Xylene is currently undergoing dossier evaluation under REACH. Isolated and inconsistent immune system findings have been reported across its dataset. On behalf of the Lower Olefins and Aromatics Xylene Working Group and the Cefic Aromatics Producers Association, the authors carried out a systematic literature review and weight of evidence evaluation of all available immunotoxicity data. This covered in vitro, in vivo and epidemiology studies, including previously unpublished guideline studies.
Searches of ProQuest and PubMed returned 2,703 unique records. The review examined haematology, globulin levels, and the immune system tissues: thymus, spleen, lymph nodes, bone marrow and gut-associated lymphoid tissue. Across multiple high-quality guideline studies, the dataset as a whole showed no signal of xylene-mediated immunosuppression. The effects that were observed were sporadic, within historical control ranges, or occurred alongside general stress or systemic toxicity.
The weight of evidence supports that xylene substances are not immunosuppressants. It does not support the need for an immunotoxicity cohort in any subsequent extended one-generation reproductive toxicity study (EOGRTS). This avoids unnecessary animal testing, in line with ECHA’s commitment to the 3Rs.
Authors
L. G. Higgins, K. Morris-Schaffer, S. Hearon, S. Dahlberg, E. Freeman, F. Faulhammer, N. Aygun Kocabas, M. Rooseboom
Society of Toxicology (SOT) 65th Annual Meeting, 2026, Board H587, Abstract ID 3442.