Human developmental toxicity mechanism of polybrominated biphenyl exposure and health risk regulation strategy for special populations

Abstract

Polybrominated biphenyls (PBBs) can bioaccumulate in nature and are toxic to humans. Long-time exposure to PBBs in pregnant women can lead to the birth of an infant with abnormal conditions. Hence, in this study, we used molecular docking, molecular dynamics, Taguchi experimental design, and fractional factorial experimental design to identify the developmental toxicity characteristics of 10 typical developmental toxic pollutants such as PBBs to which humans are frequently exposed. Furthermore, the correlation and sensitivity analyses of molecular developmental toxicity and structural parameters were performed. The molecular key structural parameters of the pollutants affecting human development were screened. Moreover, the supplementary food factors that could alleviate the developmental toxicity of pollutants were screened to develop supplementary food schemes to prevent or alleviate human developmental toxicity in the special population (e.g., pregnant women, infants) exposed to the pollutants. The results showed that the developmental toxicity was controlled by the main effects of the 10 pollutants. Among the 10 pollutants with developmental toxicity, the most significant pollutant with the main effects was PBB-153 (37.06%). In addition, the correlation and sensitivity analyses of the molecular developmental toxicity of the pollutants and structural parameters showed that the total energy value and infrared C-H vibration frequency of the pollutants were significantly correlated with human developmental toxicity. Accordingly, 15 supplementary food cofactors were selected for the Taguchi experiment design, among which the top seven cofactors were designed by fractional factorial analysis. The most significant cofactor that alleviated the developmental toxicity of PBB-153 exposure was the combination of carotene and docosahexaenoic acid (DHA), with an improvement of 17.28%. The combination of carotene and DHA significantly alleviated the effects of toxicity caused by most of the other pollutants, indicating that the selected supplementary food has certain universality. In this study, we developed a method to identify the characteristics of the developmental toxicity of pollutant exposure and developmental toxicity alleviation. Our study provided theoretical support for the regulation strategy of developmental toxicity caused by pollutants such as PBBs.

Keywords: Developmental toxicity; Molecular dynamics; Polybrominated biphenyls (PBBs); Supplementary food.