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EC number: 235-462-4 | CAS number: 12236-62-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 May 2021 to 29 November 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- 28-day (Sub-acute) inhalation toxicity study” adopted on 25 June 2018.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Version / remarks:
- 28-day (Sub-acute) inhalation toxicity study” adopted on 25 June 2018.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 2-[(4-chloro-2-nitrophenyl)azo]-N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-oxobutyramide
- EC Number:
- 235-462-4
- EC Name:
- 2-[(4-chloro-2-nitrophenyl)azo]-N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-oxobutyramide
- Cas Number:
- 12236-62-3
- Molecular formula:
- C17H13ClN6O5
- IUPAC Name:
- 2-[(4-chloro-2-nitrophenyl)diazenyl]-3-oxo-N-(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)butanamide
- Test material form:
- solid: nanoform
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Rat is the preferred laboratory rodent species for inhalation toxicity assessment and is also recommended by various regulatory guidelines.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: In-House
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7 - 8 weeks on the day of randomization
- Weight at study initiation: Males: 140.14 g to 153.11 g
Females: 120.06 g to 137.46 g
- Fasting period before study: No
- Housing: Maximum of three animals
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum):yes
- Acclimation period:7 days
DETAILS OF FOOD AND WATER QUALITY:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0°C to 22.7°C
- Humidity (%): 46% to 65%
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle
IN-LIFE DATES: From: To: 17 May 2021 to 16 August 2021
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- clean air
- Mass median aerodynamic diameter (MMAD):
- >= 1 - < 2 µm
- Geometric standard deviation (GSD):
- 3
- Remarks on MMAD:
- 1.82 to 1.97
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation exposure was conducted using a flow-past, nose-only dynamic inhalation exposure system (Refer Annexure 5) supplied by CH Technologies, USA, with a provision of at least 12 air changes per hour.
- Method of holding animals in test chamber: restraining tubes
- Source and rate of air: Compressor air and 20 L/min
- Method of conditioning air: Filtered air
- System of generating particulates/aerosols: The Rotating Brush Generator (Palas RBG 1000 - supplied by Palas GmbH) was used to generate the dust particles (aerosols) into an airborne state.
- Temperature, humidity, pressure in air chamber: 23.2, 57.6, 60psi
- Air flow rate: 20 L/min
- Air change rate: 12 air cahnges per hour
- Method of particle size determination: gravimetric
- Treatment of exhaust air: NaoH
TEST ATMOSPHERE
- Samples taken from breathing zone: yes
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 6 Hours
- Frequency of treatment:
- Weekly 5 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.003 mg/L air
- Remarks:
- Low dose
- Dose / conc.:
- 0.01 mg/L air
- Remarks:
- Mid dose
- Dose / conc.:
- 0.03 mg/L air
- Remarks:
- High dose
- No. of animals per sex per dose:
- 5 males + 5 females
- Details on study design:
- - Dose selection rationale: Inhalation is one of the most possible routes of exposure to human. Primarily used to derive regulatory concentrations for assessing worker risk in occupational settings, also used to identify and assess human residential, consumer, transportation, and environmental risk.
- Rationale for selecting satellite groups: persistence of toxic effects.
- Post-exposure recovery period in satellite groups: Following the 28 days exposure period, the animals in the recovery groups (G1R and G4R) were not be given any treatment and was maintained for 56 days post treatment period and observed for reversibility or persistence of toxic effects.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes / No / Not specified
- Time schedule: twice daily
- Cage side observations checked in table [yes] were included.
Table 1
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly once
BODY WEIGHT: Yes
- Time schedule for examinations: weekly once
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: before exposure and week 4 and week 12
- Dose groups that were examined: control and high dose
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 27 and 85
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: 60
- Parameters checked in table [yes] were examined.
table 10
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 27 and 85
- Animals fasted: Yes
- How many animals: 60
- Parameters checked in table [yes] were examined.
Table 12
URINALYSIS: Yes
- Time schedule for collection of urine: 27
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [yes] were examined.
Table 13
NEUROBEHAVIOURAL EXAMINATION: Yes / No / Not specified
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:
IMMUNOLOGY: Yes
- Time schedule for examinations: week 4 and 12
- How many animals: 40
- Dose groups that were examined: control and high dose
- Parameters checked in table [yes] were examined.
Tables 5, 6, 7 & 8
OTHER:
BALF Fluid
Table 11 - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- The raw data were subjected to statistical analysis. The computer printout of the data (in the form of the appendix) was verified with the original raw data. After verification, the data were subjected to statistical analysis using SPSS Software version 22. Body weight, percent change in body weight with respect to Day 1, feed consumption, FOB, organ weight ratios, hematology, and clinical chemistry estimations, urine volume, pH, and specific gravity 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. All analyses and comparisons were evaluated at the 95% level of confidence (P<0.05). Statistically significant changes obtained from the aforementioned tests were designated by the superscripts in the summary table throughout the study report, as stated below:
*: Statistically significant (p<0.05).
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All animals survived to scheduled sacrifice, and there were no clinical signs attributable to the test item. Post-exposure, all animals were normal throughout the experimental period. No clinical signs were noted during the recovery period.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No statistically significant treatment-related variations were observed in all the tested dose groups when compared with control group.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- No statistically significant treatment-related variations were observed in all the tested dose groups when compared with control group.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No ocular abnormalities were observed during ophthalmoscopic examination
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No toxicologically significant treatment related changes in haematology parameters were noted. However, the following statistically significant variations were noted.
In main group males, increase in RBC, haematocrit, MPV, PT in G4 and decrease in MCHC in G3 was noted. In females increase in APTT in G4 was noted.
In recovery males, decrease absolute and relative reticulocyte count (G4R) was noted. In recovery females decrease in percent lymphocytes, absolute and relative reticulocyte count and increase in percent neutrophils (G4R) was noted.
All the noted variations in main group are considered incidental in the absence of dose responsiveness. Further, in the absence of any microscopic variations in the marrow (sternum with marrow), the noted changes are not considered to be adverse. Variations noted at the end of recovery period are considered incidental as similar changes were not noted at the end of treatment period. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No toxicologically significant changes were observed in clinical chemistry parameters when compared to the control group. However, the following statistically significant variations were noted.
In main group males, increase in AST and calcium in G3 group and sodium in G4 was noted; in females increase in glucose, urea and BUN in G4 group was noted.
In recovery group females, increase in potassium (G4R) was noted.
The variations noted are considered incidental due to lack of dose responsiveness and/or could be due to random biological variation. - Urinalysis findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No significant changes were observed in main group and recovery when compared with control group.
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no adverse effects during neurological/functional examinations in main group (G1 and G4) and recovery group (G1R and G4R). However statistically significant decrease in rearing in G4 males, increase in movement counts in G4R females was noted. The noted variations are considered incidental in the absence of any changes in other neurological parameters. Also, all the animals were normal during the experimental period.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The following statistically significant variations were noted in organ weights and its ratios.
Absolute and relative to fasting body weight
In main group females, decrease in absolute and relative weight of liver (G4), thymus (G2 and G4) was noted.
In recovery group females, decrease in absolute weight of spleen, uterus and relative weight of spleen, uterus (G4R) was noted.
Organ weight changes (relative to brain weight)
In main group females, decrease in relative weight of liver (G4) and thymus (G2 and G4) was noted; in males increase in relative weight of testis (G4M) was noted.
In recovery group females, decrease in relative weight of spleen and uterus (G4R) was noted.
All the observed changes are considered incidental in the absence of any associated gross and histopathological changes in the high dose main group animals. - Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no gross pathological findings in the study.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Microscopically, test item-related changes were observed in lungs and are summarized as below.
Sex Males
Group G1 G2 G3 G4 G1R G4R
Number of Animals Examined 5 5 5 5 5 5
Lungs
Pigment, golden brown - 5 5 5 - 5
Sex Females
Group G1 G2 G3 G4 G1R G4R
Number of Animals Examined 5 5 5 5 5 5
Lungs
Pigment, golden brown - 5 5 5 - 5
In lungs, minimal to moderate, multifocal, variably sized, pigmented (golden brown) granular material was observed throughout the parenchyma of lung at low, mid, high and high dose recovery groups of rats. This pigment was distributed both in alveolar and bronchiolar spaces with no accompanying inflammation or tissue destruction to the lung parenchyma. This pigment was suggestive of inhaled test item particles. In the absence of cellular changes to lung parenchyma, mere presence of pigment in lungs could be considered as non-adverse effect up to the nominal target dose level of 0.03 mg/L. (Nikula KJ et.al., 2014).
Few microscopic findings observed in this study such as cyst/s in kidneys, dilatation of uterus and all other findings were considered incidental as they occurred randomly across the dose groups including concurrent controls and/or were expected for laboratory rats. - Histopathological findings: neoplastic:
- effects observed, non-treatment-related
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 13.6.2 BALF Fluid
The bronchio-alveolar lavage fluid measured at termination revealed the following statistically significant changes:
In main group females, decrease in percent lymphocytes and increase in percent neutrophils in G4 group was noted; increase in WBC and absolute lymphocytes in G3 group was noted.
In recovery group, males increase in LDH and decrease in percent basophils (G4R) was noted. The basophils (%) in recovery males appear decreased because of higher values in the control recovery group and hence the significance noted is of no toxicological relevance. Increase in LDH in recovery males is because of higher value in one animal, and hence considered incidental.
Few variations in differential counts could be secondary to accumulation of test item in the lungs. All other changes are considered incidental as they lack dose responsiveness and/or were noted in only one sex. - Details on results:
- Based on the observed results, it is concluded that the No Observed Adverse Effect Concentration (NOAEC) of test item was found to be 0.03 mg/L when exposed for 6 hours/day, 5 days/week, for 4 weeks by flow-past nose-only inhalation route to Sprague Dawley rats. The nominal dose of 0.03 mg/L (6 hrs/day, 5 days/week) is the actual exposure concentration in males and females.
Effect levels
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- > 30 mg/m³ air
- 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
- mortality
- organ weights and organ / body weight ratios
- serum/plasma biochemistry
- urinalysis
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
TABLE 1. SUMMARY OF CLINICAL SIGNS AND MORTALITY RECORD
Refer Appendix 1
Group, Sex & Dose (mg/L) |
No. of Animals |
Clinical Signs of Toxicity |
Mortality (No. of Incidences/ No. of Animals) |
G1, M & 0 |
5 |
N |
0/5 |
G2, M & 0.003 |
5 |
N |
0/5 |
G3, M & 0.01 |
5 |
N |
0/5 |
G4, M & 0.03 |
5 |
N |
0/5 |
G1R, M & 0 |
5 |
N |
0/5 |
G4R, M & 0.03 |
5 |
N |
0/5 |
M: Male; N: None; R: Recovery.
TABLE 1 (Contd…). SUMMARY OF CLINICAL SIGNS AND MORTALITY RECORD
Refer Appendix 1
Group, Sex & Dose (mg/L) |
No. of Animals |
Clinical Signs of Toxicity |
Mortality (No. of Incidence/ No. of Animals) |
G1, F & 0 |
5 |
N |
0/5 |
G2, F & 0.003 |
5 |
N |
0/5 |
G3, F & 0.01 |
5 |
N |
0/5 |
G4, F & 0.03 |
5 |
N |
0/5 |
G1R, F & 0 |
5 |
N |
0/5 |
G4R, F & 0.03 |
5 |
N |
0/5 |
F: Female; N: None; R: Recovery.
