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EC number: 258-221-5 | CAS number: 52846-56-7
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- repeated dose toxicity: inhalation, other
- Remarks:
- 28-Day Inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 March 2021 to 12 October 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
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:
- adopted on 25 June 2018
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Dimethyl 2-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azo]terephthalate
- EC Number:
- 252-650-1
- EC Name:
- Dimethyl 2-[[1-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-oxopropyl]azo]terephthalate
- Cas Number:
- 35636-63-6
- Molecular formula:
- C21H19N5O7
- IUPAC Name:
- dimethyl 2-({2-oxo-1-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)carbamoyl]propyl}diazenyl)terephthalate
- 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 bred animals
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: 7 weeks
- Weight at study initiation: Males: 140.06 g to 159.97 g; Females: 120.63 g to 139.41 g
- Fasting period before study: No
- Housing: Maximum of three animals per cage were housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted feed and drinking water in water bottle fitted with stainless steel sipper tube. Clean sterilized corn cob was provided as bedding material.
- Diet (e.g. ad libitum): Altromin Maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG).
- Water (e.g. ad libitum): Deep bore-well water passed through a reverse osmosis unit was provided in plastic water bottles with stainless steel sipper tubes.
- Acclimation period: 7 Days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6°C to 22.9°C
- Humidity (%): 46% to 65%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle
IN-LIFE DATES: From: 15 March 2021 To: 10 August 2021
Administration / exposure
- Route of administration:
- inhalation: dust
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Mass median aerodynamic diameter (MMAD):
- >= 2 - ca. 2 µm
- Geometric standard deviation (GSD):
- 3
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow-past, nose-only dynamic inhalation exposure system supplied by CH Technologies, USA.
- Method of holding animals in test chamber: The animals were confined separately in restraint tubes which were positioned radially around the flow-past, nose-only dynamic inhalation exposure chamber.
- Source and rate of air: Air flow from the generation system into the chamber was controlled and monitored through control panel (supplied by CH Technologies, USA) using calibrated flow-meters (rotameters) and outlet of the chamber air flow was controlled by rotameter. The actual flow rate of chamber inlet was 20 L/min with 60 psi pressure and outlet air from chamber was 15 L/min maintained throughout the exposure period. The air inlet flow rate was recorded hourly once during exposure (i.e. ± 10 minutes) after equilibration period (T95) 0.11min.
- Method of conditioning air: Compressed 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: 22 ± 3°C, 30 to 70%, 60psi
- Air flow rate: 20L/min
- Air change rate: 12 to 15 air changes per cycle
- Method of particle size determination: Cascade impactor
- Treatment of exhaust air: NaOH
TEST ATMOSPHERE
- Brief description of analytical method used: No
- Samples taken from breathing zone: yes - Duration of treatment / exposure:
- Animals were exposed to aerosolized test item continuously for 6 hours per day, 5 days per week, for a total of 20 actual exposures, after equilibration period of the chamber concentration.
Following the 28 days exposure period, the animals in the recovery groups (G1R and G4R) were not given any treatment and was maintained for 56 days post treatment period and observed for reversibility or persistence of toxic effects. - Frequency of treatment:
- 6 hours per day, 5 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/L air (nominal)
- Remarks:
- Air Only
- Dose / conc.:
- 0.001 mg/L air (nominal)
- Remarks:
- Low Dose
- Dose / conc.:
- 0.003 mg/L air (nominal)
- Remarks:
- Mid Dose
- Dose / conc.:
- 0.03 mg/L air (nominal)
- Remarks:
- High Dose
- No. of animals per sex per dose:
- 5 Males + 5 Females
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale:
- Rationale for selecting satellite groups: Following the 28 days exposure period, the animals in the recovery groups (G1R and G4R) were not given any treatment and was maintained for 56 days post treatment period and observed for reversibility or persistence of toxic effects.
- Post-exposure recovery period in satellite groups: 56 Days
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All the animals were observed for clinical signs and pre-terminal deaths at 1.5 hrs (±10 mins), 3 hrs (±10 mins), 4.5 hrs (±10 mins) and 6 hrs (±10 mins) during exposure period. Post-exposure clinical signs and 30 to 40 minutes and 1 hour (±10 mins) following exposure to the test chemical, thereafter once a day for clinical signs and twice daily for mortality.
- Cage side observations checked in table No.1
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once in a week
BODY WEIGHT: Yes
- Time schedule for examinations: Individual animal body weights were recorded at receipt, prior to exposure (Day 1) and twice weekly thereafter for first two weeks. Since there was no significant body weight effects in the first two weeks, body weights were recorded weekly thereafter (post exposure period) for remaining period of the study. Fasting body weight of all the animals of all the groups were recorded at their scheduled terminal sacrifice.
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Ophthalmological examination was carried out once during acclimatization (Pre-treatment) and during week 4 in control and high dose group animals. No, treatment related ocular changes are noted in high dose during week 4, the examination was not extended to lower dose groups (G2, G3) of main study animals and during week 12 for recovery group animals (G1R and G4R).
- Dose groups that were examined: G1/G1R and G4/G4R
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood samples were collected from all the surviving rats of each group on day 27 (within 24 hours after the last given dose) and day 85 of recovery groups respectively.
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: 60
- Parameters checked in table [No.10] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood samples were collected from all the surviving rats of each group on day 27 (within 24 hours after the last given dose) and day 85 of recovery groups respectively.
- Animals fasted: Yes
- How many animals: 60
- Parameters checked in table [No.12] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: Urine was collected and analyzed from all rats on day 27 (within 24 hours after the last given dose). The animals were kept in urine collection cages overnight for urine collection. Animal was not given access to feed but water was provided ad libitum during their stay in urine collection cages.
The recovery group animal’s urine was collected on day 85.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.13] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Neurological/Functional examination was carried out during Week 4 and 12 for vehicle control and high dose animals. Since no apparent treatment related effects persisted in high dose animals, the examination was not carried out for low and mid dose groups (G2 and G3) during Week 4 of treatment period.
- Dose groups that were examined: G1/G1R and G4/G4R
- Battery of functions tested: sensory activity / grip strength / motor activity. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table No. 19)
HISTOPATHOLOGY: Yes (see table No. 20) - 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:
- no effects observed
- 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
- Description (incidence):
- All animals survived to scheduled sacrifice, and there were no mortality attributable to the test item. Post-exposure, all animals were normal throughout the experimental period. No mortalities were noted during the recovery period.
- Body weight and weight changes:
- no effects observed
- 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:
- no effects observed
- Description (incidence and severity):
- No statistically significant treatment-related variations were observed in all the tested dose groups when compared with control group.
- 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, decrease in HCT (G2) was noted. In females decrease in APTT (G2, G3 and G4), MCV and MCH (G2 and G4) was noted.
In recovery males decrease in Percent monocytes (G4R) was noted. However, in female no significance observed.
All the noted variations in main group are considered incidental in the absence of dose responsiveness. Variations noted at the end of recovery period are considered incidental as no such variations were noted in recovery females. - 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 vehicle control group. However, the following statistically significant variations were noted.
In main group males, increase in chloride (G4) was noted; In females no significance was noted.
In recovery group no significance was observed.
The observed 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 adverse treatment-related effects were observed in urinalysis parameters when compared to the control group. However, a single incidence of a statistically significant decrease in specific gravity was observed in G4R females. This effect, which was minimal in nature, lacked dose-dependency and was therefore not attributed to the test item.
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no adverse effects during neurological/functional examinations were observed in main group (G1 and G4) and recovery group (G1R and G4R), however in females (G4R) excessive grooming was noted, this is considered as incidental due to lack of dose response.
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In main group males, decrease in absolute weight of testis in G2; increase in absolute and relative weight of lungs in G2 and G4 was noted. In females decrease in absolute and relative weight of spleen in G3 was noted.
In recovery group, increase in absolute and relative weight of thymus (G4R); decrease in absolute and relative weight in spleen (G4R) was noted. In females, increase in absolute and relative weight of ovaries (G4R) were noted.
In main group males, statistically significant increase in relative weight of lungs in G2 and G4 was noted. In females, decrease in relative weight of spleen (G3) and liver (G2); increase in relative weight of lungs (G4) were noted.
In recovery group males, decrease in relative weight of spleen (G4R); increase in relative weight of thymus (G4R) was noted. In females increase in relative weight of ovaries (G4R) was noted.
All the observed changes are considered incidental in the absence of gross and histopathological changes in the high dose group animals and also lack dose dependency. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No treatment related gross pathological lesions were observed in main group and recovery group animals.
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no test item-related, microscopic findings in animals evaluated after terminal and recovery period in the study.
Few microscopic findings observed in this study such as ultimobranchial cyst in thyroid gland, epithelial cysts in thymus and all other findings were considered incidental as they occurred randomly across the dose groups including concurrent controls and/or were expected in laboratory rats. - Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- BALF Fluid: The bronchio-alveolar lavage fluid measured at termination revealed the following statistically significant changes: In main group males, increase in percent eosinophils and basophils (G3) was noted; In females, increase in percent monocytes (G4) was noted.
In recovery group, females increase in LDH (G4R) was noted; however, in males no significance was noted.
There were no test item-related microscopic findings in animals evaluated after terminal and recovery period in the study and the noted variations are considered non adverse effect.
Effect levels
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- >= 0.03 - ca. 0.03 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food efficiency
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
- other: BALF findings
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
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 & 0.001 |
5 |
N |
0/5 |
G3, M & 0.003 |
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.
TABLE 1 (Contd…). SUMMARY OF CLINICAL SIGNS AND MORTALITY RECORD
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 & 0.001 |
5 |
N |
0/5 |
G3, F & 0.003 |
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.
