Registration Dossier
Registration Dossier
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EC number: 224-152-4 | CAS number: 4216-02-8
Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 19 September 2022 to 07 November 2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 023
- Report date:
- 2023
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 433 (Acute Inhalation Toxicity: Fixed Concentration Procedure)
- Version / remarks:
- adopted on 25 June 2018
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- fixed concentration procedure
- Limit test:
- yes
Test material
- Reference substance name:
- Bisbenzimidazo[2,1-b:1',2'-j]benzo[lmn][3,8]phenanthroline-6,9-dione
- EC Number:
- 224-152-4
- EC Name:
- Bisbenzimidazo[2,1-b:1',2'-j]benzo[lmn][3,8]phenanthroline-6,9-dione
- Cas Number:
- 4216-02-8
- Molecular formula:
- C26H12N4O2
- IUPAC Name:
- bisbenzimidazo[2,1-b:1',2'-j]benzo[lmn][3,8]phenanthroline-6,9-dione
- Test material form:
- solid: nanoform, no surface treatment
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Sighting study: 9 to 11 weeks; Main study: 9 weeks
- Weight at study initiation: Sighting Study: Males: 183.54 g to 185.38 g; Females: 173.42 g to 174.59 g
Main Study: Males: 185.38 g to 192.86 g
- Housing: polycabonate cage (size: L 430 × B 280 × H 210 mm) with stainless steel mesh top grill
- Diet (e.g. ad libitum): Altromin maintenance diet 1324 for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG)
- Water (e.g. ad libitum): Deep bore-well water passed through Reverse osmosis unit
- Acclimation period: 19 September 2022 to 23 October 2022
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8°C to 22.7°C
- Humidity (%): 43% to 66%
- 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: 19 September 2022 To: 07 November 2022
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- clean air
- Mass median aerodynamic diameter (MMAD):
- > 2.95 - <= 3.2 µm
- Geometric standard deviation (GSD):
- > 2.74 - <= 2.89
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow-past, nose-only dynamic inhalation exposure system
- Exposure chamber volume: 0.76
- Method of holding animals in test chamber: Restrainer
- Source and rate of air (airflow): 20 liters/min
- Method of conditioning air: Compressor air
- System of generating particulates/aerosols: RBG
- Method of particle size determination: Cascade impactor
- Treatment of exhaust air: NaOH
- Temperature, humidity, pressure in air chamber: 22.5 to 22.6°C, 55.7 to 56.4% & 60Psi
TEST ATMOSPHERE
- Samples taken from breathing zone: yes
- Time needed for equilibrium of exposure concentration before animal exposure: 0.11 min
- Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- > 0 - <= 4 h
- Concentrations:
- 5 mg/L of air
- No. of animals per sex per dose:
- Sighting Study: 1 Male + 1 Female
Main Study: 5 Males - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once daily thereafter for clinical signs and twice daily for mortality and body weight on day 1, 2, 4, 8 and 15
- Necropsy of survivors performed: yes
Results and discussion
- Preliminary study:
- A sighting study was performed with 1 male and 1 female, and the starting concentration for the sighting study was selected from the fixed concentration levels as per Annexure 3 i.e., 1 mg/L. No mortality was observed at concentration 1.05 mg/L of air in sighting study I and 5.03 mg/L of air in sighting study II.
Effect levels
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 5.02 mg/L air (analytical)
- Based on:
- test mat.
- Mortality:
- No treatment related clinical signs and no mortalities were observed in sighting study I, II and main study at the limit concentration of 1.05, 5.03 and 5.02 mg/L of air
- Clinical signs:
- other: No treatment related clinical signs and no mortalities were observed in sighting study I, II and main study at the limit concentration of 1.05, 5.03 and 5.02 mg/L of air
- Body weight:
- The overall body weights of the animals were unaffected by treatment.
