Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

chronic toxicity: inhalation
Adequacy of study:
other information
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


Materials and methods

Results and discussion

Applicant's summary and conclusion

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. .