Low‐dose effects of bisphenol A on mammary gland development in rats

Abstract

SUMMARYBisphenol A (BPA) is widely used in food contact materials, toys, and other products. Several studies have indicated that effects observed at doses near human exposure levels may not be observed at higher doses. Many studies have shown effects on mammary glands at low doses of BPA, however, because of small number of animals or few doses investigated these data have not been used by EFSA as point of departure for the newly assessed tolerable daily intake (TDI). We performed a study with perinatal exposure to BPA (0, 0.025, 0.25, 5, and 50 mg/kg bw/day) in rats (n = 22 mated/group). One of the aims was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose-response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg/kg BPA, indicating an increased mammary development at this low dose only. Increased prevalence of intraductal hyperplasia was observed in BPA females exposed to 0.25 mg/kg at PD 400, but not at PD 100, and not at higher or lower doses. The present findings support data from the published literature showing that perinatal exposure to BPA can induce increased mammary growth and proliferative lesions in rodents. Our results indicate that low-dose exposure to BPA can affect mammary gland development in male and female rats, although higher doses show a different pattern of effects. The observed intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may not be sufficiently protected.

CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

“…Like CLARITY, the Danish study also included additional non-guideline end-points including evaluations of behaviours (sugar preference, spatial learning ability), 129 male reproductive outcome (sperm count) 129 and mammary growth parameters (male epithelial outgrowths, female mammary intraductal hyperplasias). 130 Remarkably, the authors found that male offspring in the lowest dose group (25 μg/kg BW/d) had significantly fewer sperm and larger mammary gland epithelial trees compared to controls. Female offspring from this dose group had masculinized neurobehaviours (in spatial learning and preference for sugar) and increased body-weights in later life (9-13 months of age).…”

“…Wistar rats were gavaged with one of four BPA doses (25, 250, 5000 or 50 000 μg/kg BW/d) from GD7 through lactational day 22; this period is similar to the stop dose group in the CLARITY‐BPA study, except that the postnatal treatment continued to be given to the mother rather than the pup. Like CLARITY, the Danish study also included additional non‐guideline end‐points including evaluations of behaviours (sugar preference, spatial learning ability), male reproductive outcome (sperm count) and mammary growth parameters (male epithelial outgrowths, female mammary intraductal hyperplasias) …”

Die Belegerteilungspflicht als Verursacher von Umwelt- und Gesundheitsgefährdungen?

“…BPA kann bereits bei sehr geringen Dosen Effekte auslö-sen. Bei Ratten, welche einer Dosis von 0,025 mg/kg Körpergewicht/Tag BPA ausgesetzt wurden, entwickelten sich Veränderungen an den Brustdrüsen (Mandrup et al 2016 (Goldinger et al 2015). Mit BPS sind damit gleichartige Gesundheitsgefahren verbunden wie mit BPA (Chen et al 2016).…”

Selectivity Enhancement in Molecularly Imprinted Polymers for Binding of Bisphenol A

“…A robust experimental study has shown that developmental exposure of pregnant rats to 25 μg of BPA per kg body weight per day can cause adverse effects on fertility (decreased sperm count), neurodevelopment (masculinization of spatial learning in females) and lead to increased female body weight late in the life of their offspring [20]. This low-dose perinatal exposure can also affect mammary gland development in male and female offspring [21]. A liquid chromatography-tandem mass spectrometry analytical method was used to directly and simultaneously measure unconjugated BPA, BPA glucuronide and BPA sulfate in the urine of pregnant women in their second trimester [22].…”