Slight decrease in body weight was noted in main study animals on day 2 after to exposure. However, all animals showed increase in body weight on days 4, 8 and 15 - Gross pathology:
- No treatment related gross pathological findings were noted in sighting study I, II and main study
Any other information on results incl. tables
CLINICAL SIGNS AND MORTALITY RECORD
Group & Concentration (mg/L of air) | Animal No. | Sex | Day 1 | Days | |||||||||||
During Exposure | Post exposure | ||||||||||||||
1hr* | 2hrs* | 3hrs* | 4hrs* | 30-40 min | 1hr* | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |||
Sighting Study-I & 1.05 | Rh5201 | M | N | N | N | N | N | N | N | N | N | N | N | N | N |
Rh5202 | F | N | N | N | N | N | N | N | N | N | N | N | N | N | |
Sighting Study-II & 5.03 | Rh5203 | M | N | N | N | N | N | N | N | N | N | N | N | N | N |
Rh5204 | F | N | N | N | N | N | N | N | N | N | N | N | N | N | |
*: ± 10 minutes; N: Normal; M: Male; F: Female; min: minute; hr(s): hour(s): Post exposure test item color was retained in snout region.
TABLE 1 (Contd…). CLINICAL SIGNS AND MORTALITY RECORD
Group & Concentration (mg/L of Air) | Animal No. | Sex | Day 1 | Days | ||||||||||||||||||
During Exposure | Post exposure | |||||||||||||||||||||
1 hr* | 2 hrs* | 3 hrs* | 4 hrs* | 30-40 min | 1 hr* | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | |||
Main study & 5.02 | Rh5205 | M | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N |
Rh5206 | M | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | |
Rh5207 | M | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | |
Rh5208 | M | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | |
Rh5209 | M | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | |
*: ± 10 minutes; N: Normal; M: Male; F: Female; min: minute; hr(s): hour(s); Post exposure test item color was retained in snout region.
Group & Concentration (mg/L of air) | Animal No. | Sex | Body Weight (g) on Days |
| Percent Change in Body Weight with Respect to Day 1 | |||||||
1# | 8 | - | - | - |
| 1-8 | - | - | - | |||
Sighting study I & 1.05 | Rh5201 | M | 201.32 | 224.56 | - | - | - |
| 11.54 | - | - | - |
Rh5202 | F | 186.56 | 200.05 | - | - | - |
| 7.23 | - | - | - | |
Sighting study II & 5.03 | Rh5203 | M | 205.52 | 228.14 | - | - | - |
| 11.01 | - | - | - |
Rh5204 | F | 186.65 | 201.42 | - | - | - |
| 7.91 | - | - | - | |
#: Prior to exposure; M: Male; F: Female; SD: Standard Deviation; n: Number of animals; -: Not applicable.
TABLE 2 (Contd…). BODY WEIGHT (g) AND PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1
Group & Concentration (mg/L of air) | Animal No. | Sex | Body Weight (g) on Days |
| Percent Change in Body Weight with Respect to Day 1 | |||||||
1# | 2 | 4 | 8 | 15 |
| 1- 2 | 1-4 | 1-8 | 1-15 | |||
Main study & 5.02 | Rh5205 | M | 210.42 | 207.15 | 213.62 | 228.63 | 252.63 |
| -1.55 | 1.52 | 8.65 | 20.06 |
Rh5206 | M | 214.92 | 210.46 | 217.12 | 232.44 | 255.91 |
| -2.08 | 1.02 | 8.15 | 19.07 | |
Rh5207 | M | 211.64 | 209.34 | 215.74 | 229.86 | 254.42 |
| -1.09 | 1.94 | 8.61 | 20.21 | |
Rh5208 | M | 209.34 | 206.05 | 212.28 | 224.82 | 247.85 |
| -1.57 | 1.40 | 7.39 | 18.40 | |
Rh5209 | M | 215.77 | 212.38 | 218.44 | 233.53 | 258.90 |
| -1.57 | 1.24 | 8.23 | 19.99 | |
Mean |
| 212.42 | 209.08 | 215.44 | 229.86 | 253.94 |
| -1.57 | 1.42 | 8.21 | 19.55 | |
(±) SD |
| 2.81 | 2.54 | 2.51 | 3.43 | 4.11 |
| 0.35 | 0.34 | 0.51 | 0.78 | |
n |
| 5 | 5 | 5 | 5 | 5 |
| 5 | 5 | 5 | 5 | |
#: Prior to exposure; M: Male; SD: Standard Deviation; n: Number of animals.