TABLE 2. SUMMARY OF BODY WEIGHTS (g)RECORD
Refer Appendix 2
Group, Sex & Dose (mg/L) |
Body Weight (g) on Days |
||||||||
1 |
5 |
8 |
12 |
15 |
22 |
26 |
|||
G1, M & 0 |
Mean |
166.51 |
171.75 |
178.32 |
185.81 |
197.59 |
214.19 |
225.14 |
|
±SD |
9.48 |
10.36 |
10.11 |
10.38 |
12.00 |
12.39 |
13.10 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 0.003 |
Mean |
170.65 |
174.98 |
180.83 |
188.27 |
204.29 |
219.31 |
229.19 |
|
±SD |
14.03 |
13.78 |
13.91 |
13.41 |
13.53 |
13.31 |
11.58 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 0.01 |
Mean |
163.66 |
168.12 |
174.43 |
181.48 |
198.20 |
213.03 |
224.77 |
|
±SD |
9.42 |
9.17 |
9.25 |
9.10 |
10.10 |
9.87 |
9.39 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 0.03 |
Mean |
163.99 |
168.87 |
175.43 |
182.93 |
198.64 |
214.21 |
225.74 |
|
±SD |
9.27 |
9.25 |
8.92 |
8.36 |
8.87 |
8.00 |
8.84 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1, F & 0 |
Mean |
148.51 |
152.03 |
155.66 |
160.28 |
172.22 |
183.16 |
191.20 |
|
±SD |
11.18 |
11.98 |
11.73 |
11.04 |
11.11 |
10.71 |
11.54 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 0.003 |
Mean |
150.58 |
154.23 |
158.35 |
163.93 |
177.05 |
187.21 |
195.08 |
|
±SD |
9.04 |
8.92 |
8.43 |
8.83 |
8.94 |
8.94 |
9.12 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 0.01 |
Mean |
147.71 |
151.43 |
155.06 |
160.47 |
173.49 |
182.83 |
191.88 |
|
±SD |
9.33 |
9.83 |
9.54 |
9.60 |
9.58 |
9.25 |
9.64 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 0.03 |
Mean |
147.30 |
150.33 |
154.63 |
159.60 |
172.10 |
182.59 |
191.08 |
|
±SD |
8.92 |
9.02 |
9.36 |
8.45 |
6.81 |
6.49 |
6.69 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; SD: Standard Deviation; n: Number of animals
TABLE 2 (Contd...). SUMMARY OF BODY WEIGHTS (g) RECORD
Refer Appendix 2
Group, Sex & Dose (mg/L) |
Body Weight (g) on Days |
|||||||||||||||
1 |
5 |
8 |
12 |
15 |
22 |
29 |
36 |
43 |
50 |
57 |
64 |
71 |
78 |
84 |
||
G1R, M & 0 |
Mean |
166.20 |
171.02 |
177.66 |
185.62 |
200.07 |
214.49 |
232.63 |
253.26 |
274.79 |
299.32 |
325.27 |
349.03 |
372.79 |
397.94 |
413.98 |
±SD |
11.24 |
11.18 |
10.45 |
10.60 |
12.29 |
11.09 |
10.88 |
10.72 |
10.05 |
10.33 |
9.74 |
8.98 |
8.83 |
7.95 |
5.30 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
164.61 |
169.11 |
175.81 |
183.14 |
199.36 |
215.18 |
234.98 |
256.10 |
278.55 |
303.45 |
328.88 |
353.30 |
374.05 |
398.71 |
415.74 |
±SD |
5.82 |
6.41 |
6.91 |
6.52 |
8.72 |
7.25 |
7.24 |
8.04 |
7.24 |
7.94 |
8.28 |
7.95 |
4.25 |
4.86 |
3.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
148.78 |
151.72 |
155.52 |
160.51 |
173.51 |
184.31 |
198.22 |
210.64 |
225.19 |
239.40 |
255.46 |
270.87 |
285.04 |
301.89 |
317.03 |
±SD |
6.32 |
5.93 |
5.77 |
5.65 |
6.78 |
6.41 |
6.86 |
8.13 |
7.78 |
7.89 |
7.61 |
8.09 |
9.30 |
8.70 |
8.48 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
146.83 |
150.42 |
154.40 |
158.83 |
170.78 |
181.28 |
196.23 |
210.43 |
224.38 |
239.40 |
255.44 |
270.86 |
283.41 |
300.91 |
314.61 |
±SD |
5.66 |
5.28 |
5.62 |
5.57 |
5.71 |
4.93 |
4.84 |
5.04 |
5.63 |
4.95 |
4.82 |
4.24 |
7.37 |
7.36 |
5.82 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; -: Not applicable; SD: Standard Deviation; n: Number of animals
TABLE 3. SUMMARY OF PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1RECORD
Refer Appendix 3
Group, Sex & Dose (mg/L) |
Percent Change in Body Weight (%) during Days |
|||||||||||||||
1 to 5 |
1 to 8 |
1 to 12 |
1 to 15 |
1 to 22 |
1 to 26 |
|||||||||||
G1, M & 0 |
Mean |
3.13 |
7.09 |
11.59 |
18.65 |
28.64 |
35.21 |
|||||||||
±SD |
0.42 |
0.29 |
0.62 |
1.61 |
1.60 |
1.89 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, M & 0.003 |
Mean |
2.56 |
6.00 |
10.41 |
19.85 |
28.72 |
34.60 |
|||||||||
±SD |
0.57 |
0.62 |
1.30 |
2.90 |
3.74 |
4.82 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, M & 0.01 |
Mean |
2.74 |
6.61 |
10.93 |
21.15 |
30.24 |
37.45 |
|||||||||
±SD |
0.74 |
0.86 |
1.34 |
1.71 |
2.10 |
2.63 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, M & 0.03 |
Mean |
2.98 |
7.00 |
11.60 |
21.19 |
30.73 |
37.77 |
|||||||||
±SD |
0.25 |
0.90 |
1.19 |
1.65 |
2.41 |
3.00 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1, F & 0 |
Mean |
2.35 |
4.81 |
7.96 |
16.04 |
23.45 |
28.86 |
|||||||||
±SD |
0.73 |
0.44 |
0.97 |
1.64 |
2.43 |
2.48 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, F & 0.003 |
Mean |
2.44 |
5.19 |
8.90 |
17.64 |
24.40 |
29.64 |
|||||||||
±SD |
0.57 |
0.96 |
0.74 |
1.44 |
1.75 |
1.82 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, F & 0.01 |
Mean |
2.51 |
4.99 |
8.66 |
17.51 |
23.86 |
29.99 |
|||||||||
±SD |
0.84 |
0.80 |
0.54 |
1.62 |
1.82 |
1.86 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, F & 0.03 |
Mean |
2.06 |
4.98 |
8.39 |
16.96 |
24.11 |
29.88 |
|||||||||
±SD |
0.24 |
0.39 |
1.16 |
2.98 |
3.66 |
3.41 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; 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/L) |
Percent Change in Body Weight (%) during Days |
||||||||||||||||||||||||||||||
1 to 5 |
1 to 8 |
1 to 12 |
1 to 15 |
1 to 22 |
1 to 29 |
1 to 36 |
1 to 43 |
1 to 50 |
1 to 57 |
1 to 64 |
1 to 71 |
1 to 78 |
1 to 84 |
||||||||||||||||||
G1R, M & 0 |
Mean |
2.91 |
6.95 |
11.75 |
20.43 |
29.17 |
40.12 |
52.59 |
65.61 |
80.42 |
96.11 |
110.48 |
124.83 |
140.04 |
149.84 |
||||||||||||||||
±SD |
0.67 |
1.58 |
1.96 |
1.83 |
2.75 |
3.14 |
4.02 |
5.24 |
6.27 |
7.78 |
8.81 |
10.07 |
11.39 |
14.09 |
|||||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||||||
G4R, M & 0.03 |
Mean |
2.72 |
6.79 |
11.26 |
21.08 |
30.74 |
42.77 |
55.60 |
69.26 |
84.40 |
99.85 |
114.71 |
127.39 |
142.38 |
152.75 |
||||||||||||||||
±SD |
0.52 |
0.60 |
0.54 |
1.10 |
1.63 |
1.00 |
1.14 |
1.90 |
2.29 |
2.19 |
2.89 |
5.59 |
5.82 |
6.84 |
|||||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||||||
G1R, F & 0 |
Mean |
1.99 |
4.55 |
7.91 |
16.63 |
23.91 |
33.27 |
41.61 |
51.41 |
60.97 |
71.80 |
82.16 |
91.70 |
103.06 |
113.25 |
||||||||||||||||
±SD |
0.66 |
0.67 |
1.07 |
0.62 |
1.05 |
1.18 |
1.88 |
2.74 |
2.57 |
3.42 |
3.53 |
5.57 |
6.21 |
6.31 |
|||||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||||||
G4R, F & 0.03 |
Mean |
2.45 |
5.16 |
8.18 |
16.34 |
23.52 |
33.72 |
43.39 |
52.91 |
63.15 |
74.09 |
84.61 |
93.13 |
105.07 |
114.44 |
||||||||||||||||
±SD |
0.52 |
0.95 |
0.96 |
2.29 |
2.66 |
3.11 |
3.00 |
3.85 |
3.92 |
4.45 |
4.61 |
5.07 |
5.26 |
6.20 |
|||||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of animal
TABLE 4. SUMMARY OF AVERAGE FEED CONSUMPTION (g/rat/day)RECORD
Refer Appendix 4
Group, Sex & Dose (mg/L) |
Week 1 |
Week 2 |
Week 3 |
Week 4 |
|
G1, M & 0 |
Mean |
18.67 |
18.63 |
18.49 |
28.45 |
±SD |
2.73 |
2.83 |
2.81 |
3.70 |
|
n |
2 |
2 |
2 |
2 |
|
G2, M & 0.003 |
Mean |
18.61 |
18.66 |
18.53 |
28.03 |
±SD |
3.03 |
2.77 |
2.62 |
3.35 |
|
n |
2 |
2 |
2 |
2 |
|
G3, M & 0.01 |
Mean |
18.78 |
18.78 |
18.54 |
28.01 |
±SD |
3.04 |
2.87 |
2.77 |
3.54 |
|
n |
2 |
2 |
2 |
2 |
|
G4, M & 0.03 |
Mean |
18.53 |
18.76 |
18.56 |
28.05 |
±SD |
2.85 |
3.06 |
3.00 |
3.38 |
|
n |
2 |
2 |
2 |
2 |
|
G1, F & 0 |
Mean |
14.63 |
14.73 |
14.61 |
21.69 |
±SD |
1.59 |
1.62 |
1.48 |
1.31 |
|
n |
2 |
2 |
2 |
2 |
|
G2, F & 0.003 |
Mean |
14.65 |
14.80 |
14.64 |
21.44 |
±SD |
1.41 |
1.46 |
1.40 |
1.43 |
|
n |
2 |
2 |
2 |
2 |
|
G3, F & 0.01 |
Mean |
14.55 |
14.80 |
14.68 |
20.95 |
±SD |
1.40 |
1.41 |
1.48 |
1.22 |
|
n |
2 |
2 |
2 |
2 |
|
G4, F & 0.03 |
Mean |
14.49 |
14.66 |
14.53 |
20.60 |
±SD |
1.37 |
1.38 |
1.43 |
1.13 |
|
n |
2 |
2 |
2 |
2 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: number of cages.
TABLE 4 (Contd...). SUMMARY OF AVERAGE FEED CONSUMPTION (g/rat/day) RECORD
Refer Appendix 4
Group, Sex & Dose (mg/L) |
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
Week 7 |
Week 8 |
Week 9 |
Week 10 |
Week 11 |
Week 12 |
|
G1R, M & 0 |
Mean |
18.68 |
18.77 |
18.50 |
18.66 |
18.72 |
18.78 |
18.92 |
19.23 |
19.43 |
19.62 |
19.84 |
23.11 |
±SD |
3.04 |
3.04 |
2.90 |
2.93 |
3.02 |
3.02 |
3.00 |
3.27 |
3.32 |
3.32 |
3.44 |
4.06 |
|
n |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
G4R, M & 0.03 |
Mean |
18.69 |
18.76 |
18.59 |
18.72 |
18.73 |
18.80 |
18.96 |
19.35 |
19.41 |
19.59 |
19.76 |
23.06 |
±SD |
2.60 |
2.87 |
2.78 |
2.91 |
3.06 |
3.03 |
2.98 |
3.21 |
3.25 |
3.37 |
3.40 |
4.08 |
|
n |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
G1R, F & 0 |
Mean |
14.53 |
14.76 |
14.64 |
14.85 |
14.99 |
14.99 |
15.18 |
15.56 |
15.67 |
15.83 |
16.03 |
18.64 |
±SD |
1.39 |
1.47 |
1.34 |
1.74 |
1.77 |
1.68 |
1.78 |
1.90 |
1.91 |
1.91 |
2.12 |
2.44 |
|
n |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
G4R, F & 0.03 |
Mean |
14.38 |
14.61 |
14.59 |
14.85 |
14.94 |
14.96 |
15.21 |
15.41 |
15.59 |
15.74 |
15.87 |
18.39 |
±SD |
1.31 |
1.38 |
1.25 |
1.52 |
1.58 |
1.52 |
1.60 |
1.59 |
1.65 |
1.76 |
1.71 |
2.03 |
|
n |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: number of cages.