TABLE 2. SUMMARY OF BODY WEIGHTS (g) RECORD
Group, Sex & Dose (mg/L) |
Body Weight (g) on Days |
||||||||
1 |
5 |
8 |
12 |
15 |
22 |
26 |
|||
G1, M & 0 |
Mean |
187.88 |
191.93 |
205.03 |
209.22 |
220.95 |
234.65 |
241.23 |
|
±SD |
14.19 |
14.38 |
13.69 |
13.43 |
13.45 |
13.00 |
12.55 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 0.001 |
Mean |
183.58 |
187.41 |
199.18 |
203.48 |
214.50 |
228.10 |
235.87 |
|
±SD |
14.65 |
14.59 |
13.65 |
13.86 |
13.30 |
14.17 |
14.78 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 0.003 |
Mean |
182.16 |
185.60 |
197.45 |
201.89 |
214.35 |
228.81 |
235.88 |
|
±SD |
15.60 |
15.80 |
14.39 |
13.60 |
13.57 |
14.20 |
13.89 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 0.03 |
Mean |
180.15 |
183.99 |
196.54 |
201.16 |
213.32 |
227.63 |
235.65 |
|
±SD |
18.66 |
18.08 |
17.15 |
16.54 |
15.36 |
14.94 |
14.81 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1, F & 0 |
Mean |
152.09 |
155.06 |
161.34 |
163.66 |
172.01 |
182.69 |
189.18 |
|
±SD |
12.49 |
12.10 |
10.71 |
10.09 |
10.81 |
11.06 |
10.92 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 0.001 |
Mean |
153.99 |
157.68 |
163.82 |
166.47 |
175.30 |
184.89 |
190.90 |
|
±SD |
11.36 |
11.61 |
11.46 |
11.06 |
11.32 |
11.43 |
11.75 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 0.003 |
Mean |
149.86 |
153.07 |
160.44 |
162.55 |
170.62 |
180.12 |
186.94 |
|
±SD |
11.55 |
12.04 |
11.07 |
10.79 |
10.78 |
10.64 |
11.15 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 0.03 |
Mean |
151.90 |
154.59 |
160.20 |
162.81 |
170.66 |
180.51 |
186.39 |
|
±SD |
8.04 |
7.91 |
8.06 |
7.73 |
7.95 |
9.00 |
9.00 |
||
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
Group, Sex & Dose (mg/L) |
Body Weight (g) on Days |
||||||||||||||||
1 |
5 |
8 |
12 |
15 |
22 |
26 |
29 |
36 |
43 |
50 |
57 |
64 |
71 |
78 |
84 |
||
G1R, M & 0 |
Mean |
184.58 |
188.92 |
201.70 |
205.86 |
217.92 |
232.09 |
242.91 |
250.80 |
272.02 |
294.25 |
317.10 |
339.64 |
362.85 |
386.35 |
411.61 |
432.52 |
±SD |
10.63 |
11.00 |
10.49 |
9.66 |
9.90 |
9.61 |
9.14 |
9.32 |
9.71 |
10.66 |
10.84 |
10.19 |
10.54 |
10.56 |
10.87 |
10.69 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
182.85 |
186.62 |
199.13 |
203.34 |
215.44 |
230.12 |
243.82 |
251.75 |
272.84 |
295.09 |
317.85 |
340.56 |
363.70 |
386.94 |
412.13 |
433.06 |
±SD |
12.36 |
12.69 |
11.96 |
13.79 |
13.22 |
13.17 |
12.42 |
12.49 |
11.83 |
12.80 |
13.47 |
13.68 |
13.72 |
13.78 |
14.37 |
14.48 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
151.42 |
154.17 |
159.60 |
162.05 |
170.53 |
180.30 |
187.50 |
192.72 |
208.02 |
223.72 |
239.22 |
254.79 |
271.47 |
288.34 |
305.89 |
321.44 |
±SD |
12.00 |
11.75 |
10.93 |
10.98 |
10.61 |
8.85 |
8.38 |
8.72 |
9.15 |
8.87 |
9.39 |
9.33 |
9.70 |
9.90 |
9.79 |
9.86 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
151.49 |
154.31 |
160.21 |
162.55 |
173.23 |
182.00 |
189.45 |
194.62 |
209.88 |
225.43 |
241.03 |
256.53 |
273.35 |
290.30 |
307.74 |
323.36 |
±SD |
11.10 |
11.31 |
10.58 |
9.78 |
11.74 |
11.05 |
10.57 |
10.69 |
10.98 |
10.90 |
10.94 |
10.91 |
11.02 |
10.83 |
10.45 |
10.36 |
|
n |
5 |
5 |
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 animals.
TABLE 3. SUMMARY OF PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1 RECORD
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 |
2.16 |
9.19 |
11.44 |
17.71 |
25.05 |
28.59 |
|
±SD |
0.52 |
1.38 |
1.95 |
2.09 |
2.93 |
3.31 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, M & 0.001 |
Mean |
2.10 |
8.58 |
10.93 |
16.97 |
24.38 |
28.62 |
|
±SD |
0.42 |
1.46 |
1.86 |
2.19 |
2.28 |
2.25 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, M & 0.003 |
Mean |
1.89 |
8.50 |
10.98 |
17.87 |
25.84 |
29.76 |
|
±SD |
0.53 |
1.67 |
2.17 |
3.16 |
3.61 |
4.10 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, M & 0.03 |
Mean |
2.18 |
9.25 |
11.86 |
18.72 |
26.75 |
31.25 |
|
±SD |
0.62 |
1.77 |
2.42 |
3.76 |
4.74 |
5.28 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1, F & 0 |
Mean |
1.99 |
6.19 |
7.75 |
13.25 |
20.30 |
24.59 |
|
±SD |
0.53 |
1.70 |
2.28 |
2.33 |
2.66 |
3.28 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G2, F & 0.001 |
Mean |
2.40 |
6.41 |
8.15 |
13.90 |
20.15 |
24.06 |
|
±SD |
0.28 |
0.53 |
1.01 |
1.18 |
2.05 |
1.85 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G3, F & 0.003 |
Mean |
2.13 |
7.12 |
8.54 |
13.96 |
20.34 |
24.89 |
|
±SD |
0.72 |
1.16 |
1.75 |
2.21 |
3.07 |
2.90 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4, F & 0.03 |
Mean |
1.78 |
5.48 |
7.22 |
12.39 |
18.86 |
22.74 |
|
±SD |
0.29 |
0.59 |
1.35 |
1.44 |
0.90 |
1.30 |
||
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
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 |
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 |
2.35 |
9.31 |
11.59 |
18.14 |
25.84 |
31.73 |
36.01 |
47.54 |
59.58 |
71.99 |
84.25 |
96.85 |
109.61 |
123.32 |
134.68 |
±SD |
0.30 |
0.61 |
1.51 |
1.92 |
2.46 |
3.09 |
3.31 |
3.90 |
3.97 |
4.48 |
5.40 |
5.85 |
6.55 |
7.11 |
7.80 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
2.06 |
8.94 |
11.20 |
17.86 |
25.92 |
33.48 |
37.82 |
49.42 |
61.60 |
74.08 |
86.54 |
99.24 |
111.99 |
125.80 |
137.28 |
±SD |
0.45 |
0.81 |
0.61 |
0.99 |
1.38 |
3.24 |
3.40 |
4.36 |
4.67 |
5.39 |
5.93 |
6.81 |
7.54 |
8.13 |
8.78 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.84 |
5.48 |
7.11 |
12.75 |
19.33 |
24.13 |
27.57 |
37.71 |
48.14 |
58.41 |
68.75 |
79.81 |
90.99 |
102.65 |
112.97 |
±SD |
0.41 |
1.23 |
1.71 |
2.42 |
4.43 |
4.95 |
4.92 |
5.32 |
6.27 |
6.72 |
7.66 |
8.36 |
9.11 |
10.22 |
11.06 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
1.87 |
5.81 |
7.39 |
14.41 |
20.25 |
25.20 |
28.63 |
38.75 |
49.05 |
59.39 |
69.67 |
80.81 |
92.06 |
103.64 |
113.99 |
±SD |
0.23 |
1.11 |
1.55 |
2.31 |
2.97 |
3.11 |
3.53 |
4.27 |
4.67 |
5.22 |
6.01 |
6.67 |
7.64 |
8.66 |
9.19 |
|
n |
5 |
