Weight-of-evidence assessment of the endocrine-disrupting properties of propylene oxide

Propylene oxide (PO) is a high-production-volume chemical widely used as an industrial intermediate and classified as carcinogen and mutagen in humans. Despite its regulatory significance, a comprehensive evaluation of its endocrine-disrupting (ED) potential has not been previously conducted. This review applies a weight-of-evidence (WoE) approach, integrating data from regulatory dossiers, peer-reviewed literature, publicly accessible databases, and in silico predictions to assess whether PO meets internationally accepted ED criteria. Available evidence indicates that PO does not exhibit endocrine activity via estrogenic, androgenic, steroidogenic, thyroid (EATS), or non-EATS pathways, as supported by negative quantitative structure-activity relationship (QSAR) predictions and absence of mechanistic effects in vivo. Similarly, adverse outcomes observed in repeated-dose, reproductive, and developmental toxicity studies were either secondary to systemic toxicity, inconsistent, or unrelated to endocrine modes of action. Epidemiological findings suggesting associations with breast cancer, diabetes, or obesity were limited by methodological uncertainties and lack of causal inference. Collectively, the WoE demonstrates that PO should not be classified as an endocrine-disrupting chemical for humans or wildlife, although data gaps remain for environmental receptors and metabolites.