TABLE 5. SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Refer Appendix 5
Week 4 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G4 & M |
G1 & F |
G4 & F |
|
Dose (mg/L) |
0 |
0.03 |
0 |
0.03 |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Home cage observations |
||||||
Home Cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral Closure |
1 |
1 |
1 |
1 |
||
Handling observation |
|
|
||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur Appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye Prominence |
1 |
1 |
1 |
1 |
||
Muscle Tone |
1 |
1 |
1 |
1 |
||
Home cage observations: Home cage posture- 1=Normal,Respiratory Pattern -1=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Vocalization -1=Absent (Normal),Palpebral closure -1=Eyelids wide open (Normal),Handling observation : Ease of removal from the cage -2=Normal,Ease of handling animal in hand -2=Normal,Red/Crusty deposits -1=Absent,Lacrimation- 1=None,Salivation-1=Absent (Normal),Fur Appearance -1=Normal,Piloerection -1=None, Eye Prominence -1=Normal,Muscle tone -1=Normal |
||||||
M: Male; F: Female
TABLE 5 (Contd...). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Refer Appendix 5
Week 4 |
|||||
Parameters↓ |
Group & Sex |
G1 & M |
G4 & M |
G1 & F |
G4 & F |
Dose (mg/L) |
0 |
0.03 |
0 |
0.03 |
|
Number of Animals |
5 |
5 |
5 |
5 |
|
Open field Observation |
|||||
Mobility |
1 |
1 |
1 |
1 |
|
Gait |
1 |
1 |
1 |
1 |
|
Arousal |
3 |
3 |
3 |
3 |
|
Number of Rearing |
Mean |
8.0 |
5.4* |
8.8 |
8.6 |
±SD |
1.0 |
1.7 |
1.1 |
1.1 |
|
Numbers of Urination |
Mean |
1.2 |
1.2 |
1.4 |
1.4 |
±SD |
0.4 |
0.4 |
0.5 |
0.9 |
|
Number of Defecation |
Mean |
0.8 |
0.8 |
0.8 |
1.2 |
±SD |
0.4 |
0.4 |
0.4 |
0.8 |
|
Clonic involuntary movement |
1 |
1 |
1 |
1 |
|
Tonic involuntary movement |
1 |
1 |
1 |
1 |
|
Stereotype Behaviour |
1 |
1 |
1 |
1 |
|
Excessive Grooming |
Mean |
4.8 |
5.4 |
5.2 |
7.2 |
±SD |
0.8 |
1.1 |
0.8 |
1.8 |
|
Sensory Observations |
|
||||
Approach Response |
2 |
2 |
2 |
2 |
|
Auditory Response |
2 |
2 |
2 |
2 |
|
Touch Response |
2 |
2 |
2 |
2 |
|
Pupil Reflex |
2 |
2 |
2 |
2 |
|
Tail Pinch Response |
2 |
2 |
2 |
2 |
|
Righting Reflex |
1 |
1 |
1 |
1 |
|
Physiological observation |
|
||||
Body temperature (°F) |
Mean |
96.7 |
97.1 |
98.5 |
98.5 |
±SD |
0.8 |
1.1 |
0.1 |
0.1 |
|
Open field Observation: Mobility -1=Normal,Gait -1=Normal,Arousal -3=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Stereotype Behaviour -1=Absent, Sensory Observations: Approach response -2=Normal, Auditory Response -2=Normal,Touch Response -2=Normal,Pupil Reflex -2=Normal,Tail Pinch Response -2=Normal,Righting Reflex -1=Present |
*: Statistically significant (p<0.05)
TABLE 5 (Contd...). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Refer Appendix 5
Week 12 |
||||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
G1R & F |
G4R & F |
|
Dose (mg/L) |
0 |
0.03 |
0 |
0.03 |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Home cage observations |
||||||
Home Cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral Closure |
1 |
1 |
1 |
1 |
||
Handling observation |
|
|
||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur Appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye Prominence |
1 |
1 |
1 |
1 |
||
Muscle Tone |
1 |
1 |
1 |
1 |
||
Home cage observations: Home cage posture- 1=Normal,Respiratory Pattern -1=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Vocalization -1=Absent (Normal),Palpebral closure -1=Eyelids wide open (Normal),Handling observation : Ease of removal from the cage -2=Normal,Ease of handling animal in hand -2=Normal,Red/Crusty deposits -1=Absent,Lacrimation- 1=None,Salivation-1=Absent (Normal),Fur Appearance -1=Normal,Piloerection -1=None, Eye Prominence -1=Normal,Muscle tone -1=Normal |
||||||
M: Male; F: Female; R: Recovery
TABLE 5 (Contd...). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Refer Appendix 5
Week 12 |
|||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
G1R & F |
G4R & F |
Dose (mg/L) |
0 |
0.03 |
0 |
0.03 |
|
Number of Animals |
5 |
5 |
5 |
5 |
|
Open field Observation |
|||||
Mobility |
1 |
1 |
1 |
1 |
|
Gait |
1 |
1 |
1 |
1 |
|
Arousal |
3 |
3 |
3 |
3 |
|
Number of Rearing |
Mean |
6.8 |
5.6 |
8.8 |
8.0 |
±SD |
1.5 |
1.3 |
0.8 |
2.0 |
|
Numbers of Urination |
Mean |
1.0 |
1.2 |
1.2 |
1.2 |
±SD |
0.0 |
0.4 |
0.4 |
0.4 |
|
Number of Defecation |
Mean |
1.0 |
1.2 |
1.0 |
1.2 |
±SD |
0.7 |
0.8 |
0.7 |
0.8 |
|
Clonic involuntary movement |
1 |
1 |
1 |
1 |
|
Tonic involuntary movement |
1 |
1 |
1 |
1 |
|
Stereotype Behaviour |
1 |
1 |
1 |
1 |
|
Excessive Grooming |
Mean |
5.0 |
5.0 |
5.6 |
5.8 |
±SD |
0.7 |
0.7 |
1.3 |
0.8 |
|
Sensory Observations |
|
||||
Approach Response |
2 |
2 |
2 |
2 |
|
Auditory Response |
2 |
2 |
2 |
2 |
|
Touch Response |
2 |
2 |
2 |
2 |
|
Pupil Reflex |
2 |
2 |
2 |
2 |
|
Tail Pinch Response |
2 |
2 |
2 |
2 |
|
Righting Reflex |
1 |
1 |
1 |
1 |
|
Physiological observation |
|
||||
Body temperature (°F) |
Mean |
96.9 |
96.6 |
98.4 |
98.6 |
±SD |
0.2 |
0.4 |
0.2 |
0.2 |
|
Open field Observation: Mobility -1=Normal,Gait -1=Normal,Arousal -3=Normal,Clonic involuntary movements -1=None/Normal,Tonic involuntary movements -1=None/Normal,Stereotype Behaviour -1=Absent, Sensory Observations: Approach response -2=Normal, Auditory Response -2=Normal,Touch Response -2=Normal,Pupil Reflex -2=Normal,Tail Pinch Response -2=Normal,Righting Reflex -1=Present |
M: Male; F: Female; R: Recovery
TABLE 6. SUMMARY OF HIND LIMB FOOT SPLAY (cm)RECORD
Refer Appendix 6
# Week 4 & 12 |
|||
Group, Sex & Dose (mg/L) |
Hind Limb Foot Splay (cm) |
||
G1, M & 0 |
Mean |
6.2 |
|
±SD |
0.5 |
||
n |
5 |
||
G4, M & 0.03 |
Mean |
6.1 |
|
±SD |
0.4 |
||
n |
5 |
||
G1, F & 0 |
Mean |
5.7 |
|
±SD |
0.5 |
||
n |
5 |
||
G4, F & 0.03 |
Mean |
5.6 |
|
±SD |
0.4 |
||
n |
5 |
||
G1R, M & 0 |
Mean |
8.7 |
|
±SD |
0.5 |
||
n |
5 |
||
G4R, M & 0.03 |
Mean |
8.1 |
|
±SD |
0.5 |
||
n |
5 |
||
G1R, F & 0 |
Mean |
5.5 |
|
±SD |
0.2 |
||
n |
5 |
||
G4R, F & 0.03 |
Mean |
5.5 |
|
±SD |
0.1 |
||
n |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: number of animals
# Week 4 for main group animals and week 12 for recovery group animals.
TABLE 7.SUMMARY OF ACTIMETER READING RECORD
Refer Appendix 7
# Week 4 & 12 |
||
Group, Sex & Dose (mg/L) |
Movement Counts (no.) |
|
G1, M & 0 |
Mean |
2171.8 |
±SD |
70.6 |
|
n |
5 |
|
G4, M & 0.03 |
Mean |
2202.0 |
±SD |
53.8 |
|
n |
5 |
|
G1, F & 0 |
Mean |
2407.8 |
±SD |
28.4 |
|
n |
5 |
|
G4, F & 0.03 |
Mean |
2395.8 |
±SD |
65.2 |
|
n |
5 |
|
G1R, M & 0 |
Mean |
2239.6 |
±SD |
33.0 |
|
n |
5 |
|
G4R, M & 0.03 |
Mean |
2260.8 |
±SD |
57.3 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
2341.8 |
±SD |
39.5 |
|
n |
5 |
|
G4R, F & 0.03 |
Mean |
2420.6* |
±SD |
35.9 |
|
n |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: number of animals;
# Week 4 for main group animals and week 12 for recovery group animals; *: Statistically significant (p<0.05).
TABLE 8. SUMMARY OF GRIP STRENGTH (kgf) MEASUREMENT RECORD
Refer Appendix 8
# Week 4 & 12 |
||||
Group, Sex & Dose (mg/L) |
Fore limb |
Hind limb |
||
G1, M & 0 |
Mean |
1.505 |
0.534 |
|
±SD |
0.051 |
0.087 |
||
n |
5 |
5 |
||
G4, M & 0.03 |
Mean |
1.486 |
0.472 |
|
±SD |
0.049 |
0.022 |
||
n |
5 |
5 |
||
G1, F & 0 |
Mean |
1.432 |
0.407 |
|
±SD |
0.039 |
0.048 |
||
n |
5 |
5 |
||
G4, F & 0.03 |
Mean |
1.410 |
0.375 |
|
±SD |
0.022 |
0.058 |
||
n |
5 |
5 |
||
G1R, M & 0 |
Mean |
1.507 |
0.533 |
|
±SD |
0.052 |
0.085 |
||
n |
5 |
5 |
||
G4R, M & 0.03 |
Mean |
1.489 |
0.478 |
|
±SD |
0.056 |
0.021 |
||
n |
5 |
5 |
||
G1R, F & 0 |
Mean |
1.432 |
0.407 |
|
±SD |
0.041 |
0.048 |
||
n |
5 |
5 |
||
G4R, F & 0.03 |
Mean |
1.416 |
0.381 |
|
±SD |
0.024 |
0.062 |
||
n |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: number of animals
# Week 4 for main group animals and week 12 for recovery group animals.
TABLE 9. SUMMARY OF OPHTHALMOSCOPIC EXAMINATION RECORD
Week 4 and 12 Refer Appendix 9
Week 4 |
Week 12 |
|||||||
Group, Sex & Dose (mg/L) |
G1, M & 0 |
G4, M & 0.03 |
G1R, M & 0 |
G4R, M & 0.03 |
||||
Number of Animals |
05 |
05 |
05 |
05 |
||||
Observations |
||||||||
Eye Parameters ↓ |
||||||||
Eye |
L |
R |
L |
R |
L |
R |
L |
R |
Eye Lids |
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/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
N |
|
N |
N |
N |
N |
N |
N |
N |
N |
|
N |
N |
N |
N |
N |
N |
N |
N |
|
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 4 and 12 Refer Appendix 9
Week 4 |
Week 12 |
|||||||
Group, Sex & Dose (mg/L) |
G1, F & 0 |
G4, F & 0.03 |
G1R, F & 0 |
G4R, F & 0.03 |
||||
Number of Animals |
05 |
05 |
05 |
05 |
||||
Observations |
||||||||
Eye Parameters ↓ |
||||||||
Eye |
L |
R |
L |
R |
L |
R |
L |
R |
Eye Lids |
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/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
N: No Abnormality Detected; L: Left; R: Right; F: Female.
TABLE 10. SUMMARY OF HAEMATOLOGY RECORD
Refer Appendix 10
Group, Sex & Dose (mg/L) |
Total Leucocyte Count |
Total Erythrocyte Count |
Hemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Hemoglobin |
Mean Corpuscular Hemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, M & 0 |
Mean |
7.63 |
7.81 |
15.52 |
44.20 |
56.60 |
19.94 |
35.26 |
759.00 |
6.18 |
±SD |
2.12 |
0.60 |
0.98 |
3.50 |
0.52 |
1.32 |
2.33 |
344.07 |
0.48 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.003 |
Mean |
9.19 |
8.42 |
15.68 |
46.98 |
55.86 |
18.66 |
33.40 |
1063.80 |
6.14 |
±SD |
2.75 |
0.57 |
0.69 |
1.92 |
1.81 |
0.85 |
0.61 |
178.32 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.01 |
Mean |
9.38 |
8.17 |
15.58 |
47.12 |
57.68 |
19.06 |
33.06* |
1081.40 |
6.44 |
±SD |
3.42 |
0.34 |
1.16 |
3.13 |
1.71 |
0.78 |
0.48 |
214.16 |
0.36 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
8.11 |
8.92* |
16.50 |
49.08* |
55.04 |
18.52 |
33.64 |
1039.80 |
6.80* |
±SD |
0.95 |
0.66 |
1.00 |
2.92 |
1.46 |
0.64 |
0.39 |
149.35 |
0.40 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
9.48 |
9.58 |
16.80 |
51.10 |
53.34 |
17.54 |
32.86 |
783.60 |
6.42 |
±SD |
1.23 |
0.14 |
0.52 |
1.08 |
0.70 |
0.44 |
0.43 |
122.98 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
10.11 |
9.07 |
16.88 |
48.48 |
53.58 |
18.76 |
34.96 |
930.60 |
6.38 |
±SD |
1.65 |
0.86 |
0.15 |
3.15 |
1.88 |
1.94 |
2.50 |
172.00 |
0.33 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: number of animals; *: Statistically significant (p<0.05).
