Date of Award
Master of Science
Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide and, as a result, is universally found in environmental and human matrixes. Bisphenol A is a known endocrine disruptor that acts as an estrogen agonist and an androgen antagonist. Due to health concerns, BPA is being phased out and replaced by other bisphenol analogues structurally similar to BPA. To date, there have been little to no studies showing the effects of BP analogues on the reproductive organ development of male mice. Thus, this study aimed to compare the effects of BPA and selected analogues (including BPB, BPE, and BPS) on the reproductive organ development in male mice, and determine preliminary toxicity threshold levels, such as the lowest-observed-effect-dose (LOED) and no-observed-effect-dose (NOED). Exposure to BPA, BPB and BPE via subcutaneous injection at a dose of 10 μg/g body weight (bw)/day each significantly caused a decrease in anogenital distance and glans penis length in male mice. Testis weight was also significantly reduced by BPA and BPE. Although BPS did not cause an effect on the glans penis length, anogenital distance or testis weight, histology work indicated that the spines on the glans penis were at a different developmental stage than the control. A similar result was seen with BPA on the glans penis spines. The LOED and NOED of BPA affecting anogenital distance, penis length, or testis weight were determined to be 10 and 5 μg/g bw/day, respectively. These LOED and NOED values are preliminary for BPA, because only five dose levels are used. Further research is needed to estimate more accurate threshold levels for the studied endpoints for BPA as well as other bisphenol analogues. The results indicated that some bisphenol analogues (BPB and BPE) showed comparable effects to BPA on the reproductive organ development of male mice, including anogenital distance and penis length. This could be indicative of more severe reproductive issues later in life and raised a concern on the safety of using these analogues to replace BPA in consumer products. More research is needed to investigate the mechanisms of the observed effects on genetic or molecular levels, determine what the long-term adverse effects of bisphenol analogues are to the reproductive system of male mice, and determine whether similar effects will be seen at dose levels comparable to human exposure rates.
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