m-tolylidene diisocyanate

Endpoint summary

Description of key information

Skin sensitisation:

In an LLNA similar to OECD Guideline 429 in mice, the test substance showed a skin sensitising potential (Hilton et al., 1995).

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In a dermal sensitization study similar to OECD guideline 429 with TDI (80:20) in acetone/olive oil (4:1, v/v) Balb/c mice were tested (Hilton et al., 1995). Positive control materials were oxazolone, TMA, and DCNB. No mortality was observed. No clinical signs were reported. An EC3 of 0.02 was calculated, indicating a skin sensitising potential of the test substance.

(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.)

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 (e.g. 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.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified for skin sensitisation (Category 1, H317) and for respiratory sensitisation (Category 1, H334) under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.