Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
Toxicology and Applied Pharmacology (Impact Factor: 3.71). 07/2011; 255(3):261-70. DOI: 10.1016/j.taap.2011.07.009
Source: PubMed


Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of >90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2μg/kgbw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100μg/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral administration, and fetal age are critical in reducing exposures to the fetus.

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    • "Unfortunately, almost none of the studies evaluating the impact of prenatal exposure on postnatal/adult outcomes assessed BPA accumulation in the exposed animals, neither the effect of gender on accumulation. These parameters would be particularly important in central nervous system (CNS) studies, as BPA preferentially accumulates in the fetal brain (Doerge et al. 2011; Mita et al. 2012), where its average concentration is directly related to the dosage used and it is higher in males than in females (Mita et al. 2012). "
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    ABSTRACT: Brain development is an organized, but constantly adaptive, process in which genetic and epigenetic signals allow neurons to differentiate, to migrate, and to develop correct connections. Gender specific prenatal sex hormone milieu participates in the dimorphic development of many neuronal networks. Environmental cues may interfere with these developmental programs, producing adverse outcomes. Bisphenol A (BPA), an estrogenic/antiandrogenic endocrine disruptor widely diffused in the environment, produces adverse effects at levels below the acceptable daily intake. This review analyzes the recent literature on the consequences of perinatal exposure to BPA environmental doses on the development of a dimorphic brain. The BPA interference with the development and function of the neuroendocrine hypothalamus and of the nuclei controlling energy balance, and with the hippocampal memory processing is also discussed. The detrimental action of BPA appears complex, involving different hormonal and epigenetic pathways activated, often in a dimorphic way, within clearcut susceptibility windows. To date, discrepancies in experimental approaches and in related outcomes make unfeasible to translate the available information into clear dose–response models for human risk assessment. Evaluation of BPA brain levels in relation to the appearance of adverse effects in future basic studies will certainly give better definition of the warning threshold for human health.
    Full-text · Article · Jun 2015 · Dose-Response
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    • "All the experimental procedures were performed under the national guidelines on the proper care and use of animals in laboratory research and the Institutional Ethics Committee for the use of laboratory animals approved the study. The doses of BPA investigated in this study are much lower than the published " No Observed Adverse Effective Levels " (NOAEL) dose, i.e. 5 mg/kg body weight/day in rodents (Doerge et al., 2011; NTP, 2001). At the same time, one of the dose of BPA used in the present study (50 ␮g/kg bodyweight/day) corresponds to the " Tolerable Daily Intake " (TDI) for humans, as indicated by the U.S Environmental Protection Agency (EPA) and also by the European Food Safety Authority. "
    Dataset: Shikha3

    Full-text · Dataset · Jan 2015
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    • "mg/kg body weight/day in rodents (Doerge et al., 2011; NTP 2001). At the same time, one of the dose of BPA used in the present study (50 µg/kg bodyweight /day) corresponds to the " Tolerable Daily Intake " (TDI) for humans, as indicated by the U.S Environmental Protection Agency (EPA) and also by the European Food Safety Authority. "
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    ABSTRACT: Bisphenol A (BPA) is a well-known plasticizer and xenoestrogen that is responsible for manyacquired reproductive difficulties, especially in men. Despite the prevalence of BPA in society, the mechanism behind reproductive deficits remains elusive. The present study investigates the modeofBPA's action by evaluating its effect on the expression of inducible nitric oxide synthase (iNOS) and steriodogenic acute regulatoryprotein(StAR) in male mice testis.Swiss albino mice were treated with a range BPA concentrations of 0.5, 50 and 100 μg/kg body weight/day intraperitoneally for 60 days. Several markers of oxidative stress and male fertility were investigated. Nitrite levels, malondialdehyde levelsand testicular injury scores were elevated whereas the sperm count, serum testosterone levels and catalase activity were reduced in the BPA groups. Mechanistically, an increase in iNOS expression was observed in the testiswhereas the expression of the StAR was down regulated in the BPA treated mouse.These results suggest that BPA induces oxidative stress by altering the expression ofiNOS, which consequently leads to the down regulation of StAR expressionin the testis of male mouse.
    Full-text · Article · Oct 2014 · Environmental Toxicology and Pharmacology
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