Registration Dossier
Registration Dossier
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EC number: 810-394-3 | CAS number: 76326-99-3
Endpoint summary
Administrative data
Description of key information
The registration substance, N, N-Dimethyl-D-glucamine, 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 any 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 and recovery group consisted of 5 males and 5 females. The animals were administered N, N-Dimethyl-D-Glucamine at the dose levels of 0, 100, 300 and 1000 mg/kg/day. The vehicle and test item formulations were administered at the dose volume of 10 mL/kg body weight.
The concentration analysis of the prepared dose formulations was performed on week 1 and week 4 of the experiment as per the validated method. The results of the analysed formulations were within the range of 90 to 110% of the nominal concentration and the relative standard deviation (% RSD) is equal to or less than 10.0%.
All animals were observed for clinical signs, mortality and morbidity, detailed clinical examination, body weight and feed consumption. Ophthalmological examination and neurological/functional examination was carried out during week 4 for main groups and during week 6 for recovery groups. 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 and high dose 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.
The NOAEL of 1000 mg/kg/day was obtained.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 26 November 2016 to 21 April 2017
- 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 Guideline No. 407, “Repeated Dose 28-Day Oral Toxicity Study in Rodents” adopted on 03 October 2008
- Deviations:
- no
- 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 and RAK-KRS-00022
- Expiration date of the lot/batch: 01.04.2018
- Purity test date: 30.09.2015
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29°C)
- Stability under test conditions: Stable at 6 hours at room temperature with a concentration 100 mg/mL
- Solubility and stability of the test substance in the solvent/vehicle: Clearly miscible (at a concentration of 140 mg/mL) with Distilled water evidenced by the in-house miscibility test results and Stable at 6 hours at room temperature with a concentration 100 mg/mL
FORM AS APPLIED IN THE TEST: Liquid - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Rat is one of the recommended species by regulatory agencies for conducting preclinical toxicological studies among rodent species
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation: 100 to 160 g
- Housing:Maximum of three animals of same sex and group were housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted feed and water bottle. Clean sterilized paddy husk was provided as bedding material.
- Diet :ad libitum
- Water: ad libitum
- Acclimation period: 05 Days
DETAILS OF FOOD AND WATER QUALITY: Teklad Certified (2014SC) Global 14 % Protein Rodent Maintenance Diet - Pellet (Manufactured by Envigo); Water: eep bore-well water passed through an activated charcoal filter and exposed to ultraviolet rays in an aquaguard water filter with purifier.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1°C to 22.8°C
- Humidity (%): 46% to 67%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 2 hours fluorescent light and 12 hours dark cycle
IN-LIFE DATES: From: 26 November 2016 To: 12 January 2017 - Route of administration:
- oral: gavage
- Details on route of administration:
- The test item was administered through oral route using stainless steel gavage cannula attached to disposable syringe
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: The test item formulations were prepared by mixing to the required quantity with the vehicle to get desired concentrations 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 (if other than water): Distilled water was used as vehicle for formulation preparation as the test item was clearly miscible (at a concentration of 140 mg/mL) with Distilled water evidenced by the in-house miscibility test results.
- Concentration in vehicle: G2: 10 mg/mL; G3: 30 mg/mL; G4: 100 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg body weight - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- For active ingredient (a.i.) concentration analysis, the prepared formulations were sampled in duplicate sets (5 mL for each set from middle layer) from each dose level during week 1 and week 4 of the treatment period.
The results were considered acceptable, as the mean results are within the range of 90 to 110% of the nominal concentration and the relative standard deviation (% RSD) is equal to or less than 10.0%. - Duration of treatment / exposure:
- 28 Days
- Frequency of treatment:
- Daily once
- 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/G4R) levels based on the NOAEL)of Genamin DMG 75 (N, N-Dimethyl-D-glucamine) was 1000 mg/kg/day when administered for a period of 14 consecutive days by oral (gavage) to Sprague Dawley rats obtained from the dose range finding study.
- Rationale for animal assignment: Randamization and grouping based on the body weight
- Rationale for selecting satellite groups: based on the OECD 407 guidelines
- Post-exposure recovery period in satellite groups: 14 days
The dose applied refers to the amount of N, N-Dimethyl-D-glucamine. - Positive control:
- Not applicable
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily once
- 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: Week 4 for main group animals and week 6 for recovry group animals
- Dose groups that were examined: Vehicle control and high dose group animals of both sex.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination (Day 29 for amin group animals and Day 43 for recovery group animals)
- Anaesthetic used for blood collection: Yes (identity): isolflurane mild
- Animals fasted: Yes
- How many animals: all nimals one day prior to sacrifice
- Parameters checked in table [No.10] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination (Day 29 for amin group animals and Day 43 for recovery group animals)
- Animals fasted: Yes
- How many animals: all nimals one day prior to sacrifice
- Parameters checked in table [No.11] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: at termination (Day 29 for amin group animals and Day 43 for recovery group animals)
- 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 animals and week 6 for recovery group animals
- Dose groups that were examined: Vehicle control and high dose group animals of both sex.
- Battery of functions tested: sensory activity / grip strength / motor activity - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 15)
HISTOPATHOLOGY: Yes (see table 16) - Other examinations:
- Not applicable
- Statistics:
- SPSS software version 22. One way ANOVA followed by Dunnett’s post-test for main group parameters and independant sample t-test for recovery groups comparing with the control group data 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 and mortality/morbidity observed at any of the doses tested in both the sex.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no mortality/morbidity observed at any of the doses tested in both the sex.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- statistical significant increase in mean body weight on day 22 with respect to day 1 in G2 females; statistical significant decrease in percent change in body weight during week 1 in G3 and G4 males; statistical significant increase in percent change in body weight during week 1 and 3 in G4R females was observed when compared with respective vehicle control groups. These changes can be considered as incidental, but not treatment related as the mean body weights and feed consumption during this period was unaffected and there were no clinical signs were observed.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There were no treatment related changes noted in feed consumption at any of the tested doses in both the sex.
- 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 ophthalmological 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):
- Main group: Statistical significant increase in mean platelet volume in G2 and G4 males; statistical significant decrease in hemoglobin in G4 females; statistical significant decrease in mean corpuscular volume in G4 females; statistical significant decrease in mean corpuscular hemoglobin in G3 and G4 females; statistical significant decrease in mean corpuscular haemoglobin concentration in G4 females; statistical significant increase in percent eosinophills in G2 females; statistical significant increase in absolute eosinophills in G4 females when compared with vehicle control group animals were noted.
Recovery group: Statistical significant decrease in percent monocytes in G4R males, statistical significant decrease in absolute reticulocytes in G4R females when compared with vehicle control recovery group animals were 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):
- Statistically significant decrease in total cholesterol and statistically significant increase in sodium levels in G4R males; statistically significant decrease in glucose in G4R females; statistically significant increase in total bilurubin 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 doses tested in either sex
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- There were no treatment related 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):
- Statistically significant increase in absolute spleen weight and decrease in relative thymus weight in G2 females; statistically significant increase in relative kidneys weight in G4R males; statistically significant decrease in absolute kidneys weight in G4R females; statistically significant decrease in relative thymus, kidneys and liver weight in G4R females were noted.
