = soft/liquid faeces
Excessive vocalisation 0 = absent 1 = present
Piloerection 0 = normal 1 = roughened fur 2 = piloerection
Palpebral closure 0 = normal 1 = partially closed 2 = shut
Respiration 0 = normal 1 = rapid 2 = slow 3 = laboured
Straub tail 0 = absent 1 = present
Salivation 0 = absent 1 = present 2 = excessive
Excessive rearing 0 = absent 1 = present |
Approach response 0 = present 1 = absent 2 = excessive
Touch response 0 = present 1 = absent 2 = excessive
Aud Startle response 0 = present 1 = absent 2 = excessive
Tail pinch response 0 = present 1 = absent 2 = excessive
Forelimb reflex 0 = early extension 1 = extension after contact 2 = no extension
Righting reflex 0 = present 1 = slow 2 = absent
|
Table 5. Functional observation battery – home and arena – group mean values
Sex: Male |
Arousal open cage (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Arousal open cage (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (Continued)
Sex: Male |
Dispersion in cage (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
12 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Dispersion in cage (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Fighting (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Fighting (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Excessive vocalisation cage (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Excessive vocalisation cage (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Stereotyped behaviour (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Stereotyped behaviour (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Tabl e 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Aggressive behaviour (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Aggressive behaviour (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Convulsions cage (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Convulsions cage (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Reacting to handling (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Reacting to handling (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Lacrimation (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Lacrimation (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Salivation (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Salivation (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Chromodacryorrhea (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Chromodacryorrhea (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Exophthalmos (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Exophthalmos (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Arousal in arena (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
4 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
4 |
0 |
1 |
2 |
SD |
0 |
0 |
0 |
2 |
0 |
1 |
2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Arousal in arena (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
1 |
0 |
0 |
1 |
0 |
0 |
SD |
1 |
0 |
0 |
1 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2 |
0 |
0 |
0 |
0 |
0 |
SD |
2 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
5 |
0 |
3 |
0 |
0 |
0 |
SD |
2 |
0 |
2 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Unusual posture (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
4 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Unusual posture (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
4 |
0 |
0 |
0 |
SD |
0 |
0 |
2 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Abnormal gait (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
SD |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Abnormal gait (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
1 |
0 |
0 |
0 |
0 |
0 |
SD |
1 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1 |
1 |
0 |
0 |
0 |
0 |
SD |
1 |
1 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Convulsions arena (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Convulsions arena (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Tremors (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Tremors (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Twitches (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Twitches (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
1 |
0 |
0 |
0 |
0 |
0 |
SD |
1 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Excessive vocalisation arena (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Excessive vocalisation arena (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Piloerection (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Piloerection (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Palpebral closure (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Palpebral closure (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Respiration (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Respiration (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Straub tail (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Straub tail (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Salivation arena (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
6 |
4 |
0 |
3 |
0 |
SD |
0 |
0 |
1 |
1 |
0 |
2 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Salivation arena (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
1 |
0 |
0 |
2 |
0 |
0 |
SD |
1 |
0 |
0 |
1 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1 |
3 |
1 |
0 |
0 |
0 |
SD |
1 |
2 |
1 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Excessive rearing (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
SD |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Excessive rearing (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
1 |
0 |
0 |
SD |
0 |
0 |
0 |
1 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
1 |
0 |
0 |
SD |
0 |
0 |
0 |
1 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1 |
0 |
0 |
0 |
0 |
0 |
SD |
1 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Urination (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
5 |
1 |
0 |
7 |
2 |
3 |
5 |
SD |
1 |
1 |
0 |
1 |
1 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
5 |
0 |
1 |
6 |
5 |
3 |
5 |
SD |
1 |
0 |
1 |
1 |
2 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
3 |
2 |
0 |
6 |
6 |
6 |
4 |
SD |
1 |
1 |
0 |
1 |
2 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2 |
0 |
0 |
7 |
9 |
3 |
3 |
SD |
1 |
0 |
0 |
1 |
2 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Urination (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
4 |
3 |
1 |
4 |
5 |
7 |
SD |
1 |
1 |
1 |
1 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2 |
4 |
4 |
2 |
5 |
4 |
SD |
1 |
1 |
1 |
1 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
1 |
4 |
7 |
3 |
6 |
5 |
SD |
1 |
2 |
2 |
1 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
6 |
6 |
4 |
2 |
2 |
8 |
SD |
2 |
2 |
1 |
1 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Defecation (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
2 |
0 |
1 |
0 |
0 |
0 |
0 |
SD |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2 |
1 |
0 |
0 |
0 |
0 |
1 |
SD |
1 |
1 |
0 |
0 |
0 |
0 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Male |
Defecation (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Arousal open cage (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Arousal open cage (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Dispersion in cage (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Dispersion in cage (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Fighting (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Fighting (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Stereotyped behaviour (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Stereotyped behaviour (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Aggressive behaviour (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Aggressive behaviour (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Convulsions (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Convulsions (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Reaction to handling (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Reaction to handling (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Lacrimation (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Lacrimation (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Salivation (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
1 |
1 |
0 |
1 |
0 |
SD |
0 |
0 |
1 |
1 |
0 |
1 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
2 |
4 |
0 |
3 |
4 |
SD |
0 |
0 |
1 |
1 |
0 |
2 |
2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Salivation (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Chromodacryorrhea (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Chromodacryorrhea (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Exophthalmos (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Exophthalmos (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Arousal in arena (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
1 |
2 |
6 |
0 |
SD |
0 |
0 |
0 |
1 |
2 |
2 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Arousal in arena (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
1 |
0 |
SD |
0 |
0 |
0 |
0 |
1 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
2 |
1 |
0 |
SD |
0 |
0 |
0 |
2 |
1 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
6 |
0 |
2 |
4 |
3 |
0 |
SD |
2 |
0 |
2 |
2 |
2 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Unusual posture (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
3 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Unusual posture (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Abnormal gait (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
6 |
5 |
1 |
2 |
0 |
SD |
0 |
0 |
2 |
2 |
1 |
2 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Abnormal gait (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2 |
1 |
0 |
3 |
4 |
0 |
SD |
2 |
1 |
0 |
1 |
2 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Convulsions (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Convulsions (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Tremors (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Tremors (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Twitches (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Twitches (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
1 |
0 |
SD |
0 |
0 |
0 |
0 |
1 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Excessive vocalisation arena (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Excessive vocalisation arena (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Piloerection (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Piloerection (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Palpebral closure (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Palpebral closure (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Respiration (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Respiration (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Straub tail (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Straub tail (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Salivation arena (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
2 |
1 |
0 |
1 |
0 |
SD |
0 |
0 |
1 |
1 |
0 |
1 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
4 |
5 |
0 |
1 |
5 |
SD |
0 |
0 |
2 |
1 |
0 |
1 |
2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Salivation arena (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Excessive rearing (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Excessive rearing (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