Technical Pre-test I:
Sl. No. | Feed rate (mm/hour) | Rotation (rpm) | Initial weight (mg) (a) | Final weight (mg) (b) | Difference (mg) (c) = (b) – (a) | Air Flow Rate (L/min) (d) | Time (min) (e) | BZC (mg/L of air) |
Mean BZC (mg/L of Air) |
1 | 16 | 600 | 349.61 | 351.17 | 1.56 | 1.52 | 1 | 1.03 | 1.04 |
2 | 16 | 600 | 351.95 | 353.54 | 1.59 | 1.52 | 1 | 1.05 |
Sighting study I:
Sl. No. | Feed rate (mm/hour) | Rotation (rpm) | Initial weight (mg) (a) | Final weight (mg) (b) | Difference (mg) (c) = (b) – (a) | Air Flow Rate (L/min) (d) | Time (min) (e) | BZC (mg/L of air) | Mean BZC (mg/L of Air) |
1 | 16 | 600 | 361.71 | 363.31 | 1.60 | 1.52 | 1 | 1.05 | 1.05 |
2 | 16 | 600 | 349.07 | 350.64 | 1.57 | 1.52 | 1 | 1.03 | |
3 | 16 | 600 | 356.94 | 358.58 | 1.64 | 1.52 | 1 | 1.08 |
BZC: Breathing Zone Concentration; Sampled volume: 1.52 L/min; Sampling time: 1 minute
Mass of test item collected on the filter paper (c) | |
Volume of air passed through the filter paper (d) X time (e) |
In technical pre-test, no irregular sampling (Individual sampling was within the ±20% range, when compared with mean breathing zone concentration) was noted, hence sampling was performed three times during sighting study I.
TABLE 3 (Cont…). BREATHING ZONE CONCENTRATION (ACTUAL TEST ITEM CONCENTRATION)
Technical Pre-test II:
Sl. No. | Feed rate (mm/hour) | Rotation (rpm) | Initial weight (mg) (a) | Final weight (mg) (b) | Difference (mg) (c) = (b) – (a) | Air Flow Rate (L/min) (d) | Time (min) (e) | BZC (mg/L of air) |
Mean BZC (mg/L of Air) |
1 | 50 | 600 | 354.79 | 362.41 | 7.62 | 1.52 | 1 | 5.01 | 5.02 |
2 | 50 | 600 | 353.27 | 360.92 | 7.65 | 1.52 | 1 | 5.03 |
Sighting study II:
Sl. No. | Feed rate (mm/hour) | Rotation (rpm) | Initial weight (mg) (a) | Final weight (mg) (b) | Difference (mg) (c) = (b) – (a) | Air Flow Rate (L/min) (d) | Time (min) (e) | BZC (mg/L of air) | Mean BZC (mg/L of Air) |
1 | 50 | 600 | 351.75 | 359.42 | 7.67 | 1.52 | 1 | 5.05 | 5.03 |
2 | 50 | 600 | 348.63 | 356.24 | 7.61 | 1.52 | 1 | 5.01 | |
3 | 50 | 600 | 352.16 | 359.80 | 7.64 | 1.52 | 1 | 5.03 |
BZC: Breathing Zone Concentration; Sampled volume: 1.52 L/min; Sampling time: 1 minute
BZC (i) = | Mass of test item collected on the filter paper (f) |
volume of air passed through the filter paper (g) X time (h) |
In technical pre-test, no irregular sampling (Individual sampling was within the ±20% range, when compared with mean breathing zone concentration) was noted, hence sampling was performed three times during sighting study II.
