Registration Dossier
Registration Dossier
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EC number: 947-744-0 | CAS number: -
Endpoint summary
Administrative data
Description of key information
One dose range finding study with a 14-day oral treatment in rats is available as supporting information and one GLP conform 28-day repeated dose study in rats according to OECD 407 is available. Dose levels of 0, 100, 300 and 1000 mg/kg bw/day were applied by oral gavage once daily. The No Observed Adverse Effect Level (NOAEL) of the test item Hostacerin DGSB was found to be 1000 mg/kg body weight/day when administered for a period of 28 consecutive days repeatedly by oral (gavage) to Sprague Dawley rats with a recovery period of 14 days under the experimental conditions and the doses employed.
A total of 60 (30 males + 30 females) Sprague Dawley rats were distributed to main and recovery groups. Each main group (G1, G2, G3 and G4) and recovery group (G1R and G4R) consisted of 5 males and 5 females. The animals in G1/G1R groups were administered with vehicle [0.5 % w/v Carboxy Methyl Cellulose], the animals in G2, G3 and G4/G4R groups were administered with test item Hostacerin DGSB at the dose levels of 100, 300 and 1000 mg/kg body weight/day.
The homogeneity and formulation analysis for dose concentration verification of the prepared formulations were performed. The results of the analyzed formulations were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is <10%.
All the main and recovery group animals were observed daily for clinical signs and mortality and morbidity, weekly for detailed clinical examination, body weight and feed consumption. Opthalmoscopic examination and neurological/functional examination was carried out during week 4 for main groups (G1 and G4 group animals) and during week 6 for recovery groups (G1R and G4R group animals). Haematology, clinical chemistry analysis, urinalysis, gross pathology and organ weighing were performed on day 29 for main groups and on day 43 for recovery groups. Histopathological examination was conducted on the tissues from the vehicle control (G1) and high dose (G4) group animals.
The animals did not reveal any clinical signs of toxicity throughout the treatment and recovery period. No mortality or morbidity was observed throughout the experimental period. No treatment related changes in body weight, percent change in body weight, feed consumption, ophthalmoscopic examination, neurological/functional examination, haematology, clinical chemistry, urinalysis, organ weights (both absolute and relative) were observed.
There were no gross pathological changes observed at any of the doses tested in either sex. No treatment related histopathological findings were noticed.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: oral, other
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2017-08-17 to 2017-12-30
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- OECD Guidelines for the Testing of Chemicals (No. 407, Section 4: Health Effects) on conduct of
“Repeated Dose 28-Day Oral Toxicity Study in Rodents” adopted on 03 October 2008 - Deviations:
- no
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Clariant Produkte (Deutschland) GmbH
84504 Burgkirchen, Germany and DEG4338635
- Expiration date of the batch:04 Oct 2018
- Purity test date:04 Oct 2016
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:Ambient (21 to 29 oC)
- Stability under test conditions:not established (freshly prepared test item formulations were admi
nistered to the animals and homogeneity was achieved thorough stirring)
- Solubility and stability of the test substance in the solvent/vehicle:forms uniform suspension in 0.5% w/v carboxy
methyl cellulose at the concentration of 100 mg/mL (highest dose concentration) as evidenced by the
in-house solubility/suspendibilty test results.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:ground and made in to suspension.
-Final preparation of a solid: Suspension
FORM AS APPLIED IN THE TEST (if different from that of starting material): Suspension
OTHER SPECIFICS: - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Rat is one of the standard laboratory rodent species used for toxicity assessment and also recommended by various regulatory authorities.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Inhouse bred
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation:100 to 150 g
- Housing: Maximum of three animals were housed in a standard polypropylene cage (Size: L 430 x B 285 x H 200 mm). Clean sterilized paddy husk was provided as bedding material.
- Diet :Altromin Maintenance diet for rats and mice 1324 manufactured by Altromin Spezialfutter GmbH & Co. KG was provided ad libitum to the animals throughout the experimental period.
- Water (e.g. ad libitum):Deep bore-well water passed through activated charcoal filter and exposed to ultraviolet rays in Aquaguard water filter with purifier
- Acclimation period:17 August 2017 to 21 August 2017
DETAILS OF FOOD AND WATER QUALITY: Contaminant free
ENVIRONMENTAL CONDITIONS
- Temperature (°C):19.1°C to 23.9°C
- Humidity (%):40% to 69%
- Air changes (per hr):12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours fluorescent light and 12 hours dark cycle
IN-LIFE DATES: From:17 August 2017 To:03 October 2017 - Route of administration:
- oral: gavage
- Details on route of administration:
- The vehicle and test item formulations were administered through oral (gavage) route. The oral route is one possible route for human exposure.
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5 % w/v Carboxy Methyl Cellulose
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:The required quantity of test item ground well in a mortar and pestle by adding small quantity of 0.5% w/v Carboxy Methyl Cellulose until aclear suspension was formed. Thereafter, the entire quantity of the formulation was transferred intoa measuring cylinder. Again,a small quantity of the vehicle was added to rinse the mortar and pestleand this was transferred into the measuring cylinder. The rinsing of mortar and pestlewas repeated to ensure the complete transfer of the contents to the measuring cylinder. Finally, thevolume was made up to the required quantity with vehicle to get a desired concentration of 10, 30 and 100 mg/mL of test item for low, mid and high dose groups respectively.
VEHICLE
- Justification for use and choice of vehicle: The test item was in-soluble in distilled water and forms uniform suspension in 0.5% w/v carboxy methyl cellulose at the concentration of 100 mg/mL (highest dose concentration) as evidenced by the in-house solubility/suspendibilty test results.
- Concentration in vehicle: Low dose: 10 mg/ml; Mid dose: 30 mg/ml; High dose: 100 mg/ml
- Amount of vehicle (if gavage): 10 mL/kg body weight
-Batch no.: BCBN1690V
- Purity: 0.5 % w/v in distilled water - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Homogeneity and formulation analysis for dose concentration verification was done by Analytical Chemistry department of Bioneeds India Private Limited. Sampling and analysis of formulations were performed during first week of treatment and during week 4 of the treatment. The samples were collected in duplicates (20 mL each) from top, middle and bottom layer from low and mid dose concentrations, in duplicates (5 mL each) from top, middle and bottom layer from high dose concentrations and from middle layer in duplicate (5 ml each) sets from vehicle control.
The mean results were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is <10%. - Duration of treatment / exposure:
- 28-Days
- Frequency of treatment:
- Once daily
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- Low Dose
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- Mid Dose
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- High Dose
- No. of animals per sex per dose:
- 5 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The doses of 100, 300 and 1000 mg/kg body weight were selected as low (G2), mid (G3) and high dose (G4) levels for test item Hostacerin DGSB. The No Observed Adverse Effect Level (NOAEL) of the test item obtained from a dose range finding study (Bioneeds Study Number: BIO-TX 2503) was found to be 1000 mg/kg/day when administered for a period of 14 consecutive days by oral (gavage) to Sprague Dawley rats. In addition, a concurrent control group was included.
- Rationale for animal assignment (if not random): The body weight stratified rats were distributed to all the experimental groups using Microsoft Excel Spread sheet, such that body weight variation of animals selected for the experiment did not exceed ±20% (+11.21% to -8.42% for males and +7.61% to -8.12% for females) of the mean body weight of each sex.
- Post-exposure recovery period in satellite groups: 14 days - Positive control:
- not applicable
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:Once daily
- Cage side observations checked in table [No.1] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule: Weekly once
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly once
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: for all the animals before start of the treatment and during week 4 of treatment for G1 and G4 group animals and during week 6 for recovery group animals (G1R and G4R).
- Dose groups that were examined: G1/G1R (vehicle control) and G4/G4R (high dose).
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination (on day 29 for main groups and day 43 for recovery groups)
- Anaesthetic used for blood collection: Yes (mild isoflurane)
- Animals fasted: Yes
- How many animals:All control and tested dose group animals of either sex
- Parameters checked in table [No.10] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At termination (on day 29 for main groups and day 43 for recovery groups)
- Animals fasted: Yes
- How many animals: All control and tested dose group animals of either sex
- Parameters checked in table [No.11] were examined.
URINALYSIS: Yes
- Time schedule for collection of blood: At termination (on day 29 for main groups and day 43 for recovery groups)
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.12] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: week 4 for main group (control and high dose groups) animals and week 6 for recovery group animals.
- Dose groups that were examined: control and high dose main group animals (G1 and G4) and recovery group animals (G1R and G4R).
- Battery of functions tested: sensory activity / grip strength / motor activity - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table no. 15)
HISTOPATHOLOGY: Yes (see table no 16) - Other examinations:
- not applicable
- Statistics:
- The data was subjected to statistical analyses using SPSS software version 22. Body weight, percent change in body weight, feed consumption, organ weights and ratios, hematological and clinical chemistry estimations and urine analysis parameters were subjected to statistical analysis. One way ANOVA followed by Dunnett’s post test was done for different treatment groups comparing with the control group data. Comparison of means between the recovery groups was done using ‘t’ test based on the requirement. All analysis and comparisons were evaluated at the 95% level of confidence (P<0.05).
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no clinical signs of toxicity observed at any of the tested doses (100, 300 & 1000 mg/kg body weight) of either sex.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no mortality/morbidity observed at any of the tested doses (100, 300 & 1000 mg/kg body weight) of either sex.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There were no treatment related changes noted in mean body weight and percent change in body weight with respect to day 1 at any of the tested doses (100, 300 & 1000 mg/kg body weight) of either
sex when compared with vehicle control. - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There were no treatment related changes noted in mean feed consumption at any of the tested doses (100, 300 & 1000 mg/kg body weight) of either sex when compared with vehicle control.
- Food efficiency:
- not examined
- Description (incidence and severity):
- not applicable
- Water consumption and compound intake (if drinking water study):
- not examined
- Description (incidence and severity):
- not applicable
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- There were no ocular changes observed during the opthalmoscopic examination carried out during week 4 for vehicle control and high dose group animals and during week 6 for vehicle control recovery and high dose recovery group animals.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment related changes observed in haematology at any of the tested dose group animals of either sex.