1 |
0 |
SD |
0 |
0 |
0 |
0 |
1 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
1 |
0 |
0 |
0 |
0 |
SD |
0 |
1 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Urination (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
4 |
4 |
4 |
2 |
2 |
0 |
2 |
SD |
1 |
1 |
1 |
1 |
1 |
0 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
4 |
4 |
5 |
1 |
1 |
1 |
2 |
SD |
1 |
1 |
1 |
1 |
1 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
5 |
5 |
5 |
0 |
3 |
2 |
0 |
SD |
1 |
1 |
1 |
0 |
1 |
1 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
4 |
6 |
5 |
0 |
5 |
3 |
1 |
SD |
1 |
1 |
1 |
0 |
1 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Urination (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
2 |
0 |
2 |
0 |
0 |
0 |
SD |
1 |
0 |
1 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2 |
0 |
2 |
0 |
1 |
1 |
SD |
1 |
0 |
1 |
0 |
1 |
1 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
1 |
0 |
1 |
0 |
1 |
1 |
SD |
1 |
0 |
1 |
0 |
1 |
1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2 |
0 |
1 |
1 |
0 |
1 |
SD |
1 |
0 |
1 |
1 |
0 |
1 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Defecation (Day number) |
|||||||
Group |
-1 |
7 |
14 |
21 |
28 |
35 |
42 |
|
Group 1 Control 0 mg/kg/day |
Mean |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
SD |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 5.2. Functional observation battery – home and arena – group mean values (continued)
Sex: Female |
Defecation (Day number) |
||||||
Group |
49 |
56 |
63 |
70 |
77 |
84 |
|
Group 1 Control 0 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0 |
0 |
0 |
0 |
0 |
0 |
SD |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
9 |
10 |
10 |
|
Table 5.3. Functional observation battery – sensory reaction – group mean values
Sex: Male |
Approach response (Day Number) |
Touch response (Day Number) |
Aud startle response (Day Number) |
Tail pinch response (Day Number) |
Righting reflex (Day Number) |
Forelimb reflex (Day Number) |
|
Group |
84 |
84 |
84 |
84 |
84 |
84 |
|
Group 1 Control 0 mg/kg/day |
Sum |
0 |
0 |
0 |
0 |
0 |
0 |
Max |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 2 o-xylene 100 mg/kg/day |
Sum |
0 |
0 |
0 |
0 |
0 |
0 |
Max |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Sum |
0 |
0 |
0 |
0 |
0 |
0 |
Max |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Sum |
0 |
0 |
0 |
0 |
0 |
0 |
Max |
0 |
0 |
0 |
0 |
0 |
0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Table 6. Motor activity – group mean values
Sex: Male |
Movements Counts Period 1 (Day Number [Time]) |
Movements Counts Period 2 (Day Number [Time]) |
Movements Counts Period 3 (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#2) |
87 (Pre) (#1) |
87 (Post) (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
1626.9 |
1327.9 |
751.6 |
536.2 |
713.6 |
322.0 |
SD |
531.7 |
338.9 |
178.5 |
189.9 |
235.8 |
236.5 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↓ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
1573.9 |
1392.9 |
788.5 |
528.4 |
628.1 |
187.4 |
SD |
526.8 |
433.1 |
325.1 |
284.7 |
232.2 |
249.6 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
> 0.05 |
- |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
1715.3 |
1639.8 |
824.7 |
241.0 |
739.5 |
66.2 |
SD |
480.3 |
490.7 |
253.4 |
268.8 |
297.2 |
105.8 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
≤ 0.05* |
- |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1759.8 |
1388.4 |
846.9 |
361.9 |
653.1 |
63.1 |
SD |
420.4 |
283.3 |
185.6 |
230.2 |
191.7 |
85.0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett(Log): * = p
≤ 0.05
(#1) – Williams, Anova & Dunnett
(#2) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Male |
Movements Counts Period 4 (Day Number [Time]) |
Movements Counts Period 5 (Day Number [Time]) |
Movements Counts Period 6 (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
609.8 |
184.5 |
534.2 |
207.7 |
348.6 |
307.4 |
SD |
248.8 |
182.0 |
308.3 |
265.3 |
320.3 |
257.7 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↑ |
↓ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
511.3 |
94.1 |
388.6 |
165.7 |
483.9 |
48.4 |
SD |
250.6 |
131.8 |
182.4 |
181.6 |
263.4 |
45.3 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
618.1 |
174.0 |
482.3 |
173.5 |
619.4 |
150.1 |
SD |
236.9 |
447.4 |
326.7 |
259.0 |
239.1 |
287.1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
631.7 |
144.4 |
656.7 |
63.0 |
530.8 |
67.0 |
SD |
279.7 |
205.3 |
252.4 |
85.4 |
317.6 |
80.9 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.01** |
|
(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05, ** = p ≤ 0.01
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Male |
Distance Travelled Period 1 (cm) (Day Number [Time]) |
Distance Travelled Period 2 (cm) (Day Number [Time]) |
Distance Travelled Period 3 (cm) (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#2) |
87 (Pre) (#1) |
87 (Post) (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
5816.4 |
4677.8 |
2713.8 |
1843.6 |
2560.2 |
1150.7 |
SD |
1844.6 |
1078.4 |
617.9 |
627.7 |
805.3 |
840.3 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↓ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
5490.4 |
4891.8 |
2780.4 |
1809.1 |
2250.5 |
691.4 |
SD |
1745.2 |
1486.0 |
1045.6 |
1000.9 |
785.7 |
895.2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
> 0.05 |
- |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
5985.6 |
5742.6 |
2883.6 |
888.6 |
2614.6 |
226.3 |
SD |
1391.4 |
1698.6 |
756.4 |
985.9 |
921.2 |
378.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
≤ 0.05* |
- |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
6203.2 |
4901.9 |
3020.6 |
1325.6 |
2299.5 |
231.3 |
SD |
1458.0 |
887.0 |
672.9 |
806.6 |
725.1 |
311.6 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett(Log): * = p
≤ 0.05
(#1) – Williams, Anova & Dunnett
(#2) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Male |
Distance Travelled Period 4 (cm) (Day Number [Time]) |
Distance Travelled Period 5 (cm) (Day Number [Time]) |
Distance Travelled Period 6 (cm) (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2203.2 |
690.5 |
1872.3 |
758.4 |
1217.7 |
1105.2 |
SD |
844.1 |
678.4 |
1075.8 |
946.8 |
1128.6 |
928.5 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↑ |
↓ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
1778.3 |
335.3 |
1389.1 |
628.4 |
1736.8 |
188.7 |
SD |
805.9 |
473.1 |
631.9 |
633.4 |
902.8 |
178.6 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2208.3 |
663.9 |
1683.1 |
616.3 |
2183.2 |
583.4 |
SD |
826.5 |
1737.8 |
1129.1 |
884.6 |
867.6 |
1144.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2279.0 |
530.0 |
2389.6 |
261.1 |
1913.9 |
286.5 |
SD |
982.1 |
741.5 |
918.9 |
339.9 |
1128.2 |
379.5 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Male |
Time at Rest Period 1 (sec) (Day Number [Time]) |
Time at Rest Period 2 (sec) (Day Number [Time]) |
Time at Rest Period 3 (sec) (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#) |
87 (Pre) (#) |
87 (Post) (#) |
87 (Pre) (#) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
192.24 |
222.86 |
352.51 |
402.95 |
378.37 |
485.26 |
SD |
51.03 |
31.87 |
41.15 |
52.02 |
45.85 |
75.47 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↓ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
213.17 |
229.32 |
356.78 |
424.38 |
401.15 |
535.23 |
SD |
63.64 |
54.46 |
69.94 |
68.61 |
44.74 |
77.33 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
> 0.05 |
- |
> 0.05 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
191.09 |
210.50 |
342.61 |
509.99 |
381.13 |
573.65 |
SD |
40.81 |
55.31 |
36.64 |
85.99 |
47.78 |
38.76 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
≤ 0.01** |
- |
≤ 0.01** |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
185.55 |
251.46 |
315.97 |
478.05 |
374.80 |
576.28 |
SD |
51.53 |
56.02 |
48.14 |
57.20 |
46.83 |
30.29 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.01** |
> 0.05 |
≤ 0.01** |
|
(#) – Williams, Anova & Dunnett: ** = p ≤
0.01
(#1) – Shirley, Kruskal-Wallis & Steel: ** = P ≤ 0.01
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Male |
Time at Rest Period 4 (sec) (Day Number [Time]) |
Time at Rest Period 5 (sec) (Day Number [Time]) |
Time at Rest Period 6 (sec) (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
381.50 |
530.45 |
418.34 |
526.97 |
482.49 |
485.85 |
SD |
71.63 |
64.27 |
76.12 |
88.22 |
93.95 |
93.98 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↓ |
↑ |
↓ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
434.02 |
562.75 |
460.00 |
537.47 |
448.13 |
577.65 |
SD |
68.85 |
44.44 |
54.98 |
62.10 |
71.05 |
19.71 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
> 0.05 |
- |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
409.75 |
560.82 |
451.52 |
551.08 |
394.73 |
558.46 |
SD |
58.66 |
83.77 |
82.21 |
58.74 |
71.75 |
62.24 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
393.14 |
549.64 |
377.74 |
570.89 |
427.71 |
560.74 |
SD |
70.03 |
65.92 |
83.92 |
39.77 |
86.48 |
59.90 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett
(#1) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Female |
Movements Counts Period 1 (Day Number [Time]) |
Movements Counts Period 2 (Day Number [Time]) |
Movements Counts Period 3 (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#) |
87 (Pre) (#) |
87 (Post) (#) |
87 (Pre) (#) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2114.7 |
1665.9 |
1102.5 |
466.3 |
725.6* |
302.5 |
SD |
371.3 |
396.2 |
333.5 |
269.5 |
207.1 |
298.1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↓ |
↓ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
1857.3 |
1531.4 |
1001.0 |
451.0 |
724.2 |
148.3 |
SD |
409.8 |
400.4 |
237.0 |
369.9 |
299.5 |
212.2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2003.6 |
2051.1 |
1187.8 |
480.3 |
1016.7* |
216.9 |
SD |
470.9 |
584.9 |
352.6 |
443.9 |
284.6 |
446.7 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1915.0 |
1793.1 |
890.0 |
386.0 |
787.0 |
232.0 |
SD |
383.9 |
443.1 |
158.2 |
255.3 |
202.5 |
409.7 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett: * = p ≤ 0.05
(#1) – Williams, Anova & Dunnett(Log)
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Female |
Movements Counts Period 4 (Day Number [Time]) |
Movements Counts Period 5 (Day Number [Time]) |
Movements Counts Period 6 (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#2) |
87 (Post) (#1) |
87 (Pre) (#2) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
589.6 |
281.7* |
720.6* |
223.1* |
527.7 |
176.1 |
SD |
359.5 |
254.6 |
532.1 |
169.2 |
258.7 |
230.3 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↓ |
↓ |
↓ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
562.1 |
599.0 |
548.9 |
396.2 |
485.2 |
123.4 |
SD |
348.2 |
239.6 |
262.8 |
385.5 |
379.8 |
152.8 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
804.6 |
266.0 |
847.2 |
75.5 |
780.6 |
95.6 |
SD |
388.1 |
403.5 |
198.6 |
94.7 |
379.3 |
197.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
662.1 |
175.4 |
476.3 |
517.8 |
568.6 |
532.0 |
SD |
173.7 |
220.6 |
216.5 |
1170.3 |
214.9 |
979.6 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
(#2) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Female |
Distance Travelled Period 1 (cm) (Day Number [Time]) |
Distance Travelled Period 2 (cm) (Day Number [Time]) |
Distance Travelled Period 3 (cm) (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#) |
87 (Pre) (#) |
87 (Post) (#) |
87 (Pre) (#2) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
7391.1 |
5577.7 |
3817.2 |
1643.2 |
2587.0* |
1055.8 |
SD |
1312.6 |
1322.0 |
1250.4 |
909.6 |
725.1 |