TABLE 3 (Cont…). BREATHING ZONE CONCENTRATION (ACTUAL TEST ITEM CONCENTRATION)
Main study:
Sl. No. | Feed rate (mm/hour) | Rotation (rpm) | Initial weight (mg) (a) | Final weight (mg) (b) | Difference (mg) (c) = (b) – (a) | Air Flow Rate (L/min) (d) | Time (min) (e) | BZC (mg/L of air) | Mean BZC (mg/L of Air) |
1 | 50 | 600 | 353.75 | 361.40 | 7.65 | 1.52 | 1 | 5.03 | 5.02 |
2 | 50 | 600 | 346.05 | 353.67 | 7.62 | 1.52 | 1 | 5.01 | |
3 | 50 | 600 | 355.01 | 362.65 | 7.64 | 1.52 | 1 | 5.03 |
BZC: Breathing Zone Concentration; Sampled volume: 1.52 L/min; Sampling time: 1 minute
BZC (i) = | Mass of test item collected on the filter paper (f) |
volume of air passed through the filter paper (g) X time (h) |
In technical pre-test, no irregular sampling (Individual sampling was within the ±20% range, when compared with mean breathing zone concentration) was noted, hence sampling was performed three times during Main study.
Example for calculation of Individual actual concentration variability (%) from the mean concentration.
Individual actual conc. variability (%) of each sample from the mean conc. | = | [Mean BZC (mg/L) –BZC (mg/L) of the sample] x 100 (%) |
Mean BZC (mg/L) |
Individual actual conc. variability (%) of each sample from the mean conc. (S.I. No. 1) | = | [5.02 (mg/L) – 5.03 (mg/L)] x 100 (%) | = -0.20 |
5.02 (mg/L) |
Technical Pre-test I:
Concentration (mg/L of air) | SL. No. | Feed rate (mm/hour) | Rotation (rpm) | Total Air flow rate (L/min) (c) = (a) + (b) | Temperature (°C) | Relative Humidity (%) | Oxygen Concentration (%) | Carbon dioxide Concentration (ppm) |
1.04 | 1 | 16 | 600 | 20 | 22.7 | 54.6 | 20.4 | 619 |
2 | 16 | 600 | 20 | 22.6 | 56.7 | 20.5 | 621 |
Sighting study I:
Concentration (mg/L of air) | SL. No. | Feed rate (mm/hour) | Rotation (rpm) | Total Air flow rate (L/min) (c) = (a) + (b) | Temperature (°C) | Relative Humidity (%) | Oxygen Concentration (%) | Carbon dioxide Concentration (ppm) |
1.05 | 1 | 16 | 600 | 20 | 22.5 | 57.5 | 20.5 | 618 |
2 | 16 | 600 | 20 | 22.7 | 55.6 | 20.3 | 619 | |
3 | 16 | 600 | 20 | 22.4 | 56.8 | 20.5 | 622 | |
4 | 16 | 600 | 20 | 22.6 | 55.6 | 20.4 | 625 |
Note: 1% Carbon dioxide = 10000 ppm
TABLE 4 (Cont…). CHAMBER (EXPOSURE) CONDITIONS
Technical Pre-test II:
Concentration (mg/L of air) | SL. No. | Feed rate (mm/hour) | Rotation (rpm) | Total Air flow rate (L/min) (c) = (a) + (b) | Temperature (°C) | Relative Humidity (%) | Oxygen Concentration (%) | Carbon dioxide Concentration (ppm) |
5.02 | 1 | 50 | 600 | 20 | 22.7 | 55.1 | 20.6 | 620 |
2 | 50 | 600 | 20 | 22.5 | 56.8 | 20.3 | 611 |
Sighting study II:
