Hexamethylene diisocyanate

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

In a dermal irritation/corrosion study HDI was corrosive to the skin of rabbits according to OECD TG 404 (Schreiber, 1981). Immediately after patch removal all treated animals showed severe edema and erythema (grade 4). 24 hours after patch removal induration and necrosis at the application site of all animals were seen. No reversibility could be observed at the end of the post-observation period of 8 days.

Eye irritation

In an acute eye irritation/corrosion study HDI was corrosive to the eyes of rabbits according to OECD TG 405 (Schreiber, 1981). The examination of the eyes showed 1 hour after instillation severe effects in all animals with regard to cornea, iris and conjunctivae (left eye not rinsed). All effects had a tendency to get worse during the 8-day post-observation period. Damage to the eye was already observed 30 seconds after instillation (right eye rinsed with saline 30 sec. after instillation).

Respiratory / sensory irritation

Sensory irritation studies using laboratory animal models demonstrated evidence of sensory irritation but no evidence of pulmonary irritation to HDI. In a sensory irritation study with HDI vapour Sangha et al. (1981) reported a 3-hour RD50 (concentration required to reduce respiratory rate by 50 %) of 1.19 mg/m3 using male Swiss Webster mice. Exposure duration between 0.17-3 hours and concentrations between 1.19 -6.71 mg/m3 caused a time and concentration dependent decrease of the respiration rate. Fast recovery

after short exposure and slow recovery after longer exposure were observed. A comparable study using male Fisher 344 rats resulted in a 30-minute RD50 of 9.93 mg/m3 (Sangha, 1982). HDI vapour exposure (head-only) of female Sprague-Dawley rats revealed a 3-hour RD50 of 11.83 mg/m3 (1.69 ppm) (Shiotsuka 1987a). In a study to assess the effects of repeated exposures on respiratory rate, female Sprague-Dawley rats were head-only exposed 3 hours/day for 6 days (5 consecutive days and 2 days later for an additional day) to a mean HDI vapour concentration of 8.19 mg/m3 (1.17 ppm). The daily decrease in respiratory rate of 50 to 63 %, relative to pre-exposure mean for day 1, showed that repeated exposures did not produce a cumulative effect on respiratory rate depression during daily exposures (Shiotsuka, 1987b).

Justification for classification or non-classification

Skin irritation

Classified under Annex I of Directive 67/548/EEC with R38 (irritating to skin). This classification corresponds to Category 2 (causes skin irritation) according to Annex VI-1 of Regulation (EC) No 1272/2008. Differing from this the irreversible damage to the skin of rabbits leads to the following classification according to Annex I of Regulation (EC) No 1272/2008: Category 1C (H314: Causes severe skin burns and eye damage).

Eye irritation

Classified under Annex I of Directive 67/548/EEC with R36 (irritating to eye). This classification corresponds to Category 2 (causes serious eye irritation) according to Annex VI-1 of Regulation (EC) No 1272/2008. Differing from this the irreversible damage to the eyes of rabbits leads to the following classification according to Annex I of Regulation (EC) No 1272/2008: Category 1C (H314: Causes severe skin burns and eye damage).

Respiratory irritation

Classified under Annex I of Directive 67/548/EEC with R37 (irritating to respiratory system). This classification corresponds to STOT-SE Category 3 (H335: May cause respiratory irritation) according to Annex VI-1 of Regulation (EC) No 1272/2008.