All the observed changes are considered incidental and not treatment related because of the 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 doses of either sex during gross pathological examination.
- Neuropathological findings:
- not examined
- Description (incidence and severity):
- not applicable
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No treatment related changes observed on histopathological examination of high dose group animals.
All observed lesions were considered as spontaneous and incidental to Sprague Dawley rats. - Histopathological findings: neoplastic:
- not examined
- Description (incidence and severity):
- not applicable
- Other effects:
- not examined
- Description (incidence and severity):
- not applicable
- Details on results:
- The active ingredient (a.i.) concentration analysis of the prepared dose formulations of Genamin DMG 75 (N, N-Dimethyl-D-Glucamine) was performed on week 1 and week 4 of the experiment as per the validated method (BIO-ANM 374). The results of the analysed formulations were within the range of 90 to 110% of the nominal concentration and the relative standard deviation (% RSD) is equal to or less than 10.0%.
All animals were observed for clinical signs, mortality and morbidity, detailed clinical examination, body weight and feed consumption. Ophthalmological 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 result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
- Key result
- Critical effects observed:
- no
- Conclusions:
- The repeated dose toxicity of the registration substance was investigated according to the Guideline OECD 407. Rats were treated at dose of up to 1000 mg/kg/day. No effect was observed. The NOAEL of 1000 mg/kg/day was obtained.
- Executive summary:
The registration substance, N, N-Dimethyl-D-glucamine, 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 any 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 and recovery group consisted of 5 males and 5 females. The animals were administered N, N-Dimethyl-D-Glucamine at the dose levels of 0, 100, 300 and 1000 mg/kg/day. The vehicle and test item formulations were administered at the dose volume of 10 mL/kg body weight.
The concentration analysis of the prepared dose formulations was performed on week 1 and week 4 of the experiment as per the validated method. The results of the analysed formulations were within the range of 90 to 110% of the nominal concentration and the relative standard deviation (% RSD) is equal to or less than 10.0%.
All animals were observed for clinical signs, mortality and morbidity, detailed clinical examination, body weight and feed consumption. Ophthalmological examination and neurological/functional examination was carried out during week 4 for main groups and during week 6 for recovery groups. 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 and high dose 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.
The NOAEL of 1000 mg/kg/day was obtained.
Reference
TABLE 2. SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight) |
Body Weight on Days |
|||||
1 |
8 |
15 |
22 |
28 |
||
G1, M & 0 |
Mean |
180.39 |
218.05 |
262.18 |
285.29 |
314.09 |
±SD |
14.38 |
14.68 |
17.88 |
16.52 |
20.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
181.26 |
218.46 |
268.26 |
296.23 |
330.72 |
±SD |
9.54 |
10.58 |
9.66 |
10.36 |
13.09 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
182.53 |
213.85 |
259.27 |
292.11 |
322.75 |
±SD |
13.00 |
14.32 |
20.46 |
21.16 |
22.16 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
178.28 |
207.94 |
255.99 |
284.52 |
307.84 |
±SD |
9.94 |
8.40 |
16.36 |
14.83 |
24.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
Group, Sex & Dose (mg/kg body weight) |
Body Weight on Days |
|||||
1 |
8 |
15 |
22 |
28 |
||
G1, F & 0 |
Mean |
154.65 |
171.95 |
195.12 |
211.85 |
227.03 |
±SD |
9.72 |
11.49 |
13.22 |
14.98 |
17.61 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
152.53 |
172.77 |
198.01 |
220.45 |
232.59 |
±SD |
8.28 |
8.25 |
8.54 |
6.66 |
9.39 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
152.87 |
169.42 |
193.68 |
217.50 |
230.59 |
±SD |
7.20 |
7.03 |
11.25 |
9.30 |
7.68 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
155.74 |
172.60 |
199.21 |
219.72 |
232.71 |
±SD |
9.05 |
12.29 |
11.15 |
14.71 |
15.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
|
Group, Sex & Dose (mg/kg body weight) |
Days |
||||||||
1 |
8 |
15 |
22 |
28 |
36 |
42 |
|||
G1R, M & 0 |
Mean |
178.54 |
211.73 |
250.07 |
276.32 |
302.69 |
329.01 |
353.91 |
|
±SD |
9.08 |
8.43 |
21.25 |
19.61 |
18.03 |
18.41 |
18.96 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
179.48 |
212.43 |
255.13 |
282.25 |
310.70 |
335.70 |
360.55 |
|
±SD |
9.01 |
9.99 |
11.41 |
10.56 |
12.26 |
14.76 |
15.51 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
154.90 |
174.67 |
199.31 |
214.97 |
232.80 |
247.30 |
264.98 |
|
±SD |
6.48 |
8.93 |
10.63 |
10.58 |
13.11 |
15.16 |
