Persistent Environmental Chemicals Research Articles

Contributions of Synthetic Chemicals to Autoimmune Disease Development and Occurrence.

Exposure to many synthetic chemicals has been linked to a variety of adverse human health effects, including autoimmune diseases. In this scoping review, we summarize recent evidence detailing the effects of synthetic environmental chemicals on autoimmune diseases and highlight current research gaps and recommendations for future studies. We identified 68 recent publications related to environmental chemical exposures and autoimmune diseases. Most studies evaluated exposure to persistent environmental chemicals and autoimmune conditions including rheumatoid arthritis (RA), systemic lupus (SLE), systemic sclerosis (SSc), and ulcerative colitis (UC) and Crohn's disease. Results of recent original research studies were mixed, and available data for some exposure-outcome associations were particularly limited. PFAS and autoimmune inflammatory bowel diseases (UC and CD) and pesticides and RA appeared to be the most frequently studied exposure-outcome associations among recent publications, despite a historical research focus on solvents. Recent studies have provided additional evidence for the associations of exposure to synthetic chemicals with certain autoimmune conditions. However, impacts on other autoimmune outcomes, particularly less prevalent conditions, remain unclear. Owing to the ubiquitous nature of many of these exposures and their potential impacts on autoimmune risk, additional studies are needed to better evaluate these relationships, particularly for understudied autoimmune conditions. Future research should include larger longitudinal studies and studies among more diverse populations to elucidate the temporal relationships between exposure-outcome pairs and to identify potential population subgroups that may be more adversely impacted by immune modulation caused by exposure to these chemicals.

Genotoxicity assessment of per- and polyfluoroalkyl substances mixtures in human liver cells (HepG2)

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, toxic, and persistent environmental chemicals of concern that have been widely detected in all environmental matrices including human biological fluids. Although humans are exposed to complex mixtures of PFAS, it remains uncertain whether the co-exposure to PFAS mixtures could induce genotoxic damage in humans. Hence, this study evaluated the combined genotoxicity of PFAS mixtures in a human cell line system. To assess the possible genotoxic damage caused by human exposure to PFAS and their mixtures, we investigated their potential to induce cytotoxicity (cell viability) and genotoxicity (DNA damage) in a human liver cell line (HepG2). The selected PFAS include perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS). The interaction toxicities of these PFAS in binary mixtures were also determined using the additive index approach. The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures induced a concentration-dependent decrease in cell viability. The additive index values indicated that the binary mixtures of PFOS + PFNA, PFOS + PFDA, and PFOS + PFOA displayed synergistic interaction, whereas the binary mixtures of PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS behaved additively. Using the alkaline Comet assay, the potential of PFAS and their mixtures to induce DNA damage was evaluated based on a 1:1 ratio of the concentration of respective compounds required to produce a 1/10th of effective concentrations causing 50 % inhibition in cell viability (EC50). The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures (PFOS + PFNA, PFOS + PFDA, PFOS + PFOA, PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS) caused a moderate increase in cellular DNA damage, but no dose-response relationship was observed. Overall, this study indicates that the tested PFAS causes a concentration-dependent decrease in cell viability and only a modest increase in cellular DNA damage under these conditions.

A Generic Pharmacokinetic Model for Quantifying Mother-to-Offspring Transfer of Lipophilic Persistent Environmental Chemicals.

Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman's body and transfer to her developing child across the placenta and via breast milk. To assess health risks associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs.

Persistent, Bioaccumulative, and Toxic Chemicals in Wild Alpine Insects: A Methodological Case Study.