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
Group, Sex & Dose (mg/L) |
Week 1 |
Week 2 |
Week 3 |
Week 4 |
|
G1, M & 0 |
Mean |
18.74 |
18.84 |
18.68 |
32.63 |
±SD |
2.77 |
2.75 |
2.72 |
4.74 |
|
n |
2 |
2 |
2 |
2 |
|
G2, M & 0.001 |
Mean |
18.60 |
18.66 |
18.49 |
32.58 |
±SD |
2.42 |
2.74 |
2.71 |
4.67 |
|
n |
2 |
2 |
2 |
2 |
|
G3, M & 0.003 |
Mean |
18.63 |
18.74 |
18.55 |
32.63 |
±SD |
2.60 |
2.99 |
2.92 |
4.79 |
|
n |
2 |
2 |
2 |
2 |
|
G4, M & 0.03 |
Mean |
18.67 |
18.48 |
18.56 |
32.65 |
±SD |
2.62 |
2.67 |
2.59 |
4.99 |
|
n |
2 |
2 |
2 |
2 |
|
G1, F & 0 |
Mean |
14.20 |
14.55 |
14.39 |
32.70 |
±SD |
1.66 |
1.72 |
1.61 |
4.72 |
|
n |
2 |
2 |
2 |
2 |
|
G2, F & 0.001 |
Mean |
14.46 |
14.37 |
14.33 |
32.70 |
±SD |
1.72 |
1.44 |
1.54 |
4.86 |
|
n |
2 |
2 |
2 |
2 |
|
G3, F & 0.003 |
Mean |
14.22 |
14.39 |
14.35 |
32.66 |
±SD |
1.37 |
1.57 |
1.41 |
4.71 |
|
n |
2 |
2 |
2 |
2 |
|
G4, F & 0.03 |
Mean |
14.12 |
14.22 |
14.36 |
32.57 |
±SD |
1.47 |
1.64 |
1.60 |
4.74 |
|
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
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 |
18.58 |
18.64 |
18.42 |
18.94 |
18.81 |
19.28 |
19.29 |
19.31 |
19.34 |
19.25 |
19.39 |
22.32 |
±SD |
2.54 |
2.78 |
2.63 |
3.14 |
3.13 |
3.09 |
3.30 |
3.52 |
3.64 |
3.55 |
3.65 |
4.15 |
|
n |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
G4R, M & 0.03 |
Mean |
18.63 |
18.68 |
18.50 |
18.63 |
18.66 |
19.20 |
19.21 |
19.32 |
19.45 |
19.33 |
19.46 |
22.34 |
±SD |
2.65 |
2.89 |
2.76 |
2.78 |
2.98 |
3.14 |
3.30 |
3.21 |
3.30 |
3.24 |
3.29 |
3.79 |
|
n |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
G1R, F & 0 |
Mean |
14.24 |
14.26 |
14.25 |
14.15 |
14.30 |
15.14 |
15.26 |
15.30 |
15.57 |
15.58 |
15.67 |
18.02 |
±SD |
1.57 |
1.28 |
1.39 |
1.84 |
1.88 |
1.82 |
1.84 |
2.09 |
2.21 |
2.01 |
1.97 |
2.33 |
|
n |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
G4R, F & 0.03 |
Mean |
14.07 |
14.19 |
14.19 |
14.15 |
14.36 |
14.74 |
14.93 |
15.16 |
15.33 |
15.27 |
15.43 |
17.69 |
±SD |
1.48 |
1.88 |
1.67 |
1.78 |
1.94 |
2.25 |
2.19 |
2.27 |
2.43 |
2.11 |
2.13 |
2.41 |
|
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)
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
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 |
7.4 |
6.6 |
7.8 |
7.6 |
±SD |
1.5 |
0.9 |
1.9 |
1.1 |
|
Numbers of Urination |
Mean |
1.4 |
1.4 |
1.4 |
1.6 |
±SD |
0.5 |
0.5 |
0.5 |
0.5 |
|
Number of Defecation |
Mean |
1.0 |
1.0 |
1.0 |
0.8 |
±SD |
0.7 |
0.7 |
0.7 |
0.4 |
|
Clonic involuntary movement |
1 |
1 |
1 |
1 |
|
Tonic involuntary movement |
1 |
1 |
1 |
1 |
|
Stereotype Behaviour |
1 |
1 |
1 |
1 |
|
Excessive Grooming |
Mean |
3.8 |
4.0 |
4.2 |
4.4 |
±SD |
0.4 |
1.0 |
0.8 |
0.5 |
|
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 |
98.2 |
98.2 |
98.5 |
98.5 |
±SD |
0.2 |
0.2 |
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 |
TABLE 5 (Contd...). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
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
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 |
7.8 |
7.6 |
8.8 |
9.0 |
±SD |
0.8 |
1.7 |
0.8 |
1.0 |
|
Numbers of Urination |
Mean |
1.2 |
1.2 |
1.0 |
1.4 |
±SD |
0.8 |
0.4 |
0.7 |
0.5 |
|
Number of Defecation |
Mean |
1.0 |
1.0 |
1.2 |
1.0 |
±SD |
0.7 |
0.7 |
0.4 |
0.7 |
|
Clonic involuntary movement |
1 |
1 |
1 |
1 |
|
Tonic involuntary movement |
1 |
1 |
1 |
1 |
|
Stereotype Behaviour |
1 |
1 |
1 |
1 |
|
Excessive Grooming |
Mean |
4.2 |
3.4 |
4.0 |
5.4* |
±SD |
0.8 |
0.9 |
0.7 |
0.5 |
|
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 |
97.9 |
97.9 |
98.7 |
98.7 |
±SD |
0.2 |
0.2 |
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; *: Statistically significant (p<0.05).
TABLE 6. SUMMARY OF HIND LIMB FOOT SPLAY (cm) RECORD
# Week 4 & 12 |
|||
Group, Sex & Dose (mg/L) |
Hind Limb Foot Splay (cm) |
||
G1, M & 0 |
Mean |
6.0 |
|
±SD |
0.4 |
||
n |
5 |
||
G4, M & 0.03 |
Mean |
5.7 |
|
±SD |
0.2 |
||
n |
5 |
||
G1, F & 0 |
Mean |
6.4 |
|
±SD |
0.5 |
||
n |
5 |
||
G4, F & 0.03 |
Mean |
5.9 |
|
±SD |
0.6 |
||
n |
5 |
||
G1R, M & 0 |
Mean |
8.3 |
|
±SD |
0.4 |
||
n |
5 |
||
G4R, M & 0.03 |
Mean |
7.8 |
|
±SD |
0.5 |
||
n |
5 |
||
G1R, F & 0 |
Mean |
6.5 |
|
±SD |
0.4 |
||
n |
5 |
||
G4R, F & 0.03 |
Mean |
5.8 |
|
±SD |
0.8 |
||
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
# Week 4 & 12 |
||
Group, Sex & Dose (mg/L) |
Movement Counts (no.) |
|
G1, M & 0 |
Mean |
2114.4 |
±SD |
61.2 |
|
n |
5 |
|
G4, M & 0.03 |
Mean |
2067.8 |
±SD |
75.0 |
|
n |
5 |
|
G1, F & 0 |
Mean |
2179.2 |
±SD |
71.7 |
|
n |
5 |
|
G4, F & 0.03 |
Mean |
2164.4 |
±SD |
26.9 |
|
n |
5 |
|
G1R, M & 0 |
Mean |
2074.0 |
±SD |
54.0 |
|
n |
5 |
|
G4R, M & 0.03 |
Mean |
2117.0 |
±SD |
26.3 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
2213.2 |
±SD |
27.6 |
|
n |
5 |
|
G4R, F & 0.03 |
Mean |
2221.8 |
±SD |
9.4 |
|
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 8. SUMMARY OF GRIP STRENGTH (kgf) MEASUREMENT RECORD
# Week 4 & 12 |
||||
Group, Sex & Dose (mg/L) |
Fore limb |
Hind limb |
||
G1, M & 0 |
Mean |
1.352 |
0.330 |
|
±SD |
0.032 |
0.021 |
||
n |
5 |
5 |
||
G4, M & 0.03 |
Mean |
1.373 |
0.354 |
|
±SD |
0.034 |
0.017 |
||
n |
5 |
5 |
||
G1, F & 0 |
Mean |
1.358 |
0.316 |
|
±SD |
0.020 |
0.018 |
||
n |
5 |
5 |
||
G4, F & 0.03 |
Mean |
1.364 |
0.337 |
|
±SD |
0.009 |
0.019 |
||
n |
5 |
5 |
||
G1R, M & 0 |
Mean |
1.563 |
0.536 |
|
±SD |
0.036 |
0.020 |
||
n |
5 |
5 |
||
G4R, M & 0.03 |
Mean |
1.550 |
0.531 |
|
±SD |
0.029 |
0.025 |
||
n |
5 |
5 |
||
G1R, F & 0 |
Mean |
1.418 |
0.371 |
|
±SD |
0.053 |
0.023 |
||
n |
5 |
5 |
||
G4R, F & 0.03 |
Mean |
1.399 |
0.351 |
|
±SD |
0.056 |
0.017 |
||
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 |
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 |
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 |
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; F: Female.
