BPA a Testicular Toxin in Animal Models

Abstract:

Bisphenol A (BPA), an endocrine-disrupting compound, was found to be a testicular toxicant in animal models. Bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) were recently introduced to the market as alternatives to BPA. However, toxicological data of these compounds in the male reproductive system are still limited so far. This study developed and validated an automated multi-parametric high-content analysis (HCA) using the C18-4 spermatogonial cell line as a model. We applied these validated HCA, including nuclear morphology, DNA content, cell cycle progression, DNA synthesis, cytoskeleton integrity, and DNA damage responses, to characterize and compare the testicular toxicities of BPA and 3 selected commercial available BPA analogues, BPS, BPAF, and TBBPA. HCA revealed BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS, including dose- and time-dependent alterations in nuclear morphology, cell cycle, DNA damage responses, and perturbation of the cytoskeleton. Our results demonstrated that this specific culture model together with HCA can be utilized for quantitative screening and discriminating of chemical-specific testicular toxicity in spermatogonial cells. It also provides a fast and cost-effective approach for the identification of environmental chemicals that could have detrimental effects on reproduction.

Source:https://academic.oup.com/toxsci/article-abstract/155/1/43/2842102/High-Content-Analysis-Provides-Mechanistic?redirectedFrom=fulltext

Hepatic Detoxification of Bisphenol A is Retinoid-Dependent

Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl) propane) is a widely used industrial chemical. The extensive distribution of BPA in the environment poses risks to humans. However, the molecular mechanisms underlying BPA toxicity as well as its effective detoxification and elimination are not well understood. We have investigated specifically for BPA the notion raised in the literature that the optimal sensing, detoxification, and elimination of xenobiotics requires retinoid (natural derivatives and synthetic analogs of vitamin A) actions. The objective of the study was to explore how retinoids, both those stored in the liver and those originating from recent oral intake, help maintain an optimal xenobiotic detoxification response, affecting mRNA expression and activities of elements of xenobiotic detoxification system upon BPA administration to mice. Wild-type and mice lacking hepatic retinoid stores (Lrat−/−) were acutely treated with BPA (50 mg/kg body weight), with or without oral supplementation with retinyl acetate. Hepatic mRNA expression levels of the genes encoding nuclear receptors and their downstream targets involved in xenobiotic biotransformation, phase I and phase II enzyme activities, and levels of oxidative damage to cellular proteins and lipids in hepatic microsomes, mitochondria and cytosol, were assessed. BPA treatment induced hepatic activities needed for its detoxification and elimination in wild-type mice. However, BPA failed to induce these activities in the livers of Lrat−/− mice. Oral supplementation with retinyl acetate restored phase I and phase II enzyme activities, but accelerated BPA-induced oxidative damage through enhancement of non-mitochondrial ROS production. Thus, the activities of the enzymes involved in the hepatic elimination of BPA require hepatic retinoid stores. The extent of hepatic damage that arises from acute BPA intoxication is directly affected by retinoid administration during the period of BPA exposure and hepatic retinoid stores that have accumulated over the lifetime of the organism.

Source: https://academic.oup.com/toxsci/article/2953397/Hepatic-Detoxification-of-Bisphenol-A-is-Retinoid?searchresult=1

2006: “BPA manufacturers persist in describing BPA as a weak estrogen”

Abstract

Over 6 billion pounds per year of the estrogenic monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, in resins lining metal cans, in dental sealants, and in blends with other types of plastic products. The ester bond linking BPA molecules in polycarbonate and resins undergoes hydrolysis, resulting in the release of free BPA into food, beverages, and the environment, and numerous monitoring studies now show almost ubiquitous human exposure to biologically active levels of this chemical. BPA exerts estrogenic effects through the classical nuclear estrogen receptors, and BPA acts as a selective estrogen receptor modulator. However, BPA also initiates rapid responses via estrogen receptors presumably associated with the plasma membrane. Similar to estradiol, BPA causes changes in some cell functions at concentrations between 1 pm and 1 nm, and the mean and median range of unconjugated BPA measured by multiple techniques in human pregnant maternal, fetal, and adult blood and other tissues exceeds these levels. In contrast to these published findings, BPA manufacturers persist in describing BPA as a weak estrogen and insist there is little concern with human exposure levels. Our concern with human exposure to BPA derives from 1) identification of molecular mechanisms mediating effects in human and animal tissues at very low doses, 2) in vivo effects in experimental animals caused by low doses within the range of human exposure, and 3) widespread human exposure to levels of BPA that cause adverse effects in animals.

Source: https://academic.oup.com/endo/article-abstract/147/6/s56/2878426/Large-Effects-from-Small-Exposures-III-Endocrine?redirectedFrom=fulltext

2005: bisphenol A in dental fillings

 

A chemical found in plastics may put women exposed to it at greater risk of developing breast cancer, it seems. A study in mice has found that minute doses of the oestrogen-like substance increase breast tissue development, and higher density breast tissue is a risk factor for cancer.

Many hard plastics contain the compound bisphenol A, which can leach into food after heating. The chemical also appears in some dental fillings and the linings of tin cans. Industry began using bisphenol A in the 1950s, but in recent years scientists have documented how it mimics the hormone oestrogen.

Some scientists worry that because oestrogen plays such a crucial role in the development of a fetus’s reproductive system and other organs, exposure to bisphenol A in the womb could cause problems. A recent study of mice exposed in this way found that the artificial compound caused abnormally high levels of growth in the male animals’ prostate glands1.

Now, another team of researchers has investigated the effects of this chemical on female mice: the results are reported in the journal Endocrinology2.

Source: http://www.nature.com/news/2005/050523/full/news050523-12.html

bisphenol A replacement chemical (BHPF) also a health risk?

“In the U.S. there are no requirements for testing in animals unless a lot of the chemical gets into the food supply,” said Maffini. “There is definitely no requirement to test for potential endocrine disrupting properties in chemicals—not even doing a computer modeling study, or an invitro study, similar done to those that are done in report.”

Source: http://www.popsci.com/bpa-free-plastic-bad-for-human-health