A scoping review of the health and toxicological activity of bisphenol A (BPA) structural analogues and functional alternatives.

Recent studies report widespread usage or exposure to a variety of chemicals with structural or functional similarity to bisphenol A (BPA), referred to as BPA analogues or derivatives. These have been detected in foodstuffs, house dust, environmental samples, human urine or blood, and consumer products. Compared to BPA, relatively little is known about potential toxicity of these compounds. This scoping review aimed to summarize the human, animal, and mechanistic toxicity data for 24 BPA analogues of emerging interest to research and regulatory communities. PubMed was searched from March 1, 2015 to January 5, 2019 and combined with the results obtained from literature searches conducted through March 23, 2015, in The National Toxicology Program's Research Report 4 (NTP RR-04), "Biological Activity of Bisphenol A (BPA) Structural Analogues and Functional Alternatives". Study details are presented in interactive displays using Tableau Public. In total, 5748 records were screened for inclusion. One hundred sixty seven studies were included from NTP RR-04 and 175 studies were included from the updated literature search through January 2019. In total, there are 22, 117, and 221 human epidemiological, experimental animal, or in vitro studies included. The most frequently studied BPA analogues are bisphenol S (BPS), bisphenol F (4,4-BPF), and bisphenol AF (BPAF). Notable changes in the literature since 2015 include the growing body of human epidemiological studies and in vivo studies conducted in zebrafish. Numerous new endpoints were also evaluated across all three evidence streams including diabetes, obesity, and oxidative stress. However, few studies have addressed endpoints such as neurodevelopmental outcomes or impacts on the developing mammary or prostate glands, which are known to be susceptible to disruption by BPA. Further, there remains a critical need for better exposure information in order to prioritize experimental studies. Moving forward, researchers should also ensure that full dose responses are performed for all main effects in order to support hazard and risk characterization efforts. The evidence gathered here suggests that hazard and risk characterizations should expand beyond BPA in order to consider BPA structural and functional analogues.

A risk of bias instrument for non-randomized studies of exposures: A users' guide to its application in the context of GRADE.

The objective of this paper is to explain how to apply, interpret, and present the results of a new instrument to assess the risk of bias (RoB) in non-randomized studies (NRS) dealing with effects of environmental exposures on health outcomes. This instrument is modeled on the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) instrument. The RoB instrument for NRS of exposures assesses RoB along a standardized comparison to a randomized target experiment, instead of the study-design directed RoB approach. We provide specific guidance for the integral steps of developing a research question and target experiment, distinguishing issues of indirectness from RoB, making individual-study judgments, and performing and interpreting sensitivity analyses for RoB judgments across a body of evidence. Also, we present an approach for integrating the RoB assessments within the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess the certainty of the evidence in the systematic review. Finally, we guide the reader through an overall assessment to support the rating of all domains that determine the certainty of a body of evidence using the GRADE approach.

Evaluation of the risk of bias in non-randomized studies of interventions (ROBINS-I) and the 'target experiment' concept in studies of exposures: Rationale and preliminary instrument development.

Assessing the risk of bias (RoB) of individual studies is a critical part in determining the certainty of a body of evidence from non-randomized studies (NRS) that evaluate potential health effects due to environmental exposures. The recently released RoB in NRS of Interventions (ROBINS-I) instrument has undergone careful development for health interventions. Using the fundamental design of ROBINS-I, which includes evaluating RoB against an ideal target trial, we explored developing a version of the instrument to evaluate RoB in exposure studies. During three sequential rounds of assessment, two or three raters (evaluators) independently applied ROBINS-I to studies from two systematic reviews and one case-study protocol that evaluated the relationship between environmental exposures and health outcomes. Feedback from raters, methodologists, and topic-specific experts informed important modifications to tailor the instrument to exposure studies. We identified the following areas of distinction for the modified instrument: terminology, formulation of the ideal target randomized experiment, guidance for cross-sectional studies and exposure assessment (both quality of measurement method and concern for potential exposure misclassification), and evaluation of issues related to study sensitivity. Using the target experiment approach significantly impacts the process for how environmental and occupational health studies are considered in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence-synthesis framework.

The association between neighborhood characteristics and body size and physical activity in the California teachers study cohort.

OBJECTIVES: We considered interactions between physical activity and body mass index (BMI) and neighborhood factors. METHODS: We used recursive partitioning to identify predictors of low recreational physical activity (< 2.5 hours/week) and overweight and obesity (BMI ≥ 25.0 kg/m(2)) among 118,315 women in the California Teachers Study. Neighborhood characteristics were based on 2000 US Census data and Reference US business listings. RESULTS: Low physical activity and being overweight or obese were associated with individual sociodemographic characteristics, including race/ethnicity and age. Among White women aged 36 to 75 years, living in neighborhoods with more household crowding was associated with a higher probability of low physical activity (54% vs 45% to 51%). In less crowded neighborhoods where more people worked outside the home, the existence of fewer neighborhood amenities was associated with a higher probability of low physical activity (51% vs 46%). Among non-African American middle-aged women, living in neighborhoods with a lower socioeconomic status was associated with a higher probability of being overweight or obese (46% to 59% vs 38% in high-socioeconomic status neighborhoods). CONCLUSIONS: Associations between physical activity, overweight and obesity, and the built environment varied by sociodemographic characteristics in this educated population.