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EC number: 257-776-0 | CAS number: 52238-92-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05 July 2022 to 19 August 2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
- Report date:
- 2022
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Version / remarks:
- “28-day (Sub-acute) inhalation toxicity study” adopted on 25 June 2018
- Deviations:
- no
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- N,N'-(2,5-dichloro-1,4-phenylene)bis[4-[[2-chloro-5-(trifluoromethyl)phenyl]azo]-3-hydroxynaphthalene-2-carboxamide]
- EC Number:
- 257-776-0
- EC Name:
- N,N'-(2,5-dichloro-1,4-phenylene)bis[4-[[2-chloro-5-(trifluoromethyl)phenyl]azo]-3-hydroxynaphthalene-2-carboxamide]
- Cas Number:
- 52238-92-3
- Molecular formula:
- C42H22Cl4F6N6O4
- IUPAC Name:
- N,N'-(2,5-dichloro-1,4-phenylene)bis(4-{[2-chloro-5-(trifluoromethyl)phenyl]diazenyl}-3-hydroxy-2-naphthamide)
- Test material form:
- solid: nanoform, no surface treatment
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and batch number of test material: Clariant Chemicals India Limited and INB3229979
- Purity, including information on contaminants, isomers, etc.: 99.7 % (w/w) C.I. Pigment Red 242
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29°C)
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): No
- Preliminary purification step (if any): No
- Final concentration of a dissolved solid, stock liquid or gel: No
- Final preparation of a solid (e.g. stock crystals ground to fine powder using a mortar and pestle): No
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Sprague Dawley and 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 at the time of randomization
- Weight at study initiation: Males: 140.17 g to 159.83 g and Females: 120.19 g to 140.00 g
- Fasting period before study: No
- Housing: standard polycarbonate cage (size: L 430 x B 280 x H 210 mm)
- 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
- Acclimation period: 06 July 2022 to 11 July 2022
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7°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: 06 July 2022 To: 19 August 2022
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose/head only
- Vehicle:
- clean air
- Mass median aerodynamic diameter (MMAD):
- > 1.82 - <= 1.99 µm
- Geometric standard deviation (GSD):
- 2.52
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow-past, nose-only dynamic inhalation exposure system
- Method of holding animals in test chamber: restrainer
- Source and rate of air: filter air and 20 lt/min
- Method of conditioning air: purified filter air
- System of generating particulates/aerosols: RBG
- Temperature, humidity, pressure in air chamber: 22.1 to 22.9°C, 51.4 to 59.6%, 60 Psi
- Air flow rate: 20 liter/min
- Air change rate: 12 air changes per hour
- Method of particle size determination: Gravimetric method
- Treatment of exhaust air: NaOH
TEST ATMOSPHERE
- Brief description of analytical method used: No
- Samples taken from breathing zone: yes
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 14 days of exposure (6 hours per day)
- Frequency of treatment:
- 14 consecutive days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.1 mg/L air
- Remarks:
- G4
- Dose / conc.:
- 0.03 mg/L air
- Remarks:
- G3
- Dose / conc.:
- 0.01 mg/L air
- Remarks:
- G2
- Dose / conc.:
- 0 mg/L air
- Remarks:
- G1
- No. of animals per sex per dose:
- 5 males and 5 females per group
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: As per sponsor provided doses
- Rationale for animal assignment (if not random): randomization carried out
- Fasting period before blood sampling for clinical biochemistry: Yes
- Rationale for selecting satellite groups: No
- Post-exposure recovery period in satellite groups: No - Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily
- Cage side observations checked in table [No.1] were included.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: weekly twice
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: on the day of randomization
- Dose groups that were examined: all animals
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 15
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: 40
- Parameters checked in table [No.6] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Day 15
- Animals fasted: Yes
- How many animals: 40
- Parameters checked in table [No.8] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: Day 15
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.9] were examined.
NEUROBEHAVIOURAL EXAMINATION: No
BRONCHOALVEOLAR LAVAGE FLUID (BALF): Yes
- Time schedule for analysis: Day 15
- Dose groups that were examined: all groups
- Number of animals: 40
- Parameters checked in table [number 7] were examined.
LUNG BURDEN: No
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- The raw data were subjected to statistical analysis. The computer printout of the data (in the form of the appendix) was verified with the original raw data. After verification, the data were subjected to statistical analysis using SPSS Software version 27. Body weight, percent change in body weight with respect to Day 1, feed consumption, 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
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food efficiency:
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- 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 males, decrease in triglycerides, total protein (G3) and albumin (G4) was noted.
The observed variations noted are considered incidental due to lack of dose responsiveness and/or could be due to random biological variation. The noted significance values were within the historical control data - Urinalysis findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The following statistically significant variations were noted in organ weights and its ratios.
In Females, increase in relative weight of adrenals (G3), heart and kidneys (G4) was noted.
The variations noted in organ weights and its ratios were not associated with any macroscopic changes in all related organs in high dose group and also absolute weights were unaffected, hence considered not to be test item related and incidental - Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Microscopically, test item-related changes were observed in lungs of all the test item administered animals and were characterized by presence of multifocal, minimal to moderate, variably sized, pigmented (reddish brown) granular material throughout parenchyma of lung. This pigmented granular material was distributed both in alveolar and bronchiolar spaces. In the absence of accompanying inflammation or tissue destruction to the lung parenchyma, this change could be considered as non-adverse from dose level of 0.01mg/L
Effect levels
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- >= 100 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- haematology
- immunology
- mortality
- ophthalmological examination
- organ weights and organ / body weight ratios
- serum/plasma biochemistry
- serum/plasma hormone analyses
- urinalysis
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
- *: Values were constant throughout the exposure; hence standard deviation is zero, Temp.: Temperature; Rh: Relative Humidity; O2: Oxygen Concentration;
Refer Appendix 1
Group, Sex & Dose (mg/L) | No. of Animals | Clinical Signs of Toxicity | Mortality (No. of Incidences/ No. of Animals) |
G1, M & 0 | 5 | N | 0/5 |
G2, M & 0.01 | 5 | N | 0/5 |
G3, M & 0.03 | 5 | N | 0/5 |
G4, M & 0.1 | 5 | N | 0/5 |
G1, F & 0 | 5 | N | 0/5 |
G2, F & 0.01 | 5 | N | 0/5 |
G3, F & 0.03 | 5 | N | 0/5 |
G4, F & 0.1 | 5 | N | 0/5 |
M: Male; F: Female; N: None. The test item color was retained in snout region in test item exposure groups.