14.22 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
156.04 |
182.14 |
204.64 |
227.30 |
241.57 |
254.50 |
271.34 |
|
±SD |
6.62 |
11.49 |
14.82 |
15.80 |
16.74 |
15.94 |
16.42 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
TABLE 3. SUMMARY OF PERCENT CHANGE IN BODY WEIGHT (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight) |
Days |
||||
1 to 8 |
1 to 15 |
1 to 22 |
1 to 28 |
||
G1, M & 0 |
Mean |
20.98 |
45.46 |
58.43 |
74.30 |
±SD |
1.73 |
2.91 |
5.88 |
3.27 |
|
n |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
20.54 |
48.16 |
63.65 |
82.70 |
±SD |
0.77 |
5.63 |
7.15 |
8.70 |
|
n |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
17.19 |
42.00 |
60.02 |
76.87 |
±SD |
1.35 |
3.24 |
1.93 |
3.83 |
|
n |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
16.76 |
43.64 |
59.69 |
72.62 |
±SD |
3.79 |
6.06 |
5.37 |
7.97 |
|
n |
5 |
5 |
5 |
5 |
|
Group, Sex & Dose (mg/kg body weight) |
Days |
||||
1 to 8 |
1 to 15 |
1 to 22 |
1 to 28 |
||
G1, F & 0 |
Mean |
11.17 |
26.14 |
36.93 |
46.71 |
±SD |
1.41 |
1.57 |
1.65 |
3.78 |
|
n |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
13.31 |
30.04 |
44.76 |
52.69 |
±SD |
1.05 |
7.64 |
6.57 |
6.75 |
|
n |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
10.85 |
26.67 |
42.35 |
50.96 |
±SD |
1.44 |
3.44 |
4.43 |
4.46 |
|
n |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
10.76 |
27.96 |
41.04 |
49.39 |
±SD |
1.64 |
3.59 |
3.05 |
3.07 |
|
n |
5 |
5 |
5 |
5 |
|
Group, Sex & Dose (mg/kg body weight) |
Days |
|||||||
1 to 8 |
1 to 15 |
1 to 22 |
1 to 28 |
1 to 36 |
1 to 42 |
|||
G1R, M & 0 |
Mean |
18.67 |
39.96 |
54.72 |
69.62 |
84.35 |
98.31 |
|
±SD |
2.99 |
7.15 |
6.34 |
7.62 |
6.70 |
7.17 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
18.37 |
42.24 |
57.41 |
73.26 |
87.16 |
101.01 |
|
±SD |
0.87 |
4.78 |
5.59 |
6.05 |
5.70 |
5.89 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
12.74 |
28.68 |
38.79 |
50.30 |
59.61 |
71.04 |
|
±SD |
2.27 |
4.52 |
4.09 |
6.01 |
5.83 |
4.60 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
16.65 |
31.02 |
45.54 |
54.68 |
63.00 |
73.79 |
|
±SD |
2.89 |
4.39 |
4.13 |
4.38 |
3.65 |
3.77 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
TABLE 3. SUMMARY OF AVERAGE FEED CONSUMPTION (g/rat/day) RECORD
Group, Sex & Dose (mg/kg body weight) |
Week |
|||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
|||
G1, M & 0 |
Mean |
21.1 |
23.0 |
24.4 |
26.8 |
|
±SD |
1.2 |
0.9 |
2.1 |
1.2 |
||
n |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
21.7 |
23.3 |
23.9 |
27.4 |
|
±SD |
1.2 |
2.1 |
2.6 |
1.7 |
||
n |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
20.9 |
22.6 |
23.6 |
26.9 |
|
±SD |
0.5 |
0.7 |
1.1 |
1.8 |
||
n |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
20.6 |
21.3 |
23.8 |
26.2 |
|
±SD |
1.7 |
2.1 |
2.7 |
2.0 |
||
n |
5 |
5 |
5 |
5 |
||
Group, Sex & Dose (mg/kg body weight) |
Week |
|||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
|||
G1, F & 0 |
Mean |
18.4 |
19.4 |
20.7 |
22.8 |
|
±SD |
0.1 |
1.0 |
2.2 |
3.1 |
||
n |
5 |
5 |
5 |
5 |
||
G2, F & 100 |
Mean |
18.5 |
19.6 |
20.8 |
22.8 |
|
±SD |
0.1 |
0.5 |
0.9 |
0.8 |
||
n |
5 |
5 |
5 |
5 |
||
G3, F & 300 |
Mean |
18.8 |
20.1 |
21.0 |
22.8 |
|
±SD |
0.3 |
1.1 |
1.4 |
1.5 |
||
n |
5 |
5 |
5 |
5 |
||
G4, F & 1000 |
Mean |
18.6 |
19.6 |
20.9 |
22.2 |
|
±SD |
0.3 |
0.1 |
0.6 |
0.3 |
||
n |
5 |
5 |
5 |
5 |
||
Group, Sex & Dose (mg/kg body weight) |
Week |
|||||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
|||
G1R, M & 0 |
Mean |
20.4 |
21.9 |
24.0 |
25.7 |
24.6 |
27.0 |
|
±SD |
1.3 |
2.6 |
2.6 |
1.6 |
2.0 |
0.3 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
20.2 |
21.5 |
23.6 |
25.8 |
25.2 |
25.7 |
|
±SD |
1.4 |
2.1 |
2.3 |
1.7 |
2.4 |
0.7 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
18.6 |
19.7 |
20.3 |
21.8 |
21.6 |
25.5 |
|
±SD |
0.1 |
0.3 |
0.6 |
0.1 |
0.6 |
0.4 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
18.3 |
19.0 |
20.3 |
21.2 |
21.9 |
24.2 |
|
±SD |
0.7 |
0.5 |
0.9 |
0.8 |
0.3 |
0.8 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
TABLE 5. SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Week 4 |
Week 6 |
|||||
Parameters↓ |
Group & Sex |
G1 & M |
G4 & M |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight) |
0 |
1000 |
300 |
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 |
||||||
|
Week 4 |
Week 6 |
||||
Parameters↓ |
Group & Sex |
G1 & M |
G4 & M |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight) |
0 |
1000 |
300 |
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 |
3.2 |
3.6 |
2.0 |
2.8 |
|
±SD |
0.8 |
1.1 |
0.7 |
0.8 |
||
e. Urination |
Mean |
1.8 |
1.6 |
2.6 |
2.2 |
|
Numbers of pools of urine |
±SD |
0.8 |
1.3 |
0.5 |
0.8 |
|
f. Defecation |
Mean |
1.4 |
2.0 |
2.0 |
1.6 |
|
Number of fecal pellets |
±SD |
0.5 |
0.7 |
0.7 |
0.5 |
|
g. Stereotypies- repetitive circling |
1 |
1 |
1 |
1 |
||
h. Excessive grooming |
Mean |
2.6 |
3.0 |
2.8 |
2.8 |
|
±SD |
0.9 |
0.0 |
0.8 |
0.8 |
||
