Hexamethylene diisocyanate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

746 mg/kg bw

Quality of whole database:

The studies are of sufficient quality (Klimisch score=2)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

124 mg/m³ air

Quality of whole database:

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

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

7 000 mg/kg bw

Quality of whole database:

The study is of sufficient quality (Klimisch score=2)

Additional information

Acute toxicity: oral

The LD50 resulting from a single oral (gavage) administration ranged from 746 to approximately 959 mg/kg bw for the male rat (Smyth et al., 1969; Union Carbide Corp., 1964; Kimmerle et al., 1970). Soon after dosing the animals appeared to be extremely sluggish. All deaths occurred within the first day.

Acute toxicity: dermal

The acute dermal toxicity of HDI was low with an LD50 value > 7000 mg/kg bw for male and female rats according to OECD TG 402 (Mürmann, 1985). Single occlusive administration of 7000 mg/kg bw for 24 hours was tolerated without mortalities. The animals showed clinical signs (rough hair, crusts and scars in application area) up to the end of the 14-day observation period. Body weight gain was transiently inhibited. Gross necropsy revealed hyperemia and swelling of the gastric mucosa as well as distinct hyperemia of the small intestine mucosa, peritoneum, pleura, diaphragm and pancreas in all animals.

Acute toxicity: inhalation

The inhalation LC50 in rats of both sexes was determined to be 124 mg/m3 for 4 hours of exposure to HDI vapour according to OECD TG 403 (Pauluhn, 1997). Exposures to concentrations of 55 mg/m3 and above were followed by concentration-dependent signs indicative of respiratory tract irritation, such as bradypnea, dyspnea, laboured breathing pattern, rales, nostrils/muzzle with red encrustations, cyanosis, prostration (lying on belly), reduced motility, ungroomed haircoat, hypothermia, decreased body weights, and piloerection. Gross necropsy revealed less collapsed, discolorated (dark-red) lungs with serous mucus in trachea. The lung associated lymph nodes were enlarged. Clinical observations and necropsy findings support the conclusion that a causal relationship between lethality and lung damage existed.

Two sensory irritation studies with HDI vapour revealed 30-minute RD50 values (50 % inhibition of respiration) of 9.93 mg/m3 in male rats (Sangha, 1982) and of 2.45 mg/m3 in male mice (Sangha et al., 1981). In rats, time-response relationships showed a fast onset of the response and development of tolerance after five minutes of exposure. However, fast recovery after short exposure and slow recovery after longer exposure were observed in mice.

Justification for classification or non-classification

Acute toxicity: oral

Not classified under Annex I of Directive 67/548/EEC or Annex VI-1 of Regulation (EC) No 1272/2008. Differing from this oral LD50 values of 746-959 mg/kg bw for the male rat lead to the following classification according to Annex I of Regulation (EC) No 1272/2008: Category 4 (H302: Harmful if swallowed).

Acute toxicity: dermal

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 acute dermal toxicity (LD50: > 7000 mg/kg bw).

Acute toxicity: inhalation

Classified under Annex I of Directive 67/548/EEC with R23 (toxic by inhalation). This classification corresponds to Category 3* (minimum classification: toxic if inhaled) according to Annex VI-1 of Regulation (EC) No 1272/2008. Differing from this the LC50 value of 124 mg/m3 (vapour) for rats leads to the following classification according to Annex I of Regulation (EC) No 1272/2008: Category 1 (H330: Fatal if inhaled as vapour).

Classification of acute inhalation toxicity with regard to Specific Target Organ Toxicity - Single Exposure (STOT-SE):

Due to respiratory irritation effects HDI was 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.