Refer Appendix 2
Group, Sex & Dose (mg/L) | Body Weight (g) on Days | ||||||
1 | 5 | 8 | 12 | 14 | |||
G1, M & 0 | Mean | 169.05 | 178.89 | 191.72 | 215.49 | 219.57 | |
±SD | 7.68 | 12.14 | 10.83 | 19.16 | 19.92 | ||
n | 5 | 5 | 5 | 5 | 5 | ||
G2, M & 0.01 | Mean | 172.83 | 185.40 | 194.33 | 209.18 | 212.93 | |
±SD | 8.54 | 8.85 | 13.71 | 14.49 | 14.72 | ||
n | 5 | 5 | 5 | 5 | 5 | ||
G3, M & 0.03 | Mean | 172.04 | 187.50 | 200.34 | 218.46 | 222.93 | |
±SD | 5.55 | 5.06 | 5.96 | 7.26 | 6.61 | ||
n | 5 | 5 | 5 | 5 | 5 | ||
G4, M & 0.1 | Mean | 174.49 | 186.56 | 193.97 | 209.24 | 213.64 | |
±SD | 5.90 | 7.36 | 10.80 | 12.98 | 13.45 | ||
n | 5 | 5 | 5 | 5 | 5 | ||
G1, F & 0 | Mean | 148.35 | 155.20 | 161.69 | 174.54 | 176.27 | |
±SD | 6.67 | 6.42 | 9.32 | 16.60 | 16.41 | ||
n | 5 | 5 | 5 | 5 | 5 | ||
G2, F & 0.01 | Mean | 149.48 | 154.48 | 158.37 | 167.51 | 169.36 | |
±SD | 7.38 | 6.65 | 6.59 | 6.47 | 6.23 | ||
n | 5 | 5 | 5 | 5 | 5 | ||
G3, F & 0.03 | Mean | 150.97 | 157.56 | 160.55 | 170.59 | 172.77 | |
±SD | 8.08 | 10.01 | 9.28 | 8.24 | 7.74 | ||
n | 5 | 5 | 5 | 5 | 5 | ||
G4, F & 0.1 | Mean | 151.40 | 157.75 | 162.24 | 170.36 | 172.14 | |
±SD | 7.60 | 5.51 | 7.97 | 6.31 | 5.86 | ||
n | 5 | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: Number of animals.
Refer Appendix 3
Group, Sex & Dose (mg/L) | Percent Change in Body Weight (%) during Days | ||||
1 to 5 | 1 to 8 | 1 to 12 | 1 to 14 | ||
G1, M & 0 | Mean | 5.75 | 13.43 | 27.44 | 29.86 |
±SD | 3.40 | 4.36 | 9.26 | 9.77 | |
n | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 7.30 | 12.37 | 21.04 | 23.21 |
±SD | 1.82 | 3.41 | 6.27 | 6.46 | |
n | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 9.00 | 16.49 | 27.03 | 29.64 |
±SD | 0.85 | 3.32 | 4.15 | 4.15 | |
n | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 6.96 | 11.25 | 20.10 | 22.60 |
±SD | 3.85 | 7.09 | 9.63 | 9.60 | |
n | 5 | 5 | 5 | 5 | |
G1, F & 0 | Mean | 4.71 | 9.21 | 18.22 | 19.39 |
±SD | 4.68 | 8.68 | 16.63 | 16.59 | |
n | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 3.39 | 5.99 | 12.20 | 13.46 |
±SD | 2.43 | 2.20 | 5.27 | 5.63 | |
n | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 4.33 | 6.33 | 13.04 | 14.50 |
±SD | 2.03 | 1.83 | 2.43 | 2.63 | |
n | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 4.25 | 7.18 | 12.61 | 13.84 |
±SD | 1.63 | 2.53 | 3.23 | 4.84 | |
n | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: Number of animals
Refer Appendix 4
Group, Sex & Dose (mg/L) | Week 1 | Week 2 | |
G1, M & 0 | Mean | 19.66 | 24.91 |
±SD | 1.43 | 3.52 | |
n | 3 | 3 | |
G2, M & 0.01 | Mean | 19.18 | 20.68 |
±SD | 2.29 | 0.41 | |
n | 3 | 3 | |
G3, M & 0.03 | Mean | 18.60 | 21.27 |
±SD | 1.08 | 7.35 | |
n | 3 | 3 | |
G4, M & 0.1 | Mean | 17.42 | 20.08 |
±SD | 2.24 | 6.05 | |
n | 3 | 3 | |
G1, F & 0 | Mean | 17.76 | 17.06 |
±SD | 4.02 | 2.69 | |
n | 3 | 3 | |
G2, F & 0.01 | Mean | 13.86 | 18.60 |
±SD | 1.84 | 1.45 | |
n | 3 | 3 | |
G3, F & 0.03 | Mean | 15.08 | 17.62 |
±SD | 0.34 | 0.92 | |
n | 3 | 3 | |
G4, F & 0.1 | Mean | 13.83 | 15.41 |
±SD | 0.17 | 4.05 | |
n | 3 | 3 |
M: Male; F: Female; SD: Standard Deviation; n: number of cages.
Week 2 Refer Appendix 5
Group, Sex & Dose (mg/L) | G1, M & 0 | G4, M & 0.1 | G1, F & 0 | G4 F & 0.1 | ||||
Number of Animals | 5 | 5 | 5 | 5 | ||||
| Observations | |||||||
Eye Parameters ↓ | L | R | L | R | L | R | L | R |
Eye | N | N | N | N | N | N | N | N |
Eye Lids | N | N | N | N | N | N | N | N |
Cornea | N | N | N | N | N | N | N | N |
Iris | N | N | N | N | N | N | N | N |
Aqueous Humour | N | N | N | N | N | N | N | N |
Lens | N | N | N | N | N | N | N | N |
Vitreous Humour | N | N | N | N | N | N | N | N |
Retina/Optic disc | N | N | N | N | N | N | N | N |
N: No Abnormality Detected; L: Left; R: Right; M: Male; F: Female.