1031.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↓ |
↓ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
6428.7 |
5204.1 |
3466.0 |
1587.1 |
2576.7 |
509.9 |
SD |
1420.9 |
1331.6 |
856.8 |
1308.7 |
1047.6 |
737.6 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
6904.0 |
7088.8 |
4136.6 |
1698.9 |
3550.3* |
757.0 |
SD |
1576.0 |
2110.0 |
1201.7 |
1541.3 |
913.3 |
1511.2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
6876.3 |
6205.6 |
3111.1 |
1416.3 |
2776.5 |
811.3 |
SD |
1467.8 |
1568.0 |
576.9 |
920.5 |
694.4 |
1310.0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: * = p ≤ 0.05
(#1) – Williams, Anova & Dunnett(Log)
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Female |
Distance Travelled Period 4 (cm) (Day Number [Time]) |
Distance Travelled Period 5 (cm) (Day Number [Time]) |
Distance Travelled Period 6 (cm) (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#2) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2097.3 |
1024.7* |
2535.8* |
815.6* |
1833.5 |
640.0 |
SD |
1355.4 |
931.7 |
1774.8 |
606.9 |
939.0 |
835.5 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↓ |
↓ |
↓ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2002.8 |
2157.5 |
1956.6 |
1403.0 |
1690.7 |
448.6 |
SD |
1211.8 |
858.5 |
919.7 |
1307.8 |
1274.2 |
542.5 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2761.4 |
944.9 |
2991.4 |
272.3 |
2697.8 |
340.8 |
SD |
1208.8 |
1366.2 |
642.6 |
347.4 |
1121.6 |
687.1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2332.6 |
644.1 |
1676.2 |
1762.3 |
2017.6 |
1809.4 |
SD |
668.9 |
752.0 |
762.8 |
3809.9 |
750.0 |
3317.7 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
(#2) – Shirley, Kruskal-Wallis & Steel: * = P ≤ 0.05
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Female |
Time at Rest Period 1 (sec) (Day Number [Time]) |
Time at Rest Period 2 (sec) (Day Number [Time]) |
Time at Rest Period 3 (sec) (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#) |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
160.07 |
219.67 |
308.45 |
435.42 |
385.41 |
495.37 |
SD |
24.59 |
32.86 |
60.91 |
83.04 |
52.63 |
89.78 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↓ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
196.85 |
242.53 |
352.58 |
458.20 |
377.76 |
543.62 |
SD |
41.86 |
45.75 |
43.06 |
104.53 |
66.03 |
73.66 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
181.10 |
206.38 |
293.82 |
461.68 |
333.71 |
546.50 |
SD |
31.18 |
41.86 |
57.89 |
89.51 |
46.60 |
84.64 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
174.38 |
242.06 |
323.42 |
482.62 |
352.10 |
529.45 |
SD |
36.07 |
70.90 |
32.09 |
77.68 |
43.82 |
95.51 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
(#1) – Shirley, Kruskal-Wallis & Steel
Note: a period equates to an interval of 10 minutes
Table 6. Motor activity – group mean values (Continued)
Sex: Female |
Time at Rest Period 4 (sec) (Day Number [Time]) |
Time at Rest Period 5 (sec) (Day Number [Time]) |
Time at Rest Period 6 (sec) (Day Number [Time]) |
||||
Group |
87 (Pre) (#) |
87 (Post) (#) |
87 (Pre) (#) |
87 (Post) (#1) |
87 (Pre) (#) |
87 (Post) (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
418.03 |
507.99** |
390.11* |
519.29* |
424.27 |
545.19 |
SD |
72.03 |
87.76 |
97.35 |
56.43 |
67.91 |
65.46 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↑ |
↑ |
↓ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
425.42 |
433.41 |
429.39 |
477.85 |
448.53 |
537.92 |
SD |
89.59 |
64.02 |
71.58 |
99.69 |
99.18 |
86.64 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
373.63 |
535.23 |
358.65 |
574.15 |
382.03 |
576.31 |
SD |
70.10 |
75.36 |
40.71 |
32.05 |
57.40 |
37.08 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
381.21 |
539.32 |
443.96 |
487.60 |
416.35 |
486.54 |
SD |
55.76 |
65.39 |
48.84 |
185.18 |
68.71 |
188.67 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett* = p ≤ 0.05,
** = p ≤ 0.01
(#1) – Shirley, Kruskal-Wallis & Steel* = p ≤ 0.05
Note: a period equates to an interval of 10 minutes
Table 7. Grip strength – group mean values
Sex: Male |
Forelimb Mean (g) (Day Number [Time]) |
Hindlimb Mean (g) (Day Number [Time]) |
|||
Group |
80 (Pre) (#) |
80 (Post) (#) |
80 (Pre) (#) |
80 (Post) (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
363.40 |
244.40 |
334.37 |
238.70 |
SD |
51.49 |
64.49 |
63.75 |
79.05 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↓ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
317.13 |
221.07 |
270.83 |
271.37 |
SD |
91.79 |
77.99 |
91.58 |
80.18 |
|
N |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
317.27 |
258.00 |
305.03 |
303.53 |
SD |
86.71 |
61.10 |
73.54 |
78.44 |
|
N |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
335.27 |
262.63 |
270.00 |
254.80 |
SD |
86.06 |
100.24 |
56.60 |
64.46 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
Table 7. Grip strength – group mean values (Continued)
Sex: Female |
Forelimb Mean (g) (Day Number [Time]) |
Hindlimb Mean (g) (Day Number [Time]) |
|||
Group |
81 (Pre) (#) |
81 (Post) (#) |
81 (Pre) (#) |
81 (Post) (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
304.77 |
222.70 |
205.07 |
189.90* |
SD |
60.96 |
89.31 |
36.81 |
55.79 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
317.73 |
209.80 |
178.63 |
195.37 |
SD |
97.52 |
70.94 |
47.39 |
38.48 |
|
N |
10 |
10 |
10 |
10 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
305.83 |
209.20 |
225.70 |
221.17 |
SD |
105.24 |
48.88 |
95.66 |
41.77 |
|
N |
10 |
10 |
10 |
10 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
326.47 |
254.30 |
234.47 |
162.43 |
SD |
66.72 |
49.54 |
42.46 |
36.70 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett* = p ≤ 0.05
(#1) – Williams, Anova & Dunnett(Log)
Table 8. Haematology – group mean values
Sex: Male |
RBC 10^6/ul (Week Number) |
Hb g/dl (Week Number) |
PCV % (Week Number) |
MCV fl (Week Number) |
MCH Pg (Week Number) |
MCHC g/dl (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
8.877 |
15.51 |
45.44 |
51.22 |
17.50 |
34.14 |
SD |
0.407 |
0.38 |
1.49 |
1.34 |
0.58 |
0.57 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↑ |
↑ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
8.761 |
15.29 |
44.74 |
51.07 |
17.44 |
34.17 |
SD |
0.182 |
0.19 |
0.69 |
1.16 |
0.45 |
0.42 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
8.716 |
15.31 |
44.91 |
51.54 |
17.59 |
34.09 |
SD |
0.291 |
0.42 |
1.07 |
1.43 |
0.76 |
0.58 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
> 0.05 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
8.908 |
15.40 |
45.79 |
51.43 |
17.29 |
33.65 |
SD |
0.384 |
0.52 |
1.58 |
1.12 |
0.53 |
0.48 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett* = p ≤ 0.05
Table 8. Haematology – group mean values (Continue)
Sex: Male |
RDW % (Week Number) |
HDW g/dl (Week Number) |
Plate 10^3/ul (Week Number) |
MPV fl (Week Number) |
PDW % (Week Number) |
PCT % (Week Number) |
|
Group |
14 (#) |
14 (#1) |
14 (#1) |
14 (#1) |
14 (#1) |
14 (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
13.28 |
2.850 |
831.2 |
9.70 |
43.54 |
0.80 |
SD |
1.92 |
0.213 |
76.6 |
0.33 |
1.86 |
0.09 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↑ |
↑ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
12.77 |
2.937 |
790.7 |
9.54 |
43.19 |
0.77 |
SD |
0.71 |
0.148 |
77.6 |
0.25 |
1.54 |
0.07 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
- |
- |
- |
> 0.05 |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
13.78 |
2.924 |
809.5 |
10.06 |
43.62 |
0.80 |
SD |
3.34 |
0.196 |
72.6 |
0.43 |
2.26 |
0.07 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
> 0.05 |
≤ 0.05* |
- |
> 0.05 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
12.98 |
2.809 |
924.7 |
10.01 |
42.95 |
0.92 |
SD |
1.24 |
0.231 |
106.2 |
0.34 |
1.50 |
0.10 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
≤ 0.05* |
≤ 0.05* |
> 0.05 |
≤ 0.01** |
|
(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett* = p ≤ 0.05, ** = p ≤ 0.01
Table 8. Haematology – group mean values (Continue)
Sex: Male |
Retics %RBC (Week Number) |
A retics 10^6/ul (Week Number) |
MC/Vr fl (Week Number) |
CHr pg (Week Number) |
WBC 10^3/ul (Week Number) |
Neut 10^3/ul (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
1.80 |
0.1598 |
62.02 |
18.21 |
6.253 |
0.656 |
SD |
0.24 |
0.0243 |
0.97 |
0.50 |
1.820 |
0.160 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↓ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
1.78 |
0.1559 |
61.84 |
18.23 |
6.841 |
0.778 |
SD |
0.19 |
0.0167 |
1.34 |
0.42 |
1.431 |
0.205 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
1.89 |
0.1642 |
62.13 |
18.28 |
7.084 |
0.924 |
SD |
0.31 |
0.0252 |
0.86 |
0.37 |
1.049 |
0.262 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1.85 |
0.1639 |
62.45 |
18.10 |
6.874 |
0.863 |
SD |
0.30 |
0.0213 |
1.04 |
0.32 |
1.139 |
0.287 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett* = p ≤ 0.05
Table 8. Haematology – group mean values (Continue)
Sex: Male |
Lymph 10^3/ul (Week Number) |
Mono 10^3/ul (Week Number) |
Eosin 10^3/ul (Week Number) |
Baso 10^3/ul (Week Number) |
LUC 10^3/ul (Week Number) |
Neut % (Week Number) |
|
Group |
14 (#) |
14 (#1) |
14 (#2) |
14 (#1) |
14 (#2) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
5.379 |
0.091 |
0.070 |
0.028 |
0.029 |
12.24 |
SD |
1.767 |
0.047 |
0.029 |
0.017 |
0.021 |
8.39 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
5.823 |
0.086 |
0.101 |
0.026 |
0.031 |
11.49 |
SD |
1.228 |
0.034 |
0.058 |
0.014 |
0.020 |
2.59 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
5.898 |
0.094 |
0.101 |
0.036 |
0.034 |
12.98 |
SD |
0.863 |
0.024 |
0.044 |
0.022 |
0.011 |
2.66 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
5.772 |
0.097 |
0.083 |
0.025 |
0.036 |
12.57 |
SD |
0.991 |
0.031 |
0.034 |
0.015 |
0.013 |
3.72 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett(Log)
(#2) – Williams, Anova & Dunnett
Table 8. Haematology – group mean values (Continue)
Sex: Male |
Lymph % (Week Number) |
Mono % (Week Number) |
Eosin % (Week Number) |
Baso % (Week Number) |
LUC % (Week Number) |
APIT sec (Week Number) |
|
Group |
14 (#) |
14 (#1) |
14 (#2) |
14 (#1) |
14 (#1) |
14 (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
84.08 |
1.56 |
1.29 |
0.40 |
0.43 |
15.76 |
SD |
9.51 |
0.72 |
0.97 |
0.18 |
0.25 |
0.94 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↑ |
↓ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
85.02 |
1.26 |
1.47 |
0.38 |
0.42 |
14.96 |
SD |
2.65 |
0.37 |
0.69 |
0.13 |
0.23 |
1.04 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
83.29 |
1.34 |
1.42 |
0.47 |
0.50 |
14.68 |
SD |
2.90 |
0.34 |
0.50 |
0.26 |
0.16 |
0.97 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
83.95 |
1.45 |
1.18 |
0.35 |
0.51 |
14.68 |
SD |
4.00 |
0.40 |
0.40 |
0.15 |
0.16 |
0.94 |
|
N |
10 |
10 |
10 |
10 |
10 |
9 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
|
(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett: * = p ≤ 0.05
(#2) – Williams, Anova & Dunnett(Log)
Table 8. Haematology – group mean values (Continue)
Sex: Male |
PT sec (Week Number) |
|
Group |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
23.89 |
SD |
1.67 |
|
N |
9 |
|
Trend |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
23.03 |
SD |
0.72 |
|
N |
9 |
|
Trend |
> 0.05 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
22.26 |
SD |
0.87 |
|
N |
9 |
|
Trend |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
22.76 |
SD |
1.13 |
|
N |
9 |
|
Trend |
≤ 0.05* |
|
(#)
– Williams, Anova & Dunnett: * = p ≤ 0.05
Table 8. Haematology – group mean values (Continued)
Sex: Female |
RBC 10^6/ul (Week Number) |
Hb g/dl (Week Number) |
PCV % (Week Number) |
MCV fl (Week Number) |
MCH Pg (Week Number) |