However, in main group, statistical significant decrease in Total Leucocyte Count in G3 males, statistical significant increase in percent monocytes in G2 and G3 males; statistical significant decrease in absolute lymphocytes in G3 males; statistical significant decrease in PT in G3 and G4 males; statistical significant increase in percent monocytes in G3 females; statistical significant increase in APTT in G4 females when compared with vehicle control group animals were noted. In recovery group, statistical significant decrease in Hemoglobin and Haematocrit in G4R females when compared with vehicle control recovery group animals was noted.
All the observed changes are considered incidental and not treatment related because of the lack of dose dependency and/or due to random biological variation. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment related changes observed in clinical chemistry at any of the tested dose group animals of either sex.
However, statistically significant increase in alanine aminotransferase in G4 males; statistically significant decrease in glucose in G3 and G4 females; statistically significant increase in sodium and chloride in G3 and G4 females; statistically significant increase in creatinine in G2 females and statistically significant decrease in creatinine in G4 females were noted when compared with vehicle control group. In recovery group, statistically significant increase in albumin and sodium in G4R males; statistically significant decrease in Alanine aminotransferase in G4R females were noted when compared with vehicle control recovery group.
These observed changes are considered as incidental and not treatment related as there were no changes were noted in main group animals of the same group and these changes can be due to random biological variation. - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- There were no treatment related changes observed in the urinalysis parameters at any of the tested dose group animals of either sex.
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- There were no changes observed in neurological/functional examination battery carried out during week 4 for vehicle control and high dose group animals and during week 6 for vehicle control recovery and high dose recovery group animals.
- Immunological findings:
- not examined
- Description (incidence and severity):
- not applicable
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment related changes observed in the absolute and relative organ weights at any of the tested dose group animals of either sex.
However, statistically significant decrease in absolute brain weight in G2 males was noted when compared with vehicle control group animals.
All the observed change is considered incidental and not treatment related because of the no effect on relative organ weight, lack of dose dependency and/or there were no associated macroscopic and microscopic abnormalities noted at the high dose main groups. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no gross pathological changes observed at any of the tested dose group animals of either sex during gross pathological examination.
- Neuropathological findings:
- not examined
- Description (incidence and severity):
- not applicable
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no histopathological findings noted during microscopic examination at high dose group males and females.
However, In high dose group, one male revealed sperm granuloma in epididymis unilaterally and one male revealed interstitial MNC infiltration of prostate gland. Sperm granulomas and Interstitial MNC infiltration of prostate gland can occur as an incidental background finding in rodents, hence this findings cannot be considered as treatment related.
All other lesions observed were considered as spontaneous and incidental to Sprague Dawley rats as they lack in consistency. - Histopathological findings: neoplastic:
- not examined
- Description (incidence and severity):
- not applicable
- Other effects:
- not examined
- Description (incidence and severity):
- not applicable
- Details on results:
- Based on the results discussed, there were no toxicological effects tnoted up to 1000 mg/kg body weight/day when administered for a period of 28 consecutive days repeatedly by oral (gavage) to Sprague Dawley rats with a recovery period of 14 under the experimental conditions and the doses employed.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects were observed at all animals of all dose groups
- Key result
- Critical effects observed:
- no
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) of the test item Hostacerin DGSB was found to be 1000 mg/kg body weight/day when administered for a period of 28 consecutive days repeatedly by oral (gavage) to Sprague Dawley rats with a recovery period of 14 under the experimental conditions and the doses employed
- Executive summary:
The test item, Hostacerin DGSB was evaluated to determine the toxic potential when administered for a period of 28 consecutive days repeatedly by oral (gavage) route to Sprague Dawley rats. This study provides information on major toxic effects, target organs, possibility of cumulative effects and also to assess the reversibility of effects after 14 days recovery period and to estimate the No Observed Adverse Effect Level (NOAEL).
A total of 60 (30 males + 30 females) Sprague Dawley rats were distributed to main and recovery groups. Each main group (G1, G2, G3 and G4) and recovery group (G1R and G4R) consisted of 5 males and 5 females. The animals in G1/G1R groups were administered with vehicle [0.5 % w/v Carboxy Methyl Cellulose], the animals in G2, G3 and G4/G4R groups were administered with test item Hostacerin DGSB at the dose levels of 100, 300 and 1000 mg/kg body weight/day. The vehicle and test item formulations were administered at the dose volume of 10 mL/kg body weight.
The homogeneity and formulation analysis for dose concentration verification of the prepared formulations were collected in duplicates (20 mL each) from top, middle and bottom layer from low and mid dose concentrations, in duplicates (5 mL each) from top, middle and bottom layer from high dose concentrations and from middle layer in duplicate sets from vehicle control during week 1 and week 4 of the treatment period. The results of the analyzed formulations were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is <10%.
All the main and recovery group animals were observed daily for clinical signs and mortality and morbidity, weekly for detailed clinical examination, body weight and feed consumption. Opthalmoscopic examination and neurological/functional examination was carried out during week 4 for main groups (G1 and G4 group animals) and during week 6 for recovery groups (G1R and G4R group animals). Haematology, clinical chemistry analysis, urinalysis, gross pathology and organ weighing were performed on day 29 for main groups and on day 43 for recovery groups. Histopathological examination was conducted on the tissues from the vehicle control (G1) and high dose (G4) group animals.
The animals did not reveal any clinical signs of toxicity throughout the treatment and recovery period. No mortality or morbidity was observed throughout the experimental period. No treatment related changes in body weight, percent change in body weight, feed consumption, ophthalmoscopic examination, neurological/functional examination, haematology, clinical chemistry, urinalysis, organ weights (both absolute and relative) were observed.
There were no gross pathological changes observed at any of the doses tested in either sex. No treatment related histopathological findings were noticed.
Reference
TABLE 1. SUMMARY OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
No. of Animals |
Clinical Signs of Toxicity/Detailed Clinical Examination |
Mortality (No. of Incidences/ No. of Animals) |
G1, M & 0 |
5 |
N |
0/5 |
G2, M & 100 |
5 |
N |
0/5 |
G3, M & 300 |
5 |
N |
0/5 |
G4, M & 1000 |
5 |
N |
0/5 |
G1R, M & 0 |
5 |
N |
0/5 |
G4R, M & 1000 |
5 |
N |
0/5 |
M: Male; R: Recovery; N: Normal
TABLE 1 (Contd..,). SUMMARY OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
No. of Animals |
Clinical Signs of Toxicity/Detailed Clinical Examination |
Mortality (No. of Incidences/ No. of Animals) |
G1, F & 0 |
5 |
N |
0/5 |
G2, F & 100 |
5 |
N |
0/5 |
G3, F & 300 |
5 |
N |
0/5 |
G4, F & 1000 |
5 |
N |
0/5 |
G1R, F & 0 |
5 |
N |
0/5 |
G4R, F & 1000 |
5 |
N |
0/5 |
F: Female; R: Recovery; N: Normal
TABLE 2. SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight on Days |
|||||
1 |
8 |
15 |
22 |
28 |
||
G1, M & 0 |
Mean |
162.50 |
211.14 |
245.60 |
288.06 |
314.61 |
±SD |
13.51 |
19.22 |
16.33 |
21.02 |
