Abstract
Organophosphate flame retardants (OPFRs) have increasingly replaced polybrominated diphenyl ethers (PBDEs) in various consumer products and raw materials, due to regulatory restrictions on PBDEs. However, concerns about the toxicity and environmental persistence of OPFRs are growing. This review summarizes current research on the toxicity of OPFRs, with a focus on New Approach Methodologies (NAMs) that aim to eliminate the need for animal testing. NAMs, including in vitro models, omics technologies, and computational methods, provide valuable insights into the cellular and molecular effects of OPFR exposure. Evidence suggests that OPFRs may disrupt multiple organ systems, including the nervous, hepatic, pulmonary, reproductive, and endocrine systems. Additionally, the metabolic transformation of OPFRs can increase their toxicity, raising concerns about long-term exposure risks. While NAM studies provide valuable insights, further research is needed to refine risk-assessment frameworks and improve our understanding of the long-term effects of OPFR exposure, particularly at concentrations found in the environment. This new knowledge will help develop more accurate regulatory guidelines and ensure the better protection of public and environmental health.