Refer Appendix 6
Group, Sex & Dose (mg/L) | Total Leucocyte Count | Total Erythrocyte Count | Haemoglobin | Haematocrit | Mean Corpuscular Volume | Mean Corpuscular Haemoglobin | Mean Corpuscular Haemoglobin Concentration | Platelet Count | Mean Platelet Volume | |
(WBC) | (RBC) | (HGB) | (HCT) | (MCV) | (MCH) | (MCHC) | (PLT) | (MPV) | ||
(103 cells/µL) | (106 cells/µL) | (g/dL) | (%) | (fL) | (pg) | (g/dL) | (103 cells/µL) | (fL) | ||
G1, M & 0 | Mean | 8.64 | 7.20 | 15.90 | 50.40 | 70.40 | 22.16 | 31.54 | 820.00 | 8.60 |
±SD | 1.39 | 0.81 | 1.36 | 3.68 | 5.02 | 1.42 | 0.80 | 152.92 | 0.35 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 6.76 | 6.81 | 15.38 | 50.98 | 75.48 | 22.70 | 30.18 | 1010.60 | 9.14 |
±SD | 2.32 | 0.76 | 1.00 | 2.40 | 7.30 | 1.66 | 2.18 | 320.35 | 0.61 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 10.16 | 7.37 | 16.06 | 50.34 | 68.92 | 21.94 | 31.94 | 906.80 | 8.52 |
±SD | 2.67 | 0.68 | 0.93 | 2.96 | 8.85 | 2.15 | 1.41 | 103.97 | 0.73 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 7.35 | 7.43 | 15.24 | 49.24 | 67.00 | 20.64 | 30.92 | 837.80 | 8.76 |
±SD | 1.54 | 1.01 | 1.40 | 2.76 | 7.53 | 1.30 | 1.57 | 217.28 | 0.51 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G1, F & 0 | Mean | 9.22 | 8.19 | 15.90 | 48.16 | 59.00 | 19.54 | 33.06 | 1027.80 | 8.40 |
±SD | 1.46 | 0.79 | 0.60 | 2.67 | 2.80 | 1.29 | 0.75 | 190.32 | 0.42 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 7.07 | 7.77 | 15.72 | 49.14 | 64.18 | 20.60 | 32.04 | 1026.20 | 8.36 |
±SD | 1.52 | 1.15 | 0.69 | 2.38 | 8.33 | 3.01 | 0.67 | 192.39 | 0.17 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 9.86 | 7.71 | 15.90 | 48.16 | 62.56 | 20.64 | 33.04 | 736.80 | 8.78 |
±SD | 1.52 | 0.52 | 1.10 | 2.40 | 3.75 | 0.98 | 1.17 | 278.81 | 1.21 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 11.08 | 8.22 | 16.14 | 49.48 | 60.66 | 19.82 | 32.62 | 898.00 | 8.00 |
±SD | 4.98 | 0.82 | 0.40 | 1.22 | 6.07 | 1.87 | 0.48 | 150.67 | 0.47 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: number of animals.
TABLE 6 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Refer Appendix 6
Group, Sex & Dose (mg/L) | Reticulocyte Count | Neutrophils | Lymphocytes | Monocytes | Eosinophils | Basophils | Absolute Reticulocyte Count | |
(Retic) | (Neut) | (Lymph) | (Mono) | (Eos) | (Baso) | (Retic) | ||
(%) | (%) | (%) | (%) | (%) | (%) | (109 cells/L) | ||
G1, M & 0 | Mean | 9.43 | 20.74 | 71.22 | 5.74 | 0.60 | 0.36 | 660.60 |
±SD | 3.64 | 6.32 | 6.93 | 1.61 | 0.30 | 0.09 | 201.34 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 14.73 | 19.42 | 75.08 | 3.74 | 0.42 | 0.36 | 975.80 |
±SD | 6.17 | 5.02 | 6.42 | 1.39 | 0.16 | 0.05 | 356.74 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 6.23 | 25.68 | 68.06 | 4.36 | 0.34 | 0.34 | 441.56 |
±SD | 4.20 | 22.05 | 21.66 | 1.30 | 0.15 | 0.11 | 254.93 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 8.46 | 25.02 | 68.30 | 4.48 | 0.46 | 0.38 | 574.28 |
±SD | 7.05 | 6.00 | 4.48 | 2.79 | 0.38 | 0.18 | 364.19 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G1, F & 0 | Mean | 5.88 | 15.22 | 76.56 | 4.06 | 2.36 | 0.36 | 467.00 |
±SD | 2.56 | 1.67 | 5.23 | 1.58 | 2.25 | 0.11 | 163.09 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 7.65 | 21.04 | 73.20 | 3.80 | 0.40 | 0.32 | 591.80 |
±SD | 4.14 | 4.66 | 5.85 | 1.15 | 0.29 | 0.08 | 341.93 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 6.14 | 18.66 | 74.82 | 3.38 | 1.46 | 0.40 | 466.74 |
±SD | 2.59 | 1.07 | 1.29 | 0.82 | 1.28 | 0.07 | 193.60 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 3.78 | 17.88 | 76.20 | 3.30 | 0.84 | 0.42 | 298.06 |
±SD | 2.11 | 6.89 | 7.42 | 0.86 | 0.35 | 0.11 | 129.35 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: Number of animals
TABLE 6 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Refer Appendix 6
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) | ||
(103 cells/µL) | (103 cells/µL) | (103 cells/µL) | (103 cells/µL) | (103 cells/µL) | (Seconds) | (Seconds) | ||
G1, M & 0 | Mean | 1.75 | 6.21 | 0.49 | 0.05 | 0.03 | 22.30 | 24.06 |
±SD | 0.46 | 1.55 | 0.11 | 0.02 | 0.01 | 5.38 | 4.86 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 1.26 | 5.15 | 0.23 | 0.03 | 0.02 | 19.64 | 26.06 |
±SD | 0.33 | 2.14 | 0.05 | 0.01 | 0.01 | 1.64 | 7.49 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 2.96 | 6.57 | 0.44 | 0.04 | 0.03 | 18.90 | 25.54 |
±SD | 3.29 | 1.96 | 0.16 | 0.02 | 0.02 | 2.16 | 4.90 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 1.85 | 5.00 | 0.34 | 0.03 | 0.03 | 20.60 | 19.84 |
±SD | 0.67 | 1.02 | 0.26 | 0.02 | 0.01 | 1.60 | 3.55 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G1, F & 0 | Mean | 1.39 | 7.11 | 0.36 | 0.20 | 0.03 | 20.36 | 23.74 |
±SD | 0.08 | 1.55 | 0.11 | 0.17 | 0.01 | 0.13 | 5.39 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 1.46 | 5.21 | 0.27 | 0.03 | 0.02 | 20.78 | 23.92 |
±SD | 0.33 | 1.34 | 0.10 | 0.03 | 0.01 | 0.53 | 7.42 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 1.84 | 7.38 | 0.33 | 0.14 | 0.04 | 19.66 | 18.58 |
±SD | 0.30 | 1.17 | 0.08 | 0.13 | 0.00 | 2.76 | 1.38 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 1.79 | 8.64 | 0.34 | 0.09 | 0.05 | 20.64 | 23.22 |
