Lack of effects for dietary exposure of bisphenol A during &lt;i&gt;in utero&lt;/i&gt; and lactational periods on reproductive development in rat offspring

Kobayashi, Kenichi; Kubota, Hisayo; Ohtani, Kazuhiro; Hojo, Rieko; Miyagawa, Munéyuki

doi:10.2131/jts.37.565

Cited by 47 publications

(31 citation statements)

References 48 publications

(49 reference statements)

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“…No effect was seen on male AGDs, whereas AGDs were significantly shorter in 1-month-old females exposed to 0.17 and 1.7 mg/kg, but not at 3 months of age. As the effects were only seen in the younger females, the authors did not consider the results to be biologically significant (Kobayashi et al 2012). However, these reductions in female AGDs corroborate the findings from this study, and it is possible that measurement of AGD in newborn male and female rats, instead of 1-and 3-month-old rats, would have yielded some even more similar results to the present ones.…”

Section: Discussionsupporting

confidence: 71%

Low-dose effects of bisphenol A on early sexual development in male and female rats

Christiansen¹,

Axelstad²,

Boberg³

et al. 2014

Reproduction

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Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been reported to impair many endpoints for reproductive and neurological development; however, it is controversial whether BPA has effects in the microgram per kilogram dose range. The aim of the current study was to examine the influence of BPA on early sexual development in male and female rats at dose levels covering both regulatory no observed adverse effect levels (NOAELs) (5 and 50 mg/kg bw per day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25 mg/kg bw per day). Time-mated Wistar rats (nZ22) were gavaged during pregnancy and lactation from gestation day 7 to pup day 22 with 0, 0.025, 0.25, 5 or 50 mg/kg bw per day BPA. From 0.250 mg/kg and above, male anogenital distance (AGD) was significantly decreased, whereas decreased female AGD was seen from 0.025 mg/kg bw per day and above. Moreover, the incidence of nipple retention in males appeared to increase dose relatedly and the increase was statistically significant at 50 mg/kg per day. No significant changes in reproductive organ weights in the 16-day-old males and females and no signs of maternal toxicity were seen. The decreased AGD at birth in both sexes indicates effects on prenatal sexual development and provides new evidence of low-dose adverse effects of BPA in rats in the microgram per kilogram dose range. The NOAEL in this study is clearly below 5 mg/kg for BPA, which is used as the basis for establishment of the current tolerable daily intake (TDI) by EFSA; thus a reconsideration of the current TDI of BPA appears warranted.

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Section: Discussionsupporting

confidence: 71%

Low-dose effects of bisphenol A on early sexual development in male and female rats

Christiansen¹,

Axelstad²,

Boberg³

et al. 2014

Reproduction

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“…In females, perinatal exposure to BPA increased the number of terminal end buds in mammary tissues of CD-1 mice exposed to estradiol later in life without affecting the terminal end buds in mammary tissues of C57BL/6 mice [22]. Furthermore, BPA increased the weight of offspring born to gestationally exposed ICR and adult CD1 Swiss mice, decreased the weight of offspring born to neonatally exposed ICR mice, but did not affect the weight of offspring born to gestationally and neonatally exposed C57BL/6J mice [15,[38][39][40]. Although timing of exposure may also play a role in birth weight following exposure to BPA, future studies should directly compare BPA effects in various strains to account for other potential confounders.…”

Section: Discussionmentioning

confidence: 90%

“…Although some effects such as disrupted uterine implantation and pregnancy maintenance are supported by strong evidence [3][4][5][6][7][8], other effects such as the effects on steroidogenesis are only partially supported by existing data [4,6,[9][10][11][12][13][14][15]. The ambiguity of these studies may be due to the study design, specifically the strain of animal used in the experiments.…”

Section: Introductionmentioning

confidence: 99%

Mouse Strain Does Not Influence the Overall Effects of Bisphenol A-Induced Toxicity in Adult Antral Follicles1

