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EC number: 219-006-1 | CAS number: 2312-35-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not stated
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Reference
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 5th May 1987 to 28th August 1987
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-1 (90-Day Oral Toxicity)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OTS 798.2650 (90-Day Oral Toxicity in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan
- Housing: individually in screen bottom stainless steel cages (metabolism cages for the kinetic phase)
- Diet: Purina Rodent Laboratory Chow® #5002 ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature: 72 ± 3 ºF
- Humidity: 50 ± 20 %
- Photoperiod: 12 hours light/12 hours dark
IN-LIFE DATES: From: 5th May 1987 To: 28th August 1987 - Route of administration:
- other: oral: feed (toxicity phase); oral: gavage (kinetic phase)
- Vehicle:
- other: corn oil (toxicity study); polyethylene glycol (kinetic study)
- Details on oral exposure:
- DIET PREPARATION (TOXICOLOGY PHASE)
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): Purina Rodent Laboratory Chow® #5002
- Storage temperature of food: refrigerated
PREPARATION OF DOSING SOLUTIONS (KINETIC PHASE):
Radiolabelled test material was dissolved in a minimum amount of hexane and transferred to a tared serum vial. The hexane was evaporated with nitrogen and 18 mL polyethylene glycol 300 was added and the test material dissolved. The amount of radioactivity administered to each animal was calculated from the weight of dose solution (g) and the dose solution radioactivity concentration (dpm/g). - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- 10 g of feed was weighed into a 250 mL Erlenmeyer flask, 50 mL chloroform added and the flask shaken for 1 hour. Chloroform extract was vacuum filtered through a Whatman #2 11cm filter along with two 25 mL chloroform washing aliquots. The chloroform extracts were transferred to 250 mL boiling flasks and evaporated to dryness using a rotary flash evaporator. The dry flask were extracted with 10 mL of hexane and place on a florisil column. The flask were then extracted with two additional 25 mL rinses and the column rinsed with an additional 50 mL hexane. The test material was eluted from the column with 100 mL of 5 % acetone in hexane and collected in a 250 mL boiling flask. The 5 % acetone:hexane was evaporated to dryness using a rotary flask evaporator and the dry flask extracted with chloroform rinses and transfered quantitatively to a 10 mL volumetric flask and diluted to volume.
A 2 mL aliquot was injected into a GC-FID under the following conditions:
Column: 3 %, SP 2100 6' x 4 mm ID
Temperature:
Injector - 300 ºC
Column - 235 ºC 8 min, 32 ºC/min, 280 ºC 8 min
Detector - 300 ºC
Carrier: N2 at 60 mL/min - Duration of treatment / exposure:
- 13 weeks (toxicity study)
Once (kinetic study) - Frequency of treatment:
- Daily (toxicity study)
- Dose / conc.:
- 100 mg/kg diet
- Dose / conc.:
- 1 000 mg/kg diet
- Dose / conc.:
- 2 000 mg/kg diet
- No. of animals per sex per dose:
- Twelve (toxicity study)
- Control animals:
- yes
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: study initiation, weekly thereafter and at terminal sacrifice
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined: Yes
- Time schedule: weekly
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: before study initiation and at 13 weeks
HAEMATOLOGY: Yes
- Time schedule for collection of blood: during week 13
- Anesthetic used for blood collection: Yes
- Animals fasted: No data
- How many animals: 10 per sex per group
- Parameters checked: differential white blood cell count (relative and absolute), nucleated red blood cell count, corrected white blood cell count, segmented neutrophil count, band neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count, red blood cell count, haematocrit, hemoglobin, white blood cell count, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, platelet count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: during week 13
- Anesthetic used for blood collection: Yes
- Animals fasted: No data
- How many animals: 10 per sex per group
- Parameters checked: albumin, calcium, chloride, creatinine, globulin (and albumin/globulin ratio), glucose, phosphorus, potassium, aspartate aminotransferase/serum glutamic-oxaloacetic transamine, alanine aminotransferase/serum glutamic-pyruvic transaminase, sodium, total bilirubin, total protein, urea nitrogen
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- Parameters checked: external surfaces, all orifices, cranial cavity, carcass, external surfaces of brain and spinal cord, nasal cavity and paranasal sinuses and thoracic, abdominal and pelvic cavities and their viscera. For each sacrificed animal from the toxicity study, the kidneys, liver and testes with epididymides (males only) were weighed.
