Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
According to section 1.2 of Annex XI, reproductive toxicity/fertility testing, i.e. Screening study (Annex VIII, Section 8.7.1.; OECD TG 421) and Extended One-Generation Reproductive Toxicity study (Annex X, Section 8.7.3.; test method: EU 8.56./OECD TG 443) need not be done if there is a weight-of-evidence to conclude the substance does not have a particular property, and further testing on vertebrate animals may be omitted. The toxicological database for inhaled 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate (IPDI) demonstrates consistently that toxicity is associated only with the portal of entry (respiratory tract), any other manifestations of toxicity are secondary to this. Additionally, a study according to OECD TG 414 with rats (1st species) is available as well as other repeated dose studies (OECD TG 413, 412) and acute toxicity studies (OECD TG 403, 401) on IPDI showing all toxicity confined to the respiratory tract. In the developmental toxicity study, effects on fetal development were only observed in presence of maternal toxicity and induced by secondary systemic effects such as hypoxia. Furthermore, the information gained in developmental and reproductive toxicity studies of other aliphatic diisocyanates, i.e. HDI and H12MDI confirmed the local mode of action for the entire substance group of diisocyanates. Protection against respiratory tract toxicity will protect against any secondary effects. A full and detailed justification elaborating this data waiver is attached to this record. By weight-of-evidence, it is concluded that reproductive toxicity is not an endpoint of concern for IPDI and additional toxicity testing is not necessary.

Data source

Materials and methods

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

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