Hexamethylene diisocyanate

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 adverse effect observed

Dose descriptor:

NOAEC

2.03 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

The study is GLP compliant and is of high quality (Klimisch score=1)

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In a combined reproductive/developmental/neurotoxicity study (OECD TG 422) 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 during a 14-day premating phase, up to a 14-day mating phase, and a 21-day gestation phase (Astroff, 1999; Astroff et al., 2000). Analytically confirmed overall (for the entire study) mean HDI vapour concentrations were 0.005, 0.053 and 0.299 ppm. Following the gestation phase the dams were transferred to nesting cages and permitted to deliver. The dams and their litters were maintained for a 4-day lactation phase during which exposure to HDI was discontinued. HDI demonstrated toxicity at vapour concentrations of 0.050 and 0.300 ppm resulting in microscopic alterations in the nasal cavity (primarily epithelial hyperplasia, squamous metaplasia, chronic-active inflammation, and more seriously, degeneration of the olfactory epithelium). No effects were observed in the 0.005 ppm group, and no effects on hematology, clinical chemistry, or neurologic parameters were observed with any concentration. There were no statistically significant effects on the mating, fertility, or gestation indices. There were no effects observed on the days to insemination, gestation length, or total number of implantation sites. There were no statistically significant effects on litter size, total number of pups born, sex distribution, mean weight of viable pups, mean number of viable pups or number of stillborn pups. No statistically significant effects were observed on the live birth, viability, lactation, or birth indices.

Therefore, the no-observed-effect-level (NOEL) for reproduction (including neonatal development) as well as for hematology, clinical chemistry, and neurotoxicity was 0.300 ppm (2.03 mg/m3) and the overall NOEL was 0.005 ppm (0.034 mg/m3).

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

2.1 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

The study is GLP compliant and is of high quality (Klimisch score=1)

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

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 (Astroff, 1999; Astroff et al., 2000). 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 (0.034 mg/m3) and the developmental NOEL was 0.300 ppm (2.1 mg/m3).

Justification for classification or non-classification

Toxicity to reproduction (fertility, developmental toxicity / teratogenicity)

Not classified under Annex I of Directive 67/548/EEC. According to Annex I of Regulation (EC) No 1272/2008 no classification is required for toxicity to reproduction.