10.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
162.21 |
207.96 |
242.91 |
284.28 |
313.19 |
±SD |
9.97 |
21.36 |
21.93 |
24.26 |
34.78 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
164.23 |
211.00 |
242.14 |
286.20 |
316.23 |
±SD |
9.03 |
19.55 |
17.22 |
27.84 |
40.84 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
165.19 |
211.12 |
245.13 |
287.71 |
313.01 |
±SD |
8.46 |
9.78 |
11.04 |
19.47 |
26.25 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
M: Male; SD: Standard Deviation; n: Number of animals
TABLE 2 (Contd..,). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight on Days |
|||||
1 |
8 |
15 |
22 |
28 |
||
G1, F & 0 |
Mean |
142.92 |
168.62 |
189.37 |
218.40 |
229.43 |
±SD |
7.37 |
9.68 |
10.37 |
11.91 |
11.92 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
143.53 |
171.45 |
195.29 |
211.93 |
226.26 |
±SD |
10.11 |
8.81 |
7.06 |
7.78 |
10.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
144.20 |
176.29 |
197.52 |
219.80 |
226.41 |
±SD |
7.74 |
9.23 |
6.36 |
11.04 |
11.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
145.97 |
166.31 |
187.14 |
211.63 |
225.58 |
±SD |
9.39 |
14.05 |
13.56 |
9.49 |
9.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
F: Female; SD: Standard Deviation; n: Number of animals
TABLE 2 (Contd..,). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight on Days |
Body Weight on Days |
|||||||
1 |
8 |
15 |
22 |
28 |
36 |
42 |
|||
G1R, M & 0 |
Mean |
163.62 |
204.42 |
239.83 |
307.23 |
335.11 |
356.67 |
373.26 |
|
±SD |
6.85 |
25.49 |
20.82 |
29.09 |
37.95 |
31.72 |
26.34 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
162.89 |
219.71 |
249.50 |
305.80 |
331.43 |
354.32 |
370.11 |
|
±SD |
7.68 |
13.09 |
11.39 |
16.62 |
27.82 |
24.62 |
24.14 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
143.90 |
177.74 |
198.31 |
206.96 |
220.35 |
235.47 |
245.49 |
|
±SD |
4.92 |
4.65 |
5.53 |
7.62 |
5.78 |
7.34 |
10.13 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
144.54 |
173.60 |
192.29 |
208.37 |
225.65 |
240.44 |
249.58 |
|
±SD |
5.35 |
11.47 |
12.81 |
16.34 |
22.92 |
21.18 |
18.56 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals
TABLE 3. SUMMARY OF PERCENT CHANGE IN BODY WEIGHT (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body weight (%) during Days |
||||
1 to 8 |
1 to 15 |
1 to 22 |
1 to 28 |
||
G1, M & 0 |
Mean |
29.88 |
51.41 |
77.66 |
94.39 |
±SD |
2.02 |
5.81 |
10.60 |
12.00 |
|
n |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
28.06 |
49.69 |
75.24 |
92.89 |
±SD |
7.90 |
8.77 |
10.36 |
14.37 |
|
n |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
28.29 |
47.37 |
74.08 |
92.00 |
±SD |
5.93 |
4.78 |
11.37 |
15.79 |
|
n |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
28.22 |
48.86 |
74.84 |
90.20 |
±SD |
10.78 |
12.33 |
18.69 |
22.30 |
|
n |
5 |
5 |
5 |
5 |
|
M: Male; SD: Standard Deviation; n: Number of animals
TABLE 3 (Contd..,). SUMMARY OF PERCENT CHANGE IN BODY WEIGHT (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body weight (%) during Days |
||||
1 to 8 |
1 to 15 |
1 to 22 |
1 to 28 |
||
G1, F & 0 |
Mean |
18.03 |
32.56 |
53.04 |
60.72 |
±SD |
4.66 |
4.89 |
9.59 |
8.63 |
|
n |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
19.59 |
36.49 |
48.02 |
57.94 |
±SD |
2.71 |
8.83 |
7.19 |
6.25 |
|
n |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
22.32 |
37.16 |
52.56 |
57.10 |
±SD |
4.32 |
5.39 |
6.56 |
4.88 |
|
n |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
13.95 |
28.32 |
45.23 |
54.79 |
±SD |
6.75 |
7.62 |
6.84 |
6.49 |
|
n |
5 |
5 |
5 |
5 |
|
F: Female; SD: Standard Deviation; n: Number of animals
TABLE 3 (Contd..,). SUMMARY OF PERCENT CHANGE IN BODY WEIGHT (%) WITH RESPECT TO DAY 1 RECORD
Refer Appendix 3
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body weight (%) during Days |
Percent Change in Body weight (%) during Days |
||||||
1 to 8 |
1 to 15 |
1 to 22 |
1 to 28 |
1 to 36 |
1 to 42 |
|||
G1R, M & 0 |
Mean |
24.66 |
46.42 |
87.85 |
104.90 |
118.06 |
128.24 |
|
±SD |
11.25 |
7.95 |
17.14 |
22.46 |
18.24 |
15.09 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
34.84 |
53.22 |
87.85 |
103.43 |
117.55 |
127.22 |
|
±SD |
3.13 |
3.69 |
8.84 |
13.35 |
11.78 |
10.40 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
23.55 |
37.84 |
43.91 |
53.20 |
63.66 |
70.59 |
|
±SD |
1.66 |
2.20 |
6.00 |
4.03 |
2.29 |
3.90 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
20.02 |
32.97 |
44.00 |
55.91 |
66.18 |
72.56 |
|
±SD |
4.41 |
5.69 |
6.49 |
11.55 |
10.18 |
8.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals
TABLE 4. SUMMARY OF AVERAGE FEED CONSUMPTION (g/rat/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Feed Consumption (g/rat/day) |
|||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
|||
G1, M & 0 |
Mean |
20.61 |
22.55 |
26.08 |
29.22 |
|
±SD |
1.15 |
1.25 |
2.74 |
2.92 |
||
n |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
20.74 |
22.43 |
26.32 |
27.85 |
|
±SD |
2.80 |
3.33 |
2.45 |
2.50 |
||
n |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
20.61 |
23.15 |
26.06 |
29.71 |
|
±SD |
3.59 |
3.93 |
3.10 |
3.06 |
||
n |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
19.64 |
22.94 |
24.97 |
28.34 |
|
±SD |
0.51 |
3.39 |
1.88 |
2.58 |
||
n |
5 |
5 |
5 |
5 |
||
M: Male, SD: Standard Deviation, n: Number of animals
TABLE 4 (Contd..,). SUMMARY OF AVERAGE FEED CONSUMPTION (g/rat/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Feed Consumption (g/rat/day) |
|||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
|||
G1, F & 0 |
Mean |
16.48 |
18.69 |
20.97 |
23.84 |
|
±SD |
1.18 |
1.70 |
1.42 |
1.42 |
||
n |
5 |
5 |
5 |
5 |
||
G2, F & 100 |
Mean |
16.20 |
18.46 |
20.58 |
22.21 |
|
±SD |
1.21 |
1.79 |
1.09 |
1.28 |
||
n |
5 |
5 |
5 |
5 |
||
G3, F & 300 |
Mean |
15.98 |
18.35 |
21.03 |
23.33 |
|
±SD |
1.37 |
0.06 |
0.69 |
1.39 |
||
n |
5 |
5 |
5 |
5 |
||
G4, F & 1000 |
Mean |
16.36 |
18.99 |
20.93 |
23.46 |
|
±SD |
1.66 |
2.20 |
1.54 |
1.85 |
||
n |
5 |
5 |
5 |
5 |
||
F: Female; SD: Standard Deviation; n: Number of animals
TABLE 4 (Contd..,). SUMMARY OF AVERAGE FEED CONSUMPTION (g/rat/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Feed Consumption (g/rat/day) |
|||||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
|||
G1R, M & 0 |
Mean |
20.90 |
23.25 |
26.83 |
28.94 |
30.19 |
31.72 |
|
±SD |
1.53 |
2.81 |
2.39 |
1.89 |
3.94 |
4.51 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
20.33 |
23.12 |
26.71 |
29.57 |
31.57 |
31.58 |
|
±SD |
1.52 |
2.22 |
2.78 |
2.31 |
4.36 |
3.93 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
15.78 |
17.42 |
19.87 |
22.69 |
24.10 |
24.99 |
|
±SD |
1.18 |
0.88 |
1.84 |
0.28 |
0.48 |
1.28 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
15.69 |
17.83 |
20.12 |
22.35 |
24.52 |
25.24 |
|
±SD |
0.60 |
1.13 |
1.86 |
2.01 |
1.36 |
0.78 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
M: Male; F: Female; R: Recovery;n: Number ofanimals
TABLE 5. SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Week 4 |
Week 4 |
|||||
Parameters↓ |
Group & Sex |
G1 & M |
G4 & M |
G1 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
0 |
1000 |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Home cage observations |
|
|||||
a. Convulsions |
1 |
1 |
1 |
1 |
||
b. Tremors |
1 |
1 |
1 |
1 |
||
c. Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling observation |
|
|
|
|
||
a. Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
b. Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
c. Lacrimation |
1 |
1 |
1 |
1 |
||
d. Red deposits around |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
e. Crusty deposits around |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
f. Salivation |
1 |
1 |
1 |
1 |
||
g. Fur appearance |
1 |
1 |
1 |
1 |
||
h. Piloerection |
1 |
1 |
1 |
1 |
||
i. Palpebral closure |
1 |
1 |
1 |
1 |
||
j. Respiratory character |
1 |
1 |
1 |
1 |
||
k. Eye prominence |
1 |
1 |
1 |
1 |
||
l. Muscle tone |
1 |
1 |
1 |
1 |
||
Home cage observations: a. Convulsions - 1=Absent, 2=Present, b. Tremors- 1=Absent, 2=Present, c. Palpebral closure - 1=Normal, Handling observation : a. Ease of removal from the cage - 2=Normal, b. Ease of handling animal in hand - 2=Normal, c. Lacrimation - 1=None, 2=Slight, 3=Severe, d. Red deposits around - 1=Absent, 2=Present, e. Crusty deposits around - 1=Absent, 2=Present , f. Salivation- 1=Normal , g. Fur Appearance - 1=Normal, h. Piloerection - 1=None, 2=Slight, 3=Severe, i. Palpebral Closure - 1=Normal, j. Respiratory character 1=Normal, k. Eye Prominence - 1=Normal, l. Muscle tone - 1=Normal |
||||||
G: Group; M: Male; F: Female
TABLE 5 (Contd..,). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
|
Week 4 |
Week 4 |
||||
Parameters↓ |
Group & Sex |
G1 & M |
G4 & M |
