Registration Dossier

Administrative data

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:
Justification for type of information:
According to section 1.2 of Annex XI, the study need not be conducted if there is a weight of evidence approach (WoE) to conclude that 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 (isophorone diisocyanate; IPDI) demonstrates consistently that toxicity is associated only with the portal of entry (respiratory tract), any other manifestations of toxicity are secondary to this. While no fertility study is available for IPDI, sub-chronic study shows toxicity confined to the respiratory tract. Fertility studies with similar diisocyanates H12MDI and HDI show no effects on reproductive parameters, all effects are confined to the respiratory tract.
Hence the databases for other aliphatic diisocyanates show that primary toxicity for diisocyanates is to the respiratory tract, other effects, such as fetotoxicity in developmental studies, are secondary to this. This relationship applies to H12MDI and HDI when tested in fertility studies in the rat and is considered to apply equally to IPDI, i.e., if any effects were to be seen in a fertility study, these would occur only as a secondary effect of the toxicity to the respiratory system of the exposed rats. Protection against respiratory tract toxicity will protect against any secondary effects.
A full and detailed text "Rationale for Waiving Additional Animal Studies on Reproductive Toxicity for Aliphatic Diisocyanate Monomers and their Polyisocyanates” elaborating this data waiver is attached to this record. Using the 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