Concentration (mg/L of air) | SL. No. | Feed rate (mm/hour) | Rotation (rpm) | Total Air flow rate (L/min) (c) = (a) + (b) | Temperature (°C) | Relative Humidity (%) | Oxygen Concentration (%) | Carbon dioxide Concentration (ppm) |
5.03 | 1 | 50 | 600 | 20 | 22.5 | 53.9 | 20.4 | 611 |
2 | 50 | 600 | 20 | 22.7 | 55.7 | 20.3 | 619 | |
3 | 50 | 600 | 20 | 22.4 | 56.1 | 20.6 | 621 | |
4 | 50 | 600 | 20 | 22.5 | 57.3 | 20.3 | 625 |
Note: 1% Carbon dioxide = 10000 ppm
TABLE 4 (Cont…). CHAMBER (EXPOSURE) CONDITIONS
Main study:
Concentration (mg/L of air) | SL. No. | Feed rate (mm/hour) | Rotation (rpm) | Total Air flow rate (L/min) (c) = (a) + (b) | Temperature (°C) | Relative Humidity (%) | Oxygen Concentration (%) | Carbon dioxide Concentration (ppm) |
5.02 | 1 | 50 | 600 | 20 | 22.5 | 55.4 | 20.4 | 616 |
2 | 50 | 600 | 20 | 22.6 | 56.5 | 20.3 | 625 | |
3 | 50 | 600 | 20 | 22.3 | 57 | 20.5 | 630 | |
4 | 50 | 600 | 20 | 22.7 | 53.9 | 20.2 | 625 |
Note: 1% Carbon dioxide = 10000 ppm
Technical Pre Test I | |
Chamber Conditions | Range |
Temperature (°C) | 22.6 to 22.7 |
Relative humidity (%) | 54.6 to 56.7 |
Oxygen concentration (%) | 20.4 to 20.5 |
Carbon dioxide concentration (ppm) | 619 to 621 |
Air Flow (L/min)* | 20 |
BZC (mg/L) | 1.03 to 1.05 |
MMAD (µm) | 2.76 # |
GSD | 2.78 # |
Sighting study I | |
Temperature (°C) | 22.4 to 22.7 |
Relative humidity (%) | 55.6 to 57.5 |
Oxygen concentration (%) | 20.3 to 20.5 |
Carbon dioxide concentration (ppm) | 618 to 625 |
Air Flow (L/min)* | 20 |
BZC (mg/L) | 1.03 to 1.08 |
MMAD (µm) | 2.87 to 2.99 |
GSD | 2.88 to 2.92 |
*: Values were constant throughout the exposure; #: Individual value; BZC: Breathing Zone Concentration (Actual Concentration); MMAD: Mass Median Aerodynamic Diameter; GSD: Geometric Standard Deviation.
TABLE 7 (Cont…). SUMMARY OF CHAMBER (EXPOSURE) CONDITIONS
Technical Pre Test II | |
Chamber Conditions | Range |
Temperature (°C) | 22.5 to 22.7 |
Relative humidity (%) | 55.1 to 56.8 |
Oxygen concentration (%) | 20.3 to 20.6 |
Carbon dioxide concentration (ppm) | 611 to 620 |
Air Flow (L/min)* | 20 |
BZC (mg/L) | 5.01 to 5.03 |
MMAD (µm) | 3.50 # |
GSD | 2.87 # |
Sighting study II | |
Temperature (°C) | 22.4 to 22.7 |
Relative humidity (%) | 53.9 to 57.3 |
Oxygen concentration (%) | 20.3 to 20.6 |
Carbon dioxide concentration (ppm) | 611 to 625 |
Air Flow (L/min)* | 20 |
BZC (mg/L) | 5.01 to 5.05 |
MMAD (µm) | 3.17 to 3.37 |
GSD | 2.72 to 2.85 |
*: Values were constant throughout the exposure; #: Individual value; BZC: Breathing Zone Concentration (Actual Concentration); MMAD: Mass Median Aerodynamic Diameter; GSD: Geometric Standard Deviation.