With their high persistence in the environment and their potential for long‐range atmospheric transport, persistent, bioaccumulative, and toxic chemicals (PBTs) may be among the numerous anthropogenic threats to insect populations worldwide. The effects of PBTs on insects have been investigated in the laboratory, but topical field studies are scarce. A reason might be the multiple challenges faced by PBT‐related field studies on wild insects. We studied two species of bumblebees (Bombus spp.) and of ants (Formica spp.) in two high‐elevation locations in the Austrian and German Alps to tackle two of these challenges. First, PBTs occur in minuscule concentrations compared with other substances in the environment. Therefore, the practicability of body burden data from pooled individuals was tested. Second, fitness proxies like fecundity, which typically are endpoints for chemical toxicity, are difficult to quantify in the field. Hence, fluctuating asymmetry of bumblebee wings and ant heads was tested as an alternative endpoint. To exclude the possibility that fluctuating asymmetry was caused by genetic stressors, inbreeding levels were estimated using population‐genetic markers, and their relationships to fluctuating asymmetry in the same individuals were assessed. We successfully quantified polychlorinated biphenyls and Hg as PBTs using the pooled samples and found PBT data from pooled individuals useful, in that significant correlations to fluctuating asymmetry were identified in bumblebees and ants. This finding confirmed the potential of fluctuating asymmetry to indicate PBT effects in wild insects. Inbreeding did not interfere with PBT links to fluctuating asymmetry in any instance. Our findings contribute to the development of a quantitative methodological framework for investigating the effects of persistent environmental chemicals on wild insects. Environ Toxicol Chem 2022;41:1215–1227. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Prenatal exposure to mixtures of persistent environmental chemicals and fetal growth outcomes in Western Australia.

Environmental chemicals have been implicated in the etiology of impaired fetal growth. However, few studies have assessed the effects of chemical mixtures or considered the possibility of non-monotonic exposure-response relationships for chemicals that act through the endocrine system. We assessed exposure to polybrominated diphenyl ethers, organochlorine pesticides, metals, and perfluorinated alkyl substances in blood and urine samples collected approximately two weeks prior to delivery in 166 non-smoking pregnant women, and subsequent birth weight, length, and head circumference of neonates who were part of the Australian Maternal Exposures to Toxic Substances (AMETS) study. We used Bayesian structured additive regression models with spike-slab priors to estimate mixture effects, identify important exposures, and model non-linearity in exposure-response relationships. Mixtures of polybrominated diphenyl ethers, organochlorine pesticides, metals, and perfluorinated alkyl substances were not associated with fetal growth outcomes. Estimated change in fetal growth outcomes for an increase in exposure from the 25th to 75th percentile suggested no meaningful associations; the strongest evidence was for a small inverse association between birth weight and cesium exposure measured in whole blood (-124g, 90% credible interval: -240 to -3g). We identified several chemicals that may be associated with fetal growth non-linearly; however, 90% credible intervals contained small values consistent with no meaningful association. Using a Bayesian penalized regression method, we assessed the shapes of exposure-response relationships, controlled for confounding by co-exposure, and estimated the single and combined effects of a large mixture of correlated environmental chemicals on fetal growth. Our findings, based on a small sample of mother-neonate pairs, suggest that mixtures of persistent chemicals are not associated with birth weight, length, and head circumference. The potential for non-monotonic relationships between environmental chemicals and fetal growth outcomes warrants further study.

Impact of Bisphenol S as an Endocrine Disruptor in a Freshwater Fish, Oreochromis mossambicus

Endocrine Disrupting Chemicals (EDCs) have the potential to alter the hormonal pathways concerned with regulation of the normal homeostatic mechanisms. The adverse effects of EDCs can be observed in areas where pollution is high, particularly in aquatic ecosystems, where persistent environmental chemicals accumulate. In the present study, we investigated the endocrine disrupting effects of Bisphenol S (BPS), if any, in the levels of thyroxine, triiodothyronine, cortisol and sex steroidal [17I²estradiol (E2) and testosterone(T)] hormones in juvenile as well as adult Oreochromis mossambicus . Drastic changes in serum thyroxine and triiodothyronine levels showed that BPS treatment resulted in disruption of thyroid gland function. Alteration to significant levels in serum cortisol indicated acute stress and impairment of hypothalamic-pituitaryinterrenal axis. Significant changes (p<0.05) occurred in the steroidal hormone levels which are biomarkers of endocrine disruption as they affect hypothalamic-pituitary-gonadal axis in fish. Bisphenol S also revealed estrogenic potency by inducing significant alteration in the E2/T ratio. DNA fragmentation, if any, induced by BPS was also analyzed in juvenile fish. There was no significant DNA fragmentation observed in gel electrophoresis, but a significant elevation was seen in percent fragmented DNA in the diphenylamine method. Therefore, it could be concluded that BPS at different sublethal concentrations have a profound impact on endocrine physiology of fish.

Prenatal exposure to mixtures of persistent environmental chemicals and fetal growth outcomes in Western Australia

Background: Environmental chemicals have been implicated in the etiology of impaired fetal growth; however, few studies have assessed the effects of chemical mixtures or considered the possibility of non-monotonic exposure–response relationships for chemicals