TABLE 10 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Refer Appendix 10
Group, Sex & Dose (mg/L) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
Absolute Reticulocyte Count |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(Retic) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
(109cells/L) |
||
G1, M & 0 |
Mean |
2.94 |
23.88 |
70.18 |
3.50 |
1.16 |
0.32 |
229.14 |
±SD |
0.85 |
6.93 |
6.12 |
0.89 |
0.33 |
0.08 |
68.43 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.003 |
Mean |
2.63 |
18.86 |
76.02 |
3.10 |
0.82 |
0.34 |
221.26 |
±SD |
0.96 |
2.70 |
2.61 |
0.92 |
0.11 |
0.09 |
76.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.01 |
Mean |
2.77 |
23.30 |
71.54 |
2.48 |
1.30 |
0.38 |
225.82 |
±SD |
0.70 |
3.45 |
2.77 |
0.82 |
0.81 |
0.11 |
54.77 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
2.49 |
23.78 |
71.38 |
2.70 |
1.00 |
0.36 |
217.74 |
±SD |
0.95 |
7.63 |
8.14 |
0.83 |
0.34 |
0.11 |
67.75 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
1.81 |
25.66 |
69.22 |
2.68 |
1.32 |
0.54 |
173.32 |
±SD |
0.22 |
7.18 |
7.42 |
0.83 |
0.40 |
0.24 |
21.10 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
1.43* |
26.90 |
68.00 |
2.80 |
1.08 |
0.46 |
129.64* |
±SD |
0.11 |
2.90 |
3.09 |
0.88 |
0.29 |
0.11 |
18.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 10 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Refer Appendix 10
Group, Sex & Dose (mg/L) |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
|
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, M & 0 |
Mean |
1.82 |
5.35 |
0.27 |
0.09 |
0.02 |
14.42 |
16.94 |
±SD |
0.78 |
1.55 |
0.11 |
0.04 |
0.01 |
0.68 |
3.96 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.003 |
Mean |
1.78 |
6.94 |
0.28 |
0.07 |
0.03 |
15.82 |
19.02 |
±SD |
0.72 |
1.90 |
0.11 |
0.02 |
0.02 |
1.30 |
5.09 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.01 |
Mean |
2.10 |
6.77 |
0.24 |
0.13 |
0.04 |
15.34 |
23.22 |
±SD |
0.53 |
2.67 |
0.15 |
0.12 |
0.02 |
1.20 |
9.17 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
1.90 |
5.82 |
0.22 |
0.08 |
0.03 |
17.42* |
24.40 |
±SD |
0.53 |
1.17 |
0.06 |
0.02 |
0.01 |
1.59 |
2.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
2.48 |
6.51 |
0.26 |
0.12 |
0.05 |
16.14 |
28.36 |
±SD |
0.97 |
0.54 |
0.11 |
0.04 |
0.02 |
1.85 |
11.80 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
2.70 |
6.88 |
0.29 |
0.12 |
0.05 |
15.66 |
27.48 |
±SD |
0.45 |
1.21 |
0.12 |
0.05 |
0.01 |
1.19 |
4.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of animals
TABLE 10 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Refer Appendix 10
Group, Sex & Dose (mg/L) |
Total Leucocyte Count |
Total Erythrocyte Count |
Hemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Hemoglobin |
Mean Corpuscular Hemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
||||||||||||
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
|||||||||||||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
|||||||||||||
G1, F & 0 |
Mean |
9.14 |
8.51 |
16.12 |
48.02 |
56.32 |
18.92 |
33.66 |
906.20 |
6.96 |
|||||||||||
±SD |
2.24 |
0.30 |
0.64 |
2.65 |
1.48 |
0.71 |
1.88 |
313.91 |
0.23 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G2, F & 0.003 |
Mean |
8.33 |
8.39 |
16.02 |
48.42 |
57.76 |
19.08 |
33.08 |
782.40 |
6.90 |
|||||||||||
±SD |
1.71 |
0.45 |
0.82 |
2.72 |
1.55 |
0.48 |
0.60 |
256.78 |
0.22 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G3, F & 0.01 |
Mean |
8.87 |
9.00 |
16.52 |
51.16 |
56.86 |
18.36 |
32.28 |
1092.80 |
6.92 |
|||||||||||
±SD |
1.95 |
0.49 |
0.67 |
2.35 |
2.08 |
0.73 |
0.25 |
89.68 |
0.22 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G4, F & 0.03 |
Mean |
8.54 |
8.95 |
16.42 |
50.80 |
56.78 |
18.34 |
32.32 |
977.40 |
6.90 |
|||||||||||
±SD |
1.49 |
0.28 |
0.52 |
1.16 |
1.14 |
0.40 |
0.41 |
117.58 |
0.19 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G1R, F & 0 |
Mean |
9.67 |
8.51 |
16.04 |
47.36 |
55.70 |
18.82 |
33.80 |
918.40 |
6.62 |
|||||||||||
±SD |
2.17 |
0.44 |
0.68 |
1.43 |
2.09 |
0.65 |
0.66 |
130.17 |
0.33 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G4R, F & 0.03 |
Mean |
7.58 |
9.06 |
16.56 |
48.78 |
53.90 |
18.32 |
33.94 |
597.80 |
6.98 |
|||||||||||
±SD |
2.19 |
0.33 |
0.72 |
2.11 |
1.12 |
0.53 |
0.40 |
308.99 |
1.65 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals
TABLE 10 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Refer Appendix 10
Group, Sex & Dose (mg/L) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
Absolute Reticulocyte Count |
||||||||||
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(Retic) |
|||||||||||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
(109cells/L) |
|||||||||||
G1, F & 0 |
Mean |
2.55 |
24.28 |
69.98 |
3.34 |
1.34 |
0.26 |
217.08 |
|||||||||
±SD |
0.59 |
5.92 |
6.34 |
0.91 |
0.82 |
0.09 |
48.26 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, F & 0.003 |
Mean |
2.36 |
24.52 |
70.00 |
3.38 |
0.78 |
0.32 |
198.08 |
|||||||||
±SD |
0.37 |
5.33 |
5.42 |
1.13 |
0.36 |
0.08 |
31.99 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, F & 0.01 |
Mean |
2.64 |
25.72 |
68.92 |
3.36 |
0.82 |
0.36 |
236.94 |
|||||||||
±SD |
0.48 |
7.95 |
7.60 |
0.68 |
0.42 |
0.11 |
38.20 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, F & 0.03 |
Mean |
2.35 |
22.20 |
72.14 |
3.44 |
0.80 |
0.34 |
209.38 |
|||||||||
±SD |
0.69 |
5.59 |
6.30 |
0.80 |
0.33 |
0.05 |
55.93 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1R, F & 0 |
Mean |
2.43 |
24.74 |
69.50 |
3.04 |
1.16 |
0.54 |
205.22 |
|||||||||
±SD |
0.83 |
1.48 |
1.73 |
0.70 |
0.42 |
0.25 |
62.92 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, F & 0.03 |
Mean |
1.31* |
30.22* |
64.16* |
2.96 |
1.50 |
0.56 |
118.78* |
|||||||||
±SD |
0.16 |
3.47 |
3.51 |
0.94 |
0.72 |
0.30 |
18.19 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 10 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Refer Appendix 10
Group, Sex & Dose (mg/L) |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
||||||||||
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
|||||||||||
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
|||||||||||
G1, F & 0 |
Mean |
2.16 |
6.46 |
0.31 |
0.11 |
0.03 |
16.36 |
16.84 |
|||||||||
±SD |
0.45 |
1.93 |
0.12 |
0.05 |
0.02 |
1.87 |
2.96 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, F & 0.003 |
Mean |
2.08 |
5.80 |
0.28 |
0.07 |
0.02 |
17.10 |
21.68 |
|||||||||
±SD |
0.83 |
1.02 |
0.11 |
0.04 |
0.01 |
2.14 |
4.63 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, F & 0.01 |
Mean |
2.32 |
6.09 |
0.29 |
0.07 |
0.04 |
13.74 |
19.86 |
|||||||||
±SD |
0.98 |
1.38 |
0.05 |
0.03 |
0.02 |
1.90 |
2.10 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, F & 0.03 |
Mean |
1.91 |
6.13 |
0.30 |
0.07 |
0.03 |
16.46 |
27.30* |
|||||||||
±SD |
0.71 |
0.97 |
0.12 |
0.04 |
0.00 |
1.62 |
3.79 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1R, F & 0 |
Mean |
2.38 |
6.74 |
0.30 |
0.11 |
0.05 |
16.92 |
33.88 |
|||||||||
±SD |
0.46 |
1.64 |
0.10 |
0.03 |
0.03 |
3.47 |
3.09 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, F & 0.03 |
Mean |
2.25 |
4.88 |
0.22 |
0.12 |
0.05 |
15.44 |
33.02 |
|||||||||
±SD |
0.58 |
1.45 |
0.12 |
0.08 |
0.03 |
2.09 |
7.57 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 11.SUMMARY OF BALF RECORD
Refer Appendix 11
Group, Sex & Dose (mg/L) |
Total Leucocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
Absolute Neutrophils |
||||||||||
(WBC) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(Neut) |
|||||||||||
(103cells/µL) |
(%) |
(%) |
(%) |
(%) |
(%) |
(103cells/µL) |
|||||||||||
G1, M & 0
|
Mean |
1.19 |
29.60 |
54.24 |
3.00 |
0.86 |
1.44 |
0.58 |
|||||||||
±SD |
1.45 |
20.44 |
18.64 |
2.65 |
1.06 |
0.52 |
1.05 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, M & 0.003 |
Mean |
0.77 |
32.70 |
56.88 |
2.08 |
0.80 |
2.60 |
0.23 |
|||||||||
±SD |
0.51 |
9.76 |
10.60 |
1.55 |
0.63 |
1.89 |
0.17 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, M & 0.01 |
Mean |
0.32 |
30.42 |
59.32 |
1.92 |
0.88 |
1.84 |
0.10 |
|||||||||
±SD |
0.16 |
5.85 |
5.34 |
1.31 |
0.73 |
0.90 |
0.05 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, M & 0.03 |
Mean |
0.72 |
27.22 |
66.56 |
2.18 |
1.58 |
2.18 |
0.16 |
|||||||||
±SD |
0.85 |
10.58 |
10.94 |
0.64 |
1.06 |
0.39 |
