Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Mixed xylene (CAS 1330-20-7) comprises individual xylene isomers (m-xylene, o-xylene, p-xylene) and ethylbenzene. Data for these substances and the component substances benzene, toluene and styrene have been included as supporting information.

Non-Human Information

There is no relevant non-human information for the individual isomers or for ethylbenzene.

The results of a modified version of a local lymph node assay (LLNA) presented in a publication by Ehling (2005) indicated that xylene could be positive for sensitisation. However, the published results are considered to be of limited relevance based on a review by the European Centre for the Validation of Alternative Methods (ECVAM) which concluded that the assay used was not valid (Basketter et al., 2008).

Basketter and Kimber (2010) reviewed the available data for xylenes. They were unaware of any cell based or reactivity data on xylene that would clarify its skin sensitization potential. In addition, chemically, xylene is a mixture of dimethylbenzene isomers, none of which would be regarded as reactive chemicals, rendering them unlikely to behave as skin sensitizers.

The other potential components styrene, benzene and toluene are considered not to be skin sensitisers.

Human information

From widespread use, there have been no reports of skin sensitising properties of xylene as a result of skin contact. In a human maximization test (Kligman, 1966), xylene was tested at 100% and subjects were challenged at 25%. No skin sensitization resulted. This test is considered to be a highly sensitive detector of skin sensitizing potential; the results for more than 80 chemicals were presented in the publication which demonstrates the very considerable predictive sensitivity of this assay.

As cited in Opdyke (1975), Kligman (1974) reported that ethylbenzene produced no sensitisation reactions in 25 volunteers subjected to a maximisation test with 10% ethylbenzene (no data on purity) in petrolatum.

The component substances benzene, toluene and styrene are considered not to be skin sensitisers.

Conclusion

Xylene gave a very slightly positive result in the LLNA when tested undiluted, but the result fits well with the criteria for a false positive. It is an unreactive chemical that would not be identified on the basis of chemical structure as being a potential skin sensitizer. Added to which is the clinical evidence demonstrating that xylene does not cause skin sensitization in humans, even when tested in a very rigorous human predictive assay. Thus, the overwhelming evidence is that xylene should not be classified as a skin sensitizer.

The RAR (2008) for ethylbenzene concluded that there are no reports on skin sensitisation caused by the substance at the workplace and there no sensitisation potential is expected. 

Human data is also available for benzene (No classification): In a study using 25 male volunteers a maximisation test with induction using 50% benzene and challenge with 20% benzene no evidence of skin sensitisation was seen (Kligman, 1966).

Migrated from Short description of key information:

A human maximization test, a sensitive detector of the skin sensitising properties of chemicals, found that mixed xylene did not induce skin sensitisation.  The individual xylene isomers and ethylbenzene are not considered to be skin sensitizers. The components benzene, toluene and styrene are considered not to be skin sensitisers.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Migrated from Short description of key information:

No data available, but no evidence of rspiratory sensitisation reported from worker exposure to xylenes.

The RAR (2008) for ethylbenzene concluded that there are no reports on inhalation allergy caused by the substance at the workplace and there no sensitisation potential is expected.  

The components benzene, toluene and styrene are considered not to be skin sensitisers.

Justification for classification or non-classification

Xylene is an unreactive chemical that would not be identified on the basis of chemical structure as being a potential skin sensitizer. In addition, there is no clinical evidence demonstrating that xylene causes skin sensitization in humans, even when tested in a very rigorous human predictive assay. Therefore, mixed xylene does not warrant classification as a skin sensitizer under DSD or CLP. There are no concerns that the other potential components: styrene, benzene and toluene skin sensitisers and these do are not classified for skinor respiratory sensitisation under DSD or CLP.

In conclusion, mixed xylene streams do not warrant classification as a respiratory sensitizer under DSD or CLP.

Categories Display