The association between organophosphate esters exposure and body mass index in children and adolescents: The mediating effect of sex hormones

Organophosphate esters (OPEs), used as flame retardants and plasticizers, have been indicated to impair growth and development in toxicological studies, but current epidemiological data on their associations with body mass index (BMI) are limited and the underlying biological mechanisms remain unclear. In this study, we aim to explore the association of OPE metabolites with BMI z-score, and assess whether sex hormones mediate the relationships between OPE exposure and BMI z-score. We measured weight and height, and determined OPE metabolites in spot urine samples and sex hormones in serum samples among 1156 children and adolescents aged 6-18 years in Liuzhou city, China. The results showed that di-o-cresyl phosphate and di-pcresyl phosphate (DoCP & DpCP) levels were associated with lower BMI z-score of all participants and a similar pattern of associations were presented in prepubertal boys stratified by sex-puberty groups and male children stratified by sex-age groups. In addition, sex hormone binding globulin (SHBG) were related to reduced BMI z-score among all subgroups including prepubertal boys, prepubertal girls, pubertal boys, and pubertal girls (all Ptrend<0.05). We also found that DoCP & DpCP showed positive associations with SHBG among prepubertal boys. Mediation analysis further showed that SHBG mediated 35.0% of the association between DoCP & DpCP and reduced BMI z-score in prepubertal boys. Our results indicated that OPEs may impair growth and development by disrupting the sex hormones in prepubertal boys.