A weight of evidence evaluation on the immunosuppressive potential of xylene

Xylene substances (xylene) are high production chemicals that are currently undergoing new data generation and dossier evaluation under European Regulation on the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) including consideration of an additional immunotoxicity testing cohort to an extended one-generation reproduction toxicity study (EOGRTS). To address the need for an additional EOGRTS cohort, a weight of evidence assessment was conducted on xylene's immunosuppression potential using ToxRTool, and the World Health Organization (WHO) International Programme on Chemical Safety (IPCS) framework. The evaluation included a review of historical human and experimental animal literature as well as new toxicity data from guideline studies. Two limited epidemiology studies showed no xylene exposure-related effects on white blood cell counts. Reliable study results from a mouse host resistance model were negative. No mammalian T-cell dependent antibody response assays were located for xylene in the literature review. No xylene-related immunological change was observed in an avian T-cell antibody study. In addition, a review of immune functional data on structural analogues did not indicate a signal for immunosuppression. Lastly, in guideline studies, several statistically spurious, isolated, and/or inconsistent immune system findings were observed, but overall, the dataset in its totality demonstrated no signal of xylene-mediated immunosuppression. In conclusion, xylene shows no evidence of immunosuppression and there is no need for an immunotoxicity cohort evaluation in any subsequent EOGRTS.