(chloromethyl)vinylbenzene

Endpoint summary

Description of key information

A weight of evidence approach was used to address the endpoint of skin sensitisation

in vivo

Skin sensitisation studies conducted on guinea pigs resulted in a sensitivity response in 4 out of 6 of the surviving animals.

in vivo - read across

0.01 mg of the structural analogue substance benzyl chloride was injected in the back of guinea pigs twice a week for 12 weeks. After 2 weeks of rest tests were made with the solution used for sensitization by dropping it on the flank. Positive result was obtained using the colouring of the skin as indication. Due to the structural similarity of benzyl chloride and vinylbenzyl chloride, vinylbenzyl chloride is also expected to be sensitising in guinea pigs.

in silico

For the endpoint skin sensitisation two different, scientifically valid QSAR models were applied within a weight-of-evidence approach.

Profiling (OECD QSAR Toolbox v4.1)

Vinylbenzyl chloride was profiled with the OECD QSAR Toolbox, version 4.1. The relevant profilers associated with the Adverse Outcome Pathway of skin sensitisation were evaluated. Alerts for protein reactivity and increased keratinocyte gene expression were identified by various profilers. This gives indication that positive results can be expected for vinylbenzyl chloride in in vivo and in vitro assays.

Read-across (OECD QSAR Toolbox v4.1)

Skin sensitisation of both isomers of vinylbenzyl chloride (CAS 1592-20-7 and CAS 39833-65-3) was predicted with the OECD QSAR Toolbox v4.1 (automated workflow). The read-across analysis was performed for both isomers with the identical five analogue substances. The logKow was used as 'active descriptor'. The prediction was positive for both isomers. It lies within the applicability domain of this model.

CAESAR v2.1.6 (QSAR tool VEGA v1.1.4)

Skin sensitisation of both isomers of vinylbenzyl chloride (CAS 1592-20-7 and CAS 39833-65-3) was predicted with the Skin Sensitization model CAESAR 2.1.6, which is implemented in the QSAR tool VEGA (version 1.1.4.). Predictions for both isomers were positive. However, these prediction do not fall completely in the applicability domain of this model.

OASIS TIMES v2.27.20.1

Both isomers of vinylbenzyl chloride (CAS 1592-20-7 and CAS 39833-65-3) are predicted to be strongly skin sensitising by the skin sensitization model OASIS TIMES v2.27.20.1. However, these predictions do not fall completely in the applicability domain of this model.

Derek Nexus v5.0.2

Both isomers of vinylbenzyl chloride (CAS 1592-20-7 and CAS 39833-65-3) are predicted to be extremely skin sensitising (EC3 values of 0.014 %) by the skin sensitization model Derek Nexus v5.0.2.

Conclusion

The predictions of the applied silico methods are consistent, reliable and are in line with a mechanistic understanding of the Adverse Outcome Pathway of skin sensitisation. Identical predictions were made for both isomers. This is due to the fact that the structural alert 'alkyl halide' is the same in both isomers. The in silico results are also supported by the in vivo study on vinylbenzyl chloride and another in vivo study in guinea pigs for benzyl chloride, and further supported by a positive result for benzyl chloride in the LLNA, which serves as a suitable read-across source.

As a conclusion, vinylbenzyl chloride is considered as skin sensitising.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Vinylbenzyl chloride is classified as a skin sensitiser according to Regulation (EC) No 1272/2008 (CLP Regulation), because there is much evidence for a skin sensitising mode of action. This is underlined by one in vivo study with vinylbenzyl chloride, one in vivo study in guinea pigs with a source substance suitable for read-across which is further supported by a positive result in the LLNA for this source substance, and two scientifically valid QSAR models making a consistent prediction.

As the reported test results are not sufficient in detail for sub-categorisation into Cat. 1A or 1B the substance is classified as skin sensitiser Cat. 1 (H317: May cause an allergic skin reaction).