0.13 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1R, M & 0 |
Mean |
0.12 |
16.92 |
68.74 |
1.64 |
12.34 |
10.54 |
0.01 |
|||||||||
±SD |
0.12 |
13.35 |
32.50 |
2.05 |
20.46 |
6.17 |
0.01 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, M & 0.03 |
Mean |
0.03 |
27.54 |
63.42 |
3.88 |
4.22 |
2.94* |
0.01 |
|||||||||
±SD |
0.01 |
24.10 |
29.51 |
5.23 |
3.22 |
3.20 |
0.01 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 11 (Contd…). SUMMARY OF BALF RECORD
Refer Appendix 11
Group, Sex & Dose (mg/L) |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Lactate Dehydrogenase |
Total Protein |
|||||||||
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(LDH) |
(TPR) |
||||||||||
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(u/L) |
(g/dL) |
||||||||||
G1, M & 0 |
Mean |
0.44 |
0.07 |
0.01 |
0.01 |
135.52 |
349.19 |
||||||||
±SD |
0.25 |
0.12 |
0.01 |
0.02 |
130.92 |
127.80 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G2, M & 0.003 |
Mean |
0.43 |
0.02 |
0.00 |
0.01 |
82.20 |
321.13 |
||||||||
±SD |
0.31 |
0.02 |
0.01 |
0.00 |
39.77 |
171.66 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G3, M & 0.01 |
Mean |
0.20 |
0.01 |
0.00 |
0.01 |
56.22 |
325.64 |
||||||||
±SD |
0.11 |
0.01 |
0.00 |
0.01 |
19.47 |
107.69 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G4, M & 0.03 |
Mean |
0.51 |
0.01 |
0.01 |
0.01 |
80.04 |
299.91 |
||||||||
±SD |
0.66 |
0.02 |
0.01 |
0.02 |
51.42 |
111.84 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G1R, M & 0 |
Mean |
0.10 |
0.00 |
0.01 |
0.01 |
56.16 |
296.06 |
||||||||
±SD |
0.12 |
0.00 |
0.01 |
0.02 |
24.94 |
116.35 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G4R, M & 0.03 |
Mean |
0.02 |
0.00 |
0.00 |
0.00 |
140.88* |
185.63 |
||||||||
±SD |
0.02 |
0.00 |
0.00 |
0.00 |
56.13 |
31.78 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 11 (Contd…). SUMMARY OF BALF RECORD
Refer Appendix 11
Group, Sex & Dose (mg/L) |
Total Leucocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
Absolute Neutrophils |
||||||||||
(WBC) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(Neut) |
|||||||||||
(103cells/µL) |
(%) |
(%) |
(%) |
(%) |
(%) |
(103cells/µL) |
|||||||||||
G1, F & 0 |
Mean |
0.32 |
21.94 |
65.62 |
1.72 |
0.32 |
5.42 |
0.07 |
|||||||||
±SD |
0.07 |
2.42 |
5.73 |
0.60 |
0.18 |
4.49 |
0.01 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, F & 0.003 |
Mean |
0.43 |
27.32 |
52.80 |
1.66 |
0.30 |
1.68 |
0.12 |
|||||||||
±SD |
0.17 |
5.99 |
4.72 |
0.73 |
0.22 |
0.73 |
0.06 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, F & 0.01 |
Mean |
0.87* |
27.86 |
59.40 |
1.76 |
3.56 |
2.12 |
0.23 |
|||||||||
±SD |
0.51 |
6.20 |
7.70 |
0.55 |
6.22 |
1.10 |
0.10 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, F & 0.03 |
Mean |
0.46 |
51.66* |
42.10* |
1.66 |
2.00 |
2.78 |
0.23 |
|||||||||
±SD |
0.28 |
17.30 |
17.59 |
1.73 |
1.17 |
4.35 |
0.16 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1R, F & 0 |
Mean |
0.27 |
19.08 |
69.36 |
2.72 |
4.80 |
11.52 |
0.06 |
|||||||||
±SD |
0.17 |
6.77 |
8.10 |
1.29 |
2.53 |
6.91 |
0.05 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, F & 0.03 |
Mean |
1.89 |
22.94 |
66.34 |
4.62 |
3.28 |
9.90 |
1.08 |
|||||||||
±SD |
3.60 |
24.01 |
30.37 |
7.23 |
2.26 |
7.57 |
2.30 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 11 (Contd…). SUMMARY OF BALF RECORD
Refer Appendix 11
Group, Sex & Dose (mg/L) |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Lactate Dehydrogenase |
Total Protein |
|||||||||
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(LDH) |
(TPR) |
||||||||||
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(u/L) |
(g/dL) |
||||||||||
G1, F & 0 |
Mean |
0.21 |
0.00 |
0.00 |
0.02 |
47.56 |
322.15 |
||||||||
±SD |
0.06 |
0.01 |
0.00 |
0.01 |
6.02 |
135.05 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G2, F & 0.003 |
Mean |
0.23 |
0.01 |
0.00 |
0.01 |
41.26 |
326.31 |
||||||||
±SD |
0.09 |
0.00 |
0.00 |
0.00 |
18.91 |
87.24 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G3, F & 0.01 |
Mean |
0.50* |
0.02 |
0.05 |
0.02 |
102.52 |
369.37 |
||||||||
±SD |
0.26 |
0.02 |
0.12 |
0.01 |
39.86 |
120.36 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G4, F & 0.03 |
Mean |
0.20 |
0.01 |
0.01 |
0.02 |
146.44 |
371.40 |
||||||||
±SD |
0.13 |
0.02 |
0.01 |
0.03 |
188.18 |
300.11 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G1R, F & 0 |
Mean |
0.18 |
0.00 |
0.01 |
0.03 |
49.50 |
193.58 |
||||||||
±SD |
0.12 |
0.01 |
0.01 |
0.02 |
30.42 |
55.52 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||
G4R, F & 0.03 |
Mean |
0.46 |
0.29 |
0.04 |
0.09 |
140.56 |
229.77 |
||||||||
±SD |
0.59 |
0.65 |
0.08 |
0.15 |
175.38 |
44.27 |
|||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 12. SUMMARY OF CLINICAL CHEMISTRYRECORD
Refer Appendix 12
Group, Sex & Dose (mg/L) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
Alanine aminotransferase |
Aspartate aminotransferase |
|
(GLU) |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
(ALT) |
(AST) |
|||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
(U/L) |
(U/L) |
||
G1, M & 0 |
Mean |
96.80 |
39.10 |
0.57 |
53.20 |
39.20 |
7.22 |
3.57 |
41.20 |
92.00 |
±SD |
4.44 |
2.85 |
0.06 |
2.95 |
7.85 |
0.33 |
0.13 |
5.07 |
7.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.003 |
Mean |
103.80 |
39.82 |
0.57 |
46.80 |
37.20 |
7.42 |
3.44 |
43.20 |
103.80 |
±SD |
26.07 |
6.93 |
0.05 |
14.24 |
15.30 |
0.33 |
0.27 |
6.61 |
13.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.01 |
Mean |
90.20 |
41.28 |
0.54 |
54.60 |
40.80 |
7.58 |
3.39 |
54.00 |
112.80* |
±SD |
8.67 |
4.69 |
0.03 |
12.97 |
15.02 |
0.22 |
0.14 |
15.44 |
13.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
95.60 |
39.16 |
0.54 |
42.80 |
37.00 |
7.70 |
3.52 |
39.40 |
101.00 |
±SD |
4.83 |
6.64 |
0.04 |
13.07 |
3.94 |
0.67 |
0.23 |
7.54 |
9.67 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
107.00 |
29.42 |
0.49 |
48.80 |
40.00 |
7.14 |
3.66 |
67.60 |
129.40 |
±SD |
18.19 |
6.19 |
0.02 |
7.01 |
12.83 |
0.30 |
0.09 |
37.04 |
90.48 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
101.00 |
28.38 |
0.46 |
56.60 |
53.00 |
7.10 |
3.78 |
56.40 |
88.60 |
±SD |
10.37 |
3.04 |
0.02 |
14.66 |
6.12 |
0.48 |
0.25 |
5.37 |
10.74 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: number of animals; *: Statistically significant (p<0.05)
TABLE 12 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Refer Appendix 12
Group, Sex & Dose (mg/L) |
Alkaline phosphatase |
Total Bilirubin |
Calcium |
Phosphorous |
Globulin |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(ALP) |
(BIT) |
(CAL) |
(PHO) |
(GLO) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, M & 0 |
Mean |
135.20 |
0.01 |
9.88 |
6.22 |
3.65 |
18.25 |
141.42 |
3.50 |
110.18 |
±SD |
34.04 |
0.01 |
0.26 |
0.36 |
0.33 |
1.33 |
0.68 |
0.18 |
0.86 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.003 |
Mean |
116.80 |
0.02 |
10.06 |
6.86 |
3.98 |
18.58 |
142.36 |
4.02 |
110.62 |
±SD |
29.58 |
0.02 |
0.15 |
0.47 |
0.25 |
3.23 |
0.53 |
0.59 |
1.82 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.01 |
Mean |
142.60 |
0.03 |
10.26* |
6.86 |
4.19 |
19.26 |
143.06 |
3.92 |
110.80 |
±SD |
39.84 |
0.03 |
0.09 |
1.00 |
0.20 |
2.19 |
1.21 |
0.31 |
2.59 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
105.80 |
0.02 |
9.68 |
6.36 |
4.18 |
18.28 |
143.46* |
3.66 |
110.12 |
±SD |
11.95 |
0.01 |
0.20 |
0.45 |
0.60 |
3.10 |
1.78 |
0.25 |
2.37 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
143.00 |
0.01 |
9.44 |
6.46 |
3.48 |
13.73 |
142.42 |
3.74 |
106.80 |
±SD |
49.28 |
0.01 |
0.30 |
0.34 |
0.29 |
2.89 |
0.71 |
0.45 |
0.70 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
161.60 |
0.01 |
9.76 |
6.66 |
3.32 |
13.25 |
142.08 |
3.57 |
105.20 |
±SD |
94.73 |
0.01 |
0.23 |
0.55 |
0.28 |
1.42 |
0.73 |
0.16 |
1.51 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 12 (Contd…). SUMMARY OF CLINICAL CHEMISTRY
Refer Appendix 12
Group, Sex & Dose (mg/L) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
Alanine aminotransferase |
Aspartate aminotransferase |
|
(GLU) |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
(ALT) |
(AST) |
|||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
(U/L) |
(U/L) |
||
G1, F & 0 |
Mean |
79.80 |
39.56 |
0.52 |
42.80 |
34.40 |
7.00 |
3.41 |
52.20 |
108.60 |
±SD |
8.56 |
4.16 |
0.07 |
