Background Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used to substitute bisphenol A (BPA), a widespread environmental endocrine disruptor and putative obesogen. However, studies on effects of BPF and BPS on obesity in humans are lacking. We examined the associations of BPA, BPF, and BPS exposure with obesity in U.S. adults. Methods We included 1,521 participants aged 20 years or older from a cross-sectional study, the National Health and Nutrition Examination Survey 2013–2014. Urinary BPA, BPF, and BPS concentrations were measured using on-line solid phase extraction coupled to high performance liquid chromatography and tandem mass spectrometry. We used body mass index and waist circumference to define general obesity and abdominal obesity, respectively. We used logistic regression with sample weights to estimate the odds ratios (ORs) of obesity and 95% confidence intervals. Findings Higher BPA, BPF, and BPS concentrations were observed in obese adults than non-obese adults. After adjustment for demographic, socioeconomic, lifestyle factors, and urinary creatinine concentrations, BPA, but not BPF or BPS, was significantly associated with obesity. The OR of general obesity was 1.78 (1.10–2.89) comparing the highest with lowest quartile of BPA, 1.02 (0.70–1.47) for BPF, and 1.22 (0.81–1.83) for BPS. The corresponding OR for abdominal obesity was 1.55 (1.04–2.32) for BPA, 1.05 (0.68–1.63) for BPF, and 1.16 (0.72–1.88) for BPS. Interpretation Whereas there were significant associations of BPA exposure with general and abdominal obesity, BPF or BPS, at current exposure level, was not significantly associated with obesity in U.S. adults. Continued biomonitoring of these bisphenols in populations and further investigations on their health effects in humans are warranted.

Safeners are included in many commercial herbicide formulations to selectively protect crops from injury induced by active ingredients. Despite their bioactivity, safeners are classified as inert from a regulatory perspective, and as such, safeners have received minimal attention in the peer-reviewed literature regarding their environmental fate and effects. Herein, we review what is known about the uses, physicochemical properties, environmental transformations, and (eco)toxicological effects of dichloroacetamide safeners, which represent one of the most commonly used safener classes (estimated use of >2 × 10 6 kg/year in the United States). We particularly highlight transformation pathways that may enhance biological activity and/or persistence; for example, limited studies suggest dichloroacetamides can transform via dechlorination into products with increased bioactivity. We also identify several research needs to improve our understanding of the environmental fate and potential risks of this overlooked agrochemical class, which in turn will enhance the efficacy and safety of future herbicide safener formulations.

Widespread exposure to pyrethroid insecticides has been reported among the general population in the United States and worldwide. However, little is known about the association of pyrethroid exposure with long-term health outcomes in adults. OBJECTIVETo examine the association of pyrethroid exposure with all-cause and cause-specific mortality among adults in the United States. DESIGN, SETTING, AND PARTICIPANTS The nationally representative cohort included 2116 adults aged 20 years and older who participated in the US National Health and Nutrition Examination Survey conducted from 1999 to 2002 and provided urine samples for pyrethroid metabolite measurements. Participants were linked to mortality data from the survey date through December 31, 2015. Data were analyzed from May to August 2019.EXPOSURES Urinary levels of 3-phenoxybenzoic acid, a general pyrethroid metabolite and commonly used biomarker for pyrethroid exposure, were determined by using high-performance liquid chromatography coupled with electrospray chemical ionization and tandem mass spectrometry. MAIN OUTCOMES AND MEASURESMortality from all causes, cardiovascular disease, and cancer.RESULTS This cohort study of 2116 adults comprised 1145 women (weighted proportion, 51.6%) and 971 men (weighted, 48.4%), with a weighted mean (SE) age of 42.6 (0.5) years; 958 participants (weighted, 68.4%) were of non-Hispanic white ancestry, 646 (weighted, 14.7%) of Hispanic ancestry, 419 (weighted, 11.3%) of non-Hispanic black ancestry, and 93 (weighted, 5.6%) of other ancestry. During a median of 14.4 years (range, 0.1-16.8 years) of observation, 246 deaths occurred, including 41 associated with cardiovascular disease and 52 associated with cancer. Participants with higher urinary 3-phenoxybenzoic acid levels were at a higher risk of death during the follow-up period, with death occurring in 8.5% (unweighted, 75 of 709), 10.2% (unweighted, 81 of 701), and 11.9% (unweighted, 90 of 706) of participants across increasing tertiles of urinary 3-phenoxybenzoic acid levels. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and urinary creatinine levels, the hazard ratios for all-cause mortality, cardiovascular disease mortality, and cancer mortality among participants with the highest tertile compared with those with the lowest tertile of urinary 3-phenoxybenzoic acid levels were 1.56 (95% CI, 1.08-2.26), 3.00 (95% CI, 1.02-8.80), and 0.91 (95% CI, 0.31-2.72), respectively. CONCLUSIONS AND RELEVANCEIn this nationally representative sample of US adults, environmental exposure to pyrethroid insecticides was associated with an increased risk of all-cause and cardiovascular disease mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.

