4-methyl-m-phenylene diisocyanate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

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.

Animal  data  provide clear evidence of skin sensitisation due to TDI. Human experience finds that skin sensitization is rarely reported.  Because of the risk of sensitisation at the workplace extra protective measures are demanded in the chemical industry as routine including use of protective gloves and efficient ventilation. It can be assumed that in the industrial production sector only skilled workers will handle the substance and that protective gloves will routinely be worn so that the real skin exposure at these sites is considered to be very low.

Migrated from Short description of key information:

Animal data  provide clear evidence of skin and respiratory sensitisation due to TDI. Human experience provide clear evidence of  respiratory

sensitisation, however skin sensitization is rarely reported.  Because of the risk of sensitisation at the workplace extra protective measures

are demanded in the chemical industry as routine including use of protective gloves and efficient ventilation.  

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

At the present time, it is not possible to define reliable exposure-response relationships with regard to the risk of sensitisation for TDI (or indeed for any other known respiratory sensitiser). While thresholds are presumed to exist for induction of respiratory sensitisation, this complex aspect has not been adequately investigated in animal models. There is some evidence that respiratory sensitisation in man is associated with short duration higher level exposures (eg accidental exposures) which suggests a threshold for induction. Animal data support the hypothesis that respiratory hypersensitivity may be induced by skin contact and this possibility has not been excluded in studies involving humans. It is likely that any significant skin exposure to TDI will involve a concomitant respiratory exposure, and discrimination of the contribution of the different exposure routes is unlikely to be resolved in humans.

Nevertheless, the existing data and human experience do lead to the conclusion that if the exposure concentrations of TDI are kept below 0.01 to 0.02 ppm, generally no new cases of TDI asthma are observed. 

Migrated from Short description of key information:

TDI is also a potential respiratory sensitiser in animals and humans.  Animal studies have shown that some responses relating to respiratory sensitisation can be induced by skin contact with TDI, but it is unclear how this might apply to induction of asthma in humans. The quantitative relationships between exposure (concentration, duration, rate of exposure, route of exposure) and incidence of sensitisation have not been established.

Justification for classification or non-classification

Official EU classification according to Directive 67/548/EEC is R 42/43,May cause sensitisation by inhalation, by skin contact, and by EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008),Respiratory sensitiser 1, skin sensitiser 1.May cause allergy or asthma symptoms or breathing difficulties if inhaled, may cause an allergic skin reaction