HISTOPATHOLOGY: Yes
- Parameters checked: adrenals, aorta, bone/bone marrow (proximal femur including articular surface of head), brain, cecum, colon, duodenum, oesophagus, heart, ileum, jejunum, kidneys, lesions, liver, lungs, mesenteric lymph node, ovaries, pancreas, pituitary, rectum, salivary glands, sciatic nerve, spleen, stomach, testes with epididymides, thymus, thyroid (parathyroid), trachea, urinary bladder and uterine horn. all tissues were examined microscopically from control and high dose group animals and all animals that died or were sacrificed in a moribund condition. Lungs, liver and kidneys were examined microscopically from all low and mid dose animals.
A number of tissues were examined for possible examination if indicated by signs of toxicity or target organ involvement. - Other examinations:
- After at least 13 weeks on test diets, two animals per sex per dose were dosed by gavage with approximately 12.5 µCi 14C-test material in 1 mL PEG-300/animal. The animals were housed in individual metabolism cages for 96 hours after dosing. Blood samples were collected at 1, 2, 4, 8, 24, 48, 72 and 96 hours post-dose. Excreta were collected at 0-6, 6-12, 12-24, 24-48, 48-72 and 72-96 hours after dosing. A cage rinse was collected at the 24 hour collection interval and a cage wash was collected at the end of the 96 hour urine and faeces collection.
After 96 hours, terminal body weights were recorded. The following tissues were collected: lungs, liver, kidneys, spleen, stomach, stomach contents, intestines, intestine contents, fat (perigonadal) and muscle. - Statistics:
- Levenes test for variance homogeneity followed by standard one-way analysis of variance. If ANOVA is significant, Dunnetts t-test or the Games and Howell modified Tukey-Kramer test are used for pairwise comparisons. When no transformation established variance homogeneity at p<0.001, the data are also examined by non-parametric techniques. These include the Kruskal-Wallis H-test ANOVA and, if this test is significant, the Nemenyi-Kruskal-Wallis test for multiple group comparisons are evaluated at the 5 % two-tailed probability level.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- All of the 2000 ppm animals had a rough hair coat with many appearing thin and having a hunched posture, alopecia and rhinorrhea.
- Mortality:
- no mortality observed
- Description (incidence):
- There was no mortality throughout the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights for 1000 ppm males and females at week 13 were 30 and 31 % lower, respectively, than the controls (statistically significant). At 2000 ppm, corresponding body weights for males and females were reduced by 69 and 52 %, respectively. Male body weight gains were significantly reduced in the 100 ppm group during week 10, in the 1000 ppm group during weeks 1-6, 8, 10 and 11 and in the 2000 ppm group during weeks 1-11. Male cumulative body weight gains were significantly reduced throughout the study in the 1000 and 2000 ppm groups. Body weight gains in females were significantly reduced during weeks 1 and 5 at 1000 ppm and during weeks 1-4 in the 2000 ppm group (see Table 1).
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption was significantly reduced in 1000 and 2000 ppm males throughout the entire study, with the exception of week 12 in the 1000 ppm group. Food consumption in 1000 ppm females was reduced during weeks 1, 3, 4, 6 and 10; consumption was reduced throughout the entire study in the 2000 ppm females (see Table 2).
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Males in the 100 and 2000 ppm groups had significantly higher red blood cell count, while 2000 ppm males had significantly higher haemoglobin. The higher cell count in the 100 ppm males is considered to reflect normal biological variation and is not attributed to exposure to the test material. Mean corpuscular volume and corpuscular haemoglobin was significantly reduced in the 1000 and 2000 ppm males and in the 2000 ppm females. Females administered 1000 ppm had a significantly higher platelet count, although this is considered normal biological variation rather than test material related.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Glucose was significantly reduced in males and females receiving 1000 and 2000 ppm. Urea nitrogen was significantly increased, while creatinine was significantly reduced in the 2000 ppm males and females, although these differences were small. Total protein, albumin and globulin were significantly lower in 2000 ppm males and 1000 and 2000 ppm females. The albumin to globulin ratio was significantly higher in males and females administered 2000 ppm. Calcium was lower in males in females in the 2000 ppm group, although the difference was only significant in the females. Inorganic phosphorous and potassium were significantly higher in 2000 ppm males and females, while chloride was higher in the 2000 ppm females.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Animals administered 1000 and 2000 ppm had significantly lower terminal body weights and tended to have corresponding lower absolute organ weights. Statistically, however, only the 2000 ppm rats had significantly reduced kidney weights, while significant lower liver and testis weights were only seen in this group's males. Organ to body weight percentages for all organs were significantly higher in animals from the 1000 and 2000 ppm groups. There were no treatment-related macro- or microscopic findings.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- There were statistically significant differences for several clinical pathology variables between controls and treated animals, most of which can be attributed to decreased food consumption and body weight.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 100 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- Remarks on result:
- other: Equivalent to 7.1 mg/kg/ay (male); 8.3 mg/kg/day (female)
- Critical effects observed:
- no
- Conclusions:
- Under the conditions of the test, the No Observed Adverse Effect Level was 100 mg/kg diet which is considered to be equivalent to 7.1 mg/kg/day in males and 8.3 mg/kg/day in females.
