1,1,1,3,3,3-hexamethyldisilazane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data waiving: Data from handbook or collection of data

Data source

Reference

Title:

SIAM 29, 20-22 October 2009, SIDS INITIAL ASSESSMENT PROFILE

Applicant's summary and conclusion

Conclusions:

The repeated-dose toxicity of HMDZ has been investigated by the inhalation route in a combined repeated-dose/ reproductive/developmental toxicity screening study (OECD TG 422). The test article was administered to groups of 10 rats/sex via whole-body vapour inhalation for six hours/day, seven days/week to target concentrations of 0 (filtered air), 25, 100 and 400 ppm (0.16, 0.66, and 2.66 mg/L). Males were exposed throughout the 15 day pre-mating period and during the mating and post-mating periods, for a total of at least 4 weeks. Females were exposed throughout the pre-mating and mating periods and during pregnancy and lactation, until day 4 post-partum (or until sacrifice for un-mated females). Un-mated females were used in the repeated-dose portion of the study. Clinical signs were consistent with nervous system effects immediately after exposure at 2.66 mg/L. Significantly decreased body weight [15%] and food consumption were observed at 2.66 mg/L and absolute body weights of 0.66 mg/L females were decreased [7%; p<0.02]. Effects on haematology and serum chemistry parameters were noted at 2.66 mg/L. Decreases in absolute epididymides weight of 2.66 mg/L males and absolute lung weights of 2.66 mg/L females were observed. Increases in relative kidney weight were observed at 0.66 and 2.66 mg/L (females) and 2.66 mg/L (males). Increased relative liver weight was observed in 2.66 mg/L females. Centrilobular hypertrophy in the liver of 2.66 mg/L females was the only microscopic finding. Based on the clinical observations, body weight changes, serum chemistry, haematology and histological findings following whole body inhalation exposure, the systemic toxicity NOAEC was 0.66 mg/L and the LOAEC was 2.66 mg/L. .