±SD | 0.49 | 4.50 | 0.11 | 0.05 | 0.04 | 3.51 | 4.39 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: Number of animals
Refer Appendix 7
Group, Sex & Dose (mg/L) | Total Leucocyte Count | Neutrophils | Lymphocytes | Monocytes | Eosinophils | Basophils | Absolute Neutrophils | |
(103 cells/µL) | (%) | (%) | (%) | (%) | (%) | (103 cells/µL) | ||
G1, M & 0 | Mean | 0.32 | 34.38 | 54.74 | 4.98 | 1.50 | 3.62 | 0.10 |
±SD | 0.17 | 16.38 | 20.69 | 3.27 | 1.47 | 2.43 | 0.08 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 0.35 | 38.60 | 55.56 | 2.32 | 1.40 | 3.46 | 0.14 |
±SD | 0.16 | 4.64 | 6.40 | 0.85 | 0.41 | 0.99 | 0.08 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 0.34 | 36.78 | 55.54 | 3.30 | 2.66 | 3.06 | 0.12 |
±SD | 0.10 | 8.71 | 9.43 | 1.19 | 0.67 | 2.24 | 0.04 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 0.40 | 50.94 | 43.10 | 2.04 | 3.36* | 2.52 | 0.19 |
±SD | 0.18 | 16.36 | 15.44 | 1.42 | 0.75 | 1.36 | 0.06 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G1, F & 0 | Mean | 0.24 | 31.92 | 58.22 | 2.44 | 1.76 | 3.08 | 0.07 |
±SD | 0.09 | 8.18 | 10.34 | 1.61 | 1.43 | 1.38 | 0.02 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 0.28 | 40.10 | 52.32 | 2.52 | 1.56 | 5.20 | 0.10 |
±SD | 0.13 | 13.01 | 12.21 | 1.09 | 1.07 | 4.26 | 0.06 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 0.30 | 40.38 | 52.90 | 1.80 | 2.82 | 1.74 | 0.13 |
±SD | 0.10 | 9.34 | 12.08 | 0.78 | 1.14 | 1.30 | 0.07 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 0.38 | 46.38 | 47.52 | 1.64 | 3.78 | 1.54 | 0.17 |
±SD | 0.24 | 4.76 | 5.64 | 0.99 | 1.38 | 1.47 | 0.09 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
TABLE 7 (Contd…). SUMMARY OF BALF RECORD
Refer Appendix 7
Group, Sex & Dose (mg/L) | Absolute Lymphocytes | Absolute Monocytes | Absolute Eosinophils | Absolute Basophils | Lactate Dehydrogenase | Total Protein | |
(Lymph) | (Mono) | (Eos) | (Baso) | (LDH) | (TPR) | ||
(103 cells/µL) | (103 cells/µL) | (103 cells/µL) | (103 cells/µL) | (u/L) | (μg/mL) | ||
G1, M & 0 | Mean | 0.19 | 0.02 | 0.00 | 0.01 | 104.40 | 308.63 |
±SD | 0.12 | 0.02 | 0.00 | 0.02 | 59.75 | 61.25 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 0.19 | 0.01 | 0.00 | 0.01 | 32.80* | 268.80 |
±SD | 0.08 | 0.01 | 0.00 | 0.01 | 11.80 | 82.64 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 0.19 | 0.01 | 0.01* | 0.01 | 47.20* | 257.40 |
±SD | 0.09 | 0.00 | 0.00 | 0.01 | 17.06 | 34.26 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 0.18 | 0.01 | 0.01* | 0.01 | 46.00* | 235.45 |
±SD | 0.13 | 0.01 | 0.01 | 0.01 | 14.51 | 44.95 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | |
G1, F & 0 | Mean | 0.15 | 0.00 | 0.00 | 0.01 | 36.40 | 271.14 |
±SD | 0.07 | 0.01 | 0.01 | 0.01 | 11.72 | 25.82 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 0.15 | 0.01 | 0.00 | 0.01 | 30.80 | 260.63 |
±SD | 0.07 | 0.01 | 0.00 | 0.02 | 11.21 | 111.98 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 0.15 | 0.00 | 0.01 | 0.00 | 37.80 | 209.58 |
±SD | 0.05 | 0.01 | 0.01 | 0.00 | 9.20 | 56.34 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 0.19 | 0.01 | 0.01 | 0.00 | 47.80 | 257.45 |
±SD | 0.13 | 0.01 | 0.01 | 0.01 | 15.90 | 117.27 | |
n | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: Number of animals; *: Statistically significant (p<0.05)
Refer Appendix 8
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 | 87.40 | 33.06 | 0.52 | 54.20 | 65.00 | 6.74 | 3.43 | 55.60 | 123.60 |
±SD | 12.20 | 6.98 | 0.04 | 15.47 | 22.53 | 0.32 | 0.11 | 15.47 | 17.40 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 80.00 | 37.26 | 0.51 | 41.60 | 43.60 | 6.50 | 3.23 | 54.60 | 119.60 |
±SD | 16.08 | 5.79 | 0.02 | 5.86 | 19.97 | 0.34 | 0.19 | 15.34 | 14.03 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 83.60 | 31.76 | 0.49 | 40.40 | 33.20* | 6.14* | 3.21 | 56.20 | 125.60 |
±SD | 12.10 | 4.85 | 0.03 | 2.79 | 9.28 | 0.25 | 0.14 | 5.40 | 15.04 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 81.00 | 34.62 | 0.49 | 56.40 | 53.60 | 6.22 | 3.15* | 53.80 | 124.00 |
±SD | 6.04 | 2.29 | 0.03 | 9.40 | 19.07 | 0.48 | 0.17 | 4.60 | 16.05 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G1, F & 0 | Mean | 93.80 | 37.62 | 0.54 | 53.00 | 32.80 | 6.74 | 3.32 | 44.40 | 115.80 |
±SD | 8.17 | 6.22 | 0.04 | 5.70 | 7.89 | 0.27 | 0.20 | 7.54 | 7.60 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 87.80 | 35.41 | 0.53 | 50.60 | 38.20 | 6.68 | 3.29 | 40.40 | 125.00 |
±SD | 10.47 | 5.36 | 0.02 | 13.61 | 16.22 | 0.18 | 0.13 | 13.87 | 11.64 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 99.80 | 35.18 | 0.54 | 50.20 | 37.20 | 6.60 | 3.35 | 37.40 | 115.20 |
±SD | 12.66 | 6.78 | 0.02 | 15.69 | 2.86 | 0.34 | 0.17 | 7.44 | 12.07 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 101.60 | 35.42 | 0.52 | 60.80 | 41.60 | 6.90 | 3.33 | 43.60 | 120.80 |
±SD | 7.27 | 6.82 | 0.03 | 6.61 | 10.41 | 0.34 | 0.17 | 6.91 | 23.95 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: number of animals; *: Statistically significant (p<0.05)
TABLE 8 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Refer Appendix 8
