4-methyl-m-phenylene diisocyanate

Endpoint summary

Description of key information

Acute toxicity:

Oral: LD50 > 2000 mg/kg for rats or mice (following or equivalent to OECD TG 401)

Dermal: LD50 > 2000 mg/kg for rabbits (equivalent to OECD TG 402)

Inhalation: LC50 = 0.48 mg/l/1 hr for rats (equivalent to OECD TG 403)

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.

Acute toxicity: oral

Several tests assessing the oral toxicity of TDI in rats or mice of both sexes are available. A limit test performed by the Ministry of Health of Japan (2001) showed in rats a LD₅₀value of more than 2000 mg/kg bw for both sexes. NTP study with rats and mice showed also LD₅₀values > 2000 mg/kg bw (Rat: LD_50male= 5110 mg/kg bw; LD_50female= 4130 mg/kg bw/ Mice: LD_50male= 4130 mg/kg bw; LD_50female= 5620 mg/kg bw). At necropsy, white crystalline material was found in the stomach and dark red lungs were observed. In Wazeter F.X. (1964), the acute oral LD_50malevalue was determined to be 5840 mg/kg bw. White granular particles were also found in the stomach, and hypoactivity and reduced pain response were observed. Overall, tests assessing the acute oral toxicity of TDI provide consistent evidence of low toxicity after an oral administration.

Acute toxicity: dermal

One data is reported for this endpoint. TDI (unspecified isomers) was dermally administered to rabbits. No mortality occured and animals appeared normal throughout the 14-day observation period but skin irritation was noted at all dose levels (2500 to 9400 mg/kg b.w.), at a moderate-to-marked degree. This result shows that TDI is not acutely toxic via the dermal route, as the LD50 was greater than 9400 mg/kg b.w. in rabbits (Wazeter et al., 1964).

Acute toxicity: inhalation

Two reliable studies for the assessment of the inhalation toxicity of TDI are available. Doe and Horspool (1980) determined the 1-hour LC50 in rats at 66 ppm (0.47 mg/l). All animals were exposed whole-body. Animals dying on study or killed at the end of exposure revealed some hemorrhages or edema of the lungs. As part of a micronucleus study, a 6-hour inhalation exposure with a four-day observation period was performed using mice (Mackay, 1992). Exposures were whole body to 80:20 TDI. The LC50 was 14 ppm(0.1 mg/l)for females and 19 ppm(0.14 mg/l)for males. Overall, these results show that TDI is very toxic by inhalation.for males. Overall, these results show that TDI is very toxic by inhalation.

  

Justification for classification or non-classification

Official EU classification according to Directive 67/548/EEC is T+; R26, Very toxic by inhalation, and by EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008), Acute tox 1, fatal if inhaled.

Acute toxicity (oral): not classified (2,4/ 2,6 TDI (80/20), LD₅₀ oral rat and mouse > 2000 mg/kg bw)

Acute toxicity (dermal): not classified (TDI unspecified isomers, LD₅₀ dermal rabbit > 2000 mg/kg bw)

Acute toxicity (inhalation vapour): Category 2, fatal if inhaled (2,4/ 2,6 TDI (80/20), LC50, 1 hr, rat, 0.47 mg/l (66 ppm) (Doe and Horspool, 1980))