Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

The toxicological database for inhaled Hexamethylene diisocyanate, oligomers (biuret) 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 studies are available for Hexamethylene diisocyanate, oligomers (biuret), subchronic and subacute studies all show toxicity confined to the respiratory tract. Fertility studies with other aliphatic 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 (IPDI, H12MDI and HDI) all 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 Hexamethylene diisocyanate, oligomers (biuret), 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.

Using the weight of evidence, it is concluded that reproductive toxicity is not an endpoint of concern for Hexamethylene diisocyanate, oligomers (biuret) and additional toxicity testing is not necessary. 

Effects on developmental toxicity

Additional information

The toxicological database for inhaled Hexamethylene diisocyanate, oligomers (biuret) 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 developmental study is available for Hexamethylene diisocyanate, oligomers (biuret), subchronic and subacute (and acute) studies all show toxicity confined to the respiratory tract. Hence the databases for other aliphatic diisocyanates (IPDI, H12MDI, HDI) all 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 IPDI, H12MDI and HDI when tested in developmental toxicity studies in the rat and is considered to apply equally to Hexamethylene diisocyanate, oligomers (biuret), i.e., if any effects were to be seen in a developmental 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.

Using the weight of evidence, it is concluded that developmental toxicity is not an endpoint of concern for Hexamethylene diisocyanate, oligomers (biuret) and additional toxicity testing is not necessary.

Justification for classification or non-classification

No classification required for toxicity to reproduction according to Regulation (EC) No 1272/2008, Annex I.