3.96 |
4.67 |
0.31 |
0.11 |
7.79 |
16.70 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.003 |
Mean |
87.80 |
37.04 |
0.51 |
48.80 |
55.00 |
7.20 |
3.41 |
60.40 |
123.40 |
±SD |
11.56 |
4.05 |
0.05 |
8.58 |
30.10 |
0.32 |
0.15 |
19.63 |
32.67 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.01 |
Mean |
91.80 |
35.14 |
0.51 |
45.00 |
34.00 |
7.28 |
3.60 |
57.00 |
108.60 |
±SD |
8.14 |
1.95 |
0.03 |
6.28 |
8.54 |
0.16 |
0.11 |
11.11 |
8.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
101.20* |
49.52* |
0.52 |
40.60 |
34.20 |
7.38 |
3.50 |
62.40 |
113.60 |
±SD |
17.84 |
7.88 |
0.03 |
5.77 |
15.11 |
0.37 |
0.18 |
6.69 |
9.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
98.20 |
28.50 |
0.52 |
73.80 |
39.40 |
7.52 |
3.97 |
45.00 |
94.00 |
±SD |
6.91 |
1.52 |
0.02 |
11.28 |
6.62 |
0.36 |
0.22 |
3.54 |
8.60 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
110.60 |
40.98 |
0.63 |
67.00 |
40.40 |
7.56 |
3.92 |
57.80 |
97.80 |
±SD |
20.18 |
11.85 |
0.23 |
11.25 |
8.50 |
0.13 |
0.06 |
13.74 |
13.59 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: number of animals; *: Statistically significant (p<0.05)
TABLE 12 (Contd…). SUMMARY OF CLINICAL CHEMISTRY
Refer Appendix 12
Group, Sex & Dose (mg/L) |
Alkaline phosphatase |
Total Bilirubin |
Calcium |
Phosphorous |
Globulin |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(ALP) |
(BIT) |
(CAL) |
(PHO) |
(GLO) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, F & 0 |
Mean |
200.40 |
0.02 |
10.00 |
7.58 |
3.59 |
18.46 |
143.34 |
4.02 |
110.70 |
±SD |
35.13 |
0.02 |
0.31 |
0.62 |
0.25 |
1.94 |
0.85 |
0.26 |
1.70 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.003 |
Mean |
179.00 |
0.03 |
9.88 |
7.22 |
3.79 |
17.29 |
142.58 |
4.12 |
109.02 |
±SD |
24.21 |
0.01 |
0.37 |
0.38 |
0.22 |
1.89 |
2.66 |
0.37 |
1.99 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.01 |
Mean |
201.00 |
0.02 |
10.20 |
7.10 |
3.68 |
16.40 |
142.94 |
3.79 |
108.82 |
±SD |
27.65 |
0.02 |
0.07 |
0.32 |
0.17 |
0.91 |
1.16 |
0.05 |
1.53 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
186.80 |
0.03 |
9.92 |
7.06 |
3.88 |
23.11* |
144.54 |
3.99 |
112.36 |
±SD |
55.68 |
0.01 |
0.34 |
0.98 |
0.20 |
3.68 |
1.30 |
0.14 |
1.50 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
67.00 |
0.03 |
10.00 |
5.94 |
3.55 |
13.30 |
141.60 |
3.42 |
106.46 |
±SD |
31.44 |
0.02 |
0.30 |
0.38 |
0.29 |
0.71 |
0.95 |
0.19 |
0.94 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
95.00 |
0.03 |
9.80 |
5.72 |
3.64 |
19.12 |
141.66 |
3.82* |
106.10 |
±SD |
29.97 |
0.02 |
0.21 |
1.10 |
0.17 |
5.53 |
1.15 |
0.22 |
1.75 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 13.SUMMARY OF URINALYSIS
Refer Appendix 13
Examination |
Group, Sex & Dose (mg/L) |
G1, M & 0 |
G2, M & 0.003 |
G3, M & 0.01 |
G4, M & 0.03 |
G1R, M & 0 |
G4R, M & 0.03 |
|
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||
Physical |
Colour |
Pale Yellow |
5 |
5 |
5 |
5 |
5 |
4 |
Yellow |
- |
- |
- |
- |
- |
1 |
||
Appearance |
Clear |
5 |
5 |
5 |
5 |
4 |
3 |
|
Turbid |
- |
- |
- |
- |
1 |
2 |
||
Volume (mL) |
Mean |
4.8 |
5.9 |
6.8 |
5.9 |
5.3 |
4.2 |
|
±SD |
1.2 |
1.7 |
1.3 |
1.0 |
0.9 |
0.6 |
||
Chemical |
pH |
Mean |
7.8 |
7.8 |
7.7 |
7.6 |
7.2 |
7.4 |
±SD |
0.3 |
0.3 |
0.3 |
0.4 |
0.7 |
0.8 |
||
Specific Gravity |
Mean |
1.009 |
1.010 |
1.011 |
1.012 |
1.013 |
1.010 |
|
±SD |
0.002 |
0.000 |
0.002 |
0.003 |
0.004 |
0.004 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.2 |
0.2 |
0.2 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
1 |
4 |
4 |
3 |
5 |
4 |
|
1 |
4 |
1 |
1 |
2 |
- |
1 |
||
Ketones (mg/dL) |
Neg |
2 |
1 |
3 |
- |
- |
2 |
|
5 |
3 |
4 |
2 |
5 |
5 |
3 |
||
Blood (Ery/µL) |
Neg |
5 |
3 |
5 |
4 |
4 |
5 |
|
Ca10 |
- |
1 |
- |
1 |
1 |
- |
||
Ca25 |
- |
1 |
- |
- |
- |
- |
||
Proteins (mg/dL) |
Neg |
2 |
4 |
2 |
3 |
3 |
3 |
|
Trace |
1 |
- |
2 |
2 |
1 |
- |
||
30 |
2 |
1 |
1 |
- |
1 |
1 |
||
>=300 |
- |
- |
- |
- |
- |
1 |
||
Nitrite |
Neg |
1 |
3 |
1 |
2 |
4 |
3 |
|
Pos |
4 |
2 |
4 |
3 |
1 |
2 |
||
Leucocytes (Leu/µL) |
Neg |
- |
- |
- |
1 |
- |
1 |
|
Ca15 |
- |
2 |
1 |
2 |
2 |
2 |
||
Ca70 |
5 |
3 |
4 |
2 |
3 |
2 |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Micro albumin (MALB) (mg/dL) |
Neg |
- |
1 |
- |
1 |
- |
1 |
|
>15 |
3 |
1 |
3 |
2 |
2 |
2 |
||
15 |
2 |
3 |
2 |
2 |
3 |
2 |
||
Microscopic |
Epithelial cells |
0 |
4 |
5 |
5 |
5 |
2 |
4 |
0-1 |
1 |
- |
- |
- |
2 |
- |
||
1-2 |
- |
- |
- |
- |
1 |
1 |
||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
|
Crystals |
Present |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; Neg: Negative; Ca: Calculated Approximately; Pos: Positive; SD: Standard Deviation
TABLE 13 (Contd…). SUMMARY OF URINALYSIS
Refer Appendix 13
Examination |
Group, Sex & Dose (mg/L) |
G1, F & 0 |
G2, F & 0.003 |
G3, F & 0.01 |
G4, F & 0.03 |
G1R, F & 0 |
G4R, F & 0.03 |
|
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||
Physical |
Colour |
Pale Yellow |
5 |
5 |
5 |
5 |
4 |
5 |
Yellow |
- |
- |
- |
- |
1 |
- |
||
Appearance |
Clear |
5 |
5 |
5 |
5 |
4 |
4 |
|
Turbid |
- |
- |
- |
- |
1 |
1 |
||
Volume (mL) |
Mean |
5.8 |
5.1 |
5.2 |
5.0 |
4.0 |
4.6 |
|
±SD |
1.5 |
1.3 |
0.8 |
0.9 |
0.4 |
1.1 |
||
Chemical |
pH |
Mean |
7.3 |
7.1 |
7.7 |
7.8 |
7.3 |
7.0 |
±SD |
0.8 |
1.0 |
0.3 |
0.3 |
0.8 |
0.8 |
||
Specific Gravity |
Mean |
1.012 |
1.016 |
1.010 |
1.009 |
1.009 |
1.012 |
|
±SD |
0.008 |
0.007 |
0.000 |
0.002 |
0.004 |
0.003 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.6 |
0.2 |
0.2 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.8 |
0.0 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
4 |
3 |
5 |
4 |
4 |
5 |
|
1 |
1 |
2 |
- |
1 |
1 |
- |
||
Ketones (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Blood (Ery/µL) |
Neg |
5 |
3 |
4 |
4 |
5 |
4 |
|
Ca10 |
- |
1 |
1 |
1 |
- |
- |
||
Ca25 |
- |
1 |
- |
- |
- |
1 |
||
Proteins (mg/dL) |
Neg |
5 |
5 |
4 |
3 |
2 |
4 |
|
Trace |
- |
- |
1 |
1 |
2 |
- |
||
30 |
- |
- |
- |
- |
1 |
1 |
||
>=300 |
- |
- |
- |
1 |
- |
- |
||
Nitrite |
Neg |
3 |
2 |
4 |
4 |
3 |
4 |
|
Pos |
2 |
3 |
1 |
1 |
2 |
1 |
||
Leucocytes (Leu/µL) |
Neg |
- |
2 |
- |
- |
3 |
1 |
|
Ca15 |
5 |
3 |
2 |
2 |
1 |
4 |
||
Ca70 |
- |
- |
3 |
2 |
1 |
- |
||
Ca125 |
- |
- |
- |
1 |
- |
- |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Micro albumin (MALB) (mg/dL) |
Neg |
1 |
2 |
1 |
1 |
1 |
1 |
|
>15 |
- |
- |
1 |
2 |
3 |
1 |
||
15 |
4 |
3 |
3 |
2 |
1 |
3 |
||
Microscopic |
Epithelial cells |
0 |
4 |
4 |
4 |
3 |
1 |
3 |
0-1 |
1 |
- |
1 |
1 |
3 |
1 |
||
1-2 |
- |
1 |
- |
1 |
1 |
1 |
||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
|
Crystals |
Present |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; Neg: Negative; Ca: Calculated Approximately; Pos: Positive; SD: Standard Deviation
TABLE 14. SUMMARY OF ABSOLUTE ORGAN WEIGHTS (g)
Refer Appendix 14
Group, Sex & Dose (mg/L) |
Adrenals |
Thymus |
Spleen |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Lungs |
|
G1, M & 0 |
Mean |
0.0591 |
0.3086 |
0.4909 |
2.8529 |
0.8080 |
1.6090 |
1.8356 |
6.7114 |
0.6179 |
±SD |
0.0205 |
0.0655 |
0.0487 |
0.0423 |
0.1208 |
0.1735 |
0.0435 |
0.5112 |
0.1409 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.003 |
Mean |
0.0491 |
0.3546 |
0.4750 |
3.0797 |
0.9093 |
1.8123 |
1.8330 |
7.3951 |
0.5748 |
±SD |
0.0017 |
0.0335 |
0.0973 |
0.1235 |
0.0870 |
0.1910 |
0.0669 |
0.9794 |
0.0890 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.01 |
Mean |
0.0585 |
0.2789 |
0.4677 |
3.0948 |
0.8801 |
1.7441 |
1.7921 |
6.8768 |
0.5045 |
±SD |
0.0101 |
0.0359 |
0.0834 |
0.2170 |
0.1741 |
0.1330 |
0.1249 |
0.8572 |
0.1224 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
0.0499 |
0.2645 |
0.4638 |
3.0833 |
0.8060 |
1.5553 |
1.7554 |
6.7946 |
0.5538 |
±SD |
0.0059 |
0.0298 |
0.1002 |
0.1584 |
0.1314 |
0.1997 |
0.1222 |
0.7357 |
0.0879 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
0.0670 |
0.3694 |
0.7428 |
3.4995 |
1.3398 |
2.5617 |
1.9615 |
10.6978 |
0.6410 |
±SD |
0.0091 |
0.0663 |
0.1451 |
0.3605 |
0.2577 |
0.5982 |
0.1373 |
1.3430 |
0.0477 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
0.0705 |
0.4383 |
0.7226 |
3.1986 |
1.4393 |
2.8197 |
2.0371 |
11.1423 |
0.6347 |
±SD |
0.0132 |
0.0332 |
0.0480 |
0.1484 |
0.0975 |
0.3347 |
0.0799 |
1.4656 |
0.0587 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation, n: Number of animals
.