Group, Sex & Dose (mg/L) | Alkaline phosphatase | Total Bilirubin | Calcium | Phosphorous | Globulin | Blood Urea Nitrogen | Sodium | Potassium | Chloride | |
(ALP) | (BIT) | (CAL) | (PHO) | (GLB) | (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 | 243.00 | 0.08 | 10.40 | 3.68 | 3.31 | 15.45 | 141.58 | 3.25 | 107.32 |
±SD | 23.94 | 0.03 | 0.35 | 0.32 | 0.41 | 3.26 | 1.15 | 0.15 | 1.66 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 301.80 | 0.07 | 10.42 | 3.74 | 3.27 | 17.41 | 143.08 | 3.53 | 106.78 |
±SD | 60.54 | 0.02 | 0.37 | 0.27 | 0.43 | 2.71 | 2.55 | 0.37 | 2.03 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 230.60 | 0.06 | 10.40 | 3.35 | 2.93 | 14.84 | 142.98 | 3.58 | 107.18 |
±SD | 46.68 | 0.01 | 0.35 | 0.40 | 0.30 | 2.27 | 2.35 | 0.26 | 0.82 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 216.20 | 0.07 | 10.24 | 3.46 | 3.07 | 16.18 | 141.48 | 3.60 | 108.68 |
±SD | 67.44 | 0.03 | 0.15 | 0.29 | 0.33 | 1.07 | 0.51 | 0.21 | 0.52 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G1, F & 0 | Mean | 162.00 | 0.05 | 10.28 | 3.26 | 3.42 | 17.58 | 141.08 | 3.60 | 107.60 |
±SD | 46.14 | 0.01 | 0.34 | 0.17 | 0.33 | 2.91 | 1.19 | 0.22 | 1.29 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 173.20 | 0.06 | 10.18 | 3.36 | 3.39 | 16.54 | 140.86 | 3.70 | 108.10 |
±SD | 42.29 | 0.05 | 0.40 | 0.31 | 0.13 | 2.51 | 0.69 | 0.40 | 1.82 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 173.80 | 0.03 | 10.26 | 3.17 | 3.25 | 16.44 | 141.02 | 3.56 | 108.88 |
±SD | 58.44 | 0.02 | 0.23 | 0.26 | 0.31 | 3.17 | 0.90 | 0.17 | 1.15 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 174.20 | 0.04 | 10.18 | 3.49 | 3.57 | 16.55 | 140.94 | 3.58 | 107.54 |
±SD | 51.92 | 0.03 | 0.45 | 0.34 | 0.34 | 3.18 | 0.86 | 0.24 | 1.82 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; F: Female; SD: Standard Deviation; n: Number of animals
Refer Appendix 9
Examination | Group, Sex & Dose (mg/L) | G1, M & 0 | G2, M & 0.01 | G3, M & 0.03 | G4, M & 0.1 | |
Number of Animals | 5 | 5 | 5 | 5 | ||
Physical Examination | Color | Pale Yellow | 4 | 2 | 5 | 3 |
Yellow | 1 | 3 | - | 2 | ||
Appearance | Clear | 1 | 4 | 3 | 3 | |
Turbid | 4 | 1 | 2 | 2 | ||
Volume (mL) | Mean | 4.7 | 6.4 | 6.2 | 5.5 | |
±SD | 2.3 | 2.5 | 2.5 | 1.8 | ||
Chemical Examination | pH | Mean | 7.7 | 7.5 | 7.4 | 7.8 |
±SD | 0.8 | 0.6 | 0.2 | 0.7 | ||
Specific gravity (SG) | Mean | 1.012 | 1.012 | 1.009 | 1.011 | |
±SD | 0.008 | 0.004 | 0.007 | 0.007 | ||
Urobilinogen (UBG) (mg/dL) | Mean | 0.2 | 0.2 | 0.2 | 0.2 | |
±SD | 0.0 | 0.0 | 0.0 | 0.0 | ||
Bilirubin (BIL) (mg/dL) | Neg | 5 | 5 | 5 | 5 | |
Ketones (KET) (mg/dL) | Neg | 5 | 5 | 5 | 5 | |
Blood (BLD) (Ery/µL) | Neg | 4 | 1 | - | 2 | |
Ca10 | 1 | 1 | 5 | 3 | ||
Ca25 | - | 2 | - | - | ||
>=Ca200 | - | 1 | - | - | ||
Protein (PRO) (mg/dL) | Neg | 5 | 5 | 5 | 5 | |
Nitrite (NIT) | Neg | 2 | 2 | 3 | - | |
Pos | 3 | 3 | 2 | 5 | ||
Leucocytes (LEU) (Leu/µL) | Neg | 5 | 5 | 5 | 2 | |
Ca15 | - | - | - | 2 | ||
Ca70 | - | - | - | 1 | ||
Glucose (GLU) (mg/dL) | Neg | 5 | 5 | 5 | 5 | |
Micro Albumin (MALB) (mg/dL) | Neg | 5 | 5 | 5 | 5 | |
Microscopic Examination | Epi Cells | 0 | 5 | 4 | 4 | 5 |
0-1 | - | 1 | 1 | - | ||
Casts | Absent | 5 | 5 | 5 | 5 | |
Crystals | Absent | 2 | 1 | 1 | - | |
Present | 3 | 4 | 4 | 5 |
M: Male; Neg: Negative; Ca: Calculated Approximately; Pos: Positive; SD: Standard Deviation;
-: Not applicable.
TABLE 9 (Contd…). SUMMARY OF URINALYSIS RECORD
Refer Appendix 9
Examination | Group, Sex & Dose (mg/L) | G1, F & 0 | G2, F & 0.01 | G3, F & 0.03 | G4, F & 0.1 | |
Number of Animals | 5 | 5 | 5 | 5 | ||
Physical Examination | Color | Pale Yellow | 4 | 3 | 3 | 2 |
| 1 | 2 | 2 | 3 | ||
Appearance | Clear | 4 | 2 | 2 | 2 | |
Turbid | 1 | 3 | 3 | 3 | ||
Volume (mL) | Mean | 7.4 | 5.4 | 4.5 | 5.0 | |
±SD | 2.5 | 2.1 | 1.9 | 1.9 | ||
Chemical Examination | pH | Mean | 7.8 | 7.7 | 7.4 | 7.4 |
±SD | 0.4 | 0.4 | 0.4 | 0.2 | ||
Specific gravity (SG) | Mean | 1.007 | 1.008 | 1.009 | 1.012 | |
±SD | 0.003 | 0.004 | 0.004 | 0.004 | ||
Urobilinogen (UBG) (mg/dL) | Mean | 0.2 | 0.2 | 0.2 | 0.4 | |
±SD | 0.0 | 0.0 | 0.0 | 0.4 | ||
Bilirubin (BIL) (mg/dL) | Neg | 5 | 5 | 5 | 5 | |
Ketones (KET) (mg/dL) | Neg | 4 | 4 | 5 | 4 | |
5 | 1 | 1 | - | 1 | ||
Blood (BLD) (Ery/µL) | Neg | 2 | 1 | 2 | 1 | |
Ca10 | 1 | 1 | 1 | 1 | ||
Ca25 | 2 | 3 | 2 | 2 | ||
Ca80 | - | - | - | 1 | ||
Protein (PRO) (mg/dL) | Neg | 3 | 5 | 2 | 2 | |
Trace | 2 | - | 3 | 2 | ||
>=300 | - | - | - | 1 | ||
Nitrite (NIT) | Neg | 2 | 2 | 2 | 1 | |
Pos | 3 | 3 | 3 | 4 | ||
Leucocytes (LEU) (Leu/µL) | Neg | - | 1 | - | - | |
Ca15 | 5 | 3 | - | - | ||
Ca70 | - | 1 | 4 | 4 | ||
Ca125 | - | - | 1 | 1 | ||
Glucose (GLU) (mg/dL) | Neg | 5 | 5 | 5 | 5 | |
Micro Albumin (MALB) (mg/dL) | Neg | 3 | 5 | 2 | 2 | |
>15 | 2 | - | 3 | 3 | ||
Microscopic Examination | Epi Cells | 0 | 4 | 4 | 5 | 3 |
0-1 | 1 | 1 | - | 2 | ||
Casts | Absent | 5 | 5 | 5 | 4 | |
Crystals | Absent | 1 | 1 | 1 | 1 | |
Present | 4 | 4 | 4 | 4 |
F: Female; Neg: Negative; Ca: Calculated Approximately; Pos: Positive; SD: Standard Deviation;
-: Not applicable
Refer Appendix 10
Group, Sex & Dose (mg/L) | Adrenals | Thymus | Spleen | Testes | Epididymides | Heart | Kidneys | Brain | Liver | Lungs | |
