From repellent to risk: DEET’s adverse effects on hormones and bone health in kids

Early life bone accumulation, which predicts future fragility fracture risk, is intimately associated with sex hormones. N, N-diethyl-3-methylbenzamide (DEET) is the primary and most effective active ingredient widely used globally, especially among children and adolescents. However, the effects of DEET on sex hormones and bone mass remain unclear. We aimed to explore the adverse effects of DEET exposure on bone mass and to elucidate the potential mediating roles of sex hormones in children and adolescents. This cross-sectional study analyzed 864 children and adolescents from NHANES 2013-2016. Urinary 3-diethyl-carbamoyl benzoic acid (DCBA) was employed as a biomarker for DEET exposure. The study examined the relationships between DCBA, sex hormones, and bone mass, with a particular focus on evaluating the independent and serial mediation effects of sex hormones on DEET-bone mass associations. Increased DCBA was associated with decreased testosterone (TT), estrogen (E2), and free androgen index (FAI), alongside an increase in sex hormone-binding globulin (SHBG) levels, particularly pronounced among subjects < 12 years [β% (95 % CI) = -0.081 (-0.144, -0.017), -0.064 (-0.114, -0.013), -0.101 (-0.177, -0.024), and 0.020 (-0.009, 0.048), respectively] and non-overweight subjects [β% (95 % CI) = -0.160 (-0.234, -0.086), -0.103 (-0.158, -0.048), -0.195 (-0.282, -0.107), and 0.035 (0.012, 0.058), respectively]. Negative dose-response relationships between DCBA and bone mass were observed in non-overweight participants [β% (95 % CI) = -0.011 (-0.018, -0.005) and -0.027 (-0.041, -0.013) for total bone mineral density (BMD) and total bone mineral content (BMC), respectively], and in children < 12 years for total BMC [β% (95 % CI) = -0.012 (-0.024, 0.000)]. Additionally, TT, E2, and SHBG were found to significantly and independently mediate 15.41 % to 79.84 % of the relationship between DCBA and bone mass. Furthermore, serial mediation effects among sex hormones were detected between TT, E2, and SHBG. DEET exerts a detrimental effect on bone health by interfering with sex hormones in children and adolescents, warranting heightened public concern.