Human internal exposure to organophosphate esters: A short review of urinary monitoring on the basis of biological metabolism research

As alternatives to traditional brominated flame retardants, organophosphate flame retardants (OPFRs), especially for organophosphate esters (OPEs) -- the most widely used and investigated OPFRs, have raised people's concern on their environmental and health-related risks over the years. Considering their extensive environmental occurrence and potential adverse effects, precise estimation on the human body burden of OPEs will be conducive to the restrictions on the usage of these compounds scientifically. Biomonitoring research can provide precise information on human exposure to OPEs as it reveals the degree of external exposure from all exposure routes. Knowledge on biotransformation and metabolism of OPEs in the biosystems is of great significance for our understanding of the internal exposure to these compounds. In this study, the biological metabolic processes of nine OPEs prevalent in the environment, involving tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tripropyl phosphate (TPrP), tri-n-butyl phosphate (TnBP), tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPhP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tricresyl phosphate (TCrP), are comprehensively reviewed. Specifically, the metabolic pathway, kinetics and mechanism of OPEs are depicted in detail. Under this context, the advances and limitations on biomonitoring of OPE metabolites in human urine are summarized. The requirements of specificity, quantitative stability, high detection frequency/concentration are needed for OPE metabolites to be considered and validated as biomarkers. Thus far, deeper elucidations on the metabolic processes and identification of biomarkers of OPEs are urgently required, given that some OPEs have no suitable biomarkers in human biomonitoring. For better assessment of the body burden of OPEs in humans, reliable and effective methodologies for urine sampling and estimation on internal exposure to OPEs need to be further developed in the future.