Polychlorinated biphenyls (PCBs), a group of 209 congeners that differ in the number and position of chlorines on the biphenyl ring, are anthropogenic chemicals that belong to the persistent organic pollutants (POPs). For many years, PCBs have been a topic of interest because of their biomagnification in the food chain and their environmental persistence. PCBs with fewer chlorine atoms, however, are less persistent and more susceptible to metabolic attack, giving rise to chemicals characterized by the addition of one or more hydroxyl groups to the chlorinated biphenyl skeleton, collectively known as hydroxylated PCBs (OH-PCBs). In animals and plants, this biotransformation of PCBs to OH-PCBs is primarily carried out by cytochrome P-450-dependent monooxygenases. One of the reasons for infrequent detection of lower chlorinated PCBs in serum and other biological matrices is their shorter half-lives, and their metabolic transformation, resulting in OH-PCBs or their conjugates, such as sulfates and glucuronides, or macromolecule adducts. Recent biomonitoring studies have reported the presence of OH-PCBs in human serum. The occurrence of OH-PCBs, the size of this group (there are 837 mono-hydroxyl PCBs alone), and their wide spectra of physical characteristics (pKa's and log P's ranging over 5 to 6 orders of magnitude) give rise to a multiplicity of biological effects. Among those are bioactivation to electrophilic metabolites that can form covalent adducts with DNA and other macromolecules, interference with hormonal signaling, inhibition of enzymes that regulate cellular concentrations of active hormones, and interference with the transport of hormones. This new information creates an urgent need for a new perspective on these often overlooked metabolites.

IMPORTANCE Bisphenol A (BPA) is a major public health concern because of its high-volume industrial production, ubiquitous exposure to humans, and potential toxic effects on multiple organs and systems in humans. However, prospective studies regarding the association of BPA exposure with long-term health outcomes are sparse. OBJECTIVE To examine the association of BPA exposure with all-cause mortality and cause-specific mortality among adults in the United States. DESIGN, SETTING, AND PARTICIPANTS This nationally representative cohort study included 3883 adults aged 20 years or older who participated in the US National Health and Nutrition Examination Survey 2003-2008 and provided urine samples for BPA level measurements. Participants were linked to mortality data from survey date through December 31, 2015. Data analyses were conducted in July 2019. EXPOSURES Urinary BPA levels were quantified using online solid-phase extraction coupled to high-performance liquid chromatography-isotope dilution tandem mass spectrometry. MAIN OUTCOMES AND MEASURES Mortality from all causes, cardiovascular disease, and cancer. RESULTS This cohort study included 3883 adults aged 20 years or older (weighted mean [SE] age, 43.6 [0.3] years; 2032 women [weighted, 51.4%]). During 36 514 person-years of follow-up (median, 9.6 years; maximum, 13.1 years), 344 deaths occurred, including 71 deaths from cardiovascular disease and 75 deaths from cancer. Participants with higher urinary BPA levels were at higher risk for death. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and urinary creatinine levels, the hazard ratio comparing the highest vs lowest tertile of urinary BPA levels was 1.49 (95% CI, 1.01-2.19) for all-cause mortality, 1.46 (95% CI, 0.67-3.15) for cardiovascular disease mortality, and 0.98 (95% CI, 0.40-2.39) for cancer mortality. CONCLUSIONS AND RELEVANCE In this nationally representative cohort of US adults, higher BPA exposure was significantly associated with an increased risk of all-cause mortality. Further studies are needed to replicate these findings in other populations and determine the underlying mechanisms.