4-methyl-m-phenylene diisocyanate

Endpoint summary

Description of key information

Inhalation exposure is the most appropriate route for assessing occupational risk in humans. Effects from repeated exposure of animals to TDI are limited to effects on the respiratory tract caused by local irritation, no signs of systemic toxicity were observed.

The oral and dermal route of exposure are not relevant for assessment.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEC

0.362 mg/m³

Additional information

Data on physical and chemical properties, eco-toxicity and toxicity can be used for read-across from 2,4-TDI to 2,6-TDI and mixed TDI isomers (i.e. 80/20, 65/35, 2,4/2,6 ratios).  2,4 TDI is the major component of the TDI mixed isomers and so has the major influence on their properties and effects. The reactivity of the 2,6-TDI isomer is somewhat less than that of 2,4-TDI but is of the same order of magnitude. It may therefore be concluded that the effects of 2,6-TDI will be similar to those of 2,4-TDI. This is in fact observed where there are overlapping data.

Inhalation exposure is the most appropriate route for assessing occupational risk in humans. Effects from repeated exposure of animals to TDI are limited to effects on the respiratory tract caused by local irritation.

The most relevant evaluation of repeated dose toxicity comes from a 2-year chronic toxicity and carcinogenicity study with TDI in rats and mice (Owen, 1980 + 1986; Loeser, 1983). The animals were whole body exposed to 0, 0.05 and 0.15 ppm of TDI (80/20) vapour for 6 hours/day, 5 days/week. In both species, body weight gain was reduced at 0.15 ppm over the first 12 weeks that persisted but did not worsen over the remaining period of the study. In rats, rhinitis was observed in males at 0.15 ppm and in females beginning at 0.05 ppm, generally characterized by squamous metaplasia/hyperplasia of the respiratory mucosa, with and without exudate in the lumen, and leucocyte infiltration in the lamina propria. This finding is considered to be due to local irritation of the anterior nasal cavity. In mice, histopathology revealed marked inflammatory processes in trachea, larynx, bronchi, lungs and predominantly in nasal turbinates (chronic and necrotic rhinitis) of male and female animals beginning at 0.05 ppm. Therefore, the LOAEC for rats and mice is 0.05 ppm (0.362 mg/m3) after long-term inhalation of TDI vapour.

The findings of the key study were supported by subchronic studies in various strains and species (Henck, 1976).30 day whole body exposure of SD- and Fischer-rats, hamsters and mice to vapors of 0.1 and 0.3 ppm resulted in repiratory irritation (LOAEL 0.1 ppm) but no signs of systemic toxicity.

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: nose

Justification for classification or non-classification

According to Directive 67/548/EEC and the CLP-Regulation (EC) 1272/2008, no classification for systemic toxicity following repeated exposures is appropriate. Due to local irritationof the respiratory tract, the R37 is appropriate

according to Directive 67/548/EEC or STOT cat3 according to CLP-Regulation (EC) 1272/2008.