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 |
98.2 |
98.9 |
98.8 |
98.4 |
|
Body temperature (°F) |
±SD |
0.9 |
0.6 |
0.4 |
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,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 |
||||||
|
Week 4 |
Week 6 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Parameters↓ |
Group & Sex |
G1 & F |
G4 & F |
G1R & F |
G4R & F |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dose (mg/kg body weight) |
0 |
1000 |
300 |
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 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
TABLE 6. LANDING FOOT SPLAY (cm) RECORD
Group, Sex & Dose (mg/kg body weight) |
Landing Foot Splay (cm) |
||
G1, M & 0 |
Mean |
8.0 |
|
±SD |
1.0 |
||
n |
5 |
||
G4, M & 1000 |
Mean |
8.6 |
|
±SD |
1.5 |
||
n |
5 |
||
G1R, M & 0 |
Mean |
8.5 |
|
±SD |
1.2 |
||
n |
5 |
||
G4R, M &1000 |
Mean |
8.7 |
|
±SD |
1.2 |
||
n |
5 |
Group, Sex & Dose (mg/kg body weight) |
Landing Foot Splay (cm) |
||
G1, F & 0 |
Mean |
7.9 |
|
±SD |
0.7 |
||
n |
5 |
||
G4, F & 1000 |
Mean |
8.2 |
|
±SD |
1.1 |
||
n |
5 |
||
G1R, F & 0 |
Mean |
7.9 |
|
±SD |
0.7 |
||
n |
5 |
||
G4R, F & 1000 |
Mean |
7.3 |
|
±SD |
1.1 |
||
n |
5 |
TABLE 7. SUMMARY OF PHOTOACTOMETER READINGS (No. OF MOVEMENTS) RECORD
Group, Sex & Dose (mg/kg body weight) |
Movement Counts (no.) |
||
G1, M & 0 |
Mean |
670.0 |
|
±SD |
56.6 |
||
n |
5 |
||
G4, M & 1000 |
Mean |
629.6 |
|
±SD |
56.1 |
||
n |
5 |
||
G1R, M & 0 |
Mean |
692.2 |
|
±SD |
108.1 |
||
n |
5 |
||
G4R, M & 1000 |
Mean |
741.0 |
|
±SD |
46.7 |
||
n |
5 |
Group, Sex & Dose (mg/kg body weight) |
Movement Counts (no.) |
||
G1, F & 0 |
Mean |
651.4 |
|
±SD |
78.4 |
||
n |
5 |
||
G4, F & 1000 |
Mean |
620.0 |
|
±SD |
47.8 |
||
n |
5 |
||
G1R, F & 0 |
Mean |
754.4 |
|
±SD |
44.3 |
||
n |
5 |
||
G4R, F & 1000 |
Mean |
760.4 |
|
±SD |
52.9 |
||
n |
5 |
TABLE 8. SUMMARY OF GRIP STRENGTH (kgf) MEASUREMENT RECORD
Group, Sex & Dose (mg/kg body weight) |
Fore limb |
Hind limb |
||
G1, M & 0 |
Mean |
1.541 |
0.590 |
|
±SD |
0.077 |
0.043 |
||
n |
5 |
5 |
||
G4, M & 1000 |
Mean |
1.430 |
0.502 |
|
±SD |
0.187 |
0.073 |
||
n |
5 |
5 |
||
G1R, M & 0 |
Mean |
1.579 |
0.568 |
|
±SD |
0.038 |
0.020 |
||
n |
5 |
5 |
||
G4R, M & 1000 |
Mean |
1.558 |
0.550 |
|
±SD |
0.023 |
0.034 |
||
n |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
Fore limb |
Hind limb |
||
G1, F & 0 |
Mean |
1.567 |
0.577 |
|
±SD |
0.025 |
0.038 |
||
n |
5 |
5 |
||
G4, F & 1000 |
Mean |
1.564 |
0.557 |
|
±SD |
0.011 |
0.031 |
||
n |
5 |
5 |
||
G1R, F & 0 |
Mean |
1.565 |
0.556 |
|
±SD |
0.022 |
0.038 |
||
n |
5 |
5 |
||
G4R, F & 1000 |
Mean |
1.555 |
0.562 |
|
±SD |
0.026 |
0.020 |
||
n |
5 |
5 |
TABLE 10. SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight) |
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 |
7.99 |
7.17 |
13.50 |
41.82 |
58.28 |
18.82 |
32.32 |
1060.40 |
6.78 |
|
±SD |
0.81 |
0.20 |
0.40 |
1.26 |
0.64 |
0.46 |
0.58 |
111.01 |
0.23 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
9.40 |
7.36 |
13.96 |
43.28 |
58.86 |
19.02 |
32.28 |
871.20 |
7.34 |
|
±SD |
2.60 |
0.31 |
0.57 |
1.72 |
1.43 |
0.61 |
0.38 |
260.67 |
0.34 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
8.48 |
7.50 |
13.92 |
42.98 |
57.34 |
18.58 |
32.36 |
1073.20 |
7.18 |
|
±SD |
2.77 |
0.32 |
0.51 |
1.31 |
1.25 |
0.59 |
0.40 |
50.57 |
0.13 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
7.31 |
7.36 |
13.92 |
42.20 |
57.34 |
18.90 |
32.98 |
953.00 |
7.52 |
|
±SD |
1.70 |
0.45 |
0.59 |
2.29 |
1.09 |
0.56 |
0.53 |
138.38 |
0.33 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
Reticulocyte Count (%) |
Neutrophils (%) |
Lymphocytes (%) |
Monocytes (%) |
Eosinophils (%) |
Basophils (%) |
||
G1, M & 0 |
Mean |
2.74 |
19.30 |
75.76 |
2.36 |
0.68 |
0.18 |
|
±SD |
0.16 |
4.45 |
5.28 |
0.42 |
0.20 |
0.08 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
2.55 |
20.10 |
75.26 |
2.12 |
0.86 |
0.26 |
|
±SD |
0.22 |
2.87 |
3.96 |
0.62 |
0.47 |
0.15 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
2.56 |
20.46 |
74.46 |
2.78 |
0.70 |
0.22 |
|
±SD |
0.46 |
5.12 |
4.98 |
0.48 |
0.32 |
0.08 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
2.36 |
24.84 |
69.80 |
3.22 |
0.56 |
0.18 |
|
±SD |
0.45 |
3.19 |
3.20 |
0.83 |
0.18 |
0.04 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
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 |
196.42 |
1.53 |
6.07 |
0.19 |
0.06 |
0.01 |
14.74 |
33.06 |
|
±SD |
6.51 |
0.30 |
0.91 |
0.04 |
0.02 |
0.01 |
0.69 |
32.13 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
187.66 |
1.86 |
7.13 |
0.20 |
0.07 |
0.03 |
15.26 |
46.06 |
|
±SD |
17.80 |
0.42 |
2.21 |
0.07 |
0.03 |
0.02 |
1.56 |
6.21 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
190.70 |
1.64 |
6.41 |
0.24 |
0.06 |
0.02 |
14.36 |
49.52 |
|
±SD |
27.20 |
0.30 |
2.42 |
0.09 |
0.04 |
0.01 |
0.46 |
2.20 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
175.56 |
1.81 |
5.11 |
0.25 |
0.04 |
0.01 |
14.34 |
41.60 |
|
±SD |