G1, M & 0 | Mean | 0.0445 | 0.3048 | 1.2010 | 2.8675 | 0.6750 | 0.8806 | 1.6655 | 1.7737 | 7.2165 | 0.4442 |
±SD | 0.0060 | 0.0681 | 0.3913 | 0.2768 | 0.0632 | 0.1187 | 0.0979 | 0.0906 | 1.0042 | 0.0384 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 0.0524 | 0.2878 | 1.1673 | 2.6393 | 0.5933 | 0.8193 | 1.6265 | 1.7227 | 6.5581 | 0.4633 |
±SD | 0.0026 | 0.0764 | 0.3451 | 0.3757 | 0.1527 | 0.0949 | 0.1034 | 0.0964 | 0.5737 | 0.0709 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 0.0434 | 0.3658 | 0.8935 | 2.7219 | 0.6730 | 0.8264 | 1.6876 | 1.6954 | 6.5774 | 0.5038 |
±SD | 0.0083 | 0.0485 | 0.2797 | 0.1428 | 0.1308 | 0.0479 | 0.0647 | 0.0710 | 0.4937 | 0.2203 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 0.0444 | 0.2754 | 0.9828 | 2.8671 | 0.5905 | 0.7924 | 1.5294 | 1.7530 | 6.4106 | 0.4777 |
±SD | 0.0087 | 0.0873 | 0.5711 | 0.1836 | 0.0216 | 0.0864 | 0.1144 | 0.0529 | 0.7913 | 0.0643 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; SD: Standard Deviation, n: Number of animals
.
TABLE 10 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHTS (g) RECORD
Refer Appendix 10
Group, Sex & Dose (mg/L) | Adrenals | Thymus | Spleen | Ovaries | Uterus | Heart | Kidneys | Brain | Liver | Lungs | |
G1, F & 0 | Mean | 0.0565 | 0.3224 | 0.8817 | 0.1062 | 0.5510 | 0.6782 | 1.2103 | 1.6188 | 5.4854 | 0.4706 |
±SD | 0.0072 | 0.0497 | 0.3610 | 0.0166 | 0.1567 | 0.0425 | 0.1738 | 0.0815 | 0.8689 | 0.0517 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 0.0580 | 0.3419 | 0.9006 | 0.0998 | 0.3195 | 0.6639 | 1.2385 | 1.6232 | 5.4225 | 0.4517 |
±SD | 0.0094 | 0.0730 | 0.3347 | 0.0196 | 0.0668 | 0.0348 | 0.1216 | 0.0625 | 0.2876 | 0.1088 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 0.0635 | 0.3665 | 0.7147 | 0.1009 | 0.5523 | 0.6434 | 1.2780 | 1.8192 | 5.4926 | 0.3923 |
±SD | 0.0031 | 0.0348 | 0.1195 | 0.0171 | 0.2535 | 0.0341 | 0.0903 | 0.4821 | 0.3492 | 0.0364 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 0.0551 | 0.3200 | 0.7168 | 0.1056 | 0.3859 | 0.7002 | 1.3219 | 1.6878 | 5.3210 | 0.5259 |
±SD | 0.0040 | 0.0686 | 0.2850 | 0.0081 | 0.1229 | 0.0180 | 0.1142 | 0.1161 | 0.4879 | 0.0708 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
F: Female; SD: Standard Deviation, n: Number of animals
Refer Appendix 11
Group, Sex & Dose (mg/L) | Fasting Body Weight (g) | Adrenals | Thymus | Spleen | Testes | Epididymides | Heart | Kidneys | Brain | Liver | Lungs | |
G1, M & 0 | Mean | 197.61 | 0.0227 | 0.1534 | 0.6153 | 1.4501 | 0.3431 | 0.4447 | 0.8446 | 0.9018 | 3.6414 | 0.2255 |
±SD | 15.35 | 0.0041 | 0.0263 | 0.2292 | 0.0574 | 0.0406 | 0.0377 | 0.0447 | 0.0835 | 0.2617 | 0.0220 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 191.83 | 0.0273 | 0.1512 | 0.6127 | 1.3843 | 0.3094 | 0.4262 | 0.8487 | 0.9035 | 3.4173 | 0.2439 |
±SD | 12.90 | 0.0014 | 0.0443 | 0.1877 | 0.2429 | 0.0754 | 0.0272 | 0.0331 | 0.1100 | 0.1596 | 0.0524 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 197.12 | 0.0221 | 0.1857 | 0.4564 | 1.3817 | 0.3414 | 0.4193 | 0.8567 | 0.8611 | 3.3372 | 0.2570 |
±SD | 7.16 | 0.0049 | 0.0253 | 0.1537 | 0.0763 | 0.0647 | 0.0229 | 0.0349 | 0.0489 | 0.2324 | 0.1179 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 177.97 | 0.0258 | 0.1542 | 0.5745 | 1.6722 | 0.3439 | 0.4620 | 0.8839 | 1.0169 | 3.6754 | 0.2778 |
±SD | 31.94 | 0.0076 | 0.0362 | 0.3277 | 0.4301 | 0.0859 | 0.1298 | 0.1844 | 0.2242 | 0.6390 | 0.0755 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; SD: Standard Deviation, n: Number of animals
TABLE 11 (Contd…). SUMMARY OF ORGAN WEIGHT RELATIVE TO BODY WEIGHT (%) RECORD
Refer Appendix 11
Group, Sex & Dose (mg/L) | Fasting Body Weight (g) | Adrenals | Thymus | Spleen | Ovaries | Uterus | Heart | Kidneys | Brain | Liver | Lungs | |
G1, F & 0 | Mean | 161.11 | 0.0351 | 0.1998 | 0.5414 | 0.0661 | 0.3432 | 0.4221 | 0.7489 | 1.0088 | 3.3926 | 0.2926 |
±SD | 15.45 | 0.0034 | 0.0219 | 0.1877 | 0.0091 | 0.1013 | 0.0166 | 0.0429 | 0.0613 | 0.2715 | 0.0274 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 152.64 | 0.0379 | 0.2241 | 0.5938 | 0.0652 | 0.2082 | 0.4359 | 0.8109 | 1.0654 | 3.5523 | 0.2959 |
±SD | 7.16 | 0.0056 | 0.0469 | 0.2318 | 0.0105 | 0.0347 | 0.0326 | 0.0641 | 0.0657 | 0.0751 | 0.0704 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 152.37 | 0.0417* | 0.2415 | 0.4689 | 0.0662 | 0.3614 | 0.4225 | 0.8390 | 1.1988 | 3.6064 | 0.2575 |
±SD | 6.95 | 0.0020 | 0.0313 | 0.0755 | 0.0105 | 0.1619 | 0.0194 | 0.0516 | 0.3396 | 0.2045 | 0.0212 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 151.18 | 0.0365 | 0.2118 | 0.4737 | 0.0699 | 0.2537 | 0.4635* | 0.8741* | 1.1170 | 3.5181 | 0.3487 |
±SD | 5.58 | 0.0019 | 0.0463 | 0.1836 | 0.0058 | 0.0744 | 0.0155 | 0.0655 | 0.0777 | 0.2763 | 0.0531 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
F: Female; SD: Standard Deviation, n: Number of animals; *: Statistically significant (p<0.05)
Refer Appendix 12
Group, Sex & Dose (mg/L) | Adrenals | Thymus | Spleen | Testes | Epididymides | Heart | Kidneys | Liver | Lungs | |
G1, M & 0 | Mean | 2.5033 | 17.1259 | 67.4063 | 162.0321 | 38.2382 | 49.7679 | 94.0002 | 407.7692 | 25.1065 |