- Executive summary:
Rats were fed diets containing 0, 100, 1000 or 2000 ppm test material for at least 13 weeks. Body weights, food consumption and overt signs of toxicity were recorded during the study; blood was collected before necropsy for clinical pathology evaluation. Gross changes in the tissues and in the weights of selected organs were recorded at necropsy. Selected tissues were examined microscopically from all animals in the control and high dose groups. In addition, lungs, liver and kidneys were examined for rats treated at 100 and 1000 ppm.
There were no deaths during the 13 week feeding period or during the kinetic phase. All of the animals in the 2000 ppm dose group had a rough hair coat throughout the study; many of these animals were classified as being thin and having a hunched posture, alopecia and rhinorrhea.
Body weights for 1000 and 2000 ppm males and females were significantly lower than those of controls. Body weights for 1000 ppm males and females at week 13 were 30 and 31 % lower, respectively, than those of the controls. For 2000 ppm males and females, body weights were 69 and 52 % lower, respectively, than those of the controls. Male and female cumulative body weight gains in the 1000 and 2000 ppm groups were significantly lower throughout the study. At the end of the study, the 2000 ppm males and females had gained only 31 and 48 %, respectively, of the weight gained by the controls.
Food consumption for males in the 1000 ppm group (except week 12) and males and females in the 2000 ppm group were significantly lower than those of controls for the entire study.
There were statistically significant differences for several clinical pathology variables between control and treated animals. Nearly all of the differences represented treatment-related effects. The effects occurred at 1000 or 2000 ppm or both and, in general, males and females were affected similarly. Most of the effects were considered to be associated with decreased food consumption and body weight.
Animals treated at 1000 or 2000 ppm tended to have lower terminal body weights. Correspondingly these animals tended to have lower absolute organ weights and higher organ-to-body weight percentages. There were no treatment-related macroscopic or microscopic findings.
The NOAEL was determined to be 100 ppm.
Table 1: Mean body weights
Mean body weights (g) | |||||
Week | Sex | 0 mg/kg | 100 mg/kg | 1000 mg/kg | 2000 mg/kg |
0 | M | 119.9 | 116.9 | 120.9 | 118.6 |
F | 114.5 | 114.6 | 113.8 | 113.0 | |
1 | M | 177.1 | 171.7 | 147.2 | 113.0 |
F | 152.3 | 148.7 | 133.4 | 107.0 | |
2 | M | 228.7 | 223.3 | 185.5 | 120.2 |
F | 176.5 | 170.6 | 155.0 | 112.1 | |
3 | M | 280.5 | 276.6 | 226.2 | 137.6 |
F | 199.7 | 195.8 | 174.3 | 127.1 | |
4 | M | 325.0 | 316.1 | 254.1 | 150.9 |
F | 216.1 | 208.9 | 186.0 | 136.8 | |
5 | M | 361.6 | 353.8 | 283.2 | 170.1 |
F | 232.1 | 227.1 | 196.5 | 150.3 | |
6 | M | 390.9 | 379.8 | 299.6 | 182.7 |
F | 242.6 | 234.7 | 202.6 | 157.4 | |
7 | M | 413.9 | 403.8 | 319.7 | 195.8 |
F | 255.8 | 247.3 | 210.1 | 166.0 | |
8 | M | 437.5 | 423.9 | 337.4 | 204.3 |
F | 263.5 | 254.1 | 218.1 | 173.1 | |
9 | M | 451.4 | 437.0 | 347.6 | 210.1 |
F | 267.8 | 259.7 | 219.6 | 178.9 | |
10 | M | 469.1 | 450.3 | 357.9 | 216.3 |
F | 276.0 | 264.0 | 223.6 | 183.3 | |
11 | M | 483.5 | 466.9 | 366.8 | 224.3 |
F | 282.5 | 270.4 | 228.1 | 188.3 | |
12 | M | 485.9 | 471.9 | 371.4 | 227.9 |
F | 283.3 | 273.0 | 228.8 | 190.7 | |
13 | M | 498.4 | 479.8 | 385.8 | 236.0 |
F | 289.4 | 278.7 | 235.2 | 197.3 |
Table 2: Food consumption
Food consumption (g/week) | |||||