TABLE 7 (Cont…). SUMMARY OF CHAMBER (EXPOSURE) CONDITIONS
Main study | |
Chamber Conditions | Range |
Temperature (°C) | 22.3 to 22.7 |
Relative humidity (%) | 53.9 to 57.0 |
Oxygen concentration (%) | 20.2 to 20.5 |
Carbon dioxide concentration (ppm) | 616 to 630 |
Air inlet (L/min)* | 20 |
BZC (mg/L) | 5.01 to 5.03 |
MMAD (µm) | 3.17 to 3.21 |
GSD | 2.71 to 2.78 |
*: Values were constant throughout the exposure; BZC: Breathing Zone Concentration (Actual Concentration); MMAD: Mass Median Aerodynamic Diameter; GSD: Geometric Standard Deviation.
Group & Concentration (mg/L of Air) | Animal No. | Sex | Fate | Gross Pathological Findings | |
External | Internal | ||||
Sighting Study-I & 1.05 | Rh5201 | M | TS | NAD | NAD |
Rh5202 | F | TS | NAD | NAD | |
Sighting Study-II & 5.03 | Rh5203 | M | TS | NAD | NAD |
Rh5204 | F | TS | NAD | NAD | |
Main Study & 5.02 | Rh5205 | M | TS | NAD | NAD |
Rh5206 | M | TS | NAD | NAD | |
Rh5207 | M | TS | NAD | NAD | |
Rh5208 | M | TS | NAD | NAD | |
Rh5209 | M | TS | NAD | NAD | |
NAD: No Abnormality Detected; M: Male; F: Female; TS: Terminal Sacrifice
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- Test item has not to be classified as acutely toxic by inhalation route according to Regulation (EC) No 1272/2008.
- Conclusions:
- Under the experimental conditions employed and based on the above results of this study, there were no clinical signs and no mortalities observed at the mean maximum achievable concentration of 5.02 mg/L of air. Hence, the LC50 of the test item is > 5.02 mg/L of air.
- Executive summary:
The test item was evaluated for acute inhalation toxicity in Sprague Dawley rats.
The objective of the study was to assess the toxic potential and to determine the LC50 of the test item, when administered by inhalation route through flow-past nose-only dynamic inhalation equipment for a single 4 hours exposure to rats and also to classify for risk assessment of chemical according to globally harmonized system of classification and labelling of chemicals. One male and one female rat was used for each sighting study and five male rats were used to perform the main study.
As such the test item was used during technical pre-test, sighting study I, II and main study to generate the dust aerosols through rotating brush generator. The technical pre-test was carried out without animals. During, technical pre-test of sighting study -I and technical pre-test of sighting study -II, the limit concentration was achieved 1.04 and 5.02 mg/L of air at the feed rate of 16 and 50 mm/hour with a rotation of 600 RPM, hence the same speed was selected for sighting study and main study to generate the limit concentration of test item.
The mean chamber conditions like temperature, relative humidity, oxygen concentration, carbon dioxide concentration, MMAD and GSD were observed during the exposure and were found within the acceptable range.
All the animals were observed for clinical signs of toxicity and mortality during exposure and post exposure on day 1 and once daily thereafter for clinical signs and twice daily for mortality for 7 days for sighting study I, II and 14 days for main study post exposure period. Individual animal body weight was recorded on the day of dosing, and on days 1 and 8 for the sighting studies and on days 1, 2, 4, 8 and 15 for the main study. All rats were euthanized after 7 or 14 days post exposure by intraperitoneal administration of sodium thiopentone and they were subjected to gross necropsy.
In sighting study I and II, the animals were exposed at mean concentration of 1.05 and 5.03 mg/L of air, determined by gravimetric method. The Rotating Brush Generator was used to generate the dust particles (aerosols) into an airborne state.
In the main study five male animals were exposed at mean concentration of 5.02 mg/L of air determined by gravimetric method. During main study the target concentration of 5.02 mg/L of air was achieved at the feed rate of 50 mm/hour with a rotation of 600 RPM.
No treatment related clinical signs of toxicity and mortalities were observed in the sighting study I, II and main study. Slight decrease in body weight was noted in main study on day 2 due to exposure. All animals showed increase in body weight on days 4, 8 and 15.
No treatment related gross pathological findings were noted in any of the animals in the sighting study I, II and the main study.
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