TABLE 14 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHTS (g)
Refer Appendix 14
Group, Sex & Dose (mg/L) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus |
Heart |
Kidneys |
Brain |
Liver |
Lungs |
|
G1, F & 0 |
Mean |
0.0688 |
0.4001 |
0.5071 |
0.1062 |
0.5056 |
0.7483 |
1.3784 |
1.7000 |
6.4285 |
0.4590 |
±SD |
0.0084 |
0.0640 |
0.0527 |
0.0343 |
0.0727 |
0.1094 |
0.1386 |
0.0522 |
0.5623 |
0.0574 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.003 |
Mean |
0.0709 |
0.3071* |
0.4388 |
0.1335 |
0.6509 |
0.7224 |
1.3771 |
1.7426 |
5.7190 |
0.4886 |
±SD |
0.0109 |
0.0146 |
0.0602 |
0.0338 |
0.1297 |
0.0724 |
0.1948 |
0.0479 |
0.6038 |
0.0660 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.01 |
Mean |
0.0884 |
0.3436 |
0.4720 |
0.1027 |
0.6082 |
0.7089 |
1.3448 |
1.7532 |
6.4444 |
0.5426 |
±SD |
0.0645 |
0.0508 |
0.0590 |
0.0437 |
0.1803 |
0.0492 |
0.1877 |
0.0476 |
0.9024 |
0.0554 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
0.0581 |
0.3067* |
0.4379 |
0.0971 |
0.4466 |
0.6583 |
1.3295 |
1.7579 |
5.1555* |
0.5497 |
±SD |
0.0085 |
0.0338 |
0.1303 |
0.0283 |
0.1686 |
0.0274 |
0.0703 |
0.0731 |
0.8599 |
0.1192 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
0.0774 |
0.3357 |
0.8291 |
0.1343 |
1.1745 |
0.9412 |
1.7869 |
1.9118 |
8.5142 |
0.5585 |
±SD |
0.0140 |
0.0703 |
0.1620 |
0.0056 |
0.2419 |
0.0437 |
0.1660 |
0.0276 |
1.1044 |
0.1485 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
0.0777 |
0.2541 |
0.5076* |
0.1404 |
0.7023* |
0.9485 |
1.6055 |
1.8672 |
7.3391 |
0.5311 |
±SD |
0.0149 |
0.0375 |
0.0487 |
0.0314 |
0.1485 |
0.0838 |
0.1722 |
0.0575 |
0.6635 |
0.0730 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female, R: Recovery; SD: Standard Deviation, n: Number of animals; *: Statistically significant (p<0.05)
TABLE 15. SUMMARY OF ORGAN WEIGHT RELATIVE TO BODY WEIGHT(%)RECORD
Refer Appendix 15
Group, Sex & Dose (mg/L) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Lungs |
|
G1, M & 0 |
Mean |
219.28 |
0.0267 |
0.1414 |
0.2241 |
1.3049 |
0.3676 |
0.7334 |
0.8392 |
3.0624 |
0.2808 |
±SD |
11.91 |
0.0082 |
0.0326 |
0.0213 |
0.0893 |
0.0413 |
0.0633 |
0.0519 |
0.2050 |
0.0541 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.003 |
Mean |
221.69 |
0.0222 |
0.1606 |
0.2131 |
1.3908 |
0.4104 |
0.8163 |
0.8278 |
3.3281 |
0.2583 |
±SD |
10.68 |
0.0011 |
0.0210 |
0.0340 |
0.0630 |
0.0387 |
0.0554 |
0.0382 |
0.3134 |
0.0295 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.01 |
Mean |
217.94 |
0.0269 |
0.1279 |
0.2147 |
1.4231 |
0.4042 |
0.8012 |
0.8234 |
3.1585 |
0.2322 |
±SD |
8.20 |
0.0050 |
0.0151 |
0.0387 |
0.1334 |
0.0816 |
0.0686 |
0.0685 |
0.4111 |
0.0607 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
218.45 |
0.0229 |
0.1213 |
0.2127 |
1.4128 |
0.3682 |
0.7106 |
0.8039 |
3.1065 |
0.2540 |
±SD |
8.44 |
0.0029 |
0.0153 |
0.0480 |
0.0842 |
0.0532 |
0.0727 |
0.0529 |
0.2609 |
0.0436 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
406.82 |
0.0165 |
0.0908 |
0.1824 |
0.8601 |
0.3293 |
0.6293 |
0.4820 |
2.6288 |
0.1577 |
±SD |
5.43 |
0.0024 |
0.0158 |
0.0342 |
0.0859 |
0.0626 |
0.1442 |
0.0298 |
0.3176 |
0.0131 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
408.41 |
0.0173 |
0.1073 |
0.1770 |
0.7833 |
0.3525 |
0.6908 |
0.4988 |
2.7301 |
0.1554 |
±SD |
2.91 |
0.0033 |
0.0085 |
0.0123 |
0.0383 |
0.0254 |
0.0858 |
0.0190 |
0.3761 |
0.0144 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation, n: Number of animals
TABLE 15 (Contd…). SUMMARY OF ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) RECORD
Refer Appendix 15
Group, Sex & Dose (mg/L) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus |
Heart |
Kidneys |
Brain |
Liver |
Lungs |
|
G1, F & 0 |
Mean |
186.50 |
0.0369 |
0.2152 |
0.2733 |
0.0562 |
0.2709 |
0.4001 |
0.7379 |
0.9151 |
3.4526 |
0.2470 |
±SD |
11.64 |
0.0036 |
0.0370 |
0.0400 |
0.0154 |
0.0321 |
0.0433 |
0.0331 |
0.0779 |
0.3026 |
0.0345 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.003 |
Mean |
190.05 |
0.0374 |
0.1620* |
0.2316 |
0.0702 |
0.3417 |
0.3795 |
0.7244 |
0.9178 |
3.0099 |
0.2568 |
±SD |
8.48 |
0.0058 |
0.0136 |
0.0362 |
0.0169 |
0.0597 |
0.0268 |
0.0942 |
0.0305 |
0.2928 |
0.0299 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.01 |
Mean |
186.46 |
0.0465 |
0.1837 |
0.2538 |
0.0548 |
0.3264 |
0.3811 |
0.7206 |
0.9417 |
3.4488 |
0.2909 |
±SD |
9.23 |
0.0311 |
0.0193 |
0.0359 |
0.0222 |
0.0989 |
0.0353 |
0.0845 |
0.0436 |
0.3509 |
0.0235 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
186.01 |
0.0312 |
0.1648* |
0.2341 |
0.0522 |
0.2401 |
0.3541 |
0.7154 |
0.9454 |
2.7706* |
0.2964 |
±SD |
6.42 |
0.0038 |
0.0158 |
0.0647 |
0.0154 |
0.0926 |
0.0156 |
0.0443 |
0.0350 |
0.4482 |
0.0677 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
311.50 |
0.0249 |
0.1078 |
0.2670 |
0.0431 |
0.3782 |
0.3023 |
0.5743 |
0.6141 |
2.7364 |
0.1797 |
±SD |
8.78 |
0.0046 |
0.0227 |
0.0568 |
0.0022 |
0.0840 |
0.0165 |
0.0595 |
0.0180 |
0.3825 |
0.0500 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
309.87 |
0.0250 |
0.0819 |
0.1637* |
0.0453 |
0.2268* |
0.3061 |
0.5177 |
0.6027 |
2.3667 |
0.1715 |
±SD |
5.44 |
0.0045 |
0.0111 |
0.0142 |
0.0098 |
0.0490 |
0.0260 |
0.0500 |
0.0205 |
0.1834 |
0.0247 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female, R: Recovery; SD: Standard Deviation, n: Number of animals; *: Statistically significant (p<0.05)
TABLE 16. SUMMARY OF ORGAN WEIGHT RELATIVE TO BRAIN WEIGHT (%) RECORD
Refer Appendix 16
Group, Sex & Dose (mg/L) |
Adrenals |
Thymus |
Spleen |
Testes |
Heart |
Kidneys |
Liver |
Lungs |
|
G1, M & 0 |
Mean |
3.2084 |
16.8417 |
26.7271 |
155.4808 |
44.0710 |
87.6913 |
365.9170 |
33.6076 |
±SD |
1.0667 |
3.7434 |
2.3717 |
4.1007 |
7.0256 |
9.6107 |
30.7326 |
7.1803 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.003 |
Mean |
2.6843 |
19.3593 |
25.9283 |
168.0469 |
49.5460 |
98.9292 |
403.3509 |
31.3037 |
±SD |
0.1704 |
1.9147 |
5.3241 |
4.2249 |
3.4296 |
10.3827 |
50.1715 |
4.3567 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.01 |
Mean |
3.2578 |
15.6978 |
26.2370 |
172.9034 |
49.2188 |
97.6369 |
384.4100 |
28.5755 |
±SD |
0.4378 |
2.9017 |
4.9883 |
9.4807 |
9.2781 |
9.1659 |
45.1221 |
8.7837 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
2.8690 |
15.0658 |
26.7382 |
176.6741* |
46.0977 |
88.6284 |
389.0618 |
31.6333 |
±SD |
0.5374 |
1.2650 |
7.5037 |
19.5080 |
8.4852 |
9.9253 |
55.4416 |
5.2430 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
3.4347 |
18.7629 |
37.7116 |
179.2759 |
68.2623 |
130.2046 |
544.9017 |
32.7719 |
±SD |
0.5718 |
2.3064 |
5.4990 |
23.6753 |
11.8016 |
25.8373 |
48.5062 |
2.9682 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
3.4637 |
21.5828 |
35.4693 |
157.2705 |
70.6704 |
138.4677 |
547.5343 |
31.2402 |
±SD |
0.6484 |
2.2843 |
1.8665 |
10.6981 |
4.3381 |
16.2928 |
75.0901 |
3.6027 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation, n: Number of animals; *: Statistically significant (p<0.05)
TABLE 16 (Contd…). SUMMARY OF ORGAN WEIGHT RELATIVE TO BRAIN WEIGHT (%) RECORD
Refer Appendix 16
Group, Sex & Dose (mg/L) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus |
Heart |
Kidneys |
Liver |
Lungs |
|
G1, F & 0 |
Mean |
4.0588 |
23.5205 |
29.8022 |
6.2720 |
29.7271 |
44.1110 |
81.1947 |
378.1715 |
27.0106 |
±SD |
0.5596 |
3.6232 |
2.5080 |
2.0577 |
4.0718 |
6.9072 |
8.8951 |
31.5449 |
3.3719 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.003 |
Mean |
4.0677 |
17.6305* |
25.2137 |
7.6464 |
37.3403 |
41.4107 |
78.8936 |
327.7424 |
28.0605 |
±SD |
0.5998 |
0.9366 |
3.7009 |
1.8651 |
7.3467 |
3.4933 |
9.7042 |
27.2146 |
3.9499 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.01 |
Mean |
5.0209 |
19.6054 |
26.9066 |
5.8463 |
34.9025 |
40.4713 |
76.6939 |
367.4592 |
30.9520 |
±SD |
3.6063 |
2.8966 |
3.1648 |
2.4545 |
11.1287 |
3.1944 |
10.3619 |
48.8942 |
3.0575 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
3.3066 |
17.4195* |
24.7852 |
5.5106 |
25.3271 |
37.4696 |
75.7367 |
293.0729* |
31.3939 |
±SD |
0.4756 |
1.4201 |
7.0121 |
1.5875 |
9.5655 |
1.4874 |
5.0797 |
46.3627 |
7.3171 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
4.0565 |
17.5985 |
43.3976 |
7.0279 |
61.4346 |
49.2572 |
93.5633 |
445.8532 |
29.2652 |
±SD |
0.7920 |
3.9173 |
8.6843 |
0.3349 |
12.5922 |
2.8374 |
9.8313 |
62.6420 |
8.0534 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
4.1760 |
13.6221 |
27.2025* |
7.4981 |
37.7341* |
50.7802 |
85.9015 |
393.3327 |
28.4678 |
±SD |
0.8846 |
2.1080 |
2.6776 |
1.5337 |
8.6957 |
3.9404 |
7.7389 |
37.4725 |
4.0105 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female, R: Recovery; SD: Standard Deviation, n: Number of animals; *: Statistically significant (p<0.05)
TABLE 17. SUMMARY OF CHAMBER (EXPOSURE) CONDITIONS
Refer Appendix17
Group & Conc. (mg/L) |
|
Temp. (°C) |
Rh (%) |
O2 (%) |
CO2 (mg/L) |
Air inlet flow rate (L/min)* |
BZC (mg/L) |
|
G1/G1R & 0 |
Mean |
22.51 |
55.70 |
20.45 |
615.25 |
20.00 |
- |
|
±SD |
0.22 |
0.94 |
0.22 |
5.03 |
0.00 |
- |
||
G2 & 0.003 |
Mean |
22.53 |
55.51 |
20.48 |
615.34 |
20.00 |
0.0031 |
|
±SD |
0.21 |
1.08 |
0.21 |
4.72 |
0.00 |
0.0001 |
||
G3 & 0.01 |
Mean |
22.52 |
55.48 |
20.46 |
615.85 |
20.00 |
0.011 |
|
±SD |
0.24 |
1.01 |
0.22 |
5.22 |
0.00 |
0.001 |
||
G4/G4R & 0.03 |
Mean |
22.31 |
55.21 |
20.45 |
614.76 |
20.00 |
0.032 |
|
±SD |
2.07 |
1.27 |
0.21 |
5.21 |
0.00 |
0.0007 |
*: Values were constant throughout the exposure; hence standard deviation is zero, Temp.: Temperature; Rh: Relative Humidity; O2: Oxygen Concentration;
CO2: Carbon Dioxide Concentration;BZC: Breathing Zone Concentration:SD: Standard Deviation;R: Recovery.