MCHC g/dl (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
7.758 |
14.20 |
41.42 |
53.41 |
18.33 |
34.32 |
SD |
0.228 |
0.35 |
1.16 |
1.41 |
0.52 |
0.32 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
↓ |
↓ |
↑ |
↑ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
7.723 |
14.28 |
41.74 |
54.09 |
18.50 |
34.19 |
SD |
0.193 |
0.30 |
0.81 |
1.62 |
0.61 |
0.37 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
7.922 |
14.45 |
42.11 |
53.20 |
18.25 |
34.29 |
SD |
0.274 |
0.46 |
1.28 |
1.66 |
0.75 |
0.46 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
> 0.05 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
8.054 |
14.56 |
43.10 |
53.54 |
18.11 |
33.80 |
SD |
0.258 |
0.31 |
0.93 |
1.14 |
0.55 |
0.47 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
≤ 0.05* |
> 0.05 |
≤ 0.01** |
> 0.05 |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett* = p ≤ 0.05; ** = p ≤ 0.01
Table 8. Haematology – group mean values (Continue)
Sex: Female |
RDW % (Week Number) |
HDW g/dl (Week Number) |
Plate 10^3/ul (Week Number) |
MPV fl (Week Number) |
PDW % (Week Number) |
PCT % (Week Number) |
|
Group |
14 (#) |
14 (#1) |
14 (#1) |
14 (#1) |
14 (#1) |
14 (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
11.91 |
2.332 |
871.8 |
10.23 |
42.01 |
0.90 |
SD |
2.09 |
0.157 |
173.1 |
0.50 |
2.29 |
0.17 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
↑ |
↑ |
↓ |
↓ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
12.14 |
2.261 |
778.5 |
10.01 |
42.61 |
0.78 |
SD |
3.15 |
0.166 |
127.3 |
0.33 |
1.56 |
0.15 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
12.25 |
2.402 |
787.4 |
10.05 |
43.05 |
0.79 |
SD |
2.24 |
0.172 |
64.1 |
0.37 |
1.50 |
0.09 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
> 0.05 |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
11.71 |
2.419 |
752.0 |
10.18 |
44.37 |
0.76 |
SD |
0.36 |
0.124 |
94.8 |
0.28 |
1.65 |
0.10 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.01** |
≤ 0.05* |
|
(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett* = p ≤ 0.05, ** = p ≤ 0.01
Table 8. Haematology – group mean values (Continue)
Sex: Female |
Retics %RBC (Week Number) |
A retics 10^6/ul (Week Number) |
MC/Vr fl (Week Number) |
CHr pg (Week Number) |
WBC 10^3/ul (Week Number) |
Neut 10^3/ul (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2.26 |
0.1747 |
64.30 |
19.17 |
4.157 |
0.551 |
SD |
0.40 |
0.0337 |
1.40 |
0.60 |
0.851 |
0.168 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
↑ |
↑ |
↓ |
↓ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2.45 |
0.1897 |
64.45 |
19.16 |
3.788 |
0.438 |
SD |
0.67 |
0.0485 |
2.04 |
0.48 |
0.973 |
0.171 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2.21 |
0.1757 |
63.63 |
18.91 |
3.915 |
0.486 |
SD |
0.46 |
0.0346 |
2.12 |
0.54 |
0.810 |
0.123 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
> 0.05 |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2.42 |
0.1947 |
64.10 |
18.87 |
5.296 |
0.579 |
SD |
0.40 |
0.0279 |
1.73 |
0.44 |
0.903 |
0.162 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
> 0.05 |
|
(#) – Williams, Anova & Dunnett* = p ≤ 0.05
Table 8. Haematology – group mean values (Continue)
Sex: Female |
Lymph 10^3/ul (Week Number) |
Mono 10^3/ul (Week Number) |
Eosin 10^3/ul (Week Number) |
Baso 10^3/ul (Week Number) |
LUC 10^3/ul (Week Number) |
Neut % (Week Number) |
|
Group |
14 (#) |
14 (#1) |
14 (#1) |
14 (#) |
14 (#1) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
3.441 |
0.069 |
0.068 |
0.011 |
0.016* |
13.49 |
SD |
0.787 |
0.013 |
0.026 |
0.011 |
0.005 |
4.05 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
3.209 |
0.066 |
0.049 |
0.011 |
0.014 |
11.70 |
SD |
0.832 |
0.037 |
0.011 |
0.012 |
0.007 |
3.71 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
3.283 |
0.065 |
0.056 |
0.009 |
0.012 |
12.41 |
SD |
0.685 |
0.021 |
0.030 |
0.007 |
0.006 |
2.01 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
4.529 |
0.088 |
0.061 |
0.018 |
0.021 |
10.93 |
SD |
0.802 |
0.024 |
0.040 |
0.013 |
0.008 |
2.59 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
≤ 0.01** |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett** = p ≤ 0.01
(#1) – Williams, Anova & Dunnett(Log) * = p ≤ 0.05
Table 8. Haematology – group mean values (Continue)
Sex: Female |
Lymph % (Week Number) |
Mono % (Week Number) |
Eosin % (Week Number) |
Baso % (Week Number) |
LUC % (Week Number) |
APIT sec (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 (#1) |
14 (#) |
14 (#) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
82.50 |
1.71 |
1.64 |
0.27 |
0.40 |
16.23 |
SD |
3.83 |
0.43 |
0.42 |
0.19 |
0.16 |
1.52 |
|
N |
9 |
9 |
9 |
9 |
9 |
7 |
|
Trend |
↑ |
↓ |
↓ |
↑ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
84.52 |
1.72 |
1.37 |
0.27 |
0.40 |
16.37 |
SD |
4.47 |
0.59 |
0.55 |
0.20 |
0.19 |
1.35 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
83.91 |
1.70 |
1.42 |
0.26 |
0.32 |
15.78 |
SD |
2.36 |
0.45 |
0.57 |
0.16 |
0.08 |
1.28 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
85.46 |
1.68 |
1.17 |
0.29 |
0.43 |
15.32 |
SD |
3.06 |
0.51 |
0.55 |
0.20 |
0.19 |
1.60 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
> 0.05 |
> 0.05 |
≤ 0.05* |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova & Dunnett(Log): * = p ≤ 0.05
Table 8. Haematology – group mean values (Continue)
Sex: Female |
PT sec (Week Number) |
|
Group |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
23.61 |
SD |
2.18 |
|
N |
7 |
|
Trend |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
23.83 |
SD |
1.29 |
|
N |
10 |
|
Trend |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
23.60 |
SD |
0.85 |
|
N |
10 |
|
Trend |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
23.16 |
SD |
0.65 |
|
N |
9 |
|
Trend |
> 0.05 |
|
(#)
– Shirley, Kruskal-Wallis & Steel
Table 9. Blood chemistry – group mean values
Sex: Male |
Urea mg/dl (Week Number) |
Cren mg/dl (Week Number) |
Na mmol/l (Week Number) |
K mmol/l (Week Number) |
Cl mmol/l (Week Number) |
ALT U/l (Week Number) |
|
Group |
14 (#) |
14 (#1) |
14 (#1) |
14 (#1) |
14 (#1) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
31.29 |
0.273 |
140.1 |
4.94 |
99.9 |
42.0 |
SD |
5.65 |
0.028 |
1.5 |
0.42 |
1.3 |
10.5 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
↑ |
↓ |
↑ |
↓ |
↓ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
32.39 |
0.292 |
140.7 |
4.92 |
100.3 |
43.8 |
SD |
4.38 |
0.023 |
1.0 |
0.42 |
1.2 |
4.6 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
- |
- |
> 0.05 |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
32.34 |
0.274 |
141.8 |
4.99 |
99.9 |
46.1 |
SD |
3.23 |
0.037 |
0.9 |
0.43 |
1.2 |
6.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
≤ 0.01** |
- |
> 0.05 |
> 0.05 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
30.67 |
0.264 |
142.4 |
4.74 |
98.7 |
50.9 |
SD |
3.06 |
0.031 |
1.0 |
0.28 |
0.8 |
9.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
≤ 0.001*** |
> 0.05 |
≤ 0.05* |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett(Log)
(#1) – Williams, Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01; *** = p ≤
0.001
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl)
are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not
included
Table 9. Blood chemistry – group mean values (Continued)
Sex: Male |
AST U/l (Week Number) |
ALP U/l (Week Number) |
BiliT mg/dl (Week Number) |
B. Acids umol/l (Week Number) |
T. Prot g/dl (Week Number) |
Ab g/dl (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 |
14 (#1) |
14 (#1) |
14 (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
57.2 |
118.7 |
- |
30.80 |
6.42 |
3.84 |
SD |
11.7 |
37.1 |
- |
19.10 |
0.21 |
0.11 |
|
N |
9 |
9 |
0 |
9 |
9 |
9 |
|
Trend |
↑ |
↑ |
- |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
56.9 |
111.4 |
- |
33.70 |
6.44 |
3.93 |
SD |
4.5 |
20.4 |
- |
17.37 |
0.20 |
0.13 |
|
N |
9 |
9 |
0 |
9 |
9 |
9 |
|
Trend |
- |
- |
- |
- |
- |
> 0.05 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
57.7 |
118.2 |
- |
34.31 |
6.55 |
4.03 |
SD |
2.0 |
34.0 |
- |
13.56 |
0.22 |
0.16 |
|
N |
10 |
10 |
0 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.01** |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
58.0 |
135.0 |
0.150 |
45.26 |
6.48 |
4.11 |
SD |
6.1 |
23.4 |
- |
15.53 |
0.24 |
0.20 |
|
N |
10 |
10 |
1 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
- |
> 0.05 |
> 0.05 |
≤ 0.001*** |
|
(#) – Williams, Anova & Dunnett(Log)
(#1) – Williams, Anova & Dunnett: ** = p ≤ 0.01; *** = p ≤ 0.001
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl)
are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not
included
Table 9. Blood chemistry – group mean values (Continued)
Sex: Male |
Glob g/dl (Week Number) |
A/G ratio (Week Number) |
Ca mg/dl (Week Number) |
Chol mg/dl (Week Number) |
HDL mg/dl (Week Number) |
LDL mg/dl (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2.58 |
1.50 |
10.30 |
64.0 |
46.98 |
8.1 |
SD |
0.22 |
0.14 |
0.11 |
8.6 |
6.34 |
2.4 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
↓ |
↑ |
- |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2.51 |
1.58 |
10.32 |
73.8 |
55.11 |
10.9 |
SD |
0.23 |
0.17 |
0.22 |
16.7 |
11.96 |
4.1 |
|
N |
9 |
9 |
9 |
9 |
9 |
9 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2.52 |
1.61 |
10.40 |
67.6 |
51.16 |
8.2 |
SD |
0.23 |
0.19 |
0.12 |
11.1 |
8.25 |
2.6 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2.37 |
1.74 |
10.31 |
69.9 |
53.83 |
8.6 |
SD |
0.17 |
0.16 |
0.16 |
9.4 |
6.93 |
2.0 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.05* |
≤ 0.01** |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: * = p ≤
0.05; ** = p ≤ 0.01
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl)
are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not
included
Table 9. Blood chemistry – group mean values (Continued)
Sex: Male |
Gluc g/dl (Week Number) |
|
Group |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
198.9 |
SD |
17.3 |
|
N |
9 |
|
Trend |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
174.1 |
SD |
13.1 |
|
N |
9 |
|
Trend |
≤ 0.01** |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
174.7 |
SD |
19.0 |
|
N |
10 |
|
Trend |
≤ 0.01** |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
167.4 |
SD |
25.6 |
|
N |
10 |
|
Trend |
≤ 0.01** |
|
(#) – Williams, Anova & Dunnett: ** = p ≤
0.01
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl)
are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not
included
Table 9. Blood chemistry – group mean values (Continued)
Sex: Female |
Urea mg/dl (Week Number) |
Cren mg/dl (Week Number) |
Na mmol/l (Week Number) |
K mmol/l (Week Number) |
Cl mmol/l (Week Number) |
ALT U/l (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 (#) |
14 (#1) |
14 (#) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
36.94 |
0.304 |
141.7 |
4.00 |
101.3* |
37.6 |
SD |
5.50 |
0.022 |
0.5 |
0.69 |
1.2 |
5.4 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↑ |
↓ |
↓ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
32.21 |
0.294 |
142.3 |
3.89 |
101.9 |
39.3 |
SD |
3.87 |
0.033 |
1.1 |
0.19 |
1.7 |
12.2 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.05* |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
32.54 |
0.292 |
142.3 |
3.68 |
102.0 |
34.7 |
SD |
4.50 |
0.033 |
1.1 |
0.09 |
1.4 |
5.3 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.05* |
- |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
31.15 |
0.280 |
142.4 |
3.84 |
100.3 |
42.1 |
SD |
4.39 |
0.016 |
1.3 |
0.30 |
0.9 |
11.1 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.01** |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.05* |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: * = p ≤
0.05; ** = p ≤ 0.01
