Bisphenol A (BPA) is used as the main component of many consumer products such as infant's feeding bottles, coatings of beverages, and food cans. BPA can migrate into the environment, and it has been ...detected in the saliva, blood, and food. BPA leakage from many consumer products resulted in a ban on its use in many countries where alternatives to BPA were introduced into the market. BPA alternatives such as bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) have a similar chemical structure and binding ability for estrogen receptor (ER), which shows toxicological effects in animals. In the present study, comparative effects of exposure to BPA and its analogs BPB, BPF, and BPS on testosterone concentration in the rat testis were evaluated by in vitro and in vivo approaches in which oxidative stress markers and antioxidant enzyme activities in reproductive tissues were determined. In the in vivo study, male rats were exposed to different concentrations of BPA and its analogs BPB, BPF, and BPS (5, 25, and 50 mg/kg/day) for 28 days. In the in vitro exposure study, antioxidant enzyme activities and oxidative stress markers were induced in the testes, whereas testosterone production was reduced. In the in vivo exposure study, we observed that antioxidant enzyme activities and protein content were reduced, whereas reactive oxygen species and lipid profile were increased in the treated groups compared to the control group. The present comparative study on BPA and its analogs, namely, BPB, BPF, and BPS suggests the toxic effect of these chemicals on the testes and spermatogenesis, and we also observed that these chemicals induce oxidative stress in the reproductive tissues of male rats.
•Comparative toxicity effects of BPA and its analogs BPB, BPF, and BPS on the reproductive system of male rats.•In vitro study was conducted with cultured cells of the rat testicular tissue, BPA, BPB, BPF, and BPS induced oxidative stress.•BPA and its analogs BPB, BPF, and BPS reduced plasma and intratesticular testosterone concentrations.
Recent imposition of restriction on the use of Bisphenol-A (BPA) paved the way for entry of its analogues in the market. Bisphenol-B and Bisphenol-F are the major analogues of commercial value. Thus, ...their increasing production and application make them vulnerable to human exposure. Since these analogues have been recently reported to show toxic properties similar to BPA, so they have attracted remarkable scientific attention. This mini-review summarizes the recent reports on the occurrence, toxicity and endocrine disruption of these two BPA analogues.
Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect ...adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS, and BPF with body composition among US adults. We included 1787 participants aged 20-59 years old in the National Health and Nutrition Examination Survey 2013-2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the β (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI 0.11, 2.58, P = 0.03), 1.60 (95%CI 0.20, 3.00, P = 0.03), and 1.63 (95%CI 0.24, 3.02, P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (β 95% CI = 1.42 0.49, 2.36, P = 0.004), trunk (β95% CI = 1.92 0.86, 2.97, P = 0.001), and arm (β 95% CI = 1.60 0.49, 2.70, P = 0.01), as well as lean mass of the whole body (β 95% CI = 2610.6 1324.3, 3896.8, P < 0.001), trunk (β 95% CI = 1467.0 745.3, 2188.7, P < 0.001), arm (β 95% CI = 113.4 10.3, 216.5, P = 0.03), and leg (β 95% CI = 431.5 219.6, 643.4, P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.
Many studies show that bisphenol A (BPA) is widespread in human breast milk. However, the occurrence of other bisphenol analogues (BPs), including bisphenol S (BPS), bisphenol F (BPF), and bisphenol ...AF (BPAF), in breast milk is still not well known. In this study, breast milk samples were collected from 190 women in Hangzhou, China, with the aims to characterize the occurrence of BPA, BPS, BPF, and BPAF in these samples and to investigate their effects on postnatal growth of infants through breast milk consumption. BPA (mean 2.5 ng/mL, range < LOD–15 ng/mL) was the most abundant BP in breast milk, followed by BPS (0.19 ng/mL, <LOD–1.3 ng/mL) and BPAF (0.092 ng/mL, <LOD–0.58 ng/mL). BPF was not detected in all breast milk samples. We firstly found that breast milk concentrations of BPA were negatively correlated with infant’s weight or length gain rate. Daily intakes (DIs) of BPs via the consumption of breast milk were calculated for infants, and the mean DI values were 531 ng/kg/day, 53 ng/kg/day, and 24 ng/kg/day for BPA, BPS, and BPAF, respectively. Overall, this study firstly demonstrats that the lactation exposure to BPA through breast milk consumption may affect the postnatal growth of infants.
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•Occurrence of bisphenol analogues in Chinese breast milk were investigated.•We firstly demonstrated that lactational BPA exposure may affect the postnatal growth of infants.•Daily intakes via breast milk consumption were found highest for BPA, followed by BPS and BPAF.
We firstly found that lactation exposure to BPA through breast milk consumption could affect the postnatal growth of infants.
