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Tetrabromobisphenol-A (TBBPA) is a brominated flame retardant (BFR) commonly used in electronics to meet fire safety standards and has the largest worldwide production of any BFR. TBBPA has been detected in human breast milk and maternal/cord serum, indicating exposure to mothers, fetuses, and breastfeeding newborns although exposure to fetuses and newborns is poorly understood. Pregnant or nursing Wistar Han IGS rats were administered [ 14 C]-TBBPA in a single dose (25 mg/kg, 2.5 μCi/kg) and euthanized between 0.5&24 h post dose to determine disposition in pregnant and nursing rats and their pups. Systemic exposure was largely unchanged between 1&8 h post dose in pregnant rats; [ 14 C]-radioactivity in blood varied only slightly between 0.5&8 h (2.6 ± 0.6 → 2.6 ± 0.8 nmol-eq/mL) but was below the limit of detection at 24 h with an absorption half-life of 16min and elimination half-life of 17 h. C max was observed at 30min in lactating rats and concentrations fell steadily through 8 h. Plasma from pregnant rats contained a mixture of TBBPA and TBBPA-conjugates at 30min but only metabolites in subsequent samples. TBBPA was not detected in lactating dam plasma in this study. Placental concentrations increased through 8 h while whole-fetus C max occurred at 2 h post dose. In lactating animals, liver, uterus, and mammary time-concentration curves lagged slightly behind blood-concentration curves. It was clear from these studies that TBBPA is available to both the developing fetus and nursing pup following maternal exposure, and nursing pups are continuously exposed via contaminated milk produced by their mother. This research was supported in part by the Intramural Research Program of NIH/NCI. [ABSTRACT FROM AUTHOR]

Cypermethrin (CYP) is a widely used synthetic pyrethroid insecticide and regarded as a potential endocrine disruptor. CYP exposure may pose a great risk to human health including adverse effect on their reproductive functions. This study aimed to delineate the effects of perinatal exposure of rats to CYP on the sexual maturation and fertility of F1 male progeny. Pregnant rats (F0) were gavaged daily with CYP (0, 1, 10, 25 mg/kg BW/day) and Diethylestilbestrol (DES, 10 μg/kg BW/day), as positive control from gestation day 6 to postnatal day 21. The effects of CYP on body weight gain and reproductive functions were evaluated at the Juvenile (PND 22), peri-pubertal (PND 45) and adult (PND 75) stages of development. A significant delay in the age of testicular descent and prepuce separation was observed at 1 and 25 mg/kg doses of CYP. At the same dose level, reproductive organ development and their functions were also affected. A significant alteration in testicular histology, expression of steroid hormone receptors, and circulatory steroid hormones was observed throughout development. Reduced sperm count and motility were observed at PND 75 leading to subfertility and reduced litter size. These adult male rats when cohabitated with unexposed normal cycling females, the F2 fetuses exhibited developmental defects. Taken together, CYP perinatal exposure caused significant long lasting effects of the reproductive functions of F1 generation male rats, which were vertically transmitted to F2 generation leading to developmental defects. The mechanism of transgenerational effects needs to be explored in details. [ABSTRACT FROM AUTHOR]

Abstract: A previously developed and validated methodology based on liquid chromatography coupled to high resolution mass spectrometry was used for determine the concentration levels of 14 perfluoroalkylated substances (PFASs) in a set of 48 breast milk samples collected from French women in the frame of the ELFE pilot study. In accordance with other similar studies conducted at european and international levels, PFOS, PFOA, and PFHxS were detected and quantified in most of the analyzed samples (90%, 98% and 100%, respectively), and appeared as major contributors to the total PFAS exposure (38%, 37%, 25%, respectively), whereas the other targeted PFAS were very rarely, if not, found at the limits of detection of the method. Also in agreement with other published data, the concentration levels measured for the detected substances varied from <0.05 to 0.33μg/L for PFOS (median=0.079), from <0.05 to 0.22μg/L for PFOA (median=0.075), and from 0.04 to 0.07μg/L for PFHxS (median=0.050). On the basis of this relatively limited data set, no statistically significant relation was observed between these exposure levels and developmental outcomes, in particular the weight at birth. Similarly, no relation was observed between the measured PFAS levels and various socio-demographical parameters including the consumption of seafood, alcohol, smoking, or socio-economical level. These results suggest a need for further research and better knowledge regarding the sources, pharmacokinetics, and factors of exposure for other substances belonging to this class of emerging contaminants. [Copyright &y& Elsevier]