41.83 |
0.45 |
1.20 |
0.11 |
0.02 |
0.00 |
0.79 |
16.11 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
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 |
7.23 |
7.54 |
14.22 |
43.28 |
57.40 |
18.90 |
32.88 |
1026.80 |
7.76 |
|
±SD |
1.65 |
0.36 |
0.56 |
1.54 |
0.85 |
0.23 |
0.55 |
78.28 |
0.57 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 100 |
Mean |
5.80 |
7.48 |
14.02 |
42.10 |
56.32 |
18.74 |
33.28 |
1046.40 |
8.46 |
|
±SD |
1.01 |
0.17 |
0.52 |
1.04 |
1.19 |
0.51 |
0.36 |
76.03 |
0.34 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 300 |
Mean |
7.66 |
7.50 |
13.38 |
41.66 |
55.62 |
17.84* |
32.08 |
991.80 |
7.66 |
|
±SD |
1.44 |
0.12 |
0.54 |
1.70 |
2.65 |
0.86 |
0.57 |
141.77 |
0.27 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 1000 |
Mean |
8.27 |
7.76 |
13.32 |
41.70 |
53.78 |
17.18* |
31.98* |
978.20 |
7.12 |
|
±SD |
2.13 |
0.27 |
0.43 |
0.96 |
1.55 |
0.58 |
0.47 |
90.57 |
0.70 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
Reticulocyte Count (%) |
Neutrophils (%) |
Lymphocytes (%) |
Monocytes (%) |
Eosinophils (%) |
Basophils (%) |
||
G1, F & 0 |
Mean |
1.87 |
27.20 |
68.14 |
2.62 |
0.60 |
0.22 |
|
±SD |
0.70 |
12.07 |
12.79 |
1.44 |
0.25 |
0.08 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 100 |
Mean |
1.97 |
35.06 |
59.40 |
2.96 |
1.24 |
0.20 |
|
±SD |
0.41 |
4.87 |
4.93 |
0.78 |
0.42 |
0.10 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 300 |
Mean |
2.10 |
21.08 |
73.06 |
3.10 |
0.96 |
0.34 |
|
±SD |
0.26 |
4.43 |
3.22 |
0.72 |
0.33 |
0.21 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 1000 |
Mean |
2.30 |
21.32 |
72.28 |
3.24 |
1.10 |
0.38 |
|
±SD |
0.20 |
4.55 |
4.56 |
0.74 |
0.45 |
0.08 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
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 |
140.98 |
2.09 |
4.79 |
0.20 |
0.04 |
0.02 |
15.98 |
49.46 |
|
±SD |
53.86 |
1.46 |
0.73 |
0.16 |
0.02 |
0.01 |
0.15 |
7.98 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 100 |
Mean |
147.28 |
2.02 |
3.45 |
0.17 |
0.07 |
0.01 |
14.56 |
51.50 |
|
±SD |
29.15 |
0.40 |
0.72 |
0.07 |
0.03 |
0.00 |
0.89 |
14.74 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 300 |
Mean |
157.60 |
1.61 |
5.60 |
0.24 |
0.07 |
0.03 |
14.26 |
60.16 |
|
±SD |
21.28 |
0.47 |
1.09 |
0.07 |
0.02 |
0.02 |
0.80 |
20.82 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 1000 |
Mean |
177.92 |
1.77 |
5.98 |
0.27 |
0.09 |
0.03 |
15.26 |
50.46 |
|
±SD |
9.54 |
0.58 |
1.63 |
0.08 |
0.03 |
0.01 |
1.82 |
10.17 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
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 |
7.91 |
7.71 |
14.02 |
43.74 |
56.78 |
18.20 |
32.04 |
863.80 |
6.80 |
|
±SD |
3.10 |
0.30 |
0.61 |
1.38 |
1.37 |
0.66 |
0.52 |
133.80 |
0.32 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
8.04 |
8.05 |
14.26 |
44.94 |
55.86 |
17.74 |
31.76 |
962.60 |
6.94 |
|
±SD |
2.59 |
0.28 |
0.25 |
0.87 |
1.30 |
0.53 |
0.22 |
124.15 |
0.11 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
7.85 |
7.84 |
14.14 |
43.64 |
55.74 |
18.06 |
32.40 |
892.80 |
7.22 |
|
±SD |
1.83 |
0.58 |
0.65 |
2.09 |
1.52 |
0.71 |
0.45 |
240.59 |
0.34 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
5.78 |
7.97 |
13.98 |
43.38 |
54.42 |
17.54 |
32.30 |
1025.60 |
7.26 |
|
±SD |
1.48 |
0.28 |
0.37 |
1.54 |
1.38 |
0.53 |
0.39 |
207.18 |
0.32 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
Reticulocyte Count (%) |
Neutrophils (%) |
Lymphocytes (%) |
Monocytes (%) |
Eosinophils (%) |
Basophils (%) |
||
G1R, M & 0 |
Mean |
2.27 |
20.62 |
74.00 |
2.56 |
0.96 |
0.20 |
|
±SD |
0.35 |
6.14 |
6.01 |
0.58 |
0.48 |
0.07 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
2.18 |
19.76 |
76.00 |
1.62 |
0.80 |
0.18 |
|
±SD |
0.36 |
3.21 |
2.98 |
0.47 |
0.37 |
0.08 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
1.60 |
20.98 |
74.52 |
1.78 |
1.08 |
0.22 |
|
±SD |
0.41 |
6.18 |
6.25 |
0.22 |
0.29 |
0.04 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
1.98 |
25.24 |
69.50 |
2.04 |
1.46 |
0.16 |
|
±SD |
0.17 |
7.91 |
7.23 |
0.64 |
0.48 |
0.05 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
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 |
174.60 |
1.50 |
5.98 |
0.21 |
0.07 |
0.02 |
16.00 |
47.98 |
|
±SD |
24.51 |
0.34 |
2.59 |
0.10 |
0.02 |
0.01 |
1.14 |
6.34 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
174.66 |
1.58 |
6.11 |
0.14 |
0.06 |
0.02 |
18.50 |
49.32 |
|
±SD |
24.53 |
0.53 |
2.01 |
0.08 |
0.02 |
0.01 |
2.96 |
5.75 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
124.82 |
1.63 |
5.87 |
0.14 |
0.08 |
0.02 |
16.20 |
49.80 |
|
±SD |
28.31 |
0.54 |
1.49 |
0.05 |
0.03 |
0.01 |
3.12 |
14.47 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
157.46 |
1.43 |
4.04 |
0.13 |
0.09 |
0.01 |
16.60 |
61.16 |
|
±SD |
11.39 |
0.46 |
1.24 |
0.06 |
0.04 |
0.01 |
2.99 |
12.17 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
TABLE 11. SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight) |
Glucose (GLU) mg/dL |