G1 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
0 |
1000 |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Open field Observation |
|
|||||
a. Mobility |
1 |
1 |
1 |
1 |
||
b. Gait |
1 |
1 |
1 |
1 |
||
c. Arousal |
3 |
3 |
3 |
3 |
||
d. Rearing |
Mean |
5.4 |
5.4 |
5.6 |
5.4 |
|
±SD |
0.9 |
1.1 |
1.1 |
1.1 |
||
e. Urination |
Mean |
4.4 |
4.0 |
5.0 |
3.6 |
|
Numbers of pools of urine |
±SD |
3.0 |
2.3 |
1.6 |
2.3 |
|
f. Defecation |
Mean |
1.2 |
1.6 |
1.8 |
1.2 |
|
Number of fecal pellets |
±SD |
1.1 |
1.1 |
1.1 |
1.3 |
|
g. Stereotypies- repetitive circling |
1 |
1 |
1 |
1 |
||
h. Excessive grooming |
Mean |
3.0 |
2.4 |
2.8 |
3.0 |
|
±SD |
0.7 |
1.1 |
0.8 |
0.7 |
||
Sensory observations |
|
|||||
a. Startle response |
2 |
2 |
2 |
2 |
||
b. Touch response |
2 |
2 |
2 |
2 |
||
c. Pupil response |
2 |
2 |
2 |
2 |
||
d. Response to nociceptive stimuli |
2 |
2 |
2 |
2 |
||
e. Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological observation |
Mean |
100.1 |
99.8 |
100.1 |
99.8 |
|
Body temperature (°F) |
±SD |
0.6 |
0.7 |
1.1 |
0.6 |
|
Open field Observation: a. Mobility - 1=Normal, b. Gait - 1=Normal, c. Arousal - 3=Normal, g. Stereotypies - repetitive circling- 1= Absent, 2=Present, h: Excessive grooming: Number of times animal grooms per 2 minutes;Sensory Observations: a.Startle Response -2=Normal,b. Touch Response -2=Normal,c. Pupil Response 2=Normal,d. Response to Nociceptive stimuli - 2=Normal,e. Righting Reflex -1=Present, 2=Slow, 3=Absent |
||||||
G: Group; M: Male; F: Female
TABLE 5 (Contd..,). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
|
Week 6 |
Week 6 |
|||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
G1R & F |
G4R & F |
Dose (mg/kg body weight/day) |
0 |
1000 |
0 |
1000 |
|
Number of Animals |
5 |
5 |
5 |
5 |
|
Home cage observations |
|
||||
a. Convulsions |
1 |
1 |
1 |
1 |
|
b. Tremors |
1 |
1 |
1 |
1 |
|
c. Palpebral closure |
1 |
1 |
1 |
1 |
|
Handling observation |
|||||
a. Ease of removal from the cage |
2 |
2 |
2 |
2 |
|
b. Ease of handling animal in hand |
2 |
2 |
2 |
2 |
|
c. Lacrimation |
1 |
1 |
1 |
1 |
|
d. Red deposits around |
Eyes |
1 |
1 |
1 |
1 |
Nose |
1 |
1 |
1 |
1 |
|
Mouth |
1 |
1 |
1 |
1 |
|
e. Crusty deposits around |
Eyes |
1 |
1 |
1 |
1 |
Nose |
1 |
1 |
1 |
1 |
|
Mouth |
1 |
1 |
1 |
1 |
|
f. Salivation |
1 |
1 |
1 |
1 |
|
g. Fur appearance |
1 |
1 |
1 |
1 |
|
h. Piloerection |
1 |
1 |
1 |
1 |
|
i. Palpebral closure |
1 |
1 |
1 |
1 |
|
j. Respiratory character |
1 |
1 |
1 |
1 |
|
k. Eye prominence |
1 |
1 |
1 |
1 |
|
l. Muscle tone |
1 |
1 |
1 |
1 |
|
Home cage observations: a. Convulsions - 1=Absent, 2=Present, b. Tremors- 1=Absent, 2=Present, c. Palpebral closure - 1=Normal, Handling observation : a. Ease of removal from the cage - 2=Normal, b. Ease of handling animal in hand - 2=Normal, c. Lacrimation - 1=None, 2=Slight, 3=Severe, d. Red deposits around - 1=Absent, 2=Present, e. Crusty deposits around - 1=Absent, 2=Present , f. Salivation- 1=Normal , g. Fur Appearance - 1=Normal, h. Piloerection - 1=None, 2=Slight, 3=Severe, i. Palpebral Closure - 1=Normal, j. Respiratory character 1=Normal, k. Eye Prominence - 1=Normal, l. Muscle tone - 1=Normal |
|||||
G: Group; R: Recovery; M: Male; F: Female
TABLE 5 (Contd..,). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
|
Week 6 |
Week 6 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
0 |
1000 |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Open field Observation |
|
|||||
a. Mobility |
1 |
1 |
1 |
1 |
||
b. Gait |
1 |
1 |
1 |
1 |
||
c. Arousal |
3 |
3 |
3 |
3 |
||
d. Rearing |
Mean |
4.8 |
4.8 |
5.0 |
5.6 |
|
±SD |
0.8 |
2.4 |
1.2 |
1.1 |
||
e. Urination |
Mean |
3.8 |
3.6 |
3.6 |
4.2 |
|
Numbers of pools of urine |
±SD |
2.5 |
2.3 |
1.1 |
3.0 |
|
f. Defecation |
Mean |
1.6 |
1.6 |
1.2 |
1.8 |
|
Number of fecal pellets |
±SD |
1.1 |
1.1 |
1.1 |
1.6 |
|
g. Stereotypies- repetitive circling |
1 |
1 |
1 |
1 |
||
h. Excessive grooming |
Mean |
2.6 |
2.8 |
2.6 |
2.0 |
|
±SD |
0.5 |
0.4 |
0.5 |
0.7 |
||
Sensory observations |
|
|||||
a. Startle response |
2 |
2 |
2 |
2 |
||
b. Touch response |
2 |
2 |
2 |
2 |
||
c. Pupil response |
2 |
2 |
2 |
2 |
||
d. Response to nociceptive stimuli |
2 |
2 |
2 |
2 |
||
e. Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological observation |
Mean |
99.8 |
100.7 |
100.3 |
99.8 |
|
Body temperature (°F) |
±SD |
0.8 |
1.1 |
0.8 |
0.9 |
|
Open field Observation: a. Mobility - 1=Normal, b. Gait - 1=Normal, c. Arousal - 3=Normal, g. Stereotypies - repetitive circling- 1= Absent, 2=Present, h: Excessive grooming: Number of times animal grooms per 2 minutes;Sensory Observations: a.Startle Response -2=Normal,b. Touch Response -2=Normal,c. Pupil Response 2=Normal, d. Response to Nociceptive stimuli - 2=Normal,e. Righting Reflex -1=Present, 2=Slow, 3=Absent |
||||||
G: Group; R: Recovery; M: Male; F: Female
TABLE 6. SUMMARY OF LANDING FOOT SPLAY (cm) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Landing Foot Splay (cm) |
||
G1, M & 0 |
Mean |
8.27 |
|
±SD |
0.69 |
||
n |
5 |
||
G4, M & 1000 |
Mean |
8.59 |
|
±SD |
0.88 |
||
n |
5 |
||
G1R, M & 0 |
Mean |
9.92 |
|
±SD |
0.39 |
||
n |
5 |
||
G4R, M & 1000 |
Mean |
9.58 |
|
±SD |
0.67 |
||
n |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: number of animals
TABLE 6 (Contd..,). SUMMARY OF LANDING FOOT SPLAY (cm) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Landing Foot Splay (cm) |
||
G1, F & 0 |
Mean |
7.38 |
|
±SD |
0.62 |
||
n |
5 |
||
G4, F & 1000 |
Mean |
7.68 |
|
±SD |
1.20 |
||
n |
5 |
||
G1R, F & 0 |
Mean |
7.72 |
|
±SD |
1.04 |
||
n |
5 |
||
G4R, F & 1000 |
Mean |
8.22 |
|
±SD |
1.11 |
||
n |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: number of animals
TABLE 7. SUMMARY OF PHOTOACTOMETER READINGS (No.) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
||
G1, M & 0 |
Mean |
568.20 |
|
±SD |
73.47 |
||
n |
5 |
||
G4, M & 1000 |
Mean |
577.00 |
|
±SD |
48.20 |
||
n |
5 |
||
G1R, M & 0 |
Mean |
578.40 |
|
±SD |
54.38 |
||
n |
5 |
||
G4R, M & 1000 |
Mean |
554.00 |
|
±SD |
54.06 |
||
n |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: number of animals
TABLE 7 (Contd..,). SUMMARY OF PHOTOACTOMETER READINGS (No.) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
||
G1, F & 0 |
Mean |
631.60 |
|
±SD |
68.45 |
||
n |
5 |
||
G4, F & 1000 |
Mean |
649.80 |
|
±SD |
57.13 |
||
n |
5 |
||
G1R, F & 0 |
Mean |
672.00 |
|
±SD |
48.60 |
||
n |
5 |
||
G4R, F & 1000 |
Mean |
655.60 |
|
±SD |
51.22 |
||
n |
5 |
F: Female; R: Recovery SD: Standard Deviation; n: number of animals
TABLE 8. SUMMARY OF GRIP STRENGTH (kgf) MEASUREMENT RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fore limb Grip Strength (kgf) |
Hind limb Grip Strength (kgf) |
||
G1, M & 0 |
Mean |
1.531 |
0.543 |
|
±SD |
0.022 |
0.026 |
||
n |
5 |
5 |
||
G4, M & 1000 |
Mean |
1.539 |
0.546 |
|
±SD |
0.044 |
0.018 |
||
n |
5 |
5 |
||
G1R, M & 0 |
Mean |
1.522 |
0.545 |
|
±SD |
0.037 |
0.041 |
||
n |
5 |
5 |
||
G4R, M & 1000 |
Mean |
1.530 |
0.556 |
|
±SD |
0.021 |
0.021 |
||
n |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: number of animals
TABLE 8 (Contd..,). SUMMARY OF GRIP STRENGTH (kgf) MEASUREMENT RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fore limb Grip Strength (kgf) |
Hind limb Grip Strength (kgf) |
||
G1, F & 0 |
Mean |
1.552 |
0.556 |
|
±SD |
0.013 |
0.032 |
||
n |
5 |
5 |
||
G4, F & 1000 |
Mean |
1.545 |
0.561 |
|
±SD |
0.016 |
0.019 |
||
n |
5 |
5 |
||
G1R, F & 0 |
Mean |
1.496 |
0.492 |
|
±SD |
0.037 |
0.022 |
||
n |
5 |
5 |
||
G4R, F & 1000 |
Mean |
1.478 |
0.520 |
|
±SD |
0.048 |
0.027 |
||
n |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: number of animals
TABLE 9. SUMMARY OF OPHTHALMOSCOPIC EXAMINATION RECORD
Week 4 |
|||||||||
Group, Sex & Dose (mg/kg body weight/day) |
G1, M & 0 |
G4, M & 1000 |
G1, F & 0 |
G4, F & 1000 |
|||||
Number of Animals |
5 |
5 |
5 |
5 |
|||||
Parameters |
Observations |
||||||||
Eye |
L |
R |
L |
R |
L |
R |
L |
R |
|
Adnexa |
Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Ducts |
N |
N |
N |
N |
N |
N |
N |
N |
|
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
|
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
|
Aqueous humour |
N |
N |
N |
N |
N |
N |
N |
N |
|
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
|
Vitreous humour |
N |
N |
N |
N |
N |
N |
N |
N |
|
Retina |
Vessels |
N |
N |
N |
N |
N |
N |
N |
N |
Macula |
N |
N |
N |
N |
N |
N |
N |
N |
|
Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
|
Tapetum lucidum |
N |
N |
N |
N |
N |
N |
N |
N |
|
Tapetum nigrum |
N |
N |
N |
N |
N |
N |
N |
N |
|
N: No Abnormality Detected; L: Left; R: Right; M: Male; F: Female
TABLE 9 (Contd..,). SUMMARY OF OPHTHALMOSCOPIC EXAMINATION RECORD
Week 6 |
|||||||||
Group, Sex & Dose (mg/kg body weight/day) |
G1R, M & 0 |