TABLE 10. SUMMARY OF HAEMATOLOGY RECORD
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 |
10.44 |
8.93 |
17.14 |
53.50 |
60.02 |
19.22 |
32.06 |
972.00 |
5.90 |
±SD |
2.75 |
0.41 |
0.82 |
2.05 |
3.62 |
1.14 |
0.84 |
131.79 |
0.25 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
9.54 |
8.57 |
15.86 |
50.28* |
58.84 |
18.54 |
31.54 |
865.20 |
6.08 |
±SD |
3.23 |
0.51 |
0.51 |
1.88 |
4.30 |
1.15 |
0.33 |
28.49 |
0.41 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
10.98 |
8.30 |
16.30 |
52.12 |
63.28 |
19.72 |
31.24 |
760.80 |
7.22 |
±SD |
3.97 |
0.81 |
0.87 |
1.58 |
5.95 |
1.10 |
1.25 |
348.58 |
1.47 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
12.13 |
8.88 |
16.24 |
52.10 |
58.76 |
18.30 |
31.18 |
877.80 |
6.66 |
±SD |
3.91 |
0.56 |
0.92 |
1.78 |
2.46 |
0.60 |
0.76 |
118.40 |
1.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
9.06 |
8.85 |
16.46 |
50.18 |
56.66 |
18.60 |
32.86 |
835.00 |
6.78 |
±SD |
2.95 |
0.22 |
0.74 |
2.10 |
2.28 |
0.89 |
0.48 |
171.39 |
0.22 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
8.17 |
9.08 |
16.00 |
48.82 |
53.80 |
17.62 |
32.78 |
757.20 |
6.70 |
±SD |
1.98 |
0.33 |
0.85 |
2.43 |
2.94 |
1.04 |
0.55 |
350.57 |
0.22 |
|
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
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 |
4.03 |
20.72 |
72.38 |
4.02 |
0.66 |
1.02 |
356.90 |
±SD |
1.89 |
4.02 |
3.94 |
1.89 |
0.42 |
0.38 |
160.41 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
4.09 |
27.06 |
65.18 |
5.10 |
0.68 |
0.80 |
342.64 |
±SD |
1.83 |
2.48 |
3.20 |
0.62 |
0.13 |
0.10 |
124.07 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
7.29 |
21.04 |
71.66 |
4.18 |
0.94 |
1.06 |
571.88 |
±SD |
5.52 |
6.75 |
7.23 |
1.17 |
0.27 |
0.55 |
374.97 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
4.66 |
21.72 |
71.72 |
4.16 |
0.88 |
0.62 |
406.30 |
±SD |
2.03 |
6.20 |
6.74 |
0.88 |
0.58 |
0.22 |
156.82 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
2.75 |
24.76 |
68.60 |
3.74 |
1.36 |
0.48 |
243.48 |
±SD |
0.51 |
6.03 |
5.00 |
0.65 |
0.41 |
0.16 |
49.00 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
2.24 |
26.74 |
68.40 |
2.26* |
1.68 |
0.28 |
203.34 |
±SD |
0.23 |
5.60 |
4.67 |
0.61 |
0.71 |
0.13 |
17.59 |
|
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
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 |
2.14 |
7.57 |
0.42 |
0.06 |
0.10 |
15.72 |
20.68 |
±SD |
0.63 |
2.10 |
0.20 |
0.03 |
0.03 |
1.40 |
0.77 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
2.55 |
6.25 |
0.48 |
0.06 |
0.08 |
16.12 |
20.48 |
±SD |
0.84 |
2.21 |
0.13 |
0.03 |
0.02 |
0.56 |
2.41 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
2.21 |
8.01 |
0.43 |
0.10 |
0.11 |
16.94 |
26.86 |
±SD |
0.78 |
3.43 |
0.12 |
0.03 |
0.07 |
2.33 |
8.44 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
2.75 |
8.57 |
0.52 |
0.10 |
0.07 |
16.32 |
23.94 |
±SD |
1.41 |
2.46 |
0.23 |
0.07 |
0.03 |
1.11 |
4.54 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
2.12 |
6.32 |
0.36 |
0.13 |
0.04 |
15.32 |
21.20 |
±SD |
0.29 |
2.46 |
0.17 |
0.06 |
0.02 |
1.49 |
1.80 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
2.14 |
5.63 |
0.19 |
0.13 |
0.03 |
17.96 |
26.26 |
±SD |
0.43 |
1.63 |
0.09 |
0.05 |
0.02 |
5.13 |
6.31 |
|
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
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 |
9.06 |
8.85 |
16.60 |
49.98 |
56.50 |
18.84 |
33.30 |
1023.80 |
6.02 |
±SD |
2.15 |
0.71 |
0.75 |
3.61 |
1.04 |
1.19 |
2.14 |
93.66 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
9.75 |
9.77 |
17.18 |
52.46 |
53.74* |
17.58* |
32.74 |
1092.80 |
6.16 |
±SD |
4.30 |
1.21 |
2.04 |
6.09 |
1.24 |
0.39 |
0.21 |
213.31 |
0.30 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
9.40 |
9.63 |
17.08 |
52.46 |
54.48 |
17.76 |
32.58 |
980.00 |
6.38 |
±SD |
3.58 |
0.96 |
1.70 |
5.61 |
1.70 |
0.51 |
0.57 |
262.16 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
9.93 |
9.26 |
16.10 |
49.62 |
53.60* |
17.38* |
32.44 |
992.60 |
6.60 |
±SD |
2.52 |
0.32 |
0.60 |
1.67 |
1.50 |
0.72 |
0.62 |
290.58 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
8.38 |
8.72 |
16.10 |
47.82 |
54.82 |
18.50 |
33.70 |
711.40 |
6.58 |
±SD |
1.44 |
0.65 |
1.11 |
3.32 |
0.93 |
0.51 |
0.73 |
276.36 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
8.96 |
8.55 |
15.82 |
47.44 |
55.50 |
18.52 |
33.36 |
854.20 |
6.66 |
±SD |
1.56 |
0.41 |
0.91 |
3.04 |
1.58 |
0.56 |
0.54 |
202.83 |
0.23 |
|
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 10 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
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 |
2.43 |
21.12 |
72.62 |
3.46 |
1.26 |
0.64 |
214.50 |
±SD |
0.43 |
4.43 |
4.70 |
0.96 |
0.68 |
0.24 |
40.96 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
1.72 |
27.40 |
66.90 |
2.64 |
1.32 |
0.84 |
166.78 |
±SD |
0.56 |
6.67 |
7.47 |
0.66 |
0.34 |
0.61 |
47.63 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
2.15 |
24.56 |
70.40 |
2.38 |
1.06 |
0.76 |
204.00 |
±SD |
0.54 |
5.33 |
5.11 |
1.22 |
0.43 |
0.62 |
37.56 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
1.91 |
26.70 |
67.40 |
2.78 |
1.58 |
0.44 |
176.24 |
±SD |
0.61 |
3.96 |
5.05 |
0.88 |
0.64 |
0.11 |
51.51 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.84 |
22.58 |
71.16 |
2.90 |
2.10 |
0.38 |
161.28 |
±SD |
0.29 |
5.49 |
6.51 |
1.01 |
1.42 |
0.04 |
33.92 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
1.95 |
23.14 |
71.68 |
2.38 |
1.64 |
0.34 |
165.02 |
±SD |
0.54 |
5.94 |
6.51 |
0.31 |
0.32 |
0.09 |
40.29 |
|
n |
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
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 |
1.94 |
6.55 |
0.31 |
0.12 |
0.06 |
16.82 |
25.28 |
±SD |
0.68 |
1.48 |
0.09 |
0.07 |
0.04 |
1.78 |
1.76 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
2.51 |
6.70 |
0.25 |
0.13 |
0.07 |
17.50 |
20.36* |
±SD |
0.74 |
3.44 |
0.09 |
0.06 |
0.03 |
3.15 |
1.60 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
2.24 |
6.66 |
0.25 |
0.09 |
0.08 |
16.44 |
19.46* |
±SD |
0.82 |
2.75 |
0.21 |
0.01 |
0.06 |
2.49 |
2.35 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
2.66 |
6.69 |
0.28 |
0.15 |
0.04 |
17.50 |
17.86* |
±SD |
0.80 |
1.70 |
0.13 |
0.06 |
0.01 |
4.63 |
2.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.89 |
5.97 |
0.24 |
0.18 |
0.03 |
16.12 |
22.70 |
±SD |
0.54 |
1.25 |
0.08 |
0.12 |
0.01 |
0.82 |
4.20 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
2.10 |
6.39 |
0.21 |
0.15 |
0.03 |
16.94 |
24.66 |
±SD |
0.81 |
1.07 |
0.05 |
0.05 |
0.01 |
1.48 |
5.92 |
|
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
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 |
0.36 |
17.16 |
73.14 |
2.00 |
0.24 |
1.60 |
0.06 |
±SD |
0.16 |
5.63 |
7.02 |
1.27 |
0.29 |
1.21 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
0.54 |
22.56 |
67.02 |
2.66 |
0.70 |
3.46 |
0.14 |
±SD |
0.42 |
4.76 |
7.90 |
0.82 |
0.93 |
2.57 |
0.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
0.15 |
23.48 |
65.82 |
3.22 |
4.22* |
8.06* |
0.02 |
±SD |
0.13 |
20.92 |
26.49 |
4.01 |
3.80 |
3.11 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
0.15 |
25.36 |
66.18 |
2.70 |
1.96 |
2.16 |
0.04 |
±SD |
0.06 |
9.32 |
12.11 |
2.65 |
2.09 |
1.27 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
0.34 |
17.08 |
57.66 |
1.10 |
0.90 |
5.56 |
0.06 |
±SD |
0.12 |
3.07 |
20.72 |
0.49 |
1.33 |
3.29 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
0.40 |
17.76 |
56.22 |
1.78 |
0.88 |
3.66 |
0.07 |
±SD |
0.22 |
9.61 |
12.23 |
1.80 |
0.75 |
2.14 |
0.06 |
|
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
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 |
0.26 |
0.01 |
0.00 |
0.01 |
63.76 |
322.20 |
±SD |
0.11 |
0.00 |
0.00 |
0.01 |
27.81 |
108.59 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
0.34 |
0.01 |
0.00 |
0.02 |
83.96 |
291.48 |
±SD |
0.24 |
0.01 |
0.00 |
0.01 |
53.17 |
142.06 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
0.12 |
0.00 |
0.00 |
0.01 |
52.34 |
306.36 |
±SD |
0.10 |
0.00 |
0.00 |
0.01 |
45.59 |
105.45 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
0.10 |
0.00 |
0.00 |
0.00 |
34.26 |
281.34 |
±SD |
0.05 |
0.01 |
0.00 |
0.00 |
9.63 |
105.25 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
0.21 |
0.00 |
0.00 |
0.02 |
72.74 |
253.26 |
±SD |
0.12 |
0.00 |
0.00 |
0.02 |
29.08 |
178.66 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
0.22 |
0.01 |
0.00 |
0.01 |
149.78 |
200.61 |
±SD |
0.11 |
0.01 |
0.00 |
0.01 |
122.02 |
89.26 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of animals.
