Combined toxicity of endocrine-disrupting chemicals: A review.

The combined toxicological assessment provides a realistic approach for hazard evaluation of chemical cocktails that co-existed in the environment. This review provides a holistic insight into the studies highlighting the mixture toxicity of the endocrine-disrupting chemicals (EDCs), especially focusing on the screening of biochemical pathways and other toxicogenetic endpoints. Reviewed literature showed that numerous multiplexed toxicogenomic techniques were applied to determine reproductive effects in vertebrates, but limited studies were found in non-mammalian species after mixture chemical exposure. Further, we found that the experimental design and concentration selection are the two important parameters in mixture toxicity studies that should be time- and cost-effective, highly precise, and environmentally relevant. A summary of EDC mixtures affecting the thyroid axis, estrogen axis, androgen axis, growth stress, and immune system via in vivo bioassays was also presented. It is interesting to mention that majority of estrogenic effects of the mixtures were sex-dependent, particularly observed in male fish as compared to female fish. Further, the androgen axis was perturbed with serious malformations in male rat testis (epididymal or gubernacular lesions, and deciduous spermatids). Also, transgenerational epigenetic effects were promoted in the F

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