(#1) – Shirley, Kruskal-Wallis & Steel
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl)
are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not
included
Table 9. Blood chemistry – group mean values (Continued)
Sex: Female |
AST U/l (Week Number) |
ALP U/l (Week Number) |
BiliT mg/dl (Week Number) |
B. Acids umol/l (Week Number) |
T. Prot g/dl (Week Number) |
Ab g/dl (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 |
14 (#1) |
14 (#1) |
14 (#1) |
|
Group 1 Control 0 mg/kg/day |
Mean |
58.1 |
52.6 |
- |
33.11 |
6.82 |
4.50 |
SD |
5.2 |
17.6 |
- |
17.93 |
0.22 |
0.14 |
|
N |
10 |
10 |
0 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
- |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
63.4 |
49.9 |
- |
43.88 |
6.81 |
4.69 |
SD |
18.4 |
16.3 |
- |
25.72 |
0.30 |
0.28 |
|
N |
10 |
10 |
0 |
9 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
56.4 |
52.6 |
- |
36.63 |
6.74 |
4.66 |
SD |
9.6 |
16.0 |
- |
19.90 |
0.39 |
0.28 |
|
N |
10 |
10 |
0 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
> 0.05 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
58.7 |
64.6 |
0.150 |
43.93 |
6.90 |
4.98 |
SD |
6.0 |
21.0 |
0.000 |
23.86 |
0.32 |
0.28 |
|
N |
10 |
10 |
2 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
- |
> 0.05 |
> 0.05 |
≤ 0.001*** |
|
(#) – Shirley, Kruskal-Wallis & Steel
(#1) – Williams, Anova & Dunnett: *** = p ≤ 0.001
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl)
are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not
included
Table 9. Blood chemistry – group mean values (Continued)
Sex: Female |
Glob g/dl (Week Number) |
A/G ratio (Week Number) |
Ca mg/dl (Week Number) |
Chol mg/dl (Week Number) |
HDL mg/dl (Week Number) |
LDL mg/dl (Week Number) |
|
Group |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2.32 |
1.96 |
10.36 |
50.3 |
42.32 |
- n |
SD |
0.21 |
0.20 |
0.21 |
5.8 |
4.96 |
- |
|
N |
10 |
10 |
10 |
10 |
10 |
0 |
|
Trend |
↓ |
↑ |
↑ |
↑ |
↑ |
- |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2.12 |
2.22 |
10.42 |
54.0 |
47.30 |
5.5 n |
SD |
0.11 |
0.18 |
0.28 |
12.1 |
10.88 |
1.3 |
|
N |
10 |
10 |
10 |
10 |
10 |
4 |
|
Trend |
≤ 0.01** |
≤ 0.01** |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2.08 |
2.25 |
10.34 |
50.1 |
44.02 |
5.0 n |
SD |
0.17 |
0.17 |
0.24 |
10.3 |
9.54 |
- |
|
N |
10 |
10 |
10 |
10 |
10 |
1 |
|
Trend |
≤ 0.001*** |
≤ 0.001*** |
- |
> 0.05 |
> 0.05 |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1.91 |
2.60 |
10.44 |
62.1 |
53.94 |
5.5 n |
SD |
0.12 |
0.22 |
0.23 |
10.8 |
9.86 |
0.7 |
|
N |
10 |
10 |
10 |
10 |
10 |
2 |
|
Trend |
≤ 0.001*** |
≤ 0.001*** |
> 0.05 |
≤ 0.05* |
≤ 0.01** |
- |
|
(#) – Williams, Anova & Dunnett: * = p ≤
0.05; ** = p ≤ 0.01; *** = p ≤ 0.001
(#1) – Shirley, Kruskal-Wallis & Steel: n – inappropriate for statistics
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl)
are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not
included
Table 9. Blood chemistry – group mean values (Continued)
Sex: Female |
Gluc g/dl (Week Number) |
|
Group |
14 (#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
168.1 |
SD |
11.1 |
|
N |
10 |
|
Trend |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
168.8 |
SD |
9.9 |
|
N |
10 |
|
Trend |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
170.2 |
SD |
8.8 |
|
N |
10 |
|
Trend |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
169.5 |
SD |
20.0 |
|
N |
10 |
|
Trend |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
BiliT – individual values lower than the LOQ for the assay (0.15 mg/dl)
are not included
GGT – individual values lower than the LOQ for the assay (3 U/l) are not
included
Table 10.1. Organ weights – absolute and relative to body weight - group mean values
Sex: Male |
Brain (g) |
Adjusted Brain Wt |
Brain % Body Weight |
Pituitary (g) |
Adjusted Pituitary Wt |
Pituitary % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2.112 |
2.076 |
0.508 |
0.0077 |
0.0073 |
0.0018 |
SD |
0..95 |
- |
0.031 |
0.0020 |
- |
0.0004 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↑ |
↓ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2.115 |
2.089 |
0.516 |
0.0089 |
0.0086 |
0.0022 |
SD |
0.086 |
- |
0.032 |
0.0019 |
- |
0.0004 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2.077 |
2.092 |
0.535 |
0.0067 |
0.0069 |
0.0017 |
SD |
0.093 |
- |
0.033 |
0.0012 |
- |
0.0003 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
> 0.05 |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2.083 |
2.130 |
0.564 |
0.0080 |
0.0085 |
0.0021 |
SD |
0.097 |
- |
0.046 |
0.0026 |
- |
0.0007 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
≤ 0.01** |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: ** = p ≤
0.01
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Male |
Thymus (g) |
Adjusted Thymus Wt |
Thymus % Body Weight |
Heart (g) |
Adjusted Heart Wt |
Heart % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#2) |
(#3) |
(#2) |
|
Group 1 Control 0 mg/kg/day |
Mean |
0.3846 |
0.357 |
0.0928 |
1.153 |
1.110 |
0.279 |
SD |
0.0590 |
- |
0.0164 |
0.158 |
- |
0.057 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0.4145 |
0.394 |
0.0997 |
1.207 |
1.155 |
0.293 |
SD |
0.1070 |
- |
0.0199 |
0.156 |
- |
0.025 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0.3755 |
0.387 |
0.0957 |
1.262 |
1.160 |
0.325 |
SD |
0.0743 |
- |
0.0135 |
0.252 |
- |
0.067 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
> 0.05 |
- |
- |
≤ 0.01** |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0.3443 |
0.381 |
0.0918 |
1.208 |
1.160 |
0.325 |
SD |
0.1127 |
- |
0.0257 |
0.166 |
- |
0.034 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.001*** |
|
(#) – Williams, Anova & Dunnett: ** = p ≤
0.01
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
(#2) – Shirley, Kruskal-Wallis & Steel: * = p ≤ 0.05; ** = p ≤ 0.01; ***
= p ≤ 0.001
(#3) – Shirley, Kruskal-Wallis & Steel
(Covariate(s): Dead body weight)
Table 10.1. Organ weights –
absolute and relative to body weight - group mean values (Continued)
Sex: Male |
Spleen (g) |
Adjusted Spleen Wt |
Spleen % Body Weight |
Liver (g) |
Adjusted Liver Wt |
Liver % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
0.581 |
0.551 |
0.139 |
13.773 |
12.907 |
3.292 |
SD |
0.092 |
- |
0.013 |
1.833 |
- |
0.262 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0.605 |
0.583 |
0.147 |
13.888 |
13.246 |
3.364 |
SD |
0.076 |
- |
0.010 |
1.642 |
- |
0.154 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
> 0.05 |
> 0.05 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0.562 |
0.574 |
0.145 |
14.144 |
14.502 |
3.629 |
SD |
0.076 |
- |
0.019 |
1.199 |
- |
0.100 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
> 0.05 |
≤ 0.001*** |
≤ 0.001*** |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0.554 |
0.593 |
0.149 |
16.174 |
17.325 |
4.329 |
SD |
0.072 |
- |
0.014 |
2.375 |
- |
0.243 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.01** |
≤ 0.001*** |
≤ 0.001*** |
|
(#) – Williams, Anova & Dunnett: ** = p ≤
0.01; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: *** = p ≤ 0.001
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Male |
Adrenals (g) |
Adjusted Adrenal Wt |
Adrenals % Body Weight |
Kidneys (g) |
Adjusted Kidneys Wt |
Kidneys % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
0.0599 |
0.0569 |
0.0143 |
2.361 |
2.361 |
0.565 |
SD |
0.0128 |
- |
0.0028 |
0.313 |
- |
0.048 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0.0608 |
0.0586 |
0.0148 |
2.423 |
2.423 n |
0.589 |
SD |
0.0098 |
- |
0.0023 |
0.235 |
- |
0.036 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
> 0.05 |
> 0.05 |
> 0.05 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0.0584 |
0.0596 |
0.0149 |
2.648 |
2.648 n |
0.683 |
SD |
0.0098 |
- |
0.0018 |
0.095 |
- |
0.053 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
> 0.05 |
≤ 0.05* |
≤ 0.05* |
≤ 0.001*** |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0.0635 |
0.0675 |
0.0170 |
2.934 |
2.934 n |
0.785 |
SD |
0.0156 |
- |
0.0036 |
0.433 |
- |
0.043 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
≤ 0.05* |
≤ 0.01** |
≤ 0.001*** |
≤ 0.001*** |
|
(#) – Williams, Anova & Dunnett: * = p ≤
0.05; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: * = p ≤ 0.05; *** = p ≤ 0.001; n
= Mean = Raw Mean as Adjusted mean is not available
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Male |
Testes (g) |
Adjusted Testes Wt |
Testes % Body Weight |
Epididymides (g) |
Adjusted Epididymides Wt |
Epdidymides % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
3.612 |
3.580 |
0.872 |
1.406 |
1.359 |
0.338 |
SD |
0.323 |
- |
0.116 |
0.131 |
- |
0.035 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
3.840 |
3.816 |
0.938 |
1.444 |
1.409 |
0.352 |
SD |
0.189 |
- |
0.091 |
0.128 |
- |
0.034 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
> 0.05 |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
3.707 |
3.720 |
0.953 |
1.443 |
1.462 |
0.370 |
SD |
0.368 |
- |
0.094 |
0.191 |
- |
0.035 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
> 0.05 |
- |
- |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
3.803 |
3.846 |
1.029 |
1.401 |
1.463 |
0.377 |
SD |
0.324 |
- |
0.110 |
0.179 |
- |
0.036 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
≤ 0.01** |
> 0.05 |
> 0.05 |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett: * = p ≤
0.05; ** = p ≤ 0.01
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Male |
Prostate / Seminal Vesicles (g) |
Adjusted Prostate / Seminal Vesicles |
Prostate / Seminal Vesicles % Body Weight |
Thyroids (g) |
Adjusted Thyroids Wt |
Thyroids % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2.284 |
2.205 |
0.545 |
0.0226 |
0.0215 |
0.0054 |
SD |
0.406 |
- |
0.075 |
0.0049 |
- |
0.0009 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↓ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2.376 |
2.137 |
0.577 |
0.0243 |
0.0235 |
0.0059 |
SD |
0.301 |
- |
0.063 |
0.0050 |
- |
0.0011 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
> 0.05 |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2.515 |
2.548 |
0.650 |
0.0204 |
0.0209 |
0.0052 |
SD |
0.267 |
- |
0.094 |
0.0046 |
- |
0.0011 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
≤ 0.05* |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2.211 |
2.316 |
0.596 |
0.0197 |
0.0212 |
0.0053 |
SD |
0.264 |
- |
0.057 |
0.0035 |
- |
0.0009 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
≤ 0.05* |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: * = p ≤ 0.05
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Male |
Dead Body Weight (g) |
|
Group |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
417.24 |
SD |
33.93 |
|
N |
10 |
|
Trend |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
412.25 |
SD |
38.39 |
|
N |
10 |
|
Trend |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
389.96 |
SD |
33.70 |
|
N |
10 |
|
Trend |
> 0.05 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
372.30 |
SD |
40.15 |
|
N |
10 |
|
Trend |
≤ 0.05* |
|
(#) – Williams, Anova & Dunnett: * = p ≤ 0.05
Table 10.1. Organ weights – absolute and relative to body weight - group mean values
Sex: Female |
Brain (g) |
Adjusted Brain Wt |
Brain % Body Weight |
Pituitary (g) |
Adjusted Pituitary Wt |
Pituitary % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
1.969 |
1.969 |
0.810 |
0.0112 |
0.112 |
0.0046 |
SD |
0.113 |
- |
0.044 |
0.0018 |
- |
0.0006 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↓ |
↓ |
↓ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2.004 |
2.005 |
0.825 |
0.0105 |
0.0105 |
0.0043 |
SD |
0.097 |
- |
0.034 |
0.0028 |
- |
0.0011 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
1.945 |
1.951 |