TABLE 11 (Contd…). SUMMARY OF BALF RECORD
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 |
0.25 |
22.28 |
64.02 |
1.18 |
3.18 |
2.42 |
0.05 |
±SD |
0.13 |
1.84 |
8.09 |
0.62 |
2.18 |
1.52 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
0.21 |
24.72 |
58.52 |
1.88 |
3.64 |
7.48 |
0.05 |
±SD |
0.09 |
11.62 |
21.00 |
0.67 |
4.05 |
6.51 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
0.32 |
23.14 |
65.12 |
2.02 |
1.72 |
1.94 |
0.08 |
±SD |
0.17 |
6.81 |
9.88 |
0.69 |
1.53 |
0.98 |
0.06 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
0.23 |
16.04 |
71.72 |
3.52* |
3.48 |
4.42 |
0.04 |
±SD |
0.17 |
8.52 |
11.69 |
1.93 |
2.34 |
4.54 |
0.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
0.22 |
21.06 |
53.16 |
0.98 |
1.72 |
6.22 |
0.04 |
±SD |
0.09 |
6.39 |
7.11 |
1.31 |
1.64 |
2.01 |
0.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
0.21 |
17.64 |
61.56 |
1.86 |
0.90 |
4.18 |
0.03 |
±SD |
0.07 |
6.61 |
16.43 |
1.10 |
0.53 |
1.54 |
0.02 |
|
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
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 |
0.16 |
0.00 |
0.01 |
0.00 |
40.70 |
272.13 |
±SD |
0.10 |
0.00 |
0.00 |
0.01 |
23.61 |
89.97 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
0.13 |
0.00 |
0.01 |
0.02 |
63.46 |
302.96 |
±SD |
0.08 |
0.00 |
0.01 |
0.02 |
32.58 |
89.90 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
0.21 |
0.01 |
0.00 |
0.00 |
51.52 |
355.10 |
±SD |
0.10 |
0.01 |
0.01 |
0.01 |
21.60 |
108.66 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
0.16 |
0.01 |
0.00 |
0.01 |
46.32 |
346.50 |
±SD |
0.11 |
0.01 |
0.01 |
0.01 |
23.88 |
251.82 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
0.12 |
0.00 |
0.00 |
0.01 |
46.52 |
235.94 |
±SD |
0.06 |
0.00 |
0.00 |
0.01 |
12.39 |
96.20 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
0.13 |
0.00 |
0.00 |
0.01 |
91.78* |
151.51 |
±SD |
0.05 |
0.00 |
0.00 |
0.00 |
26.14 |
37.86 |
|
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 CHEMISTRY RECORD
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 |
91.60 |
31.90 |
0.41 |
42.00 |
44.60 |
6.82 |
3.09 |
53.20 |
94.20 |
±SD |
8.88 |
2.88 |
0.03 |
8.40 |
8.85 |
0.48 |
0.07 |
13.94 |
10.66 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
85.00 |
31.50 |
0.40 |
49.60 |
41.20 |
7.00 |
3.15 |
57.40 |
103.20 |
±SD |
8.51 |
1.64 |
0.01 |
6.43 |
12.76 |
0.20 |
0.15 |
7.57 |
12.77 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
97.00 |
32.28 |
0.39 |
47.60 |
49.20 |
6.90 |
3.10 |
53.40 |
108.20 |
±SD |
15.70 |
4.40 |
0.02 |
11.01 |
8.23 |
0.30 |
0.11 |
6.19 |
7.76 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
86.60 |
35.32 |
0.38 |
50.40 |
48.00 |
6.64 |
2.99 |
71.00 |
109.00 |
±SD |
9.71 |
11.73 |
0.03 |
12.30 |
13.67 |
0.43 |
0.17 |
15.89 |
21.51 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
77.20 |
34.62 |
0.52 |
53.60 |
29.80 |
7.52 |
3.37 |
62.20 |
106.60 |
±SD |
10.08 |
6.83 |
0.05 |
7.47 |
4.71 |
0.29 |
0.18 |
7.26 |
17.56 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
89.00 |
36.06 |
0.53 |
52.60 |
33.60 |
7.66 |
3.50 |
62.00 |
104.40 |
±SD |
6.71 |
1.99 |
0.05 |
8.68 |
9.02 |
0.15 |
0.33 |
13.62 |
14.06 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: number of animals.
TABLE 12 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
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 |
202.00 |
0.01 |
9.78 |
7.30 |
3.73 |
14.89 |
142.10 |
3.87 |
109.74 |
±SD |
79.50 |
0.02 |
0.33 |
0.63 |
0.45 |
1.34 |
0.83 |
0.18 |
0.91 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
178.80 |
0.04 |
9.92 |
7.24 |
3.85 |
14.70 |
142.12 |
3.97 |
110.44 |
±SD |
21.75 |
0.02 |
0.29 |
0.43 |
0.15 |
0.76 |
0.89 |
0.16 |
0.73 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
184.40 |
0.04 |
9.94 |
7.14 |
3.80 |
15.06 |
141.14 |
3.96 |
109.42 |
±SD |
47.26 |
0.05 |
0.21 |
0.55 |
0.33 |
2.05 |
0.91 |
0.29 |
1.27 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
188.80 |
0.03 |
9.80 |
7.44 |
3.65 |
16.48 |
142.92 |
3.94 |
111.54* |
±SD |
57.73 |
0.02 |
0.12 |
0.36 |
0.27 |
5.47 |
0.91 |
0.09 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
142.60 |
0.05 |
9.60 |
6.08 |
4.15 |
16.16 |
144.46 |
3.54 |
105.24 |
±SD |
31.91 |
0.01 |
0.28 |
0.47 |
0.26 |
3.19 |
0.27 |
0.34 |
1.42 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
163.80 |
0.05 |
9.52 |
5.36 |
4.16 |
16.83 |
144.52 |
3.55 |
106.68 |
±SD |
44.64 |
0.01 |
0.36 |
0.92 |
0.30 |
0.93 |
0.64 |
0.12 |
0.63 |
|
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
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 |
95.80 |
29.54 |
0.39 |
53.60 |
48.60 |
7.08 |
3.35 |
42.60 |
91.20 |
±SD |
9.86 |
4.95 |
0.04 |
11.74 |
5.50 |
0.36 |
0.25 |
7.44 |
8.76 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
100.20 |
28.98 |
0.37 |
54.40 |
50.80 |
7.32 |
3.33 |
44.20 |
96.00 |
±SD |
2.68 |
2.77 |
0.01 |
6.62 |
14.79 |
0.22 |
0.13 |
6.61 |
6.63 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
102.20 |
30.38 |
0.35 |
59.60 |
37.40 |
7.28 |
3.34 |
46.80 |
105.40 |
±SD |
5.45 |
5.89 |
0.03 |
14.59 |
5.94 |
0.28 |
0.11 |
12.19 |
10.31 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
108.00 |
32.98 |
0.37 |
58.20 |
45.20 |
7.20 |
3.16 |
38.20 |
92.00 |
±SD |
11.98 |
7.09 |
0.07 |
14.75 |
14.13 |
0.61 |
0.18 |
9.98 |
27.06 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
90.80 |
40.48 |
0.59 |
73.60 |
37.40 |
8.14 |
3.92 |
41.60 |
88.60 |
±SD |
8.64 |
2.53 |
0.04 |
27.56 |
10.43 |
0.58 |
0.32 |
5.03 |
14.03 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
98.00 |
36.66 |
0.57 |
72.40 |
38.20 |
8.14 |
3.95 |
40.80 |
85.60 |
±SD |
13.69 |
4.61 |
0.06 |
19.49 |
5.36 |
0.42 |
0.26 |
5.89 |
15.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: number of animals.
TABLE 12 (Contd…). SUMMARY OF CLINICAL CHEMISTRY
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 |
105.20 |
0.02 |
10.40 |
7.02 |
3.73 |
13.79 |
140.90 |
4.12 |
111.32 |
±SD |
23.99 |
0.02 |
0.31 |
0.54 |
0.24 |
2.31 |
0.99 |
0.29 |
2.77 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
96.00 |
0.03 |
10.14 |
6.98 |
3.99 |
13.53 |
141.66 |
4.05 |
111.20 |
±SD |
12.41 |
0.01 |
0.32 |
0.87 |
0.34 |
1.29 |
1.60 |
0.70 |
1.14 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
140.60 |
0.04 |
10.28 |
6.80 |
3.94 |
14.18 |
141.68 |
3.82 |
111.46 |
±SD |
71.25 |
0.01 |
0.36 |
0.94 |
0.33 |
2.75 |
1.44 |
0.23 |
1.94 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
129.80 |
0.03 |
10.34 |
7.20 |
4.04 |
15.39 |
142.58 |
4.07 |
112.06 |
±SD |
26.81 |
0.02 |
0.30 |
0.35 |
0.46 |
3.31 |
1.00 |
0.20 |
0.86 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
80.00 |
0.06 |
10.02 |
5.12 |
4.22 |
18.89 |
143.94 |
3.56 |
106.40 |
±SD |
19.27 |
0.01 |
0.49 |
0.79 |
0.32 |
1.18 |
0.88 |
0.41 |
1.02 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
62.20 |
0.07 |
10.06 |
4.72 |
4.19 |
17.11 |
143.88 |
3.17 |
106.60 |
±SD |
10.69 |
0.02 |
0.26 |
0.85 |
0.47 |
2.15 |
1.39 |
0.29 |
1.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals.