G4R, M & 1000 |
G1R, F & 0 |
G4R, F & 1000 |
|||||
Number of Animals |
5 |
5 |
5 |
5 |
|||||
Parameters |
Observations |
||||||||
Eye |
L |
R |
L |
R |
L |
R |
L |
R |
|
Adnexa |
Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Ducts |
N |
N |
N |
N |
N |
N |
N |
N |
|
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
|
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
|
Aqueous humour |
N |
N |
N |
N |
N |
N |
N |
N |
|
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
|
Vitreous humour |
N |
N |
N |
N |
N |
N |
N |
N |
|
Retina |
Vessels |
N |
N |
N |
N |
N |
N |
N |
N |
Macula |
N |
N |
N |
N |
N |
N |
N |
N |
|
Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
|
Tapetum lucidum |
N |
N |
N |
N |
N |
N |
N |
N |
|
Tapetum nigrum |
N |
N |
N |
N |
N |
N |
N |
N |
|
N: No Abnormality Detected; L: Left; R: Right; F: Female; M: Male
TABLE 10. SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count (WBC) (103cells/µL) |
Total Erythrocyte Count (RBC) (106cells/µL) |
Hemoglobin (HGB) (g/dL) |
Haematocrit (HCT) (%) |
Mean Corpuscular Volume (MCV) (fL) |
Mean Corpuscular Hemoglobin (MCH) (pg) |
Mean Corpuscular Haemoglobin Concentration (MCHC) (g/dL) |
Platelet Count (PLT) (103cells/µL) |
Mean Platelet Volume (MPV) (fL) |
||
G1, M & 0 |
Mean |
10.16 |
6.62 |
13.62 |
41.76 |
63.24 |
20.62 |
32.68 |
861.80 |
8.20 |
|
±SD |
2.87 |
0.49 |
0.79 |
2.00 |
3.24 |
0.52 |
1.02 |
98.37 |
0.42 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
8.97 |
6.28 |
13.26 |
41.06 |
65.48 |
21.14 |
32.32 |
771.60 |
8.84 |
|
±SD |
1.40 |
0.45 |
0.96 |
1.87 |
2.77 |
0.72 |
1.03 |
58.62 |
0.33 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
6.57* |
6.84 |
13.74 |
42.90 |
62.78 |
20.10 |
32.10 |
756.80 |
8.84 |
|
±SD |
2.32 |
0.39 |
0.78 |
2.92 |
4.13 |
0.25 |
1.70 |
173.21 |
0.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
7.47 |
6.42 |
12.98 |
40.24 |
63.02 |
20.26 |
32.28 |
860.40 |
9.08 |
|
±SD |
1.74 |
0.53 |
0.73 |
1.24 |
5.67 |
0.80 |
1.72 |
167.76 |
0.94 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 10 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count (%) |
Neutrophils (%) |
Lymphocytes (%) |
Monocytes (%) |
Eosinophils (%) |
Basophils (%) |
||
G1, M & 0 |
Mean |
3.81 |
17.26 |
78.24 |
2.46 |
0.82 |
0.14 |
|
±SD |
2.49 |
5.65 |
5.69 |
0.21 |
0.38 |
0.05 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
5.27 |
19.14 |
74.06 |
4.28* |
1.10 |
0.10 |
|
±SD |
2.48 |
4.83 |
5.79 |
1.25 |
0.70 |
0.00 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
3.05 |
22.00 |
71.00 |
4.18* |
1.48 |
0.20 |
|
±SD |
1.76 |
4.78 |
4.48 |
1.10 |
0.43 |
0.07 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
4.95 |
18.72 |
75.94 |
3.10 |
1.10 |
0.12 |
|
±SD |
3.69 |
2.51 |
2.92 |
0.75 |
0.34 |
0.04 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 10 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Reticulocyte Count (109cells/L) |
Absolute Neutrophils (103cells/µL) |
Absolute Lymphocytes (103cells/µL) |
Absolute Monocytes (103cells/µL) |
Absolute Eosinophils (103cells/µL) |
Absolute Basophils (103cells/µL) |
Prothrombin Time (Seconds) |
Activated Prothrombin Time (Seconds) |
||
G1, M & 0 |
Mean |
246.44 |
1.64 |
8.06 |
0.25 |
0.08 |
0.01 |
20.48 |
21.92 |
|
±SD |
142.15 |
0.16 |
2.73 |
0.08 |
0.01 |
0.01 |
2.08 |
1.55 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
325.00 |
1.70 |
6.67 |
0.37 |
0.10 |
0.01 |
18.66 |
26.80 |
|
±SD |
139.33 |
0.43 |
1.38 |
0.09 |
0.07 |
0.00 |
1.71 |
5.02 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
209.30 |
1.39 |
4.71* |
0.29 |
0.09 |
0.01 |
16.84* |
31.56 |
|
±SD |
122.85 |
0.35 |
1.91 |
0.15 |
0.03 |
0.00 |
1.00 |
11.90 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
306.04 |
1.39 |
5.67 |
0.24 |
0.08 |
0.01 |
16.60* |
32.80 |
|
±SD |
211.72 |
0.38 |
1.33 |
0.10 |
0.02 |
0.01 |
1.16 |
4.18 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 10 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count (WBC) (103cells/µL) |
Total Erythrocyte Count (RBC) (106cells/µL) |
Hemoglobin (HGB) (g/dL) |
Haematocrit (HCT) (%) |
Mean Corpuscular Volume (MCV) (fL) |
Mean Corpuscular Hemoglobin (MCH) (pg) |
Mean Corpuscular Haemoglobin Concentration (MCHC) (g/dL) |
Platelet Count (PLT) (103cells/µL) |
Mean Platelet Volume (MPV) (fL) |
||
G1, F & 0 |
Mean |
7.34 |
6.07 |
12.58 |
38.06 |
62.98 |
20.66 |
32.98 |
924.40 |
8.70 |
|
±SD |
2.63 |
0.59 |
1.44 |
2.89 |
5.04 |
0.61 |
2.37 |
78.81 |
0.53 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 100 |
Mean |
7.33 |
6.75 |
13.98 |
44.02 |
65.34 |
20.74 |
31.98 |
799.20 |
10.60 |
|
±SD |
2.29 |
1.29 |
2.75 |
10.21 |
7.67 |
0.69 |
3.02 |
286.81 |
3.96 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 300 |
Mean |
8.29 |
6.85 |
13.78 |
40.40 |
58.96 |
20.12 |
34.14 |
928.00 |
8.30 |
|
±SD |
0.93 |
0.42 |
0.66 |
1.95 |
1.19 |
0.54 |
0.65 |
133.67 |
0.22 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 1000 |
Mean |
8.84 |
6.93 |
13.88 |
42.02 |
60.80 |
20.08 |
33.00 |
923.40 |
10.06 |
|
±SD |
5.12 |
0.51 |
1.01 |
1.41 |
4.32 |
1.43 |
1.52 |
220.28 |
3.39 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of animals
TABLE 10 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count (%) |
Neutrophils (%) |
Lymphocytes (%) |
Monocytes (%) |
Eosinophils (%) |
Basophils (%) |
||
G1, F & 0 |
Mean |
3.78 |
15.72 |
79.64 |
2.38 |
0.98 |
0.12 |
|
±SD |
2.28 |
3.99 |
4.83 |
0.95 |
0.28 |
0.04 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 100 |
Mean |
3.59 |
15.84 |
79.28 |
2.70 |
0.98 |
0.10 |
|
±SD |
3.22 |
4.77 |
5.82 |
0.79 |
0.36 |
0.00 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 300 |
Mean |
1.86 |
17.32 |
75.54 |
4.10* |
1.30 |
0.18 |
|
±SD |
0.41 |
3.73 |
5.60 |
1.56 |
0.25 |
0.04 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 1000 |
Mean |
2.80 |
19.38 |
74.72 |
3.54 |
0.90 |
0.18 |
|
±SD |
2.20 |
2.68 |
2.73 |
0.47 |
0.16 |
0.04 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 10 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Reticulocyte Count (109cells/L) |
Absolute Neutrophils (103cells/µL) |
Absolute Lymphocytes (103cells/µL) |
Absolute Monocytes (103cells/µL) |
Absolute Eosinophils (103cells/µL) |
Absolute Basophils (103cells/µL) |
Prothrombin Time (Seconds) |
Activated Prothrombin Time (Seconds) |
||
G1, F & 0 |
Mean |
220.96 |
1.10 |
5.90 |
0.18 |
0.07 |
0.01 |
16.76 |
18.06 |
|
±SD |
107.38 |
0.34 |
2.35 |
0.11 |
0.02 |
0.01 |
1.94 |
4.49 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 100 |
Mean |
223.62 |
1.09 |
5.90 |
0.18 |
0.07 |
0.01 |
21.96 |
21.52 |
|
±SD |
159.86 |
0.17 |
2.29 |
0.04 |
0.02 |
0.01 |
8.30 |
7.80 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 300 |
Mean |
126.72 |
1.45 |
6.24 |
0.35 |
0.11 |
0.01 |
14.84 |
24.08 |
|
±SD |
24.51 |
0.40 |
0.64 |
0.16 |
0.03 |
0.01 |
2.94 |
3.47 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 1000 |
Mean |
185.94 |
1.69 |
6.64 |
0.31 |
0.07 |
0.02 |
22.56 |
33.76* |
|
±SD |
126.85 |
0.99 |
3.87 |
0.17 |
0.03 |
0.01 |
10.50 |
8.81 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 10 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count (WBC) (103cells/µL) |
Total Erythrocyte Count (RBC) (106cells/µL) |
Hemoglobin (HGB) (g/dL) |
Haematocrit (HCT) (%) |
Mean Corpuscular Volume (MCV) (fL) |
Mean Corpuscular Hemoglobin (MCH) (pg) |
Mean Corpuscular Haemoglobin Concentration (MCHC) (g/dL) |
Platelet Count (PLT) (103cells/µL) |
Mean Platelet Volume (MPV) (fL) |
||
G1R, M & 0 |
Mean |
8.34 |
7.48 |
14.30 |
44.64 |
59.76 |
19.16 |
32.08 |
789.00 |
6.40 |
|
±SD |
3.02 |
0.35 |
0.35 |
0.98 |
2.12 |
0.78 |
0.23 |
137.42 |
0.34 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
7.85 |
7.45 |
13.92 |
43.20 |
58.02 |
18.72 |
32.28 |
895.40 |
6.40 |
|
±SD |
2.60 |
0.32 |
0.70 |
2.07 |
1.61 |
0.83 |
0.58 |
69.77 |
0.10 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
10.47 |
7.47 |
13.96 |
42.60 |
57.08 |
18.70 |
32.78 |
846.40 |
6.80 |
|
±SD |
1.55 |
0.25 |
0.19 |
1.15 |
1.52 |
0.51 |
0.59 |
120.02 |
0.22 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
9.22 |
7.12 |
13.40* |
40.50* |
56.92 |
18.86 |
33.16 |
918.40 |
7.84 |
|
±SD |
2.96 |
0.27 |
0.31 |
1.23 |
1.12 |
0.34 |
0.34 |
99.12 |
1.21 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 10 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count (%) |
Neutrophils (%) |
Lymphocytes (%) |
Monocytes (%) |
Eosinophils (%) |
Basophils (%) |
||
G1R, M & 0 |
Mean |
2.05 |
21.76 |
71.70 |
3.48 |
1.08 |
0.12 |
|
±SD |
0.27 |
2.71 |
2.97 |
0.88 |
0.24 |
0.04 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
2.15 |
21.94 |
71.34 |
3.52 |
1.36 |
0.18 |
|
±SD |
1.37 |
2.85 |
4.65 |
1.27 |
0.44 |
0.08 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
1.73 |
21.08 |
72.88 |
3.62 |
1.14 |
0.16 |
|
