Background: Given its hormonal activity, bisphenol S (BPS) as a substitute for bisphenol A (BPA) could actually increase the risk of endocrine disruption if its toxicokinetic (TK) properties, namely its oral availability and systemic persistency, were higher than those of BPA. Objectives: The TK behavior of BPA and BPS was investigated by administering the two compounds by intravenous and oral routes in piglet, a known valid model for investigating oral TK. Methods: Experiments were conducted in piglets to evaluate the kinetics of BPA, BPS, and their glucuronoconjugated metabolites in plasma and urine after intravenous administration of BPA, BPS, and BPS glucuronide (BPSG) and gavage administration of BPA and BPS. A population semiphysiologically based TK model describing the disposition of BPA and BPS and their glucuronides was built from these data to estimate the key TK parameters that drive the internal exposure to active compounds. Results: The data indicated that almost all the BPS oral dose was absorbed and transported into the liver where only 41% of BPS was glucuronidated, leading to a systemic bioavailability of 57.4%. In contrast, only 77% of the oral dose of BPA was absorbed and underwent an extensive first-pass glucuronidation either in the gut (44%) or in the liver (53%), thus accounting for the low systemic bioavailability of BPA (0.50%). Due to the higher systemic availability of BPS, in comparison with BPA, and its lower plasma clearance (3.5 times lower), the oral BPS systemic exposure was on average about 250 times higher than for BPA for an equal oral molar dose of the two compounds. Conclusion: Given the similar digestive tracts of pigs and humans, our results suggest that replacing BPA with BPS will likely lead to increased internal exposure to an endocrine-active compound that would be of concern for human health. https://doi.org/10.1289/EHP4599

Limited information is available describing the development of the neonatal fecal microbiome in dogs. Feces from puppies were collected at 2, 21, 42, and 56 days after birth. Feces were also collected from the puppies’ mothers at a single time point within 24 hours after parturition. DNA was extracted from fecal samples and 454-pyrosequencing was used to profile 16S rRNA genes. Species richness continued to increase significantly from 2 days of age until 42 days of age in puppies. Furthermore, microbial communities clustered separately from each other at 2, 21, and 42 days of age. The microbial communities belonging to dams clustered separately from that of puppies at any given time point. Major phylogenetic changes were noted at all taxonomic levels with the most profound changes being a shift from primarily Firmicutes in puppies at 2 days of age to a co-dominance of Bacteroidetes, Fusobacteria, and Firmicutes by 21 days of age. Further studies are needed to elucidate the relationship between puppy microbiota development, physiological growth, neonatal survival, and morbidity.

Breeding kennels face a high rate of neonatal mortality, on which the impact of nutrition remains to be determined. This study was designed to evaluate the impact of birth weight (reflecting intrauterine growth) and early growth rate (reflecting colostrum intake) on risk of neonatal mortality in puppies and to determine the critical thresholds of both parameters. Puppies from various breeds were weighed at birth (n = 514) and at 2 d of age, and the growth rate over that period (early growth rate) was calculated for all survivors (n = 477). Linear mixed models evaluated the effect of birth weight on mortality between birth and 2 d of age and the effect of both birth weight and early growth rate on mortality between 2 and 21 d of age. Birth weight was influenced by litter size (P = 0.003), with more low-birth-weight puppies (the lightest 25% within a breed size) in large litters compared with smaller litters. Mortality over the first 2 d after birth was associated with birth weight (P < 0.001), with 81.1% of dying puppies characterized by a low birth weight. Mortality between 2 and 21 d of age was not related to birth weight but was found to be associated with early growth rate (P < 0.001), with higher risk of death in puppies with growth rate at or below –4% after the first 2 d of life. This study demonstrates the differential effect of intrauterine nutrition impacting mortality during the first 2 d of life and that of colostrum intake impacting mortality until 21 d of life. Birth weight and early growth rate thresholds provided in this study allow identification of puppies at risk, whereby provision can be made for adequate nursing to increase their chances to survive.

Despite the high neonatal mortality rate in puppies, pertinent criteria for health evaluation of the newborns are not defined. This study was thus designed to measure and to characterize factors of variation of six health parameters in dog neonates, and to evaluate their value as predictors of neonatal mortality. A total of 347 purebred puppies under identical conditions of housing and management were examined within the first 8h after birth and then at Day 1. The first health evaluation included Apgar score, weight, blood glucose, lactate and β-hydroxybutyrate concentration, rectal temperature and urine specific gravity (SG). The second evaluation at Day 1 included the same parameters, excluding Apgar score and weight. The mortality rate over the first 24h and over 21days of age was recorded. The early predictors of neonatal mortality in the dog were determined with generalized linear mixed models and receiver operating characteristic curves analyses. An Apgar score at or below 6 evaluated within the first 8h after birth was found associated with a higher risk of death during the first 24h. A reduced glucose concentration (≤92mg/dl) at Day 1 was found to be associated with higher mortality between 1 and 21days of age. Low-birth-weight puppies were characterized by both low viability (low Apgar score) and low blood glucose concentration, and thus were found indirectly at higher risk of neonatal mortality. This study promotes two low cost easy-to-use tests for health evaluation in puppies, i.e. Apgar scoring and blood glucose assay. Further investigation is necessary to establish if the strong relationship between blood glucose and neonatal survival reflects high energy requirements or other benefits from colostrum intake.