TABLE 13. SUMMARY OF URINALYSIS
Examination |
Group, Sex & Dose (mg/L) |
G1, M & 0 |
G2, M & 0.001 |
G3, M & 0.003 |
G4, M & 0.03 |
G1R, M & 0 |
G4R, M & 0.03 |
|
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||
Physical |
Colour |
Pale Yellow |
4 |
3 |
3 |
4 |
5 |
5 |
Yellow |
1 |
2 |
2 |
1 |
- |
- |
||
Appearance |
Clear |
4 |
3 |
2 |
3 |
5 |
5 |
|
Turbid |
1 |
2 |
3 |
2 |
- |
- |
||
Volume (mL) |
Mean |
5.5 |
5.9 |
5.7 |
5.4 |
6.5 |
6.5 |
|
±SD |
0.9 |
0.7 |
1.3 |
0.4 |
0.6 |
0.8 |
||
Chemical |
pH |
Mean |
6.4 |
6.0 |
6.8 |
6.1 |
7.5 |
7.4 |
±SD |
1.6 |
0.9 |
1.3 |
1.0 |
0.6 |
0.5 |
||
Specific Gravity |
Mean |
1.009 |
1.007 |
1.007 |
1.006 |
1.018 |
1.016 |
|
±SD |
0.002 |
0.004 |
0.003 |
0.002 |
0.007 |
0.007 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.2 |
0.2 |
0.4 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.4 |
||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Ketones (mg/dL) |
Neg |
2 |
4 |
2 |
2 |
- |
2 |
|
5 |
2 |
1 |
3 |
3 |
5 |
2 |
||
15 |
1 |
- |
- |
- |
- |
1 |
||
Blood (Ery/µL) |
Neg |
- |
- |
- |
- |
1 |
1 |
|
Ca10 |
1 |
- |
- |
- |
- |
1 |
||
Ca25 |
3 |
2 |
1 |
- |
2 |
2 |
||
Ca80 |
1 |
3 |
4 |
5 |
1 |
1 |
||
>=Ca200 |
- |
- |
- |
- |
1 |
- |
||
Proteins (mg/dL) |
Neg |
- |
- |
- |
2 |
- |
1 |
|
Trace |
2 |
4 |
3 |
1 |
- |
1 |
||
30 |
3 |
1 |
1 |
2 |
2 |
3 |
||
100 |
- |
- |
1 |
- |
2 |
- |
||
>=300 |
- |
- |
- |
- |
1 |
- |
||
Nitrite |
Neg |
3 |
5 |
4 |
5 |
4 |
5 |
|
Pos |
2 |
- |
1 |
- |
1 |
- |
||
Leucocytes (Leu/µL) |
Neg |
2 |
3 |
- |
1 |
- |
1 |
|
Ca15 |
3 |
2 |
5 |
4 |
2 |
1 |
||
Ca70 |
- |
- |
- |
- |
3 |
2 |
||
Ca125 |
- |
- |
- |
- |
- |
1 |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Micro albumin (MALB) (mg/dL) |
Neg |
- |
- |
- |
2 |
- |
- |
|
>15 |
5 |
5 |
5 |
3 |
5 |
4 |
||
15 |
- |
- |
- |
- |
- |
1 |
||
Microscopic |
Epithelial cells |
0 |
1 |
- |
1 |
1 |
4 |
3 |
0-1 |
2 |
4 |
3 |
3 |
1 |
2 |
||
0-2 |
1 |
- |
- |
- |
- |
- |
||
1-2 |
1 |
1 |
1 |
1 |
- |
- |
||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
|
Crystals |
Absent |
2 |
1 |
1 |
2 |
- |
- |
|
Present |
3 |
4 |
4 |
3 |
5 |
5 |
M: Male; Neg: Negative; Ca: Calculated Approximately; Pos: Positive; SD: Standard Deviation; R: Recovery.
TABLE 13 (Contd…). SUMMARY OF URINALYSIS
Examination |
Group, Sex & Dose (mg/L) |
G1, F & 0 |
G2, F & 0.001 |
G3, F & 0.003 |
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 |
4 |
4 |
4 |
5 |
5 |
Yellow |
- |
1 |
1 |
1 |
- |
- |
||
Appearance |
Clear |
5 |
3 |
4 |
4 |
5 |
5 |
|
Turbid |
- |
2 |
1 |
1 |
- |
- |
||
Volume (mL) |
Mean |
6.1 |
6.6 |
7.6 |
6.6 |
6.6 |
6.9 |
|
±SD |
2.3 |
0.8 |
2.3 |
2.9 |
1.0 |
1.3 |
||
Chemical |
pH |
Mean |
6.6 |
7.1 |
6.8 |
6.4 |
7.0 |
7.6 |
±SD |
1.7 |
1.3 |
1.2 |
1.0 |
0.4 |
0.7 |
||
Specific Gravity |
Mean |
1.006 |
1.005 |
1.005 |
1.005 |
1.013 |
1.009* |
|
±SD |
0.002 |
0.000 |
0.000 |
0.000 |
0.003 |
0.002 |
||
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 |
5 |
5 |
5 |
5 |
5 |
5 |
|
Ketones (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Blood (Ery/µL) |
Neg |
4 |
1 |
1 |
- |
4 |
4 |
|
Ca10 |
- |
- |
- |
3 |
1 |
- |
||
Ca25 |
- |
3 |
4 |
2 |
- |
1 |
||
Ca80 |
1 |
1 |
- |
- |
- |
- |
||
Proteins (mg/dL) |
Neg |
1 |
3 |
2 |
4 |
5 |
3 |
|
Trace |
3 |
2 |
3 |
1 |
- |
1 |
||
30 |
1 |
- |
- |
- |
- |
- |
||
100 |
- |
- |
- |
- |
- |
1 |
||
Nitrite |
Neg |
4 |
4 |
4 |
5 |
3 |
5 |
|
Pos |
1 |
1 |
1 |
- |
2 |
- |
||
Leucocytes (Leu/µL) |
Neg |
1 |
- |
- |
- |
4 |
4 |
|
Ca15 |
4 |
5 |
5 |
5 |
1 |
- |
||
Ca70 |
- |
- |
- |
- |
- |
1 |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
|
Micro albumin (MALB) (mg/dL) |
Neg |
1 |
3 |
2 |
4 |
3 |
3 |
|
>15 |
4 |
2 |
3 |
1 |
- |
2 |
||
15 |
- |
- |
- |
|
2 |
- |
||
Microscopic |
Epithelial cells |
0 |
1 |
1 |
2 |
2 |
5 |
4 |
0-1 |
3 |
1 |
1 |
3 |
- |
1 |
||
1-2 |
1 |
3 |
2 |
- |
- |
- |
||
Casts |
Absent |
4 |
5 |
4 |
5 |
5 |
5 |
|
Present |
1 |
- |
1 |
- |
- |
- |
||
Crystals |
Absent |
2 |
1 |
- |
3 |
- |
- |
|
Present |
3 |
4 |
5 |
2 |
5 |
5 |
F: Female; Neg: Negative; Ca: Calculated Approximately; Pos: Positive; SD: Standard Deviation; R: Recovery.
*: Statistically significant (p<0.05).
TABLE 14. SUMMARY OF ABSOLUTE ORGAN WEIGHTS (g)
Group, Sex & Dose (mg/L) |
Adrenals |
Thymus |
Spleen |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Lungs |
|
G1, M & 0 |
Mean |
0.0546 |
0.3164 |
1.0157 |
3.2814 |
0.9708 |
1.9636 |
1.9756 |
8.1699 |
0.5472 |
±SD |
0.0079 |
0.0341 |
0.0992 |
0.2444 |
0.0559 |
0.1238 |
0.1009 |
0.6837 |
0.0516 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
0.0507 |
0.2643 |
1.1574 |
2.8052* |
1.0410 |
1.9459 |
1.9383 |
8.4021 |
0.7314* |
±SD |
0.0057 |
0.0492 |
0.2344 |
0.2205 |
0.0990 |
0.1978 |
0.1199 |
0.5872 |
0.0658 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
0.0525 |
0.2908 |
1.1117 |
2.9190 |
0.9237 |
1.7474 |
1.8780 |
7.0657 |
0.5565 |
±SD |
0.0037 |
0.0359 |
0.1191 |
0.1732 |
0.0443 |
0.0918 |
0.0720 |
0.4982 |
0.0609 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
0.0542 |
0.2789 |
0.9743 |
3.4094 |
1.0249 |
1.9576 |
1.9070 |
7.4683 |
0.7014* |
±SD |
0.0049 |
0.0236 |
0.0965 |
0.4453 |
0.0507 |
0.1801 |
0.0340 |
0.9456 |
0.0711 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
0.0609 |
0.2117 |
1.3692 |
3.6598 |
1.4328 |
2.8445 |
2.0602 |
11.2475 |
0.7140 |
±SD |
0.0042 |
0.0517 |
0.0633 |
0.3034 |
0.1040 |
0.5484 |
0.0512 |
1.7149 |
0.0767 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
0.0631 |
0.2829* |
1.1172* |
3.3671 |
1.3194 |
2.3350 |
2.0685 |
10.1517 |
0.6762 |
±SD |
0.0048 |
0.0365 |
0.1003 |
0.2875 |
0.0756 |
0.1815 |
0.0608 |
0.0759 |
0.0505 |
|
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 14 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHTS (g)
Group, Sex & Dose (mg/L) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus |
Heart |
Kidneys |
Brain |
Liver |
Lungs |
|
G1, F & 0 |
Mean |
0.0623 |
0.3702 |
0.6049 |
0.1205 |
0.4089 |
0.7567 |
1.4280 |
1.7656 |
6.2227 |
0.5146 |
±SD |
0.0037 |
0.0701 |
0.1064 |
0.0129 |
0.0518 |
0.0741 |
0.1903 |
0.0929 |
0.4228 |
0.0453 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
0.0594 |
0.3682 |
0.4791 |
0.1181 |
0.5253 |
0.7450 |
1.3006 |
1.8402 |
5.5576 |
0.5163 |
±SD |
0.0080 |
0.0627 |
0.1005 |
0.0094 |
0.1533 |
0.0599 |
0.1535 |
0.0842 |
0.3985 |
0.0639 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
0.0561 |
0.2862 |
0.3462* |
0.0987 |
0.3390 |
0.7369 |
1.2861 |
1.7616 |
5.6863 |
0.5077 |
±SD |
0.0070 |
0.0741 |
0.0372 |
0.0138 |
0.0602 |
0.1018 |
0.1160 |
0.0763 |
0.3377 |
0.0388 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
0.0560 |
0.2707 |
0.4679 |
0.1156 |
0.3450 |
0.7066 |
1.2147 |
1.7537 |
6.0287 |
0.6040 |
±SD |
0.0056 |
0.0276 |
0.0857 |
0.0180 |
0.0603 |
0.0985 |
0.1357 |
0.0714 |
0.6349 |
0.0824 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
0.0809 |
0.2637 |
0.6039 |
0.1321 |
0.7511 |
0.9010 |
1.5550 |
1.8811 |
7.9632 |
0.4801 |
±SD |
0.0111 |
0.0441 |
0.0799 |
0.0168 |
0.2097 |
0.0950 |
0.0643 |
0.0875 |
0.4811 |
0.0316 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
0.0778 |
0.2352 |
0.5206 |
0.1647* |
0.7788 |
0.9655 |
1.5697 |
1.8020 |
7.2701 |
0.4812 |
±SD |