Week | Sex | 0 mg/kg | 100 mg/kg | 1000 mg/kg | 2000 mg/kg |
1 | M | 143.3 | 140.0 | 117.7 | 71.8 |
F | 126.7 | 119.1 | 108.6 | 78.5 | |
2 | M | 161.3 | 154.9 | 120.3 | 99.2 |
F | 125.0 | 120.2 | 117.5 | 75.8 | |
3 | M | 177.7 | 175.4 | 135.4 | 77.3 |
F | 135.2 | 133.1 | 109.9 | 69.2 | |
4 | M | 181.5 | 173.5 | 133.3 | 76.3 |
F | 130.6 | 129.6 | 106.6 | 72.9 | |
5 | M | 184.6 | 179.5 | 148.0 | 102.2 |
F | 134.2 | 134.2 | 117.8 | 79.8 | |
6 | M | 186.4 | 180.0 | 145.4 | 95.7 |
F | 139.4 | 140.6 | 108.6 | 75.9 | |
7 | M | 184.5 | 177.8 | 138.3 | 86.4 |
F | 140.9 | 133.3 | 116.7 | 79.5 | |
8 | M | 180.6 | 178.4 | 152.2 | 87.3 |
F | 138.4 | 132.6 | 116.4 | 89.4 | |
9 | M | 178.2 | 176.6 | 150.8 | 98.5 |
F | 143.8 | 133.5 | 120.0 | 82.7 | |
10 | M | 178.6 | 171.8 | 145.3 | 82.1 |
F | 137.4 | 130.1 | 106.6 | 84.9 | |
11 | M | 181.5 | 180.5 | 139.0 | 85.6 |
F | 144.1 | 129.7 | 119.1 | 87.6 | |
12 | M | 169.5 | 172.3 | 145.7 | 104.8 |
F | 128.4 | 144.7 | 111.2 | 82.5 | |
13 | M | 182.6 | 175.1 | 157.5 | 85.4 |
F | 134.4 | 136.3 | 111.2 | 94.9 |
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
- Objective of study:
- excretion
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- A single oral dose of 1500 mg/kg bw 14C labelled test material was administered to six male rats. Urine samples were taken at the conclusion of 0-24, 24-48 and 48-72 sampling intervals. The quantity of parent compound-equivalents was measured by LSC and expressed as percentage of administered dose. Metabolites were isolated and purified through the use of TLC and HPLC and identified by high resolution NMR spectroscopy and MS.
- GLP compliance:
- yes
Test material
- Reference substance name:
- Propargite
- EC Number:
- 219-006-1
- EC Name:
- Propargite
- Cas Number:
- 2312-35-8
- Molecular formula:
- C19H26O4S
- IUPAC Name:
- propargite
- Test material form:
- liquid
- Details on test material:
- - Name of test material (as cited in study report): Omite
- Radiochemical purity (if radiolabelling): 97.5 %
- Specific activity (if radiolabelling): 11.6 mCi/mmole
- Locations of the label (if radiolabelling): phenyl ring
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilington, MA, USA
- Weight at study initiation: 142-163 g
- Fasting period before study: 18 hours
- Housing: Nalgene metabolism cages
- Individual metabolism cages: yes
- Diet: Charles River Rat, Mouse and Hamster formula ad libitum
- Water: ad libitum
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
1400 mg unlabelled test material was mixed with 12.6 mg labelled test material in 1 mL hexane. After mixing, the hexane was evaporated and the residue dissolved in 3 mL corn oil and mixed. Each animals was administered approximately 0.7 mL of dosing solution. - Duration and frequency of treatment / exposure:
- Once
Doses / concentrations
- Dose / conc.:
- 1.5 other: g/kg
- Control animals:
- yes, concurrent vehicle
- Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces
- Time and frequency of sampling: 24, 48 and 72 hours after dosing.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on excretion:
- Of the applied dose, 12 % was excreted in the urine.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- HPLC radiochromatograms generated for the 0-24, 24-48 and 48-72 hour urine samples all qualitatively resemble each other in that there are five major zones of radioactivity. Moreover, the HPLC profiles are qualitatively the same as profiles obtained in an earlier oral dose study and 13 week dietary study (Banijamali and Tortora, 1998a) in spite of different dose levels and exposure regimes. In addition, the parent compound was not detected in the urine.