In this study, a novel liquid chromatography - tandem mass spectrometry method for the simultaneous determination of bisphenols (BPA, BPS, BPF, BPAF), parabens (methyl-, ethyl-, propyl-, butyl-, ...benzyl-paraben) and estrogens (estrone, estradiol, estriol) in human plasma is presented. Since all analytes possess the phenolic group, dansyl chloride derivatization was applied in order to gain high sensitivity. The method was validated according to FDA guidelines, and all validation requirements were satisfactory. The lower limits of quantifications were 41.6, 54.9, 43.5 and 150.8pg/mL for BPA, BPS, BPF and BPAF; 172, 149, 171, 134 and 202pg/mL for methyl-, ethyl-, propyl-, butyl- and benzyl-paraben; 10.5, 6.7 and 9.4pg/mL for estrone, estradiol and estriol, respectively. This is the first method allowing the determination of plasma bisphenols, parabens and estrogens in one run, and also the first determination of BPF levels in human plasma. The method was used to examine the plasma levels of healthy normospermic men, where three times higher plasma levels of BPF than BPA were found.
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•First method for the determination of bisphenols, parabens and estrogens in one run.•Quantitation of alternative plasma bisphenols (BPS, BPF, BPAF) for the first time.•The method was validated according to the FDA guidelines.•The method revealed three times higher plasma levels of BPF than BPA in healthy men.
Bisphenol A (BPA), a plastic additive, is ubiquitous in the environment and has endocrine disrupting effects. As many countries have prohibited the manufacture and sale of plastic products with BPA, ...BPA analogs have been used to replace BPA during production, including bisphenol S (BPS) and bisphenol B (BPB). To investigate the toxicities of BPA and its analogs on neurons, reactive oxygen species (ROS) assay, Annexin V-FITC (fluorescein) apoptosis detection assay, lactate dehydrogenase (LDH) cytotoxicity assay, and Cell Counting Kit-8 assay were conducted to comprehensively assess the influence of different concentrations of BPA, BPB, and BPS on ROS, apoptosis, damage, and proliferation for hippocampal HT-22 cells, respectively. Results showed that 6 h of exposure to bisphenols (BPs) could increase the ROS levels, 24 h and 48 h of exposure could induce higher apoptosis and LDH leakage rates for HT-22 cells, and 7 d of exposure could inhibit the cell proliferations. In addition, non-monotonic dose-response relationships were observed between the concentrations of bisphenols and the toxic effects mentioned above. The neurotoxic effects of BPA, BPB and BPS on HT-22 cells were in the increasing order of BPS, BPA, and BPB. In conclusion, these results showed that exposure to BPA and its analogs may result in adverse effects on hippocampal neuronal cell lines. BPS is a surrogate with lower neurotoxicity to replace BPA in production of plastic utensils.
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•BPA, BPS and BPB exhibit different cytotoxicity to HT-22 cells.•Non-monotonic relationships existed between BPs levels and toxic effects of HT-22 cells.•BPS might be surrogate to replace BPA in plastic production with its lower neurotoxicity.
Bisphenols (BPs) are common environmental pollutants that are ubiquitous in the natural environment and can affect human health. In this study, we explored the effects of perinatal exposure to BPA, ...BPF and BPAF on liver function involving in oxidative damage and metabolic disorders in male mouse offspring. We found that BPA exposure impairs the antioxidant defense system, increases lipid peroxidation, and causes oxidative damage in the liver. Furthermore, the levels of 13 metabolites were significantly altered following BPA exposure. We found that BPF exposure significantly increased the expression and activity of CAT, suggesting disturbances in the antioxidant defense system. Moreover, BPF exposure led to metabolic disorders in the liver due to changes in the levels of 8 key metabolites. Exposure to BPAF caused no negative effects on oxidative damage, but altered the levels of β-glucose and glycogen. In summary, perinatal exposure to BPA, BPF and BPAF differentially influence oxidative damage and metabolic disorders in the livers of male mouse offspring. The impact of early life exposure to BPs now warrants future investigations.
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•Oxidative damage and metabolism disruption were induced with BPA exposure.•Exposure to BPF affected the liver antioxidant defense system and disrupt the metabolic profiles of the liver.•Exposure to BPAF had no negative effects on the oxidative system but altered the levels of β-glucose and glycogen.•Perinatal exposure to BPA, BPF and BPAF have different effects on liver oxidative damage and metabolic disorder in male mouse offspring.
Perinatal exposure to BPA, BPF and BPAF differentially influence oxidative damage, metabolic disorders, and subsequent liver function in male mouse offspring.