±SD | 0.2830 | 3.4494 | 20.3471 | 17.3991 | 5.0531 | 7.1856 | 5.5530 | 60.3251 | 2.6547 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, M & 0.01 | Mean | 3.0494 | 16.6633 | 68.3240 | 153.0890 | 34.6489 | 47.8413 | 94.6904 | 382.7882 | 26.9255 |
±SD | 0.2609 | 4.2600 | 22.5065 | 19.9272 | 9.8429 | 7.3154 | 8.2349 | 50.5382 | 4.1169 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, M & 0.03 | Mean | 2.5655 | 21.6784 | 52.7006 | 161.0187 | 39.9951 | 48.8780 | 99.7918 | 389.2587 | 29.8785 |
±SD | 0.5277 | 3.5311 | 16.9064 | 14.8943 | 9.3704 | 4.4985 | 7.8113 | 43.0293 | 13.6400 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, M & 0.1 | Mean | 2.5450 | 15.7349 | 56.7751 | 163.7452 | 33.7253 | 45.2854 | 87.4396 | 366.3883 | 27.2410 |
±SD | 0.5528 | 5.0037 | 34.7609 | 12.7295 | 1.9116 | 5.4793 | 8.8662 | 49.8428 | 3.4646 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
M: Male; SD: Standard Deviation, n: Number of animals
TABLE 12 (Contd…). SUMMARY OF ORGAN WEIGHT RELATIVE TO BRAIN WEIGHT (%) RECORD
Refer Appendix 12
Group, Sex & Dose (mg/L) | Adrenals | Thymus | Spleen | Ovaries | Uterus | Heart | Kidneys | Liver | Lungs | |
G1, F & 0 | Mean | 3.4853 | 19.8850 | 54.1090 | 6.5472 | 33.9043 | 41.9010 | 74.5850 | 337.5615 | 29.1192 |
±SD | 0.3725 | 2.6554 | 20.6012 | 0.8302 | 8.8902 | 1.5974 | 7.9652 | 38.0367 | 3.3758 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G2, F & 0.01 | Mean | 3.5857 | 21.1022 | 55.1615 | 6.1736 | 19.7611 | 40.9567 | 76.4331 | 334.4461 | 27.8514 |
±SD | 0.6850 | 4.7489 | 18.7195 | 1.3398 | 4.5076 | 2.8477 | 8.8241 | 21.7247 | 6.7452 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G3, F & 0.03 | Mean | 3.6548 | 21.0145 | 40.2693 | 5.8620 | 32.4794 | 36.8407 | 73.7372 | 313.2089 | 22.3524 |
±SD | 0.7972 | 4.6605 | 7.1752 | 1.7790 | 17.4461 | 7.2615 | 17.1155 | 56.1181 | 4.1577 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
G4, F & 0.1 | Mean | 3.2700 | 19.1635 | 41.8617 | 6.2556 | 23.0893 | 41.6881 | 78.4275 | 315.0087 | 31.4645 |
±SD | 0.1666 | 4.9612 | 14.0226 | 0.1283 | 8.0301 | 3.7770 | 6.2328 | 13.6036 | 6.4251 | |
n | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
F: Female; SD: Standard Deviation, n: Number of animals
Group & Conc. (mg/L)
|
| Temp. (°C) | Rh (%) | O2 (%) | CO2 (ppm) | Air inlet flow rate (L/min)* | BZC (mg/L)
| |
G1 & 0 | Mean | 22.51 | 55.87 | 20.41 | 619.18 | 20.00 | - | |
±SD | 0.14 | 1.36 | 0.16 | 5.07 | 0.00 | - | ||
G2 & 0.01 | Mean | 22.55 | 56.15 | 20.45 | 618.82 | 20.00 | 0.011 | |
±SD | 0.17 | 1.47 | 0.18 | 6.14 | 0.00 | 0.001 | ||
G3 & 0.03 | Mean | 22.52 | 55.66 | 20.43 | 619.51 | 20.00 | 0.030 | |
±SD | 0.18 | 1.47 | 0.17 | 5.52 | 0.00 | 0.001 | ||
G4 & 0.1 | Mean | 22.52 | 55.92 | 20.43 | 618.81 | 20.00 | 0.102 | |
±SD | 0.18 | 1.45 | 0.16 | 5.82 | 0.00 | 0.001 |
CO2: Carbon Dioxide Concentration; BZC: Breathing Zone 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 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5210 | 20 | 360 | 0.72 | |
7400 | 1.03 | ||||
11070 | 1.54 | ||||
2 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5240 | 20 | 360 | 0.73 | |
7350 | 1.02 | ||||
11140 | 1.55 | ||||
3 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5110 | 20 | 360 | 0.71 | |
7430 | 1.03 | ||||
11120 | 1.54 | ||||
4 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5260 | 20 | 360 | 0.73 | |
7480 | 1.04 | ||||
11220 | 1.56 | ||||
5 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5150 | 20 | 360 | 0.72 | |
7340 | 1.02 | ||||
11070 | 1.54 | ||||
6 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5190 | 20 | 360 | 0.72 | |
7390 | 1.03 | ||||
11150 | 1.55 | ||||
7 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5130 | 20 | 360 | 0.71 | |
7320 | 1.02 | ||||
11110 | 1.54 |
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 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5190 | 20 | 360 | 0.72 | |
7430 | 1.03 | ||||
11150 | 1.55 | ||||
9 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5060 | 20 | 360 | 0.70 | |
7340 | 1.02 | ||||
11020 | 1.53 | ||||
10 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5190 | 20 | 360 | 0.72 | |
7300 | 1.01 | ||||
11150 | 1.55 | ||||
11 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5110 | 20 | 360 | 0.71 | |
7380 | 1.03 | ||||
11090 | 1.54 | ||||
12 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5210 | 20 | 360 | 0.72 | |
7400 | 1.03 | ||||
11060 | 1.54 | ||||
13 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5140 | 20 | 360 | 0.71 | |
7240 | 1.01 | ||||
11040 | 1.53 | ||||
14 | G1 (Air Only) | - | 20 | 360 | - |
G2, G3 and G4 (Test Item) | 5170 | 20 | 360 | 0.72 | |
7240 | 1.01 | ||||
11120 | 1.54 |
Route of administration | Inhalation route | |||
Sex | Male | |||
Treatment | Air only | Low Dose | Mid Dose | High Dose |
Group | G1 | G2 | G3 | G4 |
Dose (mg/L) | 0 | 0.01 | 0.03 | 0.1 |
Number of animals | 5 | 5 | 5 | 5 |
No. of dead rats during treatment | - | - | - | - |
No. of moribund sacrificed rats | - | - | - | - |
No. of terminally sacrificed rats | 5 | 5 | 5 | 5 |
No. of animals with gross pathology | - | - | 5 | 5 |
Caecum- contents, discoloration, reddish | - | - | 5 | 5 |
-: No incidence.