TABLE 18.SUMMARY OF NOMINAL CONCENTRATION
Refer Appendix 18
Day |
Group |
Test item Used (mg) (a) |
Air flow rate (L/minute)(b) |
Minute (min) (c) |
Nominal Concentration (mg/L) (a) / (b) × (c) |
1 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1690 |
20 |
360 |
0.23 |
|
2650 |
0.37 |
||||
3440 |
0.48 |
||||
2 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1750 |
20 |
360 |
0.24 |
|
2600 |
0.36 |
||||
3650 |
0.51 |
||||
3 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1530 |
20 |
360 |
0.21 |
|
2570 |
0.36 |
||||
3590 |
0.50 |
||||
4 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1690 |
20 |
360 |
0.23 |
|
2700 |
0.38 |
||||
3440 |
0.48 |
||||
5 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1490 |
20 |
360 |
0.21 |
|
2670 |
0.37 |
||||
3500 |
0.49 |
||||
6 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1600 |
20 |
360 |
0.22 |
|
2780 |
0.39 |
||||
3480 |
0.48 |
||||
7 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1540 |
20 |
360 |
0.21 |
|
2680 |
0.37 |
||||
3440 |
0.48 |
TABLE 18 (Contd…). SUMMARY OF NOMINAL CONCENTRATION
Refer Appendix 18
Day |
Group |
Test item Used (mg) (a) |
Air flow rate (L/minute)(b) |
Minute (min) (c) |
Nominal Concentration (mg/L) (b) / (b) × (c) |
8 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1530 |
20 |
360 |
0.21 |
|
2700 |
0.37 |
||||
3510 |
0.49 |
||||
9 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1500 |
20 |
360 |
0.21 |
|
3040 |
0.42 |
||||
3570 |
0.50 |
||||
10 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1730 |
20 |
360 |
0.24 |
|
2750 |
0.38 |
||||
3650 |
0.51 |
||||
11 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1780 |
20 |
360 |
0.25 |
|
2490 |
0.35 |
||||
3440 |
0.48 |
||||
12 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1820 |
20 |
360 |
0.25 |
|
2530 |
0.35 |
||||
3410 |
0.47 |
||||
13 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1720 |
20 |
360 |
0.24 |
|
2650 |
0.37 |
||||
3680 |
0.51 |
||||
14 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1780 |
20 |
360 |
0.25 |
|
2520 |
0.35 |
||||
4040 |
0.56 |
TABLE 18 (Contd…). SUMMARY OF NOMINAL CONCENTRATION
Refer Appendix 18
Day |
Group |
Test item Used (mg) (a) |
Air flow rate (L/minute)(b) |
Minute (min) (c) |
Nominal Concentration (mg/L) (c) / (b) × (c) |
15 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1910 |
20 |
360 |
0.27 |
|
2510 |
0.35 |
||||
3560 |
0.49 |
||||
16 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1630 |
20 |
360 |
0.23 |
|
2880 |
0.40 |
||||
3610 |
0.50 |
||||
17 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1660 |
20 |
360 |
0.23 |
|
2700 |
0.37 |
||||
3750 |
0.52 |
||||
18 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1510 |
20 |
360 |
0.21 |
|
2790 |
0.39 |
||||
3690 |
0.51 |
||||
19 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1530 |
20 |
360 |
0.21 |
|
2660 |
0.37 |
||||
3590 |
0.50 |
||||
20 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1720 |
20 |
360 |
0.24 |
|
2730 |
0.38 |
||||
3630 |
0.50 |
TABLE 1. SUMMARY OF GROSS PATHOLOGY FINDINGS
Refer Appendices 1 & 2
Sex |
Male |
|||||
Route of administration |
Inhalation |
|||||
Treatment |
Air only |
Low Dose |
Mid Dose |
High Dose |
Air only |
High Dose Recovery |
Group |
G1 |
G2 |
G3 |
G4 |
G1R |
G4R |
Nominal Target Dose (mg/L) |
0 |
0.003 |
0.01 |
0.03 |
0 |
0.03 |
Number of animals |
5 |
5 |
5 |
5 |
5 |
5 |
No. of dead rats during treatment |
- |
- |
- |
- |
- |
- |
No. of moribund sacrificed rats |
- |
- |
- |
- |
- |
- |
No. of terminally sacrificed rats |
5 |
5 |
5 |
5 |
5 |
5 |
No. of rats showing gross pathology |
- |
- |
- |
- |
- |
- |
Sex |
Female |
|||||
Route of administration |
Inhalation |
|||||
Treatment |
Air only |
Low Dose |
Mid Dose |
High Dose |
Air only |
High Dose Recovery |
Group |
G1 |
G2 |
G3 |
G4 |
G1R |
G4R |
Nominal Target Dose (mg/L) |
0 |
0.003 |
0.01 |
0.03 |
0 |
0.03 |
Number of animals |
5 |
5 |
5 |
5 |
5 |
5 |
No. of dead rats during treatment |
- |
- |
- |
- |
- |
- |
No. of moribund sacrificed rats |
- |
- |
- |
- |
- |
- |
No. of terminally sacrificed rats |
5 |
5 |
5 |
5 |
5 |
5 |
No. of rats showing gross pathology |
- |
- |
- |
- |
- |
- |
R: Recovery; - : No incidence.
TABLE 2. SUMMARY OF HISTOPATHOLOGY FINDINGS– MAIN GROUP
Refer Appendices 3 & 4
Route of administration |
Inhalation |
|||||
Treatment |
Air only |
High Dose |
||||
Nominal Target Dose (mg/L) |
0 |
0.03 |
||||
Group |
G1 |
G4 |
||||
Sex |
M |
F |
M |
F |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Adrenals |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Brain |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Cervical lymph nodes |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Esophagus |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Eyes with optic nerve and eye lids |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Heart |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Hilar lymph nodes |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Kidneys |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
4 |
5 |
3 |
5 |
||
Cysts |
Present |
1 |
- |
2 |
- |
|
Basophilia, tubules |
Minimal |
- |
- |
1 |
- |
|
Larynx |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Liver |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Lungs |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
4 |
- |
- |
||
Pigment, golden brown |
Moderate |
- |
- |
5 |
5 |
|
Infiltrate, mononuclear cells |
Minimal |
- |
1 |
- |
- |
|
Mandibular lymph nodes |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Mesenteric lymph nodes |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Nasopharyngeal tissue |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Olfactory bulb |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Ovaries |
Number examined |
X |
5 |
X |
5 |
|
Within normal limits |
X |
5 |
X |
5 |
||
Parathyroid |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Seminal vesicles |
Number examined |
5 |
X |
5 |
X |
|
Within normal limits |
5 |
X |
5 |
X |
M: Male; F: Female; -: no incidence; X: not applicable.
TABLE 2 (Contd…). SUMMARY OF HISTOPATHOLOGY FINDINGS – MAIN GROUP
Refer Appendices 3 & 4
Route of administration |
Inhalation |
|||||
Treatment |
Air only |
High Dose |
||||
Nominal Target Dose (mg/L) |
0 |
0.03 |
||||
Group |
G1 |
G4 |
||||
Sex |
M |
F |
M |
F |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Spinal cord |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Spleen |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Stomach |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Testes |
Number examined |
5 |
X |
5 |
X |
|
Within normal limits |
4 |
X |
5 |
X |
||
Degeneration/atrophy, tubule |
Moderate |
1 |
X |
- |
X |
|
Thymus |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Thyroid |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Trachea |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Urinary bladder |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Uterus |
Number examined |
X |
5 |
X |
5 |
|
Within normal limits |
X |
4 |
X |
5 |
||
Dilatation, glandular |
Minimal |
X |
1 |
X |
- |
M: Male; F: Female; -: no incidence; X: not applicable.
TABLE 3. SUMMARY OF HISTOPATHOLOGY FINDINGS – RECOVERY GROUP
Refer Appendices 5 & 6
Route of administration |
Inhalation |
||||||
Treatment |
Air only |
High Dose Recovery |
|||||
Nominal Target Dose (mg/L) |
0 |
0.03 |
|||||
Group |
G1R |
G4R |
|||||
Sex |
M |
F |
M |
F |
|||
Number of Animals |
5 |
5 |
5 |
5 |
|||
Adrenals |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Brain |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Cervical lymph nodes |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Esophagus |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Eyes with optic nerve and eye lids |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Heart |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Hilar lymph nodes |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Kidneys |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
3 |
5 |
|||
Cysts |
Present |
- |
- |
2 |
- |
||
Basophilia, tubules |
Minimal |
- |
- |
1 |
- |
||
Larynx |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Liver |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Lungs |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
- |
- |
|||
Pigment, golden brown |
Mild |
- |
- |
- |
1 |
||
Moderate |
- |
- |
5 |
4 |
|||
Mandibular lymph nodes |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Mesenteric lymph nodes |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Nasopharyngeal tissue |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Olfactory bulb |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
5 |
5 |
5 |
5 |
|||
Ovaries |
Number examined |
X |
5 |
X |
5 |
||
Within normal limits |
X |
5 |
X |
5 |
|||
Parathyroid |
Number examined |
5 |
5 |
5 |
5 |
||
Within normal limits |
4 |
- |
- |
- |
|||
Hyperplasia |
Mild |
1 |
- |
- |
- |
||
M: Male; F: Female; R: Recovery; -: no incidence; X: not applicable.
TABLE 3 (Contd…). SUMMARY OF HISTOPATHOLOGY FINDINGS – RECOVERY GROUP
Refer Appendices 5 & 6
Route of administration |
Inhalation |
|||||
Treatment |
Air only |
High Dose Recovery |
||||
Nominal Target Dose (mg/L) |
0 |
0.03 |
||||
Group |
G1R |
G4R |
||||
Sex |
M |
F |
M |
F |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Seminal vesicles |
Number examined |
5 |
X |
5 |
X |
|
Within normal limits |
5 |
X |
5 |
X |
||
Spinal cord |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Spleen |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Stomach |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Testes |
Number examined |
5 |
X |
5 |
X |
|
Within normal limits |
5 |
X |
5 |
X |
||
Thymus |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Thyroid |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Trachea |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Urinary bladder |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
5 |
5 |
5 |
||
Uterus |
Number examined |
X |
5 |
X |
5 |
|
Within normal limits |
X |
4 |
X |
4 |
||
Dilatation, lumen |
Minimal |
X |
1 |
X |
1 |
|
M: Male; F: Female; R: Recovery; -: no incidence; X: not applicable.
TABLE 4. SUMMARY OF HISTOPATHOLOGY FINDINGS – LOW DOSE AND MID DOSE GROUP
Refer Appendices 7 & 8
Route of administration |
Inhalation |
|||||
Treatment |
Low Dose |
Mid Dose |
||||
Nominal Target Dose (mg/L) |
0.003 |
0.01 |
||||
Group |
G2 |
G3 |
||||
Sex |
M |
F |
M |
F |
||
Number of Animals |
5 |
5 |
5 |
5 |
||
Lungs |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
- |
- |
- |
- |
||
Pigment, golden brown |
Minimal |
3 |
4 |
2 |
3 |
|
Mild |
2 |
1 |
3 |
2 |
M: Male; F: Female; -: No incidence.
Applicant's summary and conclusion
- Conclusions:
- Based on the observed results, it is concluded that the No Observed Adverse Effect Concentration (NOAEC) of test item,Novoperm Orange HLwas found to be 0.03 mg/L when exposed for 6 hours/day, 5 days/week, for 4 weeks by flow-past nose-only inhalation route to Sprague Dawley rats. The nominal dose of 0.03 mg/L (6 hrs/day, 5 days/week) is the actual exposure concentration in males and females..
- Executive summary:
The objective of this study was to determine the toxic potential of the test item when administered for 6 hours/day, 5 days per week, for 4 consecutive weeks by flow-past nose-only inhalation route to Sprague Dawley rats. This study provides information on toxic effects, target organs, the possibility of cumulative effects, the reversibility of effects (after 56 days recovery period), and an estimate of the No Observed Adverse Effects Concentration (NOAEC).A total of 60 (30 males + 30 females) healthy young Sprague Dawley rats were distributed to four main groups viz., control (G1), low dose (G2), mid dose (G3), high dose (G4) and two recovery groups [(G1R (Air only) and G4R (high dose)]. Each main and recovery group comprised of 10 animals (5 males and 5 females). Animals allocated to groups G2, G3 and G4/G4R were exposed to test item for 6 hours per day, 5 days per week, for 4 consecutive weeks., at a nominal target concentration of 0.003, 0.01 and 0.03 mg/L. Animals of the control group (G1/G1R) received air only inhalation for 6 hours/day for 4 consecutive weeks. The inhalation exposure of test item/air was achieved by a flow-past, nose-only dynamic inhalation exposure system supplied by CH Technologies, USA.All animals were observedonce daily for clinical signs and twice daily for mortality. Body weightwas recorded before exposure (day 1and twice weekly for initial two weeks during treatment period and thereafter once weekly.Feed consumption was recorded weekly.Ophthalmoscopic examinationswereperformed duringtheacclimatizationperiodfor all groups, andduringWeek4for main groups (G1and G4),and duringWeek12for recovery groups (G1Rand G4R).Neurological/Functionaltestswereperformed duringWeek4forG1 and G4groupsand duringWeek12for recovery groupanimals.At the end of treatment and recovery periods, all animals were fasted overnight (water was availablead libitum), and the next day, blood, urine, and Broncho alveolar lavage fluid (BALF) samples were collected and analysed. Subsequently, the animals were sacrificed and subjected to gross pathological examination, and the organs were collected, weighed, and preserved. The tissues/organs in vehicle control and high dose group animals including recovery animals were subjected to histopathological examinations.The data recorded for all exposure days relating to the chamber conditions like particle size, temperature, relative humidity, oxygen, and carbon dioxide concentrations determined during the exposure period were found within the specified range.No treatment-related changes in body weight, percent change in body weight with respect to day 1, feed consumption,or ophthalmology were noted.No adverse effects were observed in the neurological/functional examination tests.No adverse effects were observed in haematology, clinical chemistry, coagulation, BALF analysis,or urinalysis parameters. No toxicologically significant changes were observed infasting body weight, absoluteorgan weight, or relative organ weight.There were no test item-related, microscopic findings in animals evaluated after terminal and recovery period in the study.In lungs, minimal to moderate, multifocal, variably sized, pigmented (golden brown) granular material was observed throughout the parenchyma of lung at low, mid, high and high dose recovery groups of rats. This pigment was distributed both in alveolar and bronchiolar spaces with no accompanying inflammation or tissue destruction to the lung parenchyma. This pigment was suggestive of inhaled test item particles. In the absence of cellular changes to lung parenchyma, mere presence of pigment in lungs could be considered as non-adverse effect up to the nominal target dose level of0.03mg/L. (Nikula KJet.al., 2014).
Conclusion: Based on the observed results, it is concluded that the No Observed Adverse Effect Concentration (NOAEC) of test item,Novoperm Orange HLwas found to be 0.03 mg/L when exposed for 6 hours/day, 5 days/week, for 4 weeks by flow-past nose-only inhalation route to Sprague Dawley rats. The nominal dose of 0.03 mg/L (6 hrs/day, 5 days/week) is the actual exposure concentration in males and females.
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