Abstract: Perfluorinated compounds (PFCs) are man-made chemicals for which endocrine disrupting properties and related possible side effects on human health have been reported, particularly in the case of an exposure during the early stages of development, (notably the perinatal period). Existing analytical methods dedicated to PFCs monitoring in food and/or human fluids are currently based on liquid chromatography coupled to tandem mass spectrometry, and were recently demonstrated to present some limitations in terms of sensitivity and/or specificity. An alternative strategy dedicated to the analysis of fourteen PFCs in human breast milk was proposed, based on an effective sample preparation followed by a liquid chromatography coupled to high resolution mass spectrometry measurement (LC–HRMS). This methodology confirmed the high interest for HRMS after negative ionization for such halogenated substances, and finally permitted to reach detection limits around the pgmL−1 range with an outstanding signal specificity compared to LC–MS/MS. The proposed method was applied to a first set of 30 breast milk samples from French women. The main PFCs detected in all these samples were PFOS and PFOA with respective median values of 74 (range from 24 to 171) and 57 (range from 18 to 102) pgmL−1, respectively. These exposure data appeared in the same range as other reported values for European countries. [Copyright &y& Elsevier]

Increasing evidence has highlighted the critical role of early life environment in shaping the future health outcomes of individuals in subsequent generations. Bisphenol S (BPS) has been widely used as a substitute for various plastic materials due to the limited application of Bisphenol A (BPA) which is an endocrine disruptor. However, the lack of efficient evaluation of BPS leaves doubts about the relevant substitute of BPA. Few studies of transgenerational inheritance have examined the effects of environmental exposures to endocrine disruptors on the immune system. In this study, we analyzed the transgenerational effects of BPS on intestinal inflammation and its consequence in metabolism. In this study, only F0 pregnant mice were exposed to BPS (1.5 μg/kg bw/day) from gestational day 0 until weaning of offspring. In this work, both F1 and F2 male offspring developed an inflammatory response in the ileum and colon at adulthood after F0 mothers were exposed to BPS; this phenomenon disappeared in F3. This inflammatory response in F1 male offspring is associated with a significant decrease of blood cholesterol without modification of metabolic status. Further, in F3 offspring male, the decrease of gut inflammatory response is associated with a decrease of fat weight and with an increase of blood glucose and cholesterol level. A sex-specific profile is observed in female offspring. We also observed that early life exposure to BPS was associated with strong abnormal intestinal immune status. The study presented here demonstrates that the immune system, like other organ systems, is vulnerable to transgenerational effects caused by environmental exposures. • Perinatal BPS exposure induces sex-dependent effects in intestinal inflammation. • Intestinal inflammation induced by BPS exhibits a multigenerational and transgenerational pattern. • Intestinal inflammation induced by BPS is associated with biochemical plasma changes. [ABSTRACT FROM AUTHOR]

Perinatal exposure to bisphenol A (BPA) contributes to neurological disorders in offspring, but the underlying mechanisms are still poorly understood. The abnormal release of neuroactive metabolites in the tryptophan (TRP) and dopamine (DA) pathways is considered to be closely associated with some disorders. Thus, in this study, TRP and DA pathways in adult female mouse offspring were investigated when the pregnant mice were given either vehicle or BPA (2, 10, or 100 μg/kg/d) from day 6 of gestation until weaning. Then, the serum and brain samples of offspring were collected at 3, 6 and 9 months, and 12 neuroactive metabolites in the TRP and DA pathways were detected. The results showed that, in the TRP pathway, TRP levels decreased, whereas kynurenine (KYN) levels and TRP turnover increased in the brain. In the serum, TRP, KYN and 5-hydroxytryptamine (5-HT) levels decreased significantly. For the DA pathway, DA and DA metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA), reduced significantly in the brain and serum. DA turnover decreased dramatically in the brain but enhanced in the serum. The disturbance of these two metabolic pathways might be one of the potential mechanisms of BPA-induced neuropsychiatric disorders. • Perinatal exposure to BPA affected tryptophan and dopamine metabolism in offspring mice. • Tryptophan downstream metabolic pathways: the KYN and 5-HT pathways were affected by perinatal exposure to BPA. • Perinatal exposure to BPA caused a long-time disturbance on tryptophan and dopamine metabolism in offspring mice. [ABSTRACT FROM AUTHOR]

Parabens are a class of preservatives widely used in the majority of personal care products, cosmetics, medicines, and food products. However, current literature suggests its plausible role as an endocrine disruptor, hence the present study was undertaken to delineate the effects of n-butyl paraben on perinatally exposed F1 female rats. F 0 dams were exposed subcutaneously to n-butylparaben from gestation day 6 (GD 6) to postnatal day (PND) 21 with doses of 10, 100, and 1000 mg/kg Bw/day in corn oil. The F1 female rats were monitored for pubertal development and sexual maturation through PND 30, 45, and 75; which were subsequently subjected to fertility assessment at PND 75. Perinatal exposure to n-butylparaben resulted in- This study documents impaired steroidogenesis and folliculogenesis might be the prime reason for the reduced fertility of F1 female rats. Hence, our study suggests that health monitors need to counsel potential females planning for pregnancy to avoid exposure to parabens., (Copyright © 2018. Published by Elsevier Ltd.)