Cash register receipts made of thermal paper expose workers and shoppers to endocrine-disrupting chemicals and contaminate paper recycling streams. In 2022, 571 receipts were collected from retail ...stores in the United States and tested for developer chemicals using attenuated total reflection infrared spectroscopy. The results were compared to a 2017 study of 167 receipts to determine changes in color developer use over time. Receipts were tested as-is and a subset were additionally subjected to a simple extraction that improved detection of receipt chemicals. Bisphenol S was the most frequently detected developer (85% of tested receipts), followed by Pergafast 201 (12%), bisphenol A (1%); and Appvion Alpha Free, D-8, and NKK-1304 (each below 1%). NKK-1304 is reported here for the first time in a scientific journal. The frequency of bisphenol A usage in receipts decreased and the frequency of bisphenol S and Pergafast 201 increased between 2017 and 2022, particularly among large companies. National retailers were more likely than regional or local retailers to have adopted non-bisphenol alternatives. Potential health and environmental hazards of the detected developer chemicals and strategies for reduction are discussed.
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•Infrared spectroscopy was used to identify thermal paper receipt chemicals.•BPS is a major replacement chemical for BPA in U.S. thermal paper receipts.•Non-bisphenol receipt frequency was 5% in 2017 and 16% in 2022.•Between 2017 and 2022 large national businesses mostly replaced BPA with non-bisphenols.•Between 2017 and 2022 local/regional businesses mostly replaced BPA with BPS.
Abstract
Bisphenol A (BPA) has been recognized as an endocrine disrupting chemical and identified as an obesogen. Although once ubiquitous, human exposure to BPA has been declining owing to its ...substitution with other bisphenols. Two structurally similar substitutes, bisphenol S (BPS) and bisphenol F (BPF), have raised similar concerns, although fewer studies have been conducted on these newer derivatives. We used data from the US National Health and Nutrition Examination Surveys from 2013 to 2016 to evaluate associations between BPA, BPS, and BPF and body mass outcomes among children and adolescents aged 6 to 19 years. Concentrations of BPA, BPS, and BPF were measured in spot urine samples using HPLC with tandem mass spectrometry. General obesity was defined as ≥95th percentile of the age- and sex-standardized body mass index (BMI) z-scores according to the 2000 US norms. Abdominal obesity was defined as a waist circumference/height ratio of ≥0.5. BPA, BPS, and BPF were detected in 97.5%, 87.8%, and 55.2% of urine samples, respectively. Log-transformed urinary BPS concentrations were associated with an increased prevalence of general obesity (OR, 1.16; 95% CI, 1.02 to 1.32) and abdominal obesity (OR, 1.13; 95% CI, 1.02 to 1.27). BPF detection (vs not detected) was associated with an increased prevalence of abdominal obesity (OR, 1.29; 95% CI, 1.01 to 1.64) and continuous BMI z-score (β = 0.10; 95% CI, 0.01 to 0.20). BPA and total bisphenols were not statistically significantly associated with general obesity, abdominal obesity, or any body mass outcome. These results suggest that BPA substitute chemicals are correlated with obesity in contemporary children.
Bisphenol A (BPA) and its analogues (BPAF, BPS) are ubiquitous environmental contaminants used as plastic additives in various daily life products, with many concerns on their role as environmental ...estrogens. Uterine leiomyomas (fibroids) are highly prevalent gynecologic tumors with progressive fibrosis. Fibroids are hormone-responsive and may be the target of environmental estrogens. However, the effects of BPA, BPAF, and BPS exposure on uterine fibrosis are largely unknown. Here, we evaluated fibrosis and the crucial role of TGF-beta signaling in human fibroid tumors, the profibrotic effects of BPA, BPAF or BPS in a human 3D uterine leiomyoma (ht-UtLM) in vitro model, and the long-term outcomes of BPAF exposure in rat uterus. In 3D ht-UtLM spheroids, BPA, BPAF, and BPS all promoted cell proliferation and fibrosis by increasing the production of extracellular matrices. Further mechanistic analysis showed the profibrotic effects were induced by TGF-beta signaling activation mainly through SMAD2/3 pathway and crosstalk with multiple non-SMAD pathways. Furthermore, the profibrotic effects of BPAF were supported by observation of uterine fibrosis in vivo in rats following long-term BPAF exposure. Overall, the 3D ht-UtLM spheroid can be an important model for investigating environment-induced fibrosis in uterine fibroids. BPA and its analogues can induce fibrosis via TGF-beta signaling.
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•A 3D system is an effective model for studying fibrosis in human uterine fibroids.•BPA, BPS and BPAF can promote fibrosis in uterine fibroid spheroids.•Environmentally-induced uterine fibrosis is through activation of TGF-beta signaling.•TGF-beta downstream signaling is through SMAD2/3 with crosstalk with non-SMAD pathways.