Urea mg/dL |
Creatinine (CRE) mg/dL |
Total Cholesterol (CHO) mg/dL |
Trigly- cerides (TRI) mg/dL |
Total Protein (TPR) g/dL |
Albumin (ALB) g/dL |
Alanine Amino Transferase (ALT) U/L |
Aspartate Amino Transferase (AST) U/L |
Alkaline phosphatase (ALP) U/L |
Total Bilirubin (BIT) mg/dL |
||
G1, M & 0 |
Mean |
103.00 |
23.72 |
0.52 |
67.80 |
65.60 |
5.52 |
3.26 |
41.60 |
86.80 |
158.40 |
0.01 |
|
±SD |
12.90 |
2.32 |
0.05 |
6.76 |
18.51 |
0.26 |
0.14 |
3.51 |
14.20 |
35.06 |
0.02 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 100 |
Mean |
97.80 |
23.96 |
0.51 |
60.80 |
67.00 |
5.46 |
3.24 |
42.00 |
85.40 |
140.80 |
0.01 |
|
±SD |
14.81 |
4.36 |
0.04 |
12.46 |
22.62 |
0.25 |
0.16 |
6.20 |
10.95 |
36.68 |
0.01 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 300 |
Mean |
105.80 |
28.46 |
0.54 |
59.00 |
70.40 |
5.42 |
3.30 |
37.60 |
81.60 |
208.20 |
0.02 |
|
±SD |
18.29 |
4.55 |
0.05 |
8.37 |
34.44 |
0.13 |
0.08 |
5.77 |
13.46 |
43.03 |
0.02 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 1000 |
Mean |
110.00 |
28.40 |
0.51 |
58.40 |
46.80 |
5.56 |
3.18 |
44.60 |
93.00 |
194.60 |
0.03 |
|
±SD |
5.61 |
5.51 |
0.04 |
6.54 |
12.34 |
0.24 |
0.13 |
8.41 |
8.46 |
62.62 |
0.02 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
Group, Sex & Dose (mg/kg body weight) |
Calcium (CAL) mg/dL |
Phosphorous (PHO) (mg/dL) |
Globulin (g/dL) |
Albumin/ Globulin Ratio |
BUN (mg/dL) |
Choline- esterase |
Sodium (Na) mmol/L |
Potassium (K) mmol/L |
Chloride (CLO) mmol/L |
|
G1, M & 0 |
Mean |
9.92 |
6.76 |
2.26 |
1.44 |
11.07 |
110.20 |
151.36 |
3.99 |
106.24 |
±SD |
0.08 |
0.58 |
0.14 |
0.06 |
1.08 |
31.46 |
0.76 |
0.51 |
0.88 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
9.90 |
6.94 |
2.22 |
1.47 |
11.18 |
102.00 |
152.06 |
4.08 |
108.04 |
±SD |
0.77 |
0.46 |
0.17 |
0.13 |
2.04 |
30.34 |
1.15 |
0.40 |
0.67 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
10.22 |
6.90 |
2.12 |
1.56 |
13.28 |
93.60 |
153.26 |
3.78 |
107.04 |
±SD |
0.13 |
0.52 |
0.07 |
0.05 |
2.13 |
13.35 |
2.80 |
0.26 |
2.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
9.76 |
6.32 |
2.38 |
1.35 |
13.25 |
111.40 |
152.04 |
3.86 |
107.72 |
±SD |
0.34 |
0.71 |
0.21 |
0.13 |
2.57 |
19.88 |
1.18 |
0.14 |
0.87 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
Glucose (GLU) mg/dL |
Urea mg/dL |
Creatinine (CRE) mg/dL |
Total Cholesterol (CHO) mg/dL |
Tri- glycerides (TRI) mg/dL |
Total Protein (TPR) g/dL |
Albumin (ALB) g/dL |
Alanine Amino Transferase (ALT) U/L |
Aspartate Amino Transferase (AST) U/L |
Alkaline Phosphatase (ALP) U/L |
Total Bilirubin (BIT) mg/dL |
|
G1, F & 0 |
Mean |
117.80 |
35.64 |
0.58 |
70.20 |
29.20 |
6.04 |
3.61 |
36.20 |
87.60 |
88.60 |
0.02 |
±SD |
10.64 |
6.91 |
0.08 |
17.68 |
9.31 |
0.46 |
0.26 |
5.26 |
23.46 |
11.41 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
120.60 |
40.46 |
0.57 |
70.00 |
32.40 |
5.70 |
3.33 |
33.80 |
87.40 |
84.00 |
0.01 |
±SD |
15.47 |
6.85 |
0.03 |
5.24 |
6.27 |
0.22 |
0.20 |
3.70 |
9.50 |
20.75 |
0.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
110.60 |
41.48 |
0.56 |
68.20 |
29.00 |
6.00 |
3.72 |
45.60 |
113.80 |
95.00 |
0.02 |
±SD |
16.20 |
2.41 |
0.03 |
7.50 |
8.66 |
0.44 |
0.34 |
21.62 |
65.57 |
29.72 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
112.00 |
36.28 |
0.54 |
61.80 |
34.40 |
6.00 |
3.01 |
32.20 |
89.80 |
99.40 |
0.03 |
±SD |
4.74 |
4.48 |
0.03 |
4.38 |
6.58 |
0.10 |
1.09 |
5.40 |
16.28 |
13.99 |
0.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
Calcium (CAL) mg/dL |
Phosphorous (PHO) (mg/dL) |
Globulin (g/dL) |
Albumin/Globulin Ratio |
BUN (mg/dL) |
Choline- esterase |
Sodium (Na) mmol/L |
Potassium (K) mmol/L |
Chloride (CLO) mmol/L |
|
G1, F & 0 |
Mean |
9.96 |
6.66 |
2.43 |
1.48 |
16.63 |
483.20 |
152.46 |
3.64 |
107.24 |
±SD |
0.42 |
0.91 |
0.20 |
0.05 |
3.22 |
127.64 |
1.24 |
0.32 |
1.07 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
10.08 |
6.16 |
2.37 |
1.41 |
18.88 |
708.20 |
153.30 |
3.81 |
107.32 |
±SD |
0.45 |
0.59 |
0.19 |
0.15 |
3.20 |
168.26 |
2.00 |
0.26 |
0.90 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
10.68 |
6.96 |
2.28 |
1.70 |
19.36 |
662.80 |
154.04 |
3.80 |
109.30 |
±SD |
0.90 |
0.53 |
0.48 |
0.49 |
1.13 |
264.33 |
1.49 |
0.50 |
1.74 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
10.38 |
6.90 |
2.99 |
1.16 |
16.93 |
584.80 |
153.56 |
3.70 |
108.42 |
±SD |
1.53 |
0.86 |
1.09 |
0.53 |
2.09 |
134.92 |
1.00 |
0.38 |
1.58 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
Glucose (GLU) mg/dL |
Urea mg/dL |
Creatinine (CRE) mg/dL |
Total Cholesterol (CHO) mg/dL |
Triglycerides (TRI) mg/dL |
Total Protein (TPR) g/dL |
Albumin (ALB) g/dL |
Alanine Amino Transferase (ALT) U/L |
Aspartate Amino Transferase (AST) U/L |
Alkaline Phosphatase (ALP) U/L |
Total Bilirubin (BIT) mg/dL |
|
G1R, M & 0 |
Mean |
107.80 |
28.58 |
0.57 |
57.20 |
39.80 |
5.84 |
3.41 |
45.00 |
97.40 |
218.80 |
0.02 |
±SD |
5.40 |
1.87 |
0.03 |
11.52 |
12.76 |
0.29 |
0.29 |
