[No public or meaningful name is available]

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In rats effects from acute aerosol exposure are limited to the respiratory tract caused by local irritation (BASF SE, 2003; Bayer AG, 2011). This distinct portal of entry toxicity can be assigned to the residual isocyanate (NCO)-groups of the substance. This reactive functional group is also common to HDI monomers which is not classifiable as reproductive toxin. All effects observed in reproductive and developmental toxicity studies with HDI are confined to the respiratory tract. This confirms that primary toxicity for diisocyanates is to the respiratory tract. Other effects, such as fetotoxicity in developmental studies, are not to be expected or only occur secondary to this. This applies to HDI when tested in reproductive toxicity studies in the rat and is considered to apply equally to the allophanate-type HDI oligomer, i.e., if any effects were to be seen, 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 the allophanate-type HDI oligomer and additional reproductive toxicity testing is not necessary. 

Effects on developmental toxicity

Additional information

In rats effects from acute aerosol exposure are limited to the respiratory tract caused by local irritation (BASF SE, 2003; Bayer AG, 2011).This distinct portal of entry toxicity can be assigned to the residual isocyanate (NCO)-groups of the substance. This reactive functional group is also common to HDI monomers which is not classifiable as reproductive toxin.All effects observed in reproductive and developmental toxicity studies with HDI are confined to the respiratory tract. This confirms that primary toxicity for diisocyanates is to the respiratory tract. Other effects, such as fetotoxicity in developmental studies, are not to be expected or only occur secondary to this. This applies to HDI when tested in reproductive toxicity studies in the rat and is considered to apply equally to the allophanate-type HDI oligomer, i.e., if any effects were to be seen, 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.

This is demonstrated by a developmental toxicity study with HDI (Astroff, 1999):

In a developmental toxicity study (OECD TG 414) with 1,6-hexamethylene diisocyanate (HDI) rats were exposed, via whole-body exposure, to HDI vapour concentrations of 0, 0.005, 0.050, or 0.300 ppm for 6 hours/day on days 0 through 19 of gestation. Analytically confirmed overall (for the entire study) mean HDI vapour concentrations were 0.005, 0.052 and 0.308 ppm. Maternal toxicity was demonstrated in the 0.300 and to a lesser extent in the 0.050 ppm exposure groups. No maternal effects were noted in the 0.005 ppm dose group. Test compound-related maternal effects were restricted to histopathological findings, and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/post-implantation loss and resorptions. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-

related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed and there was no difference in the incidence of malformations between males and females.

In summary, HDI produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm. No developmental toxicity was observed at any concentration level. Therefore, the maternal no-observed-effect-level (NOEL) was 0.005 ppm and the developmental NOEL was 0.300 ppm.

Justification for classification or non-classification

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