Route of administration | Inhalation route | |||
Sex | Female | |||
Treatment | Air only | Low Dose | Mid Dose | High Dose |
Group | G1 | G2 | G3 | G4 |
Dose (mg/L) | 0 | 0.01 | 0.03 | 0.1 |
Number of animals | 5 | 5 | 5 | 5 |
No. of dead rats during treatment | - | - | - | - |
No. of moribund sacrificed rats | - | - | - | - |
No. of terminally sacrificed rats | 5 | 5 | 5 | 5 |
No. of animals with gross pathology | - | - | 5 | 5 |
Caecum- contents, discoloration, reddish | - | - | 5 | 5 |
-: No incidence.
Refer Appendices 3, 4, 5 & 6
Route of administration | Inhalation route | ||||||||
Treatment | Air only | Low Dose | Mid Dose | High Dose | |||||
Dose (mg/L) | G1 | G2 | G3 | G4 | |||||
Group | 0 | 0.01 | 0.03 | 0.1 | |||||
Sex | M | F | M | F | M | F | M | F | |
Number of Animals | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | |
Lung (Left lobe) | Number examined | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
Within normal limits | - | - | - | 1 | - | - | - | - | |
Pigment, Reddish Brown | Minimal | - | - | 4 | 4 |
| - | - | - |
Mild | - | - | 1 | - |
| 5 | - | 2 | |
Moderate | - | - | - | - |
| - | 5 | 3 |
M: Male; F: Female; -: No incidence.
Applicant's summary and conclusion
- Conclusions:
- Based on the observed results, it is concluded that the No Observed Adverse Effect Concentration (NOAEC) of test item, PV-Fast Scarlet 4RF was found to be 0.1 mg/L when exposed for 6 hours/day for 14 days by flow-past nose-only inhalation route to Sprague Dawley rats. The Maximum Tolerated Concentration (MTC) is more than the maximum concentration tested in the study i.e., >0.1 mg/L. Hence, for the subsequent repeated dose study, the concentrations of 0.01, 0.03 and 0.1 mg/L can be selected.
- Executive summary:
The objective of this study was to determine the toxic potential of test item, PV-Fast Scarlet 4RF, when Sprague Dawley rats are exposed for 6 hours/day for 14 days by flow-past nose-only inhalation route. This study provides information on toxic effects, data for quantitative inhalation risk assessment, possible target organs, the estimated No Observed Adverse Effects Concentration (NOAEC), and maximum Tolerated Concentration (MTC), and information on the concentration levels to be selected for the main study.
A total of 40 (20 males + 20 females) healthy young Sprague Dawley rats were distributed to four groups viz., control (G1), low dose (G2), mid dose (G3) and high dose (G4). Each group comprised of 10 animals (5 males and 5 females). Animals allocated to Groups G2, G3 and G4 were exposed to test item PV-Fast Scarlet 4RF for 6 hours per day, for 14 days, at a nominal target concentration of 0.01(G2), 0.03(G3) and 0.1(G4) mg/L. Animals of the control group (G1) received air only inhalation for 6 hours/day for 14 days. 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 first exposure (day 1) and further twice weekly during treatment period. Feed consumption was recorded weekly. Ophthalmoscopic examination was performed during acclimatization (pre-treatment) and during week 2 of the treatment period for control and high dose group animals (G1 and G4).
At the end of the exposure period, all animals were fasted overnight (water was provided ad libitum) and the next day the animals were subjected to necropsy. Blood, urine samples, and broncho-alveolar lavage fluid (BALF) were collected for analysis. Haematology, coagulation, clinical chemistry, urinalysis, and BALF fluid analysis were performed. All animals were subjected to necropsy and detailed gross pathology examination. The tissues mentioned in the study plan were collected, weighed, and preserved. Histopathological examination was carried out for left lung from control and high dose group animals (G1 and G4).
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 clinical signs of toxicity or mortality were noted in any of the dose groups.
There were no treatment-related changes in mean body weight, percent change in body weight with respect to day 1. There was no treatment related variation noted in feed consumption and no ocular changes were observed during the ophthalmoscopy examination.
No adverse treatment related variations in haematology, clinical chemistry and urinalysis parameters were noted.
The test item being a fine powder, there is a chance that it has reached intestine through mouth during nose only exposure owing to continuous exposure and some inevitable movements of animal in the restrainer. This is a routine observation with such test items as per laboratory experience.
There were no treatment-related adverse changes noted in organ weights or their ratios. Grossly, reddish discoloration of the caecal contents was observed in animals of both sexes from group G3 and G4 and this was attributable to the physical nature of the test item.
Microscopically, test item-related changes were observed in lungs of all the test item administered animals and were characterized by, presence of multifocal, minimal to moderate, variably sized, pigmented (reddish brown) granular material throughout parenchyma of lung. This pigmented granular material was distributed both in alveolar and bronchiolar spaces. In the absence of accompanying inflammation or tissue destruction to the lung parenchyma, this change could be considered as non-adverse from dose level of 0.01mg/L.
During BALF analysis, few significant changes were noted: increase in absolute and relative eosinophils (G4) and decrease in LDH (G2, G3 and G4). The noted variations are considered to be secondary due to accumulation of test item particles in the lungs, and in the absence of any inflammation and/or microscopic changes of the lungs, the noted variations are considered not to be adverse.
There were no test item-related, microscopic findings in the study.
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