The molecular weights of metabolites 1 to 5 were determined to be 294, 382, 296, 296 and 280. In order of increasing polarity the following urinary metabolites were identified:
Metabolite 5: 1-[4-{1.1-dimethyl-2-hydroxyethyl)phenoxy]-2,x-cyclohexane-diol (HOMe-TBOC-diol)
Metabolite 4: 1-[4-{1.1-dimethyl-2-hydroxyethyl)phenoxy]-2,x,x'-cyclohexane-triol (HOMe-TBOC-triol)
Metabolite 3: 1-[4-(1,1-dimethyl-2-hydroxyethyl)phenoxy]-2,4,5-cyclohexane-triol (HOMe-TBPC-triol)
Metabolite 2: 1-[4-(2,x-dihydroxycyclohexoxy)phenyl]-2,2-dimethyl sodium sulphate (HOMe-TBPC-diol sulphate)
Metabolite 1: 1-{4-(2,x-dihydroxycyclohexoxy)phenyl]-2,2-dimethyl acetic acid (Carboxy-TBPC diol)
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: bioaccumulation potential cannot be judged based on study results
Urinary HPLC radiochromatograms taken over time and mass spectral analysis indicate that the test material is rapidly and completely metabolised in male rats to five major metabolites of greater polarity than the parent compound. The data indicate a metabolic pathway that involves hydrolysis and hydroxylation of the parent compound to 1-[4-(1,1-dimethyl-2-hydroxyethyl)phenoxy]-2,x-cyclohexane-diol (HOMe-TBPC-diol). This metabolite is then subject to either sulphate conjugation to give 1-[4-(2,x-dihydroxycyclohexoxy)phenyl-2,2-dimethylethyl sodium sulphate (HOMe-TBPC-diol sulphate) or further oxidation to give 1-[4-(2,x-dihydroxycyclohexoxy)phenyl]-2,2-dimethyl acetic acid (Carboxy-TBPC-diol) or hydroxylation to give 1-[4-(1,1-dimethyl-2-hydroxyethyl)phenoxy]-2,4,5-cyclohexane-triol (HOMe-TBPC-triol) and 1-[4-(1,1-dimethyl-2-hydroxyethyl)phenoxy]-2,x,x'-cyclohexane-triol (HOMe-TBPC-triol). Moreover, the same degradation pathway is apparent regardless of dose level or route of administration. - Executive summary:
Male rats were treated with an oral dose (1.5 g/kg) of 14C-test material. Urine and faeces were collected for 72 hours after treatment. During this time, 12 % of the applied dose was excreted in the urine. Five major metabolites were detected by HPLC and identified by high resolution FT-NMR and MS. Spectral analysis indicated that test material was rapidly degraded by rats to more polar products and metabolism of cyclohexyl ring is strongly favoured.
In order of increasing polarity, the following metabolites were isolated in rat urine and identified as:
1-[4-(1,1-dimethyl-2-hydroxyethyl)phenoxy]-2, x-cyclohexane-diol
1-[4-(1,1-dimethyl-2-hydroxyethyl)phenoxy]-2,x,x'-cyclohexane-triol
1-[4-(1,1-dimethyl-2-hydroxyethyl)phenoxy]-2,4,5-cyclohexane-triol
1-[4-(2,x-dihydroxycyclohexoxy)phenyl]-2,2-dimethylethyl sodium sulfate
1-[4-(2,x-dihydroxycyclohexy)phenyl]-2,2-dimethyl acetic acid
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