±SD |
0.62 |
5.82 |
5.65 |
0.61 |
0.31 |
0.05 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
1.83 |
20.98 |
71.58 |
4.00 |
1.50 |
0.16 |
|
±SD |
0.37 |
3.71 |
3.85 |
0.57 |
0.47 |
0.05 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals
TABLE 10 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Reticulocyte Count (109cells/L) |
Absolute Neutrophils (103cells/µL) |
Absolute Lymphocytes (103cells/µL) |
Absolute Monocytes (103cells/µL) |
Absolute Eosinophils (103cells/µL) |
Absolute Basophils (103cells/µL) |
Prothrombin Time (Seconds) |
Activated Prothrombin Time (Seconds) |
||
G1R, M & 0 |
Mean |
152.30 |
1.85 |
5.92 |
0.30 |
0.08 |
0.01 |
16.46 |
23.08 |
|
±SD |
17.19 |
0.87 |
1.96 |
0.15 |
0.02 |
0.01 |
0.34 |
9.76 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
159.78 |
1.72 |
5.60 |
0.28 |
0.10 |
0.01 |
16.20 |
26.18 |
|
±SD |
100.78 |
0.56 |
1.92 |
0.14 |
0.03 |
0.01 |
1.15 |
9.66 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
128.84 |
2.24 |
7.62 |
0.37 |
0.12 |
0.02 |
16.06 |
30.34 |
|
±SD |
44.80 |
0.84 |
1.19 |
0.02 |
0.04 |
0.01 |
1.28 |
11.57 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
129.94 |
1.87 |
6.68 |
0.37 |
0.13 |
0.01 |
17.06 |
24.64 |
|
±SD |
27.39 |
0.43 |
2.44 |
0.12 |
0.02 |
0.01 |
3.58 |
17.08 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals
TABLE 11. SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Creatinine |
Total Cholesterol |
Triglycerides |
Urea |
Total Protein |
Albumin |
Alanine aminotransferase |
Aspartate aminotransferase |
Alkaline phosphatase |
Total Bilirubin |
|
(GLU) |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
(ALT) |
(AST) |
(ALP) |
(BIT) |
|||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
||
G1, M & 0 |
Mean |
126.80 |
0.41 |
56.00 |
38.40 |
27.12 |
6.04 |
3.22 |
44.40 |
103.80 |
261.80 |
0.07 |
±SD |
12.99 |
0.01 |
10.17 |
11.89 |
3.28 |
0.17 |
0.16 |
7.44 |
10.33 |
31.00 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
126.20 |
0.39 |
56.20 |
35.00 |
29.68 |
5.98 |
3.22 |
52.20 |
111.40 |
257.20 |
0.09 |
±SD |
17.71 |
0.03 |
8.04 |
13.49 |
3.66 |
0.13 |
0.17 |
4.97 |
16.95 |
52.48 |
0.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
101.80 |
0.38 |
56.00 |
34.80 |
25.48 |
5.94 |
3.21 |
48.20 |
104.00 |
219.80 |
0.09 |
±SD |
18.42 |
0.02 |
9.43 |
8.93 |
2.65 |
0.17 |
0.07 |
5.07 |
20.37 |
10.03 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
109.60 |
0.37 |
51.00 |
69.80 |
28.84 |
5.94 |
3.19 |
55.60* |
109.80 |
276.20 |
0.04 |
±SD |
17.47 |
0.04 |
5.24 |
47.82 |
4.47 |
0.27 |
0.10 |
8.26 |
20.22 |
174.89 |
0.06 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 11 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Cholinesterase |
Calcium |
Phosphorous |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(CHE) |
(CAL) |
(PHO) |
(GLB) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(U/L) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
|||
G1, M & 0 |
Mean |
261.20 |
9.78 |
6.34 |
2.82 |
1.15 |
12.65 |
143.50 |
4.14 |
105.74 |
±SD |
33.08 |
0.40 |
0.63 |
0.20 |
0.12 |
1.53 |
0.39 |
0.44 |
0.47 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
236.40 |
9.94 |
5.84 |
2.76 |
1.17 |
13.85 |
143.38 |
3.86 |
105.74 |
±SD |
34.61 |
0.56 |
0.62 |
0.08 |
0.08 |
1.71 |
1.21 |
0.43 |
1.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
258.60 |
10.22 |
6.20 |
2.73 |
1.18 |
11.89 |
143.62 |
4.04 |
105.08 |
±SD |
48.35 |
0.40 |
0.31 |
0.21 |
0.11 |
1.24 |
0.94 |
0.28 |
0.57 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
237.00 |
9.60 |
5.94 |
2.75 |
1.16 |
13.46 |
144.36 |
4.22 |
105.72 |
±SD |
13.82 |
0.41 |
0.51 |
0.22 |
0.09 |
2.08 |
1.37 |
0.46 |
2.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of animals
TABLE 11 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Creatinine |
Total Cholesterol |
Triglycerides |
Urea |
Total Protein |
Albumin |
Alanine aminotransferase |
Aspartate aminotransferase |
Alkaline phosphatase |
Total Bilirubin |
|
(GLU) |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
(ALT) |
(AST) |
(ALP) |
(BIT) |
|||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
||
G1, F & 0 |
Mean |
128.60 |
0.41 |
62.60 |
22.80 |
29.44 |
6.18 |
3.28 |
38.40 |
87.80 |
150.20 |
0.08 |
±SD |
16.13 |
0.02 |
9.84 |
8.17 |
4.97 |
0.30 |
0.15 |
6.50 |
9.52 |
35.67 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
125.60 |
0.45* |
57.80 |
14.40 |
29.04 |
6.50 |
3.27 |
33.00 |
102.80 |
141.60 |
0.09 |
±SD |
11.41 |
0.04 |
4.32 |
4.93 |
3.68 |
0.20 |
0.17 |
7.07 |
14.34 |
30.53 |
0.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
102.40* |
0.40 |
58.60 |
29.40 |
27.26 |
6.16 |
3.21 |
34.00 |
93.60 |
152.40 |
0.07 |
±SD |
12.99 |
0.02 |
10.95 |
13.78 |
3.77 |
0.35 |
0.25 |
3.08 |
10.74 |
34.76 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
111.40* |
0.38* |
57.00 |
34.00 |
27.96 |
6.56 |
3.34 |
33.40 |
101.00 |
117.40 |
0.08 |
±SD |
21.70 |
0.05 |
10.51 |
22.25 |
4.57 |
0.24 |
0.18 |
9.04 |
13.47 |
12.46 |
0.06 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 11 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Cholinesterase |
Calcium |
Phosphorous |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(CHE) |
(CAL) |
(PHO) |
(GLB) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(U/L) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
|||
G1, F & 0 |
Mean |
603.00 |
9.94 |
5.16 |
2.90 |
1.14 |
13.74 |
144.36 |
3.44 |
105.88 |
±SD |
166.39 |
0.32 |
0.42 |
0.27 |
0.12 |
2.32 |
1.11 |
0.16 |
1.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
696.40 |
9.44 |
4.98 |
3.23 |
1.02 |
13.55 |
145.20 |
3.43 |
106.54 |
±SD |
227.64 |
0.25 |
0.73 |
0.26 |
0.12 |
1.72 |
1.83 |
0.43 |
1.99 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
710.20 |
9.98 |
5.74 |
2.95 |
1.09 |
12.72 |
147.18* |
3.20 |
109.46* |
±SD |
371.95 |
0.36 |
0.67 |
0.22 |
0.12 |
1.76 |
0.63 |
0.23 |
1.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
1016.60 |
9.88 |
5.46 |
3.22 |
1.05 |
13.05 |
148.22* |
3.18 |
109.60* |
±SD |
289.16 |
0.63 |
0.63 |
0.34 |
0.15 |
2.13 |
2.26 |
0.34 |
1.73 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 11 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Creatinine |
Total Cholesterol |
Triglycerides |
Urea |
Total Protein |
Albumin |
Alanine aminotransferase |
Aspartate aminotransferase |
Alkaline phosphatase |
Total Bilirubin |
|
(GLU) |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
(ALT) |
(AST) |
(ALP) |
(BIT) |
|||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
||
G1R, M & 0 |
Mean |
106.00 |
0.47 |
39.60 |
45.60 |
31.16 |
6.08 |
3.02 |
45.60 |
104.20 |
176.00 |
0.03 |
±SD |
17.61 |
0.05 |
6.58 |
14.40 |
4.48 |
0.25 |
0.10 |
10.74 |
14.89 |
55.65 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
115.40 |
0.46 |
46.00 |
42.40 |
30.94 |
6.10 |
3.13* |
43.00 |
107.00 |
182.20 |
0.03 |
±SD |
9.18 |
0.04 |
3.81 |
13.45 |
1.93 |
0.19 |
0.05 |
8.25 |
16.11 |
39.76 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male;R: Recovery; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 11 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY
Group, Sex & Dose (mg/kg body weight/day) |
|
Cholinesterase |
Calcium |
Phosphorous |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
(CHE) |
(CAL) |
(PHO) |
(GLB) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(U/L) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
|||
G1R, M & 0 |
Mean |
249.20 |
9.96 |
6.54 |
3.06 |
0.99 |
14.54 |
144.62 |
3.41 |
105.32 |
±SD |
21.44 |
0.19 |
0.77 |
0.21 |
0.07 |
2.09 |
0.93 |
0.33 |
0.54 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
264.00 |
10.00 |
6.14 |
2.97 |
1.06 |
14.44 |
146.14* |
3.43 |
106.50 |
±SD |
18.72 |
0.37 |
0.35 |
0.18 |
0.07 |
0.90 |
0.67 |
0.15 |
1.32 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male;R: Recovery; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 11 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Creatinine |
Total Cholesterol |
Triglycerides |
Urea |
Total Protein |
Albumin |
Alanine aminotransferase |
Aspartate aminotransferase |
Alkaline phosphatase |
Total Bilirubin |
|
(GLU) |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
(ALT) |
(AST) |
(ALP) |
(BIT) |
|||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
||
G1R, F & 0 |
Mean |
114.80 |
0.52 |
51.40 |
43.60 |
41.78 |
6.62 |
3.29 |
42.20 |
126.60 |
121.80 |
0.05 |
±SD |
11.12 |
0.04 |
13.35 |
17.73 |
4.59 |
0.37 |
0.41 |
6.98 |
50.79 |
11.61 |
0.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
117.60 |
0.53 |
57.60 |
38.00 |
38.76 |
6.68 |
3.44 |
31.00* |
108.80 |
97.20 |
0.05 |
±SD |
11.01 |
0.02 |
7.89 |
12.04 |
5.38 |
0.38 |
0.29 |
5.79 |
5.17 |
21.58 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals
*. The mean difference is significant at the 0.05 level.