6.63 |
13.01 |
24.91 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
104.00 |
30.88 |
0.55 |
43.80 |
31.40 |
5.46 |
3.25 |
40.00 |
86.80 |
175.20 |
0.02 |
±SD |
6.44 |
2.99 |
0.02 |
5.67 |
7.89 |
0.23 |
0.11 |
6.04 |
10.31 |
38.65 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
127.40 |
35.30 |
0.61 |
69.40 |
61.40 |
6.36 |
3.87 |
32.60 |
69.20 |
72.20 |
0.01 |
±SD |
5.59 |
5.43 |
0.03 |
13.96 |
32.85 |
0.21 |
0.16 |
2.88 |
18.29 |
9.26 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
105.00 |
40.52 |
0.61 |
75.00 |
34.40 |
6.18 |
3.83 |
32.00 |
70.80 |
70.80 |
0.05 |
±SD |
13.44 |
4.51 |
0.03 |
19.10 |
4.56 |
0.38 |
0.22 |
4.53 |
5.12 |
15.09 |
0.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Group, Sex & Dose (mg/kg body weight) |
Calcium (CAL) mg/dL |
Phosphorous (PHO) (mg/dL) |
Globulin (g/dL) |
Albumin/ Globulin Ratio |
BUN (mg/dL) |
Cholinesterase |
Sodium (Na) mmol/L |
Potassium (K) mmol/L |
Chloride (CLO) mmol/L |
|
G1R, M & 0 |
Mean |
10.16 |
6.92 |
2.43 |
1.41 |
13.34 |
98.60 |
143.16 |
3.94 |
102.52 |
±SD |
0.69 |
0.80 |
0.21 |
0.19 |
0.87 |
22.41 |
0.22 |
0.26 |
0.58 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
9.74 |
7.22 |
2.21 |
1.47 |
14.41 |
83.00 |
145.02 |
3.59 |
103.22 |
±SD |
0.23 |
0.59 |
0.13 |
0.05 |
1.40 |
17.89 |
0.65 |
0.34 |
0.84 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
10.24 |
6.26 |
2.49 |
1.56 |
16.48 |
926.80 |
145.42 |
3.35 |
102.90 |
±SD |
0.44 |
0.88 |
0.08 |
0.06 |
2.53 |
248.64 |
1.47 |
0.33 |
2.00 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
10.56 |
6.00 |
2.35 |
1.63 |
18.91 |
872.00 |
144.38 |
3.31 |
102.86 |
±SD |
0.27 |
0.51 |
0.20 |
0.10 |
2.10 |
199.89 |
2.72 |
0.13 |
0.88 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
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) |
0 |
100 |
300 |
1000 |
0 |
1000 |
||
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||
Physical |
Colour |
Pale Yellow |
5 |
5 |
5 |
4 |
4 |
3 |
Yellow |
- |
- |
- |
1 |
1 |
2 |
||
Appearance |
Clear |
4 |
5 |
5 |
4 |
5 |
5 |
|
Turbidity |
1 |
- |
- |
1 |
- |
- |
||
Volume (mL) |
Mean |
4.5 |
2.6 |
5.3 |
4.2 |
3.9 |
4.5 |
|
±SD |
1.7 |
1.1 |
2.6 |
2.1 |
1.3 |
1.4 |
||
Chemical |
pH |
Mean |
6.7 |
6.8 |
6.9 |
7.1 |
6.8 |
6.8 |
±SD |
0.5 |
0.5 |
0.2 |
0.6 |
0.5 |
0.3 |
||
Specific Gravity |
Mean |
1.027 |
1.030 |
1.021 |
1.022 |
1.028 |
1.030 |
|
±SD |
0.007 |
0.000 |
0.005 |
0.008 |
0.004 |
0.000 |
||
Urobilinogen (mg/dL) |
Mean |
0.4 |
0.4 |
0.2 |
0.4 |
0.4 |
0.5 |
|
±SD |
0.4 |
0.4 |
0.0 |
0.4 |
0.4 |
0.4 |
||
Bilirubin (mg/dL) |
Neg |
4 |
3 |
4 |
3 |
4 |
4 |
|
1 |
1 |
2 |
1 |
2 |
1 |
1 |
||
Ketones (mg/dL) |
Neg |
- |
- |
- |
2 |
- |
- |
|
5 |
5 |
5 |
5 |
3 |
5 |
5 |
||
Blood (Ery/µL) |
Neg |
4 |
5 |
5 |
3 |
4 |
4 |
|
Ca10 |
1 |
- |
- |
2 |
1 |
1 |
||
Proteins (mg/dL) |
Trace |
4 |
3 |
5 |
2 |
1 |
2 |
|
100 |
- |
1 |
- |
- |
1 |
|
||
30 |
1 |
1 |
- |
2 |
3 |
3 |
||
Neg |
- |
- |
- |
1 |
- |
- |
||
Nitrite |
Neg |
1 |
4 |
3 |
4 |
3 |
3 |
|
Pos |
4 |
1 |
2 |
1 |
2 |
2 |
||
Leucocytes (Leu/µL) |
Neg |
5 |
5 |
5 |
4 |
5 |
5 |
|
Ca15 |
- |
- |
- |
1 |
- |
- |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Microscopic |
Epithelial cells |
0 |
- |
- |
1 |
- |
- |
- |
0-1 |
1 |
2 |
3 |
|
1 |
1 |
||
1-2 |
3 |
3 |
1 |
3 |
4 |
3 |
||
2-3 |
1 |
- |
- |
1 |
- |
1 |
||
3-4 |
- |
- |
- |
1 |
- |
- |
||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
|
Crystals |
Present |
5 |
5 |
5 |
5 |
5 |
5 |
|
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) |
0 |
100 |
300 |
1000 |
0 |
1000 |
||
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||
Physical |
Colour |
Pale yellow |
5 |
5 |
3 |
5 |
4 |
5 |
Yellow |
- |
- |
2 |
- |
1 |
- |
||
Appearance |
Clear |
5 |
3 |
4 |
5 |
5 |
4 |
|
Turbidity |
- |
2 |
1 |
- |
- |
1 |
||
Volume (mL) |
Mean |
4.8 |
6.2 |
5.9 |
4.2 |
3.5 |
3.6 |
|
±SD |
2.1 |
2.5 |
1.7 |
1.6 |
0.8 |
1.3 |
||
Chemical |
pH |
Mean |
6.8 |
7.1 |
7.1 |
6.7 |
6.8 |
6.8 |
±SD |
0.7 |
0.4 |
1.1 |
0.3 |
0.4 |
0.4 |
||
Specific Gravity |
Mean |
1.021 |
1.021 |
1.020 |
1.028 |
1.027 |
1.026 |
|
±SD |
0.008 |
0.007 |
0.010 |
0.004 |
0.004 |
0.007 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.2 |
0.4 |
0.2 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.0 |
0.4 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
4 |
4 |
4 |
4 |
4 |
5 |
|
1 |
1 |
1 |
1 |
1 |
1 |
- |
||
Ketones (mg/dL) |
Neg |
5 |
5 |
5 |
4 |
4 |
5 |
|
5 |
- |
- |
- |
1 |
1 |
- |
||
Blood (Ery/µL) |
Neg |
3 |
4 |
4 |
5 |
4 |
5 |
|
Ca10 |
- |
- |
- |
- |
1 |
- |
||
Ca25 |
- |
1 |
1 |
- |
- |
- |
||
Ca200 |
2 |
- |
- |
- |
- |
- |
||
Proteins (mg/dL) |
Trace |
2 |
1 |
2 |
4 |
5 |
1 |
|
30 |
- |
- |
- |
1 |
- |
- |
||
Neg |
3 |
4 |
3 |
- |
- |
4 |
||
Nitrite |
Neg |
4 |
3 |
3 |
5 |
4 |
3 |
|
Pos |
1 |
2 |
2 |
|
1 |
2 |
||
Leucocytes (Leu/µL) |
Neg |
5 |
5 |
4 |
5 |
5 |
5 |
|
Ca15 |
- |
- |
1 |
- |
- |
- |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Microscopic |
Epithelial cells |
0-1 |
1 |
1 |
2 |
- |
