Advances in biomarkers of benzene exposure and toxicity: From mechanistic insights to occupational health applications (Review).

Benzene is a toxic aromatic hydrocarbon widely used in industrial production, posing a notable occupational health threat. Classified as a Group 1 carcinogen, chronic benzene exposure primarily targets the hematopoietic system, causing leukopenia, thrombocytopenia, aplastic anemia and acute myeloid leukemia. Furthermore, emerging evidence highlights its multi‑systemic toxicity, inducing oxidative stress, DNA damage and cellular dysfunction, across the nervous, respiratory, dermatological, reproductive, immune and cardiovascular systems. The present review systematically summarizes recent advances in these occupational hazards and the evolving landscape of benzene biomonitoring. Traditional exposure biomarkers, such as urinary phenol and hydroquinone, are increasingly being supplemented by highly specific metabolites, notably S‑phenylmercapturic acid, for low‑dose exposure assessments. Effect biomarkers capture early biological damage through hematological indices and molecular alterations, while susceptibility biomarkers, such as cytochrome P450 2E1, glutathione S‑transferase mu 1 and DNA repair gene polymorphisms, identify genetically vulnerable populations. Additionally, emerging non‑invasive tools, particularly exhaled breath metabolomics, show promise in correlating specific metabolites with hematopoietic function. By integrating mechanistic insights into multi‑organ toxicity with advanced multi‑omics profiling, the present review highlights a critical paradigm shift from reactive traditional monitoring to artificial intelligence‑driven, multi-biomarker integration frameworks. Ultimately, it provides a forward-looking roadmap for individualized risk stratification and precision occupational health surveillance in the low‑dose exposure era.