TABLE 11 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Cholinesterase |
Calcium |
Phosphorous |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(CHE) |
(CAL) |
(PHO) |
(GLB) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(U/L) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
|||
G1R, F & 0 |
Mean |
747.80 |
10.20 |
5.40 |
3.33 |
1.00 |
19.50 |
145.08 |
3.44 |
107.30 |
±SD |
365.42 |
0.67 |
0.48 |
0.41 |
0.20 |
2.14 |
0.67 |
0.24 |
1.08 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
816.40 |
10.34 |
5.60 |
3.24 |
1.07 |
18.09 |
145.36 |
3.61 |
107.74 |
±SD |
271.52 |
0.30 |
0.70 |
0.28 |
0.14 |
2.51 |
0.93 |
0.24 |
0.69 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals
TABLE 12. SUMMARY OF URINALYSIS RECORD
Examination |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
100 |
300 |
1000 |
0 |
1000 |
||
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||
Physical |
Colour |
Pale yellow |
5 |
5 |
5 |
5 |
4 |
5 |
Yellow |
- |
- |
- |
- |
1 |
- |
||
Appearance |
Clear |
4 |
4 |
4 |
3 |
3 |
2 |
|
Turbidity |
1 |
1 |
1 |
2 |
2 |
3 |
||
Volume (mL) |
Mean |
6.3 |
6.8 |
6.8 |
6.4 |
4.8 |
5.2 |
|
±SD |
2.0 |
1.7 |
1.8 |
1.6 |
1.4 |
1.4 |
||
Chemical |
pH |
Mean |
8.0 |
8.1 |
8.4 |
7.3 |
8.5 |
8.5 |
±SD |
0.5 |
0.2 |
0.5 |
0.8 |
0.0 |
0.0 |
||
Specific gravity |
Mean |
1.010 |
1.010 |
1.011 |
1.016 |
1.008 |
1.007 |
|
±SD |
0.000 |
0.004 |
0.005 |
0.004 |
0.003 |
0.003 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.4 |
0.4 |
0.2 |
0.2 |
|
±SD |
0.0 |
0.0 |
0.4 |
0.4 |
0.0 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Ketones (mg/dL) |
Neg |
- |
1 |
2 |
1 |
1 |
1 |
|
5 |
5 |
3 |
3 |
3 |
3 |
4 |
||
15 |
- |
1 |
- |
1 |
1 |
- |
||
Blood (Ery/µL) |
Neg |
2 |
1 |
3 |
- |
4 |
5 |
|
Ca10 |
- |
1 |
- |
1 |
1 |
- |
||
Ca25 |
3 |
1 |
1 |
3 |
- |
- |
||
Ca80 |
- |
2 |
1 |
1 |
- |
- |
||
Proteins (mg/dL) |
Trace |
4 |
1 |
2 |
1 |
- |
- |
|
30 |
1 |
1 |
2 |
3 |
2 |
2 |
||
100 |
- |
2 |
- |
1 |
2 |
- |
||
>=300 |
- |
- |
1 |
- |
1 |
3 |
||
Neg |
- |
1 |
- |
- |
- |
- |
||
Nitrite |
Neg |
5 |
4 |
4 |
5 |
5 |
5 |
|
Pos |
- |
1 |
1 |
- |
- |
- |
||
Leucocytes (Leu/µL) |
Neg |
3 |
3 |
4 |
3 |
2 |
3 |
|
Ca15 |
2 |
2 |
- |
2 |
3 |
1 |
||
Ca70 |
- |
- |
1 |
- |
- |
1 |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Microscopic |
Epithelial cells |
0 |
2 |
2 |
2 |
2 |
4 |
1 |
0-1 |
2 |
2 |
2 |
2 |
1 |
3 |
||
1-2 |
1 |
1 |
1 |
1 |
- |
1 |
||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
|
Crystals |
Present |
5 |
5 |
5 |
5 |
5 |
5 |
|
M: Male; R: Recovery; Neg: Negative; Ca: Calculated Approximately; Pos: Positive; SD: Standard Deviation
TABLE 12 (Contd..,). SUMMARY OF URINALYSIS RECORD
Examination |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
100 |
300 |
1000 |
0 |
1000 |
||
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||
Physical |
Colour |
Pale yellow |
4 |
5 |
5 |
5 |
5 |
5 |
Yellow |
1 |
- |
- |
- |
- |
- |
||
Appearance |
Clear |
4 |
5 |
5 |
3 |
2 |
3 |
|
Turbidity |
1 |
- |
- |
2 |
3 |
2 |
||
Volume (mL) |
Mean |
6.1 |
6.3 |
8.1 |
6.7 |
5.9 |
5.1 |
|
±SD |
2.1 |
2.0 |
1.3 |
0.8 |
1.2 |
1.0 |
||
Chemical |
pH |
Mean |
8.1 |
8.2 |
7.7 |
8.0 |
8.5 |
8.5 |
±SD |
0.5 |
0.4 |
0.6 |
0.5 |
0.0 |
0.0 |
||
Specific gravity |
Mean |
1.009 |
1.011 |
1.013 |
1.011 |
1.005 |
1.005 |
|
±SD |
0.002 |
0.002 |
0.004 |
0.004 |
0.000 |
0.000 |
||
Urobilinogen (mg/dL) |
Mean |
0.4 |
0.2 |
0.4 |
0.4 |
0.2 |
0.2 |
|
±SD |
0.4 |
0.0 |
0.4 |
0.4 |
0.0 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
1 |
- |
- |
- |
- |
- |
- |
||
Ketones (mg/dL) |
Neg |
5 |
5 |
5 |
4 |
4 |
5 |
|
5 |
- |
- |
- |
1 |
1 |
- |
||
Blood (Ery/µL) |
Neg |
4 |
5 |
5 |
5 |
5 |
4 |
|
Ca10 |
- |
- |
- |
- |
- |
1 |
||
Ca25 |
1 |
- |
- |
- |
- |
- |
||
Proteins (mg/dL) |
Trace |
1 |
3 |
2 |
1 |
2 |
1 |
|
30 |
- |
1 |
1 |
2 |
- |
1 |
||
100 |
1 |
- |
- |
2 |
- |
2 |
||
>=300 |
1 |
1 |
- |
- |
2 |
- |
||
Neg |
2 |
- |
2 |
- |
1 |
1 |
||
Nitrite |
Neg |
4 |
4 |
4 |
5 |
5 |
5 |
|
Pos |
1 |
1 |
1 |
- |
- |
- |
||
Leucocytes (Leu/µL) |
Neg |
4 |
4 |
3 |
2 |
2 |
2 |
|
Ca15 |
- |
1 |
- |
- |
2 |
3 |
||
Ca70 |
1 |
- |
2 |
2 |
1 |
- |
||
Ca125 |
- |
- |
- |
1 |
- |
- |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Microscopic |
Epithelial cells |
0 |
2 |
3 |
2 |
1 |
- |
- |
0-1 |
2 |
2 |
2 |
2 |
2 |
3 |
||
1-2 |
1 |
- |
1 |
2 |
2 |
2 |
||
2-3 |
- |
- |
- |
- |
1 |
- |
||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
|
Crystals |
present |
5 |
5 |
5 |
5 |
5 |
5 |
|
F: Female; R: Recovery; Neg: Negative; Ca: Calculated Approximately; Pos: Positive; SD: Standard Deviation
TABLE 13. SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Epididymes |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Prostate+Seminal vesicles with coagulating glands (PSC) |
|
G1, M & 0 |
Mean |
0.0590 |
0.5886 |
0.7578 |
1.1294 |
2.9150 |
1.3598 |
2.8636 |
2.0903 |
10.8946 |
2.5250 |
±SD |
0.0047 |
0.0753 |
0.1244 |
0.1256 |
0.1152 |
0.0744 |
0.1979 |
0.0465 |
0.6925 |
0.2141 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
0.0584 |
0.5199 |
0.9614 |
1.0654 |
2.9501 |
1.2001 |
2.5589 |
1.9604* |
11.3615 |
2.4262 |
±SD |
0.0082 |
0.1336 |
0.1461 |
0.1163 |
0.2741 |
0.1174 |
0.3653 |
0.0831 |
1.5996 |
0.3100 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
0.0648 |
0.6085 |
0.8437 |
1.1972 |
2.9369 |
1.3087 |
2.7161 |
2.0135 |
12.1895 |
2.3569 |
±SD |
0.0044 |
0.0209 |
0.1644 |
0.2682 |
0.2448 |
0.1781 |
0.3276 |
0.0715 |
1.0176 |
0.6238 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
0.0588 |
0.5779 |
0.8591 |
1.0242 |
3.1581 |
1.2859 |
2.7091 |
2.0835 |
11.1804 |
2.1416 |
±SD |
0.0078 |
0.0741 |
0.1604 |
0.1192 |
0.2885 |
0.1120 |
0.3825 |
0.0728 |
1.8764 |
0.5694 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation, n: Number of animals; PSC: Prostate gland + Seminal vesicles with Coagulating gland
*. The mean difference is significant at the 0.05 level.
