Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The purpose of this study was to determine the 4-hour inhalation median lethal concentration (LC50) for the test substance in male and female rats by the EPA protocol. The LC50 was defined as the calculated atmospheric concentration of test material expected to cause the death of 50% of exposed animals either on the day of exposure or within 14 days post exposure.
GLP compliance:
yes
Test type:
traditional method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Purity: 96.8%

Test animals

Species:
rat
Strain:
other: Crl:CD®BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles
River Breeding Laboratories, Kingston, New York
- Females (if applicable) nulliparous and non-pregnant: No data are provided in the report
- Age at study initiation: 8 weeks old
- Weight at study initiation: Males: 227-263 g and Females: 165-205 g
- Fasting period before study: No data are provided in the report
- Housing: rats were housed in pairs of the same sex in 8" x 14" x 8" suspended, stainless steel, wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow® #5002
- Water (e.g. ad libitum): Source of the water is not provided in the report
- Acclimation period: One week prior to testing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): humidity ranged from 33-36%
- Air changes (per hr): No data are provided in the report
- Photoperiod (hrs dark / hrs light): No data are provided in the report

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Remark on MMAD/GSD:
MMAD for the 5.1 mg/L exposure was 9.5 µm and for the 5.7 mg/L exposure, 9.0 µm
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 38 liter
- Method of holding animals in test chamber: Rats were restrained in perforated, stainless steel cylinders with conical nose pieces
- Source and rate of air: Room air
- Method of conditioning air: No conditioning
- System of generating particulates/aerosols: Dust atmospheres of the test substance were generated with a K-tron® Bin Feeder equipped with twin feed screws. The feed rate was regulated with a K-tron® volumetric feed controller. The bin feeder metered the test material into a plastic funnel which dropped the test substance into a glass transfer tube, where regulated high pressure air swept the test material through a 90° dust dispersion tube into the exposure chamber

- Method of particle size determination: Particle size (mass median aerodynamic diameter and percent < 10 µm) was determined with a Sierra Series 210 cascade impactor during each exposure.
- Treatment of exhaust air: Chamber exhaust was drawn through a coarse dust trap then through a MSA filter prior to being discharged through the hood exhaust
- Temperature, humidity, pressure in air chamber: Test chamber temperature ranged between 20-22°C, relative humidity ranged from 33-36%, and oxygen concentration was 21%; Control chamber temperature was 25°C, relative humidity was 30% and oxygen concentration was 21%.

TEST ATMOSPHERE
- Samples taken from breathing zone: yes/no
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric analysis
Duration of exposure:
4 h
Concentrations:
5.1 and 5.7 mg/L
No. of animals per sex per dose:
10 males and 10 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were weighed and observed daily for 14 days post exposure, weekends and holidays excluded
- Necropsy of survivors performed: yes, 3 males and 3 females from the 5.1 mg/L exposure were necropsied for gross examination immediately after exposure
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
No

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.7 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: no deaths at highest dose tested
Mortality:
No mortality
Clinical signs:
During exposure test dust accumulated on the rat noses and rats showed a diminished response to sound. Immediately after exposure rats showed a red nasal and ocular discharge. This is a common clinical sign in restrained rats.
Body weight:
During the 14-day post-exposure recovery period, rats showed a slight weight loss (8 out of 10 males, 1 out of 10 females) on the first post-exposure day, but resumed a normal weight gain through the remainder of the recovery period.
Gross pathology:
Rats examined by gross necropsy immediately after exposure to 5.1 mg/L of the test substance dust showed no effects due to the test treatment.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the LC50 for the test substance dust was greater than 5.7 mg/L. No exposure-related effects were observed in 3 male and 3 female rats examined by gross necropsy immediately after exposure to 5.1 mg/L of the test substance dust.
Executive summary:

Groups of 10 male and 10 female Crl:CD®BR rats were exposed, nose only, to atmospheres containing the test substance dust for a single 4-hour period.

 

Under the conditions of this test, the LC50 for the test substance was greater than 5.7 mg/L, the highest dose tested. No exposure-related effects were observed in 3 male and 3 female rats examined by gross necropsy immediately after exposure to 5.1 mg/L of the test substance dust.