0.812 |
0.0104 |
0.0105 |
0.0043 |
SD |
0.071 |
- |
0.071 |
0.0028 |
- |
0.0011 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1.913 |
1.906 |
0.782 |
0.0094 |
0.0093 |
0.0038 |
SD |
0.099 |
- |
0.060 |
0.0020 |
- |
0.0007 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Female |
Thymus (g) |
Adjusted Thymus Wt |
Thymus % Body Weight |
Heart (g) |
Adjusted Heart Wt |
Heart % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
0.3438 |
0.344 |
0.1411 |
0.833 |
0.833 |
0.343 |
SD |
0.0449 |
- |
0.0163 |
0.062 |
- |
0.035 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↓ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0.3091 |
0.310 |
0.1268 |
0.895 |
0.896 |
0.368 |
SD |
0.0590 |
- |
0.0208 |
0.079 |
- |
0.038 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0.2821 |
0.284 |
0.1170 |
0.878 |
0.882 |
0.365 |
SD |
0.0616 |
- |
0.0234 |
0.129 |
- |
0.053 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0.3151 |
0.313 |
0.1290 |
0.815 |
0.811 |
0.332 |
SD |
0.0712 |
- |
0.0299 |
0.080 |
- |
0.021 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
Table 10.1. Organ weights –
absolute and relative to body weight - group mean values (Continued)
Sex: Female |
Spleen (g) |
Adjusted Spleen Wt |
Spleen % Body Weight |
Liver (g) |
Adjusted Liver Wt |
Liver % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
0.431 |
0.431 |
0.176* |
7.969 |
7.964 |
3.276 |
SD |
0.062 |
- |
0.015 |
0.698 |
- |
0.251 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0.489 |
0.490 |
0.201* |
8.493 |
8.510 |
3.492 |
SD |
0.072 |
- |
0.027 |
0.956 |
- |
0.339 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
≤ 0.05* |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0.423 |
0.428 |
0.176 |
8.311 |
8.418 |
3.453 |
SD |
0.056 |
- |
0.018 |
0.955 |
- |
0.235 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
> 0.05 |
≤ 0.05* |
≤ 0.05* |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0.456 |
0.450 |
0.185 |
10.841 |
10.742 |
4.403 |
SD |
0.083 |
- |
0.025 |
1.161 |
- |
0.107 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.001*** |
≤ 0.001*** |
≤ 0.001*** |
|
(#) – Williams, Anova & Dunnett: * = p ≤
0.05; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: * = p ≤ 0.05; *** = p ≤ 0.001
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Female |
Adrenals (g) |
Adjusted Adrenal Wt |
Adrenals % Body Weight |
Kidneys (g) |
Adjusted Kidneys Wt |
Kidneys % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
0.0712 |
0.0712 |
0.0291 |
1.509 |
1.508 |
0.620 |
SD |
0.0127 |
- |
0.0039 |
0.100 |
- |
0.029 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0.0677 |
0.0678 |
0.0279 |
1.577 |
1.579 |
0.649 |
SD |
0.0143 |
- |
0.0062 |
0.106 |
- |
0.039 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
> 0.05 |
≤ 0.05* |
≤ 0.05* |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0.0707 |
0.0713 |
0.0294 |
1.598 |
1.609 |
0.665 |
SD |
0.0108 |
- |
0.0044 |
0.083 |
- |
0.035 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
≤ 0.05* |
≤ 0.01** |
≤ 0.01** |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0.0703 |
0.0696 |
0.0286 |
1.719 |
1.707 |
0.699 |
SD |
0.0159 |
- |
0.0057 |
0.147 |
- |
0.019 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
0.05 |
≤ 0.001*** |
≤ 0.001*** |
≤ 0.001*** |
|
(#) – Williams, Anova & Dunnett: * = p ≤
0.05; ** = p ≤ 0.01; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: * = p ≤ 0.05; ** = p ≤ 0.01; ***
= p ≤ 0.001
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Female |
Ovaries (g) |
Adjusted Ovaries Wt |
Ovaries % Body Weight |
Uterus (g) |
Adjusted Uterus Wt |
Uterus % Body Weight |
|
Group |
(#) |
(#1) |
(#) |
(#2) |
(#3) |
(#2) |
|
Group 1 Control 0 mg/kg/day |
Mean |
0.0872 |
0.0872 |
0.0359 |
0.822 |
0.7320 |
0.3450 |
SD |
0.0168 |
- |
0.0070 |
0.450 |
- |
0.2059 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0.0900 |
0.0902 |
0.0371 |
0.631 |
0.6080 |
0.2604 |
SD |
0.0156 |
- |
0.0066 |
0.197 |
- |
0.0838 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0.1002 |
0.1010 |
0.0414 |
0.632 |
0.6030 |
0.2629 |
SD |
0.0163 |
- |
0.0040 |
0.219 |
- |
0.0919 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0.0934 |
0.0925 |
0.0381 |
0.677 |
0.6310 |
0.2758 |
SD |
0.0214 |
- |
0.0083 |
0.294 |
- |
0.1198 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett
(#1) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
(#2) – Williams, Anova & Dunnett(Log)
(#3) – Williams, Anova/Anova & Dunnett
(Covariate(s): Dead body weight)
Table 10.1. Organ weights – absolute and relative to body weight - group mean values (Continued)
Sex: Female |
Thyroids (g) |
Adjusted Thyroids Wt |
Thyroids % Body Weight |
Dead Body Weight (g) |
|
Group |
(#) |
(#) |
(#) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
0.0174 |
0.0174 |
0.0072 |
243.65 |
SD |
0.0035 |
- |
0.0017 |
18.19 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
0.0186 |
0.0186 |
0.0077 |
243.07 |
SD |
0.0028 |
- |
0.0011 |
12.07 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
0.0190 |
0.0190 |
0.0079 |
241.20 |
SD |
0.0034 |
- |
0.0017 |
21.45 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
0.0235 |
0.0235 |
0.0096 |
246.14 |
SD |
0.0033 |
- |
0.0013 |
24.57 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.001*** |
≤ 0.001*** |
≤ 0.01** |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: ** = p ≤
0.01; *** = p ≤ 0.001
(#1) – Williams, Anova/Anova & Dunnett: *** = p ≤ 0.001
(Covariate(s): Dead body weight)
Table 10.2. Organ weights – relative to brain weight - group mean values
Sex: Male |
Brain (g) |
Pituitary % Brain |
Thymus % Brain |
Heart % Brain |
Spleen % Brain |
Liver % Brain |
Adrenals % Brain |
|
Group |
(#) |
(#) |
(#) |
(#) |
(#1) |
(#) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
2.112 |
0.3629 |
18.2834 |
54.776 |
27.433 |
651.021 |
2.8287 |
SD |
0.095 |
0.0873 |
3.1413 |
8.986 |
3.650 |
73.244 |
0.5587 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↑ |
↓ |
↑ |
↓ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2.115 |
0.4208 |
19.4780 |
56.971 |
28.553 |
655.321 |
2.8799 |
SD |
0.086 |
0.0899 |
4.4219 |
5.624 |
2.892 |
57.041 |
0.4688 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
2.077 |
0.3236 |
17.9913 |
60.779 |
27.120 |
680.905 |
2.8119 |
SD |
0.093 |
0.0614 |
2.9087 |
11.833 |
3.969 |
46.905 |
0.4588 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
> 0.05 |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
2.083 |
0.3807 |
16.5254 |
57.997 |
26.536 |
774.952 |
3.0393 |
SD |
0.097 |
0.1114 |
5.2816 |
7.264 |
2.716 |
96.415 |
0.6922 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.001*** |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: *** = p ≤
0.001
(#1) – Shirley, Kruskal-Wallis & Steel
Table 10.2. Organ weights – relative to brain weight - group mean values (Continued)
Sex: Male |
Kidneys % Brain |
Testes % Brain |
Epididymides % Brain |
Prostate/Seminal Vesicles % Brain |
Thyroids % Brain |
|
Group |
(#) |
(#) |
(#) |
(#) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
111.525 |
171.470 |
66.612 |
107.790 |
1.0677 |
SD |
11.534 |
18.410 |
6.063 |
16.758 |
0.2082 |
|
N |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↑ |
↑ |
↓ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
114.541 |
181.831 |
68.302 |
112.328 |
1.1467 |
SD |
9.719 |
11.508 |
5.730 |
13.472 |
0.2194 |
|
N |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
127.698 |
178.552 |
69.348 |
121.650 |
0.9800 |
SD |
6.766 |
16.851 |
7.508 |
17.369 |
0.2127 |
|
N |
10 |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.01** |
- |
- |
- |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
140.568 |
182.798 |
67.210 |
105.847 |
0.9454 |
SD |
17.332 |
16.490 |
7.618 |
8.184 |
0.1583 |
|
N |
10 |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.001** |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: ** = p ≤ 0.01; *** = p ≤ 0.001
Table 10.2. Organ weights – relative to brain weight - group mean values (Continued)
Sex: Female |
Brain (g) |
Pituitary % Brain |
Thymus % Brain |
Heart % Brain |
Spleen % Brain |
Liver % Brain |
Adrenals % Brain |
|
Group |
(#) |
(#) |
(#) |
(#) |
(#1) |
(#) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
1.969 |
0.5677 |
17.4350 |
42.494 |
21.880 |
405.271 |
3.6106 |
SD |
0.113 |
0.0785 |
1.8612 |
4.851 |
2.771 |
34.390 |
0.5934 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
↓ |
↓ |
↓ |
↑ |
↑ |
↑ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
2.004 |
0.5222 |
15.3804 |
44.647 |
24.355 |
423.402 |
3.3807 |
SD |
0.097 |
0.1272 |
2.5131 |
3.132 |
3.098 |
39.853 |
0.7085 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
1.945 |
0.5319 |
14.4757 |
45.122 |
21.712 |
427.949 |
3.6392 |
SD |
0.071 |
0.1304 |
2.9491 |
6.138 |
2.351 |
42.274 |
0.5491 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
- |
- |
- |
- |
- |
> 0.05 |
- |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
1.913 |
0.4927 |
16.5734 |
42.571 |
23.778 |
566.272 |
3.6741 |
SD |
0.099 |
0.1016 |
4.1431 |
3.125 |
3.688 |
47.251 |
0.7690 |
|
N |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
> 0.05 |
≤ 0.001*** |
> 0.05 |
|
(#) – Williams, Anova & Dunnett: *** = p ≤ 0.001
Table 10.2. Organ weights – relative to brain weight - group mean values (Continued)
Sex: Female |
Kidneys % Brain |
Ovaries % Brain |
Uterus % Brain |
Thyroids % Brain |
|
Group |
(#) |
(#) |
(#1) |
(#) |
|
Group 1 Control 0 mg/kg/day |
Mean |
76.672 |
4.4277 |
41.760 |
0.8902 |
SD |
3.349 |
0.8274 |
22.997 |
0.1964 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
↑ |
↑ |
↓ |
↑ |
|
Group 2 o-xylene 100 mg/kg/day |
Mean |
78.773 |
4.4844 |
31.509 |
0.9313 |
SD |
5.252 |
0.6896 |
9.662 |
0.1573 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
> 0.05 |
- |
- |
- |
|
Group 3 o-xylene 300 mg/kg/day |
Mean |
82.191 |
5.1599 |
32.259 |
0.9785 |
SD |
3.847 |
0.8705 |
10.091 |
0.1792 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.01** |
- |
- |
> 0.05 |
|
Group 4 o-xylene 1000 mg/kg/day |
Mean |
89.819 |
4.8763 |
35.237 |
1.2302 |
SD |
5.293 |
1.0270 |
14.803 |
0.1774 |
|
N |
10 |
10 |
10 |
10 |
|
Trend |
≤ 0.001*** |
> 0.05 |
> 0.05 |
≤ 0.001*** |
|
(#) – Williams, Anova & Dunnett: ** = p ≤
0.01; *** = p ≤ 0.001
(#1) – Williams, Anova & Dunnett(Log)
Microscopic Pathology
|
Males |
Females |
|||||||
Group |
1 |
2 |
3 |
4 |
1 |
2 |
3 |
4 |
|
Dose Level (mg/kg/day) |
0 |
100 |
300 |
1000 |
0 |
100 |
300 |
1000 |
|
Number of rats examined |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|
Liver |
|||||||||
Hypertrophy, centrilobular hepatocytes |
Minimal |
0 |
0 |
2 |
7 |
0 |
0 |
2 |
6 |
Slight |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
1 |
|
Total |
0 |
0 |
2 |
8 |
0 |
0 |
2 |
7 |
|
Thyroid Gland |
|||||||||
Hypertrophy, follicular epithelium |
Minimal |
1 |
2 |
3 |
3 |
1 |
1 |
1 |
5 |
Slight |
0 |
2 |
1 |
3 |
0 |
0 |
0 |
0 |
|
Moderate |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Total |
1 |
4 |
4 |
6 |
1 |
1 |
1 |
5 |
|
Kidney |
|||||||||
Eosinophilic inclusions, proximal tubule |
Minimal |
0 |
0 |
0 |
0 |
0 |
- |
- |
0 |
Slight |
0 |
6 |
9 |
7 |
0 |
- |
- |
0 |
|
Moderate |
0 |
0 |
0 |
2 |
0 |
- |
- |
0 |
|
Total |
0 |
6 |
9 |
9 |
0 |
- |
- |
0 |
|
Basophilia, cortex, tubules |
Minimal |
1 |
3 |
8 |
4 |
0 |
- |
- |
0 |
Slight |
0 |
0 |
0 |
1 |
0 |
- |
- |
0 |
|
Moderate |
0 |
0 |
0 |
0 |
0 |
- |
- |
0 |
|
Total |
1 |
3 |
8 |
5 |
0 |
- |
- |
0 |
|
α2μ-globulin positive staining |
Minimal |
2 |
0 |
0 |
2 |
- |
- |
- |
- |
Moderate |
0 |
0 |
0 |
1 |
- |
- |
- |
- |
|
Total |
2 |
0 |
0 |
3 |
- |
- |
- |
- |
|
Table 7: Summary incidence of clinical signsa |
||||||||
|
Males |
Females |
||||||
Observation |
Group 1 |