TABLE 13 (Contd..,). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Uterus |
Ovaries |
Heart |
Kidneys |
Brain |
Liver |
|
G1, F & 0 |
Mean |
0.0662 |
0.6285 |
0.8321 |
0.6700 |
0.1813 |
0.9970 |
1.9269 |
1.9956 |
8.9253 |
±SD |
0.0039 |
0.0722 |
0.1901 |
0.1375 |
0.0079 |
0.0589 |
0.1686 |
0.0652 |
0.8680 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
0.0680 |
0.6654 |
0.7888 |
0.7642 |
0.1943 |
0.9213 |
2.0209 |
2.0100 |
9.0406 |
±SD |
0.0039 |
0.0467 |
0.2106 |
0.1608 |
0.0129 |
0.0635 |
0.2084 |
0.1226 |
1.0299 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
0.0613 |
0.5754 |
0.6707 |
0.6033 |
0.1920 |
0.9433 |
1.9716 |
2.0048 |
8.5774 |
±SD |
0.0020 |
0.0511 |
0.0420 |
0.0771 |
0.0084 |
0.0637 |
0.0547 |
0.1068 |
0.3312 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
0.0643 |
0.5966 |
0.6707 |
0.5689 |
0.1912 |
0.7523 |
1.9140 |
1.9592 |
8.6077 |
±SD |
0.0106 |
0.0828 |
0.1899 |
0.0822 |
0.0322 |
0.4156 |
0.1505 |
0.1216 |
0.5588 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female, SD: Standard Deviation, n: Number of animals
TABLE 13 (Contd..,). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Epididymes |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Prostate+Seminal vesicles with coagulating glands (PSC) |
|
G1R, M & 0 |
Mean |
0.0776 |
0.6155 |
1.1666 |
1.2778 |
3.3205 |
1.4264 |
3.0655 |
2.1063 |
12.6212 |
2.8119 |
±SD |
0.0279 |
0.1882 |
0.2893 |
0.0422 |
0.3984 |
0.2407 |
0.5757 |
0.0424 |
1.9425 |
0.5826 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.0758 |
0.5152 |
0.7903 |
1.3399 |
3.0499 |
1.4145 |
3.0622 |
2.0386 |
11.5559 |
2.4338 |
±SD |
0.0216 |
0.1357 |
0.2902 |
0.1648 |
0.2155 |
0.2354 |
0.7496 |
0.1228 |
2.2702 |
0.4457 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery: SD: Standard Deviation, n: Number of animals
TABLE 13 (Contd..,). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Uterus |
Ovaries |
Heart |
Kidneys |
Brain |
Liver |
|
G1R, F & 0 |
Mean |
0.0774 |
0.4368 |
0.7732 |
0.6762 |
0.1750 |
0.9609 |
1.6585 |
1.9382 |
7.8861 |
±SD |
0.0117 |
0.0547 |
0.2559 |
0.2991 |
0.0431 |
0.0787 |
0.0601 |
0.0380 |
0.2642 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
0.0722 |
0.5284 |
0.5811 |
0.5713 |
0.3799 |
1.0949 |
1.7577 |
1.9548 |
8.4476 |
±SD |
0.0111 |
0.1589 |
0.0579 |
0.1377 |
0.4301 |
0.3160 |
0.3140 |
0.0946 |
1.3451 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery: SD: Standard Deviation, n: Number of animals
TABLE 14. SUMMARY OF FASTING BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO BODY WEIGHT(%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Epididymes |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Prostate+Seminal vesicles with coagulating glands (PSC) |
|
G1, M & 0 |
Mean |
288.44 |
0.0205 |
0.2043 |
0.2640 |
0.3911 |
1.0114 |
0.4719 |
0.9925 |
0.7258 |
3.7753 |
0.8750 |
±SD |
10.74 |
0.0020 |
0.0270 |
0.0515 |
0.0353 |
0.0470 |
0.0300 |
0.0542 |
0.0402 |
0.1470 |
0.0590 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
290.12 |
0.0203 |
0.1795 |
0.3335 |
0.3695 |
1.0185 |
0.4155 |
0.8932 |
0.6823* |
3.9182 |
0.8439 |
±SD |
31.08 |
0.0038 |
0.0445 |
0.0566 |
0.0483 |
0.0356 |
0.0414 |
0.1845 |
0.0812 |
0.3929 |
0.1447 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
293.05 |
0.0224 |
0.2113 |
0.2961 |
0.4076 |
1.0155 |
0.4507 |
0.9310 |
0.6979 |
4.2155 |
0.8045 |
±SD |
42.83 |
0.0032 |
0.0329 |
0.0853 |
0.0567 |
0.1350 |
0.0615 |
0.0652 |
0.0952 |
0.5728 |
0.1642 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
291.25 |
0.0203 |
0.1995 |
0.2982 |
0.3539 |
1.0877 |
0.4421 |
0.9306 |
0.7182 |
3.8349 |
0.7475 |
±SD |
22.03 |
0.0031 |
0.0313 |
0.0714 |
0.0526 |
0.1150 |
0.0342 |
0.1234 |
0.0523 |
0.5638 |
0.2375 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation, n: Number of animals; PSC: Prostate gland + Seminal vesicles with Coagulating gland
*. The mean difference is significant at the 0.05 level.
TABLE 14 (Contd..,). SUMMARY OF FASTING BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO BODY WEIGHT(%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Uterus |
Ovaries |
Heart |
Kidneys |
Brain |
Liver |
|
G1, F & 0 |
Mean |
214.26 |
0.0311 |
0.2957 |
0.3937 |
0.3146 |
0.0849 |
0.4660 |
0.9001 |
0.9331 |
4.1637 |
±SD |
13.66 |
0.0038 |
0.0508 |
0.1135 |
0.0756 |
0.0058 |
0.0264 |
0.0667 |
0.0358 |
0.2737 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
210.78 |
0.0323 |
0.3163 |
0.3775 |
0.3624 |
0.0925 |
0.4372 |
0.9586 |
0.9557 |
4.2871 |
±SD |
9.56 |
0.0025 |
0.0277 |
0.1146 |
0.0730 |
0.0092 |
0.0242 |
0.0879 |
0.0796 |
0.4288 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
210.11 |
0.0293 |
0.2749 |
0.3205 |
0.2888 |
0.0917 |
0.4495 |
0.9464 |
0.9581 |
4.0917 |
±SD |
12.95 |
0.0023 |
0.0320 |
0.0318 |
0.0460 |
0.0068 |
0.0286 |
0.0422 |
0.0927 |
0.2433 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
211.06 |
0.0305 |
0.2836 |
0.3167 |
0.2696 |
0.0907 |
0.3556 |
0.9077 |
0.9286 |
4.0832 |
±SD |
5.89 |
0.0052 |
0.0423 |
0.0837 |
0.0396 |
0.0158 |
0.1975 |
0.0793 |
0.0591 |
0.3270 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female, SD: Standard Deviation, n: Number of animals
TABLE 14 (Contd..,). SUMMARY OF FASTING BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO BODY WEIGHT(%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Epididymes |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Prostate+Seminal vesicles with coagulating glands (PSC) |
|
G1R, M & 0 |
Mean |
343.52 |
0.0227 |
0.1788 |
0.3406 |
0.3737 |
0.9656 |
0.4130 |
0.8874 |
0.6158 |
3.6584 |
0.8182 |
±SD |
25.61 |
0.0089 |
0.0525 |
0.0816 |
0.0309 |
0.0715 |
0.0415 |
0.1167 |
0.0467 |
0.3255 |
0.1605 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
338.24 |
0.0225 |
0.1524 |
0.2374 |
0.3976 |
0.9055 |
0.4166 |
0.9030 |
0.6043 |
3.3966 |
0.7220 |
±SD |
23.90 |
0.0067 |
0.0384 |
0.1014 |
0.0535 |
0.0900 |
0.0500 |
0.1994 |
0.0438 |
0.4804 |
0.1371 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male, R: Recovery; SD: Standard Deviation, n: Number of animals; PSC: Prostate gland + Seminal vesicles with Coagulating gland
TABLE 14 (Contd..,). SUMMARY OF FASTING BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO BODY WEIGHT(%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Uterus |
Ovaries |
Heart |
Kidneys |
Brain |
Liver |
|
G1R, F & 0 |
Mean |
230.84 |
0.0337 |
0.1898 |
0.3356 |
0.2960 |
0.0761 |
0.4164 |
0.7198 |
0.8403 |
3.4236 |
±SD |
9.32 |
0.0063 |
0.0276 |
0.1112 |
0.1381 |
0.0206 |
0.0311 |
0.0484 |
0.0236 |
0.2392 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
236.20 |
0.0307 |
0.2218 |
0.2475 |
0.2415 |
0.1603 |
0.4593 |
0.7442 |
0.8292 |
3.5675 |
±SD |
16.90 |
0.0052 |
0.0526 |
0.0354 |
0.0566 |
0.1787 |
0.0992 |
0.1173 |
0.0391 |
0.3877 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation, n: Number of animals; PSC: Prostate gland + Seminal vesicles with Coagulating gland
TABLE 15. SUMMARY OF GROSS PATHOLOGY FINDINGS RECORD
Organs/ Lesions |
Group |
G1 |
G1R |
G2 |
G3 |
G4 |
G4R |
||||||
Dose (mg/kg body weight/day) |
0 |
0 |
100 |
300 |
1000 |
1000 |
|||||||
Sex |
M |
F |
M |
F |
M |
F |
M |
F |
M |
F |
M |
F |
|
No. of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
No Abnormality Detected |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
The numeral indicates number of animal/s without lesion. M: Male; F: Female
TABLE 16. SUMMARY OF HISTOPATHOLOGY FINDINGS RECORD
Group |
G1 |
G4 |
||
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Sex |
M |
F |
M |
F |
No. of Animals |
5 |
5 |
5 |
5 |
ORGANS AND OBSERVATIONS |
||||
LIVER |
|
|
|
|
MNC infiltration |
1 |
1 |
0 |
0 |
KIDNEYS |
|
|
|
|
Cortex; Basophilic tubules; unilateral |
0 |
1 |
0 |
0 |
Interstitial MNC infiltration; unilateral |
0 |
0 |
1 |
0 |
THYROID |
|
|
|
|
Ectopic thymus |
0 |
0 |
1 |
0 |
EPIDIDYMIDES |
|
|
|
|
Sperm granuloma; unilateral |
0 |
X |
1 |
X |
PROSTATE GLAND |
|
|
|
|
Interstitial MNC infiltration |
0 |
X |
1 |
X |
Note: The numeral indicates number of animal/s with lesion; M: Male; F: Female; X: Organs not subjected for histopathological examination due to sex difference.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The study is a GLP conform 28-day repeated dose study in rats according to OECD 407.
Additional information
Justification for classification or non-classification
According to Regulation (EC) No 1272/2008 of the European Parliament and of the council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006, the test substance Hostacerin DGSB has not to be classified.
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