1 |
- |
1-2 |
4 |
2 |
3 |
3 |
3 |
4 |
||
2-3 |
- |
1 |
- |
2 |
1 |
1 |
||
3-4 |
- |
1 |
- |
- |
- |
- |
||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
|
Crystals |
Present |
5 |
5 |
5 |
5 |
5 |
5 |
|
TABLE 13. SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight) |
Adrenals |
Thymus |
Spleen |
Epididymes |
Testes |
Heart |
Kidneys |
Brain |
Liver |
PSC |
|
G1, M & 0 |
Mean |
0.0604 |
0.7514 |
0.6342 |
1.0064 |
3.1735 |
1.2125 |
2.2590 |
2.0835 |
10.5344 |
2.3816 |
±SD |
0.0119 |
0.1533 |
0.0738 |
0.0640 |
0.1397 |
0.0614 |
0.2240 |
0.1289 |
1.1741 |
0.3663 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 100 |
Mean |
0.0630 |
0.6919 |
0.6735 |
1.0010 |
2.9228 |
1.1877 |
2.5969 |
2.1525 |
10.8162 |
2.2128 |
±SD |
0.0065 |
0.1076 |
0.0667 |
0.0443 |
0.1672 |
0.0647 |
0.2891 |
0.1217 |
0.9876 |
0.2863 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 300 |
Mean |
0.0572 |
0.6269 |
0.5922 |
1.0242 |
3.1694 |
1.1864 |
2.3507 |
2.0956 |
10.3840 |
2.3975 |
±SD |
0.0049 |
0.0664 |
0.1458 |
0.0415 |
0.2142 |
0.1443 |
0.2566 |
0.1243 |
1.4737 |
0.1569 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
0.0605 |
0.5860 |
0.5928 |
1.0397 |
3.1413 |
1.2067 |
2.2968 |
2.0724 |
9.4292 |
2.2865 |
±SD |
0.0077 |
0.1830 |
0.1249 |
0.1030 |
0.3287 |
0.1716 |
0.1797 |
0.0997 |
0.7478 |
0.2833 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
TABLE 13 (Contd..,). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight) |
|
Adrenals |
Thymus |
Spleen |
Uterus |
Ovaries |
Heart |
Kidneys |
Brain |
Liver |
G1, F & 0 |
Mean |
0.0648 |
0.5093 |
0.4214 |
0.5513 |
0.1470 |
0.8857 |
1.9527 |
2.0259 |
7.4806 |
±SD |
0.0078 |
0.1181 |
0.0275 |
0.1162 |
0.0144 |
0.0824 |
0.1765 |
0.0857 |
0.7090 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 100 |
Mean |
0.0703 |
0.3810 |
0.5137 |
0.6402 |
0.1526 |
0.9369 |
1.7481 |
1.9522 |
7.5152 |
±SD |
0.0115 |
0.0378 |
0.0586 |
0.2055 |
0.0172 |
0.1019 |
0.1312 |
0.0413 |
0.5203 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 300 |
Mean |
0.0705 |
0.4218 |
0.4418 |
0.4521 |
0.1531 |
0.9352 |
1.9264 |
1.9350 |
7.3831 |
±SD |
0.0094 |
0.0893 |
0.0454 |
0.0523 |
0.0225 |
0.0600 |
0.1232 |
0.0525 |
0.3699 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
0.0708 |
0.4073 |
0.4270 |
0.4558 |
0.1571 |
0.8627 |
1.7695 |
1.9476 |
7.4482 |
±SD |
0.0061 |
0.0781 |
0.0400 |
0.1060 |
0.0151 |
0.1085 |
0.1630 |
0.1456 |
0.6254 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
TABLE 13 (Contd..,). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight) |
Adrenals |
Thymus |
Spleen |
Epididymes |
Testes |
Heart |
Kidneys |
Brain |
Liver |
PSC |
|
G1R, M & 0 |
Mean |
0.0647 |
0.5413 |
0.6230 |
1.2683 |
3.2340 |
1.2561 |
2.3803 |
2.1835 |
10.7767 |
2.4993 |
±SD |
0.0082 |
0.0443 |
0.0542 |
0.0911 |
0.2266 |
0.0549 |
0.1389 |
0.1071 |
0.9928 |
0.2145 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.0624 |
0.5626 |
0.6442 |
1.3105 |
3.1893 |
1.2834 |
2.5415 |
2.2298 |
11.2594 |
2.9348 |
±SD |
0.0039 |
0.0494 |
0.0530 |
0.0328 |
0.1477 |
0.0958 |
0.1937 |
0.1037 |
1.8236 |
0.4075 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
TABLE 13 (Contd..,). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight) |
Adrenals |
Thymus |
Spleen |
Uterus |
Ovaries |
Heart |
Kidneys |
Brain |
Liver |
|
G1R, F & 0 |
Mean |
0.0709 |
0.6198 |
0.5040 |
0.5658 |
0.1688 |
1.0534 |
1.8789 |
2.0390 |
9.0836 |
±SD |
0.0059 |
0.0445 |
0.0623 |
0.0621 |
0.0205 |
0.0846 |
0.0549 |
0.0810 |
0.7625 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
0.0722 |
0.5087 |
0.4635 |
0.5721 |
0.1695 |
1.0817 |
1.6534 |
2.0396 |
8.3174 |
±SD |
0.0036 |
0.0983 |
0.0519 |
0.0801 |
0.0085 |
0.1088 |
0.1034 |
0.0974 |
0.5321 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
TABLE 15. SUMMARY OF GROSS PATHOLOGY 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 |
|
TABLE 16. SUMMARY OF HISTOPATHOLOGY RECORD
Group No. |
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 |
||||
KIDNEYS |
|
|
|
|
Dilation, renal pelvis, bilateral |
1 |
0 |
0 |
0 |
THYMUS |
|
|
|
|
Hemorrhage |
1 |
0 |
1 |
0 |
LUNGS |
|
|
|
|
Alveolar macrophages |
0 |
0 |
1 |
0 |
Hemorrhage |
0 |
0 |
0 |
1 |
THYROID |
|
|
|
|
Ultimobranchial cyst |
0 |
1 |
0 |
0 |
Ectopic thymus |
0 |
0 |
0 |
2 |
RECTUM |
|
|
|
|
Parasite |
1 |
0 |
0 |
0 |
MANDIBULAR LYMPH NODES |
|
|
|
|
Sinus dilatation |
0 |
1 |
0 |
0 |
UTERUS |
X |
|
X |
|
Dilated lumen |
|
1 |
|
0 |
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
- Quality of whole database:
- One recently performed guideline study
Additional information
Justification for classification or non-classification
The repeated dose toxicity of the registration substance was investigated according to the Guideline OECD 407. Rats were treated via gavage for 28 -days. No effects was found up to the highest dose of 1000 mg/kg/bw. No specific organ toxicity was found. No classification is justified.
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