Group 2 |
Group 3 |
Group 4 |
Group 1 |
Group 2 |
Group 3 |
Group 4 |
Malocclusion |
2 |
2 |
2 |
0 |
1 |
0 |
0 |
0 |
Salivation |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
Urine stains |
0 |
0 |
0 |
3 |
0 |
0 |
0 |
4 |
Alopecia |
0 |
0 |
0 |
1 |
0 |
0 |
2 |
1 |
Sores |
0 |
1 |
0 |
2 |
2 |
0 |
0 |
0 |
Bloody crust |
1 |
0 |
0 |
2 |
1 |
0 |
0 |
0 |
Chromodacryorrhea |
3 |
1 |
2 |
2 |
2 |
0 |
0 |
0 |
Small moveable tissue mass |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
aTotal incidence for entire study |
||||||||
Table 8: Overall mean body weight change (Week 0-13) |
|||||
Sex |
Group |
Dose level (mg/kg) |
Body weight |
||
Mean |
S.D. |
N |
|||
Male |
1 |
0 |
293.3 |
43.46 |
20 |
2 |
100 |
289.5 |
30.61 |
17 |
|
3 |
200 |
265.2S |
30.37 |
15 |
|
4 |
800 |
219.5S |
26.16 |
18 |
|
Female |
1 |
0 |
115.9 |
18.00 |
20 |
2 |
100 |
113.2 |
14.06 |
20 |
|
3 |
200 |
107.2 |
14.86 |
16 |
|
4 |
800 |
98.1S |
16.21 |
16 |
|
Sstatistically significant result |
|||||
Table 9: Mean total food consumption |
||||||
Sex |
Group |
Dose level (mg/kg) |
|
Week |
||
1-5 |
6-9 |
10-13 |
||||
Male |
1 |
0 |
Mean |
860.0A |
667.8 |
644.3 |
S.D. |
66.03 |
48.31 |
52.29 |
|||
N |
10 |
20 |
9 |
|||
2 |
100 |
Mean |
831.4 |
640.6 |
611.6 |
|
S.D. |
46.07 |
42.88 |
39.33 |
|||
N |
6 |
14 |
6 |
|||
3 |
200 |
Mean |
849.5 |
661.7S |
614.6 |
|
S.D. |
25.81 |
30.73 |
23.15 |
|||
N |
6 |
14 |
4 |
|||
4 |
800 |
Mean |
773.6S |
612.0S |
586.8 |
|
S.D. |
59.64 |
55.08 |
28.92 |
|||
N |
8 |
14 |
5 |
|||
Female |
1 |
0 |
Mean |
634.9 |
511.4 |
472.4 |
S.D. |
56.91 |
46.89 |
28.32 |
|||
N |
8 |
13 |
9 |
|||
2 |
100 |
Mean |
650.1 |
505.4 |
478.0 |
|
S.D. |
56.50 |
48.52 |
52.80 |
|||
N |
9 |
17 |
8 |
|||
3 |
200 |
Mean |
678.9 |
493.4 |
465.6 |
|
S.D. |
38.24 |
50.78 |
40.62 |
|||
N |
5 |
15 |
6 |
|||
4 |
800 |
Mean |
656.8 |
479.7 |
488.8 |
|
S.D. |
46.35 |
33.23 |
43.20 |
|||
N |
5 |
10 |
6 |
|||
Adata analysed following log10transformation SStatistically significant result |
||||||
Table 10: Mean body weight changes and the percentage difference from controls. |
||||
Doses (mg/kg bw/day) |
0 |
100 |
200 |
800 |
Males (g) |
293.2 |
289.5 |
265.2 (s) |
219.5 (s) |
% difference from controls |
-- |
1.26 |
9.5 |
25.1 |
Females (g) |
115.9 |
113.2 |
107.2 |
98.1 (s) |
% difference from controls |
-- |
2.33 |
7.5 |
15.4 |
S = significant result |
||||
Please see the 'Attached background material' section for all tables
Table 1: Mean body weight changes and the percentage difference from controls. |
||||
Doses (mg/kg bw/day) |
0 |
100 |
200 |
800 |
Males (g) |
305.9 |
320.7 |
327.8 |
272.2 |
% difference from controls |
-- |
-4.8 |
-7.16 |
11.02 (s) |
Females (g) |
135.1 |
134.9 |
148.2 |
120 |
% difference from controls |
-- |
0.15 |
-9.7 |
11.2 (s) |
S = significant result |
||||
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Results are available from key sub-chronic studies that have investigated the repeated dose toxicity of o-, m- and p-xylene.
o-xylene NOAELs: 100 mg/kg bw/day (based on kidney findings, which are not relevant to humans) in males and 300 mg/kg bw/day in females.
m-xylene NOAELs: 100 mg/kg bw/day in males and 200 mg/kg bw/day in females.
p-xylene NOAEL: 200 mg/kg bw/day (both sexes).
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP status not known, non-guideline study, published in peer reviewed literature, limitations in design and/or reporting but otherwise adequate for assessment.
- Qualifier:
- no guideline followed
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- No details reported
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: air
- Details on inhalation exposure:
- no details
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Gas chromatography.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hours/day, 5 days/week
- Remarks:
- Doses / Concentrations:
0, 180, 460 or 810 ppm
Basis:
analytical conc. - Remarks:
- Doses / Concentrations:
0, 781, 1996 and 3515 mg/m3
Basis:
analytical conc. - No. of animals per sex per dose:
- 25 males
- Control animals:
- yes
- Details on study design:
- Groups of 25 male rats were assigned randomly to each of three graded levels of mixed xylenes or to the solvent- free air-control. Three rats from each group were killed for histological examination after 3 and 7 week intervals. Ten rats per group that survived 13 weeks were used for a challenge exposure to determine whether they had become more or less sensitive as a result of the repeated inhalation of vapour. The remaining rats were terminated after 13 weeks (65 days of exposure).
- Positive control:
- No
- Observations and examinations performed and frequency:
- Measurements included body weight change and urine and blood analysis. Evaluations on blood included: haematocrit, total erythrocyte count, reticulocyte count, total and differential leucocyte counts, serum alkaline phosphatase (SAP), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxalacetic transaminase (SGOT) and blood urea nitrogen (BUN).
- Sacrifice and pathology:
- At termination, the following tissues were taken for microscopic examination: adrenal, brain, pituitary, trachea, thyroid, parathyroid, lung, heart, liver, kidney, spleen, stomach, duodenum, pancreas, ileum, jejunum, colon, skeletal muscle, sciatic nerve, and bone marrow impression smear. All tissues were examined at each time point for the high dose and control groups, but for the low and intermediate dose only lung, liver, kidney, heart, spleen, adrenal, thyroid, parathyroid, trachea, oesophagus, and bone marrow impression smears were examined.
- Other examinations:
- Groups of ten rats per group that survived exposure over 13 weeks, were subjected to a 4-hr challenge period during which time they inhaled 29.0 mg/L (6700 ppm) of mixed xylenes. Their response was compared to the similarly handled control group and to 20 naive rats that were randomized from the same production lot as those under test but not subjected to daily handling.
- Statistics:
- No details
- Details on results:
- Two rats (one control and one low dose) died of extraneous pneumonic infections. All other rats gained weight normally. Minor differences in blood clinical chemistry and haematology were considered not to be adverse effects. Urinalyses performed before rats were sacrificed at 3, 7, and 13 wk revealed no abnormalities. No lesions ascribed to inhalation of mixed xylenes were found at any time point.
No statistically significant differences in median time to death were apparent following the challenge at the end of the study. No protective adaptive mechanism could be claimed as a result of exposure to concentrations as high as 3.5 mg/L (810 ppm) for 6 hr/day x 65 days (5 days /week for 13 weeks. - Dose descriptor:
- NOAEC
- Effect level:
- 810 ppm
- Sex:
- male
- Basis for effect level:
- other: 3515 mg/m3. No effects at the highest dose tested.
- Critical effects observed:
- not specified
- Conclusions:
- The NOAEC of mixed xylenes for male rats exposed 6h/day for 5 days in each of 13 weeks was 3515 mg/m3 (3.5 mg/L).
- Executive summary:
Male rats were exposed 6h/day for 5 days in each of 13 weeks to 0, 0.77, 2.0 or 3.5 mg/L (0, 180, 460 or 810 ppm) mixed xylenes. The NOAEC was 3515 mg/m3 (3.5 mg/L).
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 3 515 mg/m³
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- A NOAEC of 3515 mg/m3 was reported by Carpenter et al. (1975) for generalised systemic effects in male rats and male dogs. Other studies have shown that some xylene isomers adversely affect hearing in the rat, with a sub-chronic NOAEC of 1950 mg/m3 reported for p-xylene; the NOAEC for ototoxicity of m-xylene and o-xylene was greater than 7810 mg/m3 (Gagnaire et al., 2001). The ototoxicity of mixed xylenes appears to be dependent upon composition (Gagnaire et al., 2007), with a sub-chronic LOAEC of 1080 mg/m3 reported for one sample while another had a NOAEC of 2170 mg/m3.
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity: oral
o-xylene
A guideline OECD 408 90-day oral rat study with o-xylene was conducted (Britton LD, 2020).
The test material, o-xylene (CAS 95-47-6), was administered to male and female rats by oral gavage in order to evaluate its sub chronic toxicity. Dose levels were 0, 100, 300, and 1000 mg/kg/day (Groups 1 through 4, respectively), with 10 animals/sex/group dosed daily for at least 90 days. The following were investigated: clinical observations, ophthalmoscopy, body weight, food intake, functional observation battery, haematology, blood chemistry, thyroid hormone analysis, organ weights, macroscopic and microscopic pathology.
There were no deaths during the study. Males and females given 1000 mg/kg/day showed decreased activity and unsteady gait from Days 19/18 of dosing onwards (persisting for up to 4 hours after dosing), respectively. The incidence of these clinical signs decreased with time and by Day 72 of dosing, only one male was showing decreased activity and abnormal gait. Over Days 84 to 92 of dosing at most eight out of ten females showed one or both of these signs after dosing. No effects on sensory reaction or grip strength were elicited by o-xylene. In open arena testing, males given 1000 mg/kg/day exhibited effects on arousal, unusual posture and abnormal gait. Twitches or extended rearing were also observed in a small number of individual males given 1000 mg/kg/day. Increased episodes of arousal in the arena and abnormal gait were observed between Days 21 to 70 and Days 21 to 56 of dosing, respectively. Excessive salivation in the arena was also noted between Days 14 and 70 of dosing for males given 300 or 1000 mg/kg/day, with incidence increasing with time. Females given 1000 mg/kg/day also exhibited effects on arousal in the arena, abnormal gait and salivation. Although incidences increased with time similarly to the males, these observations were not seen in either sex after Day 77 of dosing. Movement counts and distance travelled were reduced in males given 100, 300 or 1000 mg/kg/day and this was occasionally accompanied by an increased time at rest. Males given 300 or 1000 mg/kg/day gained less weight over the study than Controls with terminal body weights that were 6 % and 11 % respectively, lower than those of the Controls. There was no effect on body weight for females and no effect on food intake in either sex. There were slight increases in Thyroxine (T4) and no effect on thyroid stimulating hormone (TSH) or triiodothyronine (T3) levels at the end of the treatment period and no adverse effects on haematology, coagulation or blood chemistry parameters. Both sexes given 300 or 1000 mg/kg/day and females given 100 mg/kg/day had statistically significantly higher liver and kidney weights when compared with Controls. In addition, thyroid weights for females given 1000 mg/kg/day were also higher than Controls.
Histopathology findings considered to be related to o-xylene were seen in the liver (hepatocellular hypertrophy) and thyroid (follicular cell hypertrophy) in both sexes and, in the kidneys, eosinophilic inclusions (hyaline droplets) in the tubular epithelium (males only). Following α2μ-globulin staining of the kidneys, although positive staining was observed in 3/10 high dose males, minimal staining was also observed in 2/10 Controls. The precise content of the hyaline droplets observed at an increased incidence/severity of within the cortical tubules of male kidneys therefore remained unestablished. Given the physiological differences between the male rat kidney and human, these findings are considered unlikely to represent a hazard to man.