Peretz

Neese

Flaws

2013

Biology of Reproduction

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Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) widely used in common consumer products containing polycarbonate plastics and epoxy resins. Previous studies indicate that other EDCs have species-dependent effects. Furthermore, some EDCs are known to have different effects in different strains within the same species. Little information, however, is known about whether the effects of BPA on the ovary differ by strain. Previous studies have shown that BPA inhibits follicle growth, induces atresia, and inhibits steroidogenesis and expression of steroidogenic enzymes in antral follicles from adult FVB mice. Thus, this study was designed to expand previous work by testing the hypothesis that mouse strain may differentially affect the susceptibility of adult antral follicles to BPA-induced toxicity. To test this hypothesis, antral follicles were mechanically isolated from adult FVB, CD-1, and C57BL/6 mice, individually cultured for 6-120 h and treated with either vehicle control (dimethylsulfoxide) or various concentrations of BPA (1.0 μg/ml, 10 μg/ml, or 100 μg/ml). After culture, media were subjected to measurements of hormone production via ELISA, and follicles were subjected to real-time PCR for analysis of genes known to regulate steroidogenesis, the cell cycle, and atresia. Overall, BPA inhibited follicle growth and steroidogenesis in all tested strains, but CD-1 follicles were slightly more sensitive to BPA at early time points than FVB and C57BL/6 follicles. These data suggest that CD-1, FVB, and C57BL/6 mice can all be used to investigate the effects of BPA on ovarian follicles.

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“…Extensive toxicology studies have established no-observedadverse-effect-levels (NOAELs) ranging from 5 to 50 mg/kg/day, further reinforcing the significance of first pass metabolism for mitigating BPA's potential risk (Ema et al, 2001;Tyl et al, 2002Tyl et al, , 2008Howdeshell et al, 2008;Ryan et al, 2010;Kobayashi et al, 2010Kobayashi et al, , 2012Stump et al, 2010). Delclos et al (2014) and Churchwell et al (2014) reported reproductive effects in rat pups after gavage dosing of dams from gestational day 6 and subsequent gavage dosing of pups from PND1 with 100 and 300 mg/kg/day BPA but not with dosages of 2.7 mg/kg/day or lower.…”

Section: Introductionmentioning

confidence: 98%

Extensive metabolism and route-dependent pharmacokinetics of bisphenol A (BPA) in neonatal mice following oral or subcutaneous administration

et al. 2015

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Orally administered bisphenol A (BPA) undergoes efficient first-pass metabolism to produce the inactive conjugates BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). This study was conducted to evaluate the pharmacokinetics of BPA, BPA-G and BPA-S in neonatal mice following the administration of a single oral or subcutaneous (SC) dose. This study consisted of 3 phases: (1) mass-balance phase in which effective dose delivery procedures for oral or SC administration of (3)H-BPA to postnatal day three (PND3) mice were developed; (2) pharmacokinetic phase during which systemic exposure to total (3)H-BPA-derived radioactivity in female PND3 mice was established; and (3) metabolite profiling phase in which 50 female PND3 pups received either a single oral or SC dose of (3)H-BPA. Blood was collected from 5 pups/route/time-point at various times post-dosing, the blood plasma samples were pooled by group, and time-point and samples were profiled by HPLC with fraction collection. Fractions were analyzed for total radioactivity and data used to reconstruct radiochromatograms and to integrate individual peaks. The identity of the BPA, BPA-G, and BPA-S peaks was confirmed using authentic standards and LC-MS/MS analysis. The result of this study revealed that female PND3 mice have the capacity to metabolize BPA to BPA-G, BPA-S and other metabolites after both routes of administration. Systemic exposure to free BPA is route-dependent as the plasma concentrations were lower following oral administration compared to SC injection.

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Lack of effects for dietary exposure of bisphenol A during <i>in utero</i> and lactational periods on reproductive development in rat offspring

Cited by 47 publications

References 48 publications

Low-dose effects of bisphenol A on early sexual development in male and female rats

Low-dose effects of bisphenol A on early sexual development in male and female rats

Mouse Strain Does Not Influence the Overall Effects of Bisphenol A-Induced Toxicity in Adult Antral Follicles1

Extensive metabolism and route-dependent pharmacokinetics of bisphenol A (BPA) in neonatal mice following oral or subcutaneous administration

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