Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Standard laboratory conditions. Air-conditioned with 10 - 15 air changes per hour, continuously monitored environmental conditions (temp. range: 22 ± 3 °C;
relative humidity range: 30 - 70 %). On some isolated occasions, the relative humidity in the animal room exceeded the upper limit of 70 %. This is considered to
have no impact on the scientific validity of the study. The light cycle was set to 12-hour fluorescent light / 12-hour dark cycle with at least eight hours music during the light period.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
> 1.89 - < 2.18 µm
Geometric standard deviation (GSD):
> 1.5 - < 3
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
No. of animals per sex per dose:
5

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
> 5.1 mg/L air
Based on:
other: gravimetrically determined mean aerosol concentration
Exp. duration:
4 h
Mortality:
All animals exposed to 2.0 mg/L air survived the scheduled observation period. One female exposed to 5.1 mg/L air was found dead on test day 5. All other animals exposed to 5.1 mg/L air survived the scheduled observation period
Clinical signs:
other: Clinical signs were limited to the day of exposure. All animals of both groups showed slightly ruffled fur after exposure. Two males and four females exposed to 5.1 mg/L air additionally showed salivation during the second half of exposure. The animal whi
Body weight:
Between test days 1 and 2, reduced body weight gain or slight body weight loss was noted in all males exposed to 2.0 or 5.1 mg/L air. This continued in one male exposed to 5.1 mg/L air until test day 8. Thereafter, normal body weight development was noted in all males.
Between test days 1 and 4, reduced body weight gain or slight body weight loss was noted in all females exposed to 2.0 or 5.1 mg/L air. This continued in to females exposed to 2.0 mg/L air until test day 8 and in another two females exposed to 2.0 mg/L air until test day 15.
Other findings:
Macroscopic Findings
No test item-related macroscopic findings were present at necropsy. All findings observed were within the range of spontaneous background lesions which may occasionally be recorded in rats of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the findings of this study, the LC50 for 4-hour exposure of Azo Initiator VA044 was greater than 5.1 mg/L air (gravimetrically determined mean aerosol concentration). Based on mortality and body weight data, females are considered to be more susceptible to the toxicity of the test item.
Executive summary:

Treatment of RccHanTM:WIST(SPF) rats with Azo Initiator VA044 at gravimetrically determined mean concnentrations of 2.0 mg/L air and 5.1 mg/L air for 4 hours did not result in any deaths at 2.0 mg/L air. One female died on test day 5 after exposure to 5.1 mg/L air. Clinical signs of toxicity were limited to the day of exposure and no test item-related macroscopic findings were observed. Between test days 1 and 2, reduced body weight gain or slight body weight loss was noted in all males exposed to 2.0 or 5.1 mg/L air. This continued in one male exposed to 5.1 mg/L air until test day 8. Thereafter, normal body weight development was noted in all males. Between test days 1 and 4, reduced body weight gain or slight body weight loss was noted in all females exposed to 2.0 or 5.1 mg/L air. This continued in to females exposed to 2.0 mg/L air until test day 8 and in another two females exposed to 2.0 mg/L air until test day 15. Although body weight loss or stagnation of body weight gain is not unusual in inhalation studies due to the restraining of the animals in the tubes during nose-only exposure, the effect in females exposed to 2.0 mg/L air and in both sexes exposed to 5.1 mg/L air is considered to be test itemrelated due to the magnitude and duration of body weight loss observed. Based on the findings of this study, the LC50 for 4-hour exposure of Azo Initiator VA044 was greater than 5.1 mg/L air (gravimetrically determined mean aerosol concentration). Based on mortality and body weight data, females are considered to be more susceptible to the toxicity of the test item.