0.0035 |
0.0293 |
0.0647 |
0.0077 |
0.2014 |
0.0968 |
0.1387 |
0.1353 |
0.9500 |
0.0610 |
|
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
Group, Sex & Dose (mg/L) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Lungs |
|
G1, M & 0 |
Mean |
229.55 |
0.0237 |
0.1385 |
0.4480 |
1.4392 |
0.4259 |
0.8641 |
0.8683 |
3.5879 |
0.2396 |
±SD |
20.95 |
0.0018 |
0.0167 |
0.0808 |
0.1679 |
0.0480 |
0.1288 |
0.1105 |
0.4917 |
0.0270 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
225.52 |
0.0225 |
0.1174 |
0.5200 |
1.2504 |
0.4629 |
0.8621 |
0.8604 |
3.7368 |
0.3261* |
±SD |
15.25 |
0.0022 |
0.0207 |
0.1333 |
0.1495 |
0.0523 |
0.0501 |
0.0388 |
0.3325 |
0.0437 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
228.80 |
0.0230 |
0.1278 |
0.4869 |
1.2795 |
0.4045 |
0.7658 |
0.8230 |
3.1008 |
0.2440 |
±SD |
14.36 |
0.0012 |
0.0204 |
0.0550 |
0.1057 |
0.0231 |
0.0593 |
0.0548 |
0.3321 |
0.0305 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
229.21 |
0.0236 |
0.1220 |
0.4252 |
1.4888 |
0.4480 |
0.8539 |
0.8344 |
3.2547 |
0.3068* |
±SD |
15.64 |
0.0009 |
0.0117 |
0.0314 |
0.1825 |
0.0220 |
0.0491 |
0.0454 |
0.3036 |
0.0339 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
423.01 |
0.0144 |
0.0499 |
0.3236 |
0.8657 |
0.3385 |
0.6744 |
0.4873 |
2.6686 |
0.1692 |
±SD |
11.01 |
0.0008 |
0.0116 |
0.0088 |
0.0748 |
0.0194 |
0.1410 |
0.0183 |
0.4805 |
0.0227 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
418.89 |
0.0151 |
0.0676* |
0.2670* |
0.8047 |
0.3150 |
0.5574 |
0.4939 |
2.4239 |
0.1613 |
±SD |
6.76 |
0.0013 |
0.0089 |
0.0268 |
0.0797 |
0.0187 |
0.0407 |
0.0156 |
0.0366 |
0.0098 |
|
n |
5 |
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 15 (Contd…). SUMMARY OF ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/L) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus |
Heart |
Kidneys |
Brain |
Liver |
Lungs |
|
G1, F & 0 |
Mean |
183.73 |
0.0340 |
0.2021 |
0.3302 |
0.0659 |
0.2228 |
0.4117 |
0.7780 |
0.9621 |
3.3918 |
0.2801 |
±SD |
10.58 |
0.0031 |
0.0399 |
0.0616 |
0.0093 |
0.0267 |
0.0288 |
0.0967 |
0.0446 |
0.2396 |
0.0176 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
184.83 |
0.0323 |
0.1989 |
0.2584 |
0.0639 |
0.2833 |
0.4037 |
0.7078 |
0.9991 |
3.0179 |
0.2812 |
±SD |
11.27 |
0.0057 |
0.0301 |
0.0468 |
0.0023 |
0.0773 |
0.0323 |
0.1163 |
0.0846 |
0.3169 |
0.0489 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
181.71 |
0.0308 |
0.1592 |
0.1918* |
0.0546 |
0.1868 |
0.4045 |
0.7093 |
0.9707 |
3.1331 |
0.2800 |
±SD |
11.37 |
0.0027 |
0.0487 |
0.0310 |
0.0094 |
0.0339 |
0.0379 |
0.0690 |
0.0360 |
0.1629 |
0.0240 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
180.35 |
0.0312 |
0.1505 |
0.2599 |
0.0643 |
0.1925 |
0.3923 |
0.6760 |
0.9740 |
3.3548 |
0.3360 |
±SD |
8.36 |
0.0040 |
0.0179 |
0.0485 |
0.0111 |
0.0407 |
0.0568 |
0.0940 |
0.0590 |
0.4502 |
0.0522 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
313.71 |
0.0258 |
0.0840 |
0.1930 |
0.0423 |
0.2400 |
0.2871 |
0.4958 |
0.5996 |
2.5426 |
0.1531 |
±SD |
9.95 |
0.0035 |
0.0141 |
0.0286 |
0.0065 |
0.0704 |
0.0272 |
0.0176 |
0.0176 |
0.2084 |
0.0095 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
315.75 |
0.0247 |
0.0746 |
0.1648 |
0.0522* |
0.2452 |
0.3060 |
0.4971 |
0.5706 |
2.2994 |
0.1527 |
±SD |
10.67 |
0.0011 |
0.0098 |
0.0187 |
0.0037 |
0.0568 |
0.0317 |
0.0403 |
0.0362 |
0.2605 |
0.0212 |
|
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
Group, Sex & Dose (mg/L) |
Adrenals |
Thymus |
Spleen |
Testes |
Heart |
Kidneys |
Liver |
Lungs |
|
G1, M & 0 |
Mean |
2.7788 |
16.0226 |
51.3579 |
166.1722 |
49.2449 |
99.5469 |
413.9069 |
27.8307 |
±SD |
0.4854 |
1.5547 |
3.4144 |
10.1365 |
3.9319 |
7.2237 |
33.9594 |
3.9036 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 0.001 |
Mean |
2.6222 |
13.6994 |
60.4701 |
145.6095 |
53.8465 |
100.3085 |
435.2792 |
37.9309* |
±SD |
0.3220 |
2.6851 |
15.6939 |
19.4023 |
5.9632 |
6.4199 |
47.2753 |
5.0597 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 0.003 |
Mean |
2.7980 |
15.4923 |
59.2262 |
155.4821 |
49.2030 |
93.0155 |
376.2989 |
29.7121 |
±SD |
0.2108 |
1.8488 |
6.3794 |
8.1774 |
2.0680 |
1.8959 |
23.2915 |
3.8733 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 0.03 |
Mean |
2.8385 |
14.6201 |
51.0374 |
178.7947 |
53.7343 |
102.6157 |
391.1467 |
36.7839* |
±SD |
0.2285 |
1.1804 |
4.1897 |
23.3721 |
2.2678 |
8.8050 |
44.0085 |
3.7514 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, M & 0 |
Mean |
2.9629 |
10.3105 |
66.5051 |
177.9219 |
69.6012 |
137.7537 |
545.6673 |
34.6491 |
±SD |
0.2716 |
2.6969 |
3.8161 |
17.8584 |
5.7242 |
24.4075 |
79.4291 |
3.5038 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 0.03 |
Mean |
3.0525 |
13.6603* |
53.9801* |
162.9183 |
63.8029 |
112.8276 |
491.1223 |
32.6866 |
±SD |
0.2426 |
1.5808 |
4.1095 |
15.1124 |
3.4811 |
7.0959 |
14.6572 |
2.1792 |
|
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
Group, Sex & Dose (mg/L) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus |
Heart |
Kidneys |
Liver |
Lungs |
|
G1, F & 0 |
Mean |
3.5292 |
20.9151 |
34.2411 |
6.8497 |
23.1571 |
42.7947 |
80.6817 |
352.3827 |
29.1361 |
±SD |
0.1907 |
3.3835 |
5.4867 |
0.8875 |
2.5721 |
2.2916 |
7.4942 |
13.8956 |
1.8218 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 0.001 |
Mean |
3.2258 |
20.0988 |
26.2348 |
6.4392 |
28.7329 |
40.5900 |
70.6182 |
302.3913* |
28.0970 |
±SD |
0.4068 |
3.9272 |
6.4878 |
0.7038 |
9.0904 |
4.1657 |
6.8405 |
23.1828 |
3.5362 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 0.003 |
Mean |
3.1860 |
16.3556 |
19.7471* |
5.6262 |
19.2871 |
41.7060 |
73.1094 |
323.1543 |
28.8421 |
±SD |
0.3606 |
4.8290 |
2.9899 |
0.9687 |
3.6096 |
4.1403 |
7.2204 |
21.4424 |
2.1647 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 0.03 |
Mean |
3.1976 |
15.4181 |
26.5831 |
6.6137 |
19.7461 |
40.2033 |
69.2865 |
343.4061 |
34.3678* |
±SD |
0.3393 |
1.1681 |
3.8553 |
1.1811 |
3.8810 |
4.5301 |
7.6436 |
28.5407 |
3.6477 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
4.2971 |
14.0269 |
32.2042 |
7.0595 |
40.0258 |
47.8431 |
82.7173 |
424.6109 |
25.5294 |
±SD |
0.4989 |
2.4052 |
4.8172 |
1.1360 |
11.8751 |
3.5805 |
2.8224 |
39.7625 |
1.4101 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 0.03 |
Mean |
4.3383 |
13.1595 |
29.1223 |
9.1710* |
43.1295 |
53.6468 |
87.3998 |
403.2624 |
26.7929 |
±SD |
0.3998 |
2.2296 |
5.0961 |
0.7043 |
10.4359 |
4.6557 |
8.9537 |
40.2997 |
3.4916 |
|
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
Group & Conc. (mg/L) |
|
Temp. (°C) |
Rh (%) |
O2 (%) |
CO2 (mg/L) |
Air inlet flow rate (L/min)* |
BZC (mg/L) |
G1/G1R & 0 |
Mean |
22.55 |
55.52 |
20.39 |
617.48 |
20.00 |
- |
±SD |
0.31 |
1.90 |
0.19 |
5.43 |
0.00 |
- |
|
G2 & 0.001 |
Mean |
22.66 |
55.95 |
20.47 |
619.67 |
20.00 |
0.0011 |
±SD |
0.31 |
1.35 |
0.21 |
4.84 |
0.00 |
0.0001 |
|
G3 & 0.003 |
Mean |
22.64 |
55.88 |
20.50 |
619.73 |
20.00 |
0.0032 |
±SD |
0.31 |
1.32 |
0.23 |
5.31 |
0.00 |
0.0001 |
|
G4/G4R & 0.03 |
Mean |
22.59 |
55.10 |
20.38 |
617.74 |
20.00 |
0.032 |
±SD |
0.31 |
1.59 |
0.20 |
5.12 |
0.00 |
0.001 |
*: 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.