In conclusion, when administered by gavage to the Han Wistar rat, once daily for at least 90 days, o-xylene was generally well tolerated in-life at 100 and 300 mg/kg/day with, at the latter dose, only a mild retardation of body weight gain in males and clinical signs being limited to some transient excessive salivation after dosing. However, more profound (decreased activity, unsteady gait, effects on arousal, unusual posture), but transient, clinical signs were apparent at 1000 mg/kg/day and a more marked retardation of body weight gains in males. Target organ pathology was restricted to rat specific adaptive responses consisting of hepatic centrilobular hypertrophy and secondary thyroid follicular hypertrophy consistent with enzyme induction and adverse renal tubular changes in males only likely reflecting proteinuria and inclusion of non α2μ-globulin proteins. Therefore, the No Observed Adverse Effect Level (NOAEL) was defined as 300 mg/kg/day o-xylene in the female rat because of the severity of clinical signs at 1000 mg/kg/day and as 100 mg/kg/day in the male rat, because of the incidence and severity of the renal changes. However, given the physiological differences between the male rat kidney and human, the observed tubular changes are unlikely to represent a hazard to man. Therefore, if the findings in the kidney are disregarded as being human relevant, the NOAEL for the male would be 300 mg/kg/day.
m-xylene
A GLP 90-day oral rat study with m-xylene was conducted (Wolfe GW, 1988).
The test material, m-xylene (CAS 108-38-3), was administered to male and female rats by oral gavage in order to evaluate its sub chronic toxicity. Dose levels were 0, 100, 200, and 800 mg/kg/day (Groups 1 through 4, respectively), with 20 animals/sex/group dosed daily for at least 90 days. Criteria evaluated included mortality, clinical signs, body weights, food consumption, ophthalmologic examinations, haematology, clinical chemistry, organ weights, organ-to-body weight ratios, gross pathology, and histopathology.
Mortality was significantly increased in male Group 3 and female Groups 3 and 4; however, based on histopathology findings, these deaths were most likely the result of vehicle and/or compound aspiration. Salivation was frequently observed in both sexes of Group 4 and only rarely in the other treated groups. Total body weight gain was significantly decreased in male Groups 3 and 4, and female Group 4. Food consumption was significantly decreased from Week 1 to 5 in Group 4 males and from Week 6 to 9 in Groups 3 and 4 males. A few clinical pathology parameters were significantly increased or decreased and with one exception (female Group 3), all were in Group 4. A few significant changes were seen in absolute or relative organ weights, all of which were in male Group 4. The most commonly observed lesions at necropsy were in the lungs (mottled and failure to collapse). These lesions were only seen in the animals found dead. No apparent compound-related effects were present in the ophthalmology or histopathology findings.
Based on the results of this study, with the assumption that the decrease in survival was the result of vehicle and/or compound aspiration, the no-observed-adverse-effect level (NOAEL) of m-Xylene was 200 mg/kg/day in the females. However, due to significantly decreased body weight gain in Groups 3 and 4, the NOAEL for the males was 100 mg/kg/day.
Data are available for laboratory animals exposed to high doses of mixed xylenes, adverse effects have been observed in the kidney and liver (IARC, 1989).
A near-guideline (equivalent or similar to OECD 408) subchronic oral gavage study with mixed xylenes (20% ethylbenzene) was conducted by Condie et al. (1988). It includes the range of toxicological endpoints routinely investigated in regulatory subchronic studies and is a key study for identifying the effects of mixed xylenes. In the study, groups of 10 male and 10 female rats were given 0, 150, 750, or 1500 mg/kg bw/day of mixed xylenes in corn oil for 90 consecutive days. A decrease in body weight was observed in males only at 1500 mg/kg bw/day. Although increased relative liver weights were seen at all dose levels in males and in females at 750 and 1500 mg/kg bw/day there were no adverse histopathology findings in the liver. An increased relative kidney weight was observed in high dose males and females and in intermediate dose males. In males there was a dose-related increase in the incidence of slight to mild hyaline droplet formation in tubules at all dose levels. This finding is indicative of alpha-2u-globulin which is considered to be male rat-specific and is not relevant for humans. In females the incidence of minimal nephropathy in females was statistically significantly increased in the 750 and 1500 mg/kg bw/day groups. This finding described as scattered tubular dilation and atrophy, with occasional regeneration and is the chronic progressive nephropathy typically seen in ageing rats.
No NOAEL was established in this study for males based on liver weight increases. However increases in liver weight with no adverse histopathological findings are considered to be an adaptive response to administration of mixed xylenes rather than an adverse toxicological effect. A dose of 750 mg/kg bw/day is the NOAEL based on effects on male body weight. In females a NOAEL of 150 mg/kg bw/day is based on liver weight increases and the kidney effects observed at dose levels of 750 mg/kg bw/day and higher.
Treatment levels between 150 and 750 mg/kg bw/day are covered in a carcinogenicity study in rats (NTP, 1986). Although this study did not include all of the end points included in chronic studies to current guidelines, the key parameters affected in the sub chronic study, i.e. body weights and detailed pathology and histopathology are included. Rats were dosed with mixed xylenes at concentrations of 0, 250 or 500 mg/kg bw /day 5 days per week for 103 weeks. The main finding was a decrease in body weights in males receiving 500 mg/kg bw/day in the second year of the study. There was no other evidence of systemic toxicity including no treatment-related pathology findings. A dose of 250 mg/kg/day was a NOAEL for both sexes and this is considered to be the key study for determining the NOAEL for repeated dose exposure to mixed xylenes via the oral route.
p-xylene
A GLP 90-day oral rat study with m-xylene was conducted (Wolfe GW, 1988).
The test material, p-Xylene (CAS 106-42-3), 99% pure, was administered to male and female Sprague-Dawley rats by oral gavage in order to evaluate its sub-chronic toxicity. Dose levels were 0, 100, 200, and 800 mg/kg/day (Groups 1 through 4, respectively), with 20 animals/sex/group dosed daily for at least 90 days. Criteria evaluated included mortality, clinical signs, body weights. food consumption, ophthalmologic examinations, haematology, clinical chemistry, organ weights, organ-to-body weight ratios, gross pathology, and histopathology.
At least one animal in each treated group died before termination of the study and there was a significant increase in mortality in Group 4 males. However, based on histopathology findings, nearly all of the unscheduled deaths were related to aspiration of the vehicle/test material. Salivation was frequently observed and exclusively in both sexes of Group 4. Mean body weights were slightly decreased in Group 4 males and females while total food consumption was slightly increased in these groups. There was one incidental finding in the haematology results. In the clinical chemistries, a few significant differences were present in the Group 4 females at Week 5; however, none were present at Week 13. No apparent compound-related effects were present in the ophthalmology, organ weight, gross pathology, or histopathology data.
Based on the results of this study, with the consideration of vehicle/test material aspiration producing the deaths in the treated groups, the no-observed-effect level (NOEL) of p-xylene was 200 mg/kg/day.
In addition, LOA considers that useful supportive information is also available from: the NTP 13-week oral gavage toxicity studies with mixed xylene in F344 rats and B6C3F1 mice, which were well conducted and reported Klimisch 2 studies that, in many respects, followed the US EPA sub-chronic toxicity and the original OECD 408 guidelines. In the NTP 13-week studies, the test item contained 82.9% of the o-, m- and p-xylene isomers. The level of p-xylene in the NTP tested sample was slightly below the range specified in the CSR (13.6% vs >15%) however LOA does not consider that this had a significant impact on the outcome of the study. Furthermore, a published 90-day oral rat study with mixed xylene (Condie et al., 1988) is available and is also considered to be well conducted and reported and followed the US EPA and the original OECD 408 sub-chronic toxicity guidelines, with a Klimisch 2 rating. In addition, a GLP 90-day study with m-xylene is also available (Wolfe, 1988a). LOA plans to update the p-xylene IUCLID dossier with this GLP with m-xylene study and considers that it also provides useful supportive information regarding the sub-chronic oral toxicity of p-xylene, as explained below.
Data are available for laboratory animals exposed to high doses of mixed xylenes, adverse effects have been observed in the kidney and liver (IARC, 1989).
A near-guideline (equivalent or similar to OECD 408) subchronic oral gavage study with mixed xylenes (20% ethylbenzene) was conducted by Condie et al. (1988). It includes the range of toxicological endpoints routinely investigated in regulatory subchronic studies and is a key study for identifying the effects of mixed xylenes. In the study, groups of 10 male and 10 female rats were given 0, 150, 750, or 1500 mg/kg bw/day of mixed xylenes in corn oil for 90 consecutive days. A decrease in body weight was observed in males only at 1500 mg/kg bw/day. Although increased relative liver weights were seen at all dose levels in males and in females at 750 and 1500 mg/kg bw/day there were no adverse histopathology findings in the liver. An increased relative kidney weight was observed in high dose males and females and in intermediate dose males. In males there was a dose-related increase in the incidence of slight to mild hyaline droplet formation in tubules at all dose levels. This finding is indicative of alpha-2u-globulin which is considered to be male rat-specific and is not relevant for humans. In females the incidence of minimal nephropathy in females was statistically significantly increased in the 750 and 1500 mg/kg bw/day groups. This finding described as scattered tubular dilation and atrophy, with occasional regeneration and is the chronic progressive nephropathy typically seen in ageing rats. No NOAEL was established in this study for males based on liver weight increases. However increases in liver weight with no adverse histopathological findings are considered to be an adaptive response to administration of mixed xylenes rather than an adverse toxicological effect. A dose of 750 mg/kg bw/day is the NOAEL based on effects on male body weight. In females a NOAEL of 150 mg/kg bw/day is based on liver weight increases and the kidney effects observed at dose levels of 750 mg/kg bw/day and higher. Treatment levels between 150 and 750 mg/kg bw/day are covered in a carcinogenicity study in rats (NTP, 1986). Although this study did not include all of the end points included in chronic studies to current guidelines, the key parameters affected in the sub chronic study, i.e. body weights and detailed pathology and histopathology are included. Rats were dosed with mixed xylenes at concentrations of 0, 250 or 500 mg/kg bw /day 5 days per week for 103 weeks. The main finding was a decrease in body weights in males receiving 500 mg/kg bw/day in the second year of the study. There was no other evidence of systemic toxicity including no treatment-related pathology findings. A dose of 250 mg/kg/day was a NOAEL for both sexes and this is considered to be the key study for determining the NOAEL for repeated dose exposure to mixed xylenes via the oral route.
Repeated dose toxicity: dermal No studies are available for mixed xylenes or the xylene isomers.
Repeated
dose toxicity: inhalation The
available subchronic inhalation studies are designed primarily to
address neurological endpoints in male rats and dogs. These
endpoints are discussed in section 5.10.1.1. In
a recent study by Gagnaire (2001) the potential ototoxicity of
individual xylene isomers was evaluated using electrophysiological
methods in male rats exposed by inhalation to three different
concentrations 6 hours/day, 5 days/week for 13 weeks. The
highest exposure concentration of 1800 ppm had no significant effect on
body weight or body weight gain. Results
of audiological testing include in this study are discussed in section
5.10.1.3. In
an older study by Carpenter et al (1975), male rats and male dogs were
exposed 6h/day for 5 days in each of 13 weeks to 0, 0.77, 2.0 or 3.5
mg/L (0, 180, 460 or 810 ppm) mixed xylenes. The highest exposure level,
equivalent to 3515 mg/m3, was a NOAEC for both species.
Justification for selection of repeated
dose toxicity via oral route - systemic effects endpoint:
Results from an oral repeated dose study conducted on o-xylene in
the rat indicate a sub-chronic NOAEL of 100 mg/kg bw/d for males and 300
mg/kg bw/d for females (Britton, 2020). If the findings in the kidney
are disregarded as being human relevant, the NOAEL for the male would be
300 mg/kg/day.
Results
from oral repeated dose studies conducted on m-xylene in the rat
indicate a sub-chronic NOAEL of 100 mg/kg bw/d for males and 200 mg/kg
bw/d for females (Wolfe et al., 1988). Results
from oral repeated dose studies conducted on p-xylene in the rat
indicate a sub-chronic NOAEL of 200 mg/kg bw/d (Wolfe et al., 1988).
Repeated dose toxicity: via oral
route - systemic effects (target organ) other: all gross lesions and
masses
Repeated dose toxicity: inhalation - systemic effects (target organ)
other: all gross lesions and masses
Justification for classification or non-classification
Xylene isomers do not warrant classification under CLP.
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