TABLE 18. SUMMARY OF NOMINAL CONCENTRATION
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) |
1150 |
20 |
360 |
0.16 |
|
4370 |
0.61 |
||||
5230 |
0.73 |
||||
2 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1120 |
20 |
360 |
0.16 |
|
4440 |
0.62 |
||||
5110 |
0.71 |
||||
3 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1200 |
20 |
360 |
0.17 |
|
4380 |
0.61 |
||||
5140 |
0.71 |
||||
4 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1160 |
20 |
360 |
0.16 |
|
4350 |
0.60 |
||||
5160 |
0.72 |
||||
5 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1180 |
20 |
360 |
0.16 |
|
4430 |
0.62 |
||||
5200 |
0.72 |
||||
6 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1090 |
20 |
360 |
0.15 |
|
4340 |
0.60 |
||||
5180 |
0.72 |
||||
7 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1170 |
20 |
360 |
0.16 |
|
4430 |
0.62 |
||||
5190 |
0.72 |
TABLE 18 (Contd…). SUMMARY OF NOMINAL CONCENTRATION
Day |
Group |
Test item Used (mg) (a) |
Air flow rate (L/minute)(b) |
Minute (min) (c) |
Nominal Concentration (mg/L) (a) / (b) × (c) |
8 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1140 |
20 |
360 |
0.16 |
|
4570 |
0.63 |
||||
5200 |
0.72 |
||||
9 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1150 |
20 |
360 |
0.16 |
|
4330 |
0.60 |
||||
5280 |
0.73 |
||||
10 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1190 |
20 |
360 |
0.17 |
|
4410 |
0.61 |
||||
5110 |
0.71 |
||||
11 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1130 |
20 |
360 |
0.16 |
|
4440 |
0.62 |
||||
5210 |
0.72 |
||||
12 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1170 |
20 |
360 |
0.16 |
|
4580 |
0.64 |
||||
5290 |
0.73 |
||||
13 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1190 |
20 |
360 |
0.17 |
|
4320 |
0.60 |
||||
5150 |
0.72 |
||||
14 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1160 |
20 |
360 |
0.16 |
|
4440 |
0.62 |
||||
5120 |
0.71 |
TABLE 18 (Contd…). SUMMARY OF NOMINAL CONCENTRATION
Day |
Group |
Test item Used (mg) (a) |
Air flow rate (L/minute)(b) |
Minute (min) (c) |
Nominal Concentration (mg/L) (a) / (b) × (c) |
15 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1170 |
20 |
360 |
0.16 |
|
4400 |
0.61 |
||||
5170 |
0.72 |
||||
16 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1170 |
20 |
360 |
0.16 |
|
4460 |
0.62 |
||||
5210 |
0.72 |
||||
17 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1190 |
20 |
360 |
0.17 |
|
4400 |
0.61 |
||||
5270 |
0.73 |
||||
18 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1140 |
20 |
360 |
0.16 |
|
4360 |
0.61 |
||||
5200 |
0.72 |
||||
19 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1190 |
20 |
360 |
0.17 |
|
4590 |
0.64 |
||||
5230 |
0.73 |
||||
20 |
G1/G1R (Air Only) |
- |
20 |
360 |
- |
G2, G3 and G4/G4R (Test Item) |
1160 |
20 |
360 |
0.16 |
|
4590 |
0.64 |
||||
5270 |
0.73 |
TABLE 19. SUMMARY OF GROSS PATHOLOGY FINDINGS
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 Concentration (mg/L) |
0 |
0.001* |
0.003* |
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 Concentration (mg/L) |
0 |
0.001* |
0.003* |
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 |
- |
- |
1 |
- |
- |
- |
Uterus– small in size |
- |
- |
1 |
- |
- |
- |
R: Recovery; *: Above doses were provided by the sponsor; - : No incidence.
TABLE 20. SUMMARY OF HISTOPATHOLOGY FINDINGS – MAIN GROUP
Route of administration |
Inhalation |
||||
Treatment |
Air only |
High Dose |
|||
Nominal Target Concentration (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 |
4 |
3 |
4 |
|
Cyst |
Present |
1 |
1 |
2 |
- |
Cast |
Minimal |
1 |
- |
- |
- |
Basophilia, tubules |
Minimal |
- |
- |
1 |
- |
Dilatation, 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(left lobe) |
Number examined |
5 |
5 |
5 |
5 |
Within normal limits |
5 |
5 |
5 |
5 |
|
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 |
M: Male; F: Female; -: no incidence; X: not applicable.
TABLE 20 (Contd..). SUMMARY OF HISTOPATHOLOGY FINDINGS – MAIN GROUP
Route of administration |
Inhalation |
|||||
Treatment |
Air only |
High Dose |
||||
Nominal Target Concentration (mg/L) |
0 |
0.03 |
||||
Group |
G1 |
G4 |
||||
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 |
4 |
X |
||
Inflammation |
Mild |
- |
X |
1 |
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 |
4 |
X |
5 |
X |
||
Atrophy, tubules |
Minimal |
1 |
X |
- |
X |
|
Thymus |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
3 |
5 |
4 |
||
Cyst, epithelial |
Present |
- |
2 |
- |
1 |
|
Thyroid |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
5 |
3 |
3 |
5 |
||
Cyst, ultimobranchial |
Present |
- |
1 |
2 |
- |
|
Ectopic tissue, thymus |
Present |
- |
1 |
- |
- |
|
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 |
5 |
X |
4 |
||
Dilatation, lumen |
Minimal |
X |
- |
X |
1 |
M: Male; F: Female; -: no incidence; X: not applicable.
TABLE 21. SUMMARY OF HISTOPATHOLOGY FINDINGS – RECOVERY GROUP
Route of administration |
Inhalation |
||||
Treatment |
Air only |
High Dose Recovery |
|||
Nominal Target Concentration (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 |
4 |
5 |
4 |
5 |
|
Ectopic tissue, adrenocortical |
Present |
1 |
- |
1 |
- |
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 |
4 |
5 |
5 |
5 |
|
Cellularity, increased, lymphocytes |
Mild |
1 |
- |
- |
- |
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 |
2 |
5 |
5 |
|
Infiltrate, mononuclear cells |
Minimal |
1 |
1 |
- |
- |
Cyst |
Present |
- |
1 |
- |
- |
Dilatation, 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(left lobe) |
Number examined |
5 |
5 |
5 |
5 |
Within normal limits |
3 |
3 |
3 |
3 |
|
Pigment (background finding-likely hemosiderin) |
Minimal |
2 |
2 |
2 |
1 |
Mild |
- |
- |
- |
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 |
R: Recovery; M: Male; F: Female; -: no incidence; X: not applicable.
TABLE 21 (Contd…). SUMMARY OF HISTOPATHOLOGY FINDINGS – RECOVERY GROUP
Route of administration |
Inhalation |
|||||
Treatment |
Air only |
High Dose Recovery |
||||
Nominal Target Concentration (mg/L) |
0 |
0.03 |
||||
Group |
G1R |
G4R |
||||
Sex |
M |
F |
M |
F |
||
Number of Animals |
5 |
5 |
5 |
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 |
||
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 |
3 |
4 |
3 |
||
Cyst, epithelial |
Present |
- |
2 |
1 |
2 |
|
Cellularity, increased, epithelial cells |
Minimal |
- |
- |
1 |
- |
|
Thyroid |
Number examined |
5 |
5 |
5 |
5 |
|
Within normal limits |
4 |
4 |
3 |
4 |
||
Cyst, ultimobranchial |
Present |
1 |
1 |
1 |
1 |
|
Ectopic tissue, thymus |
Present |
- |
- |
1 |
- |
|
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 |
3 |
||
Dilatation, lumen |
Minimal |
X |
1 |
X |
- |
|
Mild |
X |
- |
X |
2 |
R: Recovery; M: Male; F:
Female; -: no incidence; X: not applicable.
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 was found to be 0.03 mg/L when exposed for 6 hours/day, 5 days/week, for 04 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 04 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 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 Hostaperm Yellow H6G for 6 hours per day, 5 days per week, for 04 consecutive weeks, at a nominal target concentration of 0.001, 0.003 and 0.03 mg/L. Animals of the control group (G1/G1R) received air only inhalation for 6 hours/day for 04 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 observed once daily for clinical signs and twice daily for mortality. Body weight was recorded before exposure (day 1) and weekly twice first two weeks during exposure period and weekly once for remaining two weeks during exposure period and recovery period. Feed consumption was recorded weekly. Ophthalmoscopic examinations were performed during the acclimatization period for all groups, and during Week4 for main groups (G1and G4), and duringWeek12 for recovery groups (G1Rand G4R). Neurological/Functional tests were performed during Week4 for G1 and G4 groups and during Week12 for recovery group animals.
At the end of treatment and recovery periods, all animals were fasted overnight (water was available ad 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, absolute organ weight, or relative organ weight.
There were no test item-related, microscopic findings in animals evaluated after terminal and recovery period in the study.
Few microscopic findings observed in this study such as ultimobranchial cyst in thyroid gland, epithelial cysts in thymus and all other findings were considered incidental as they occurred randomly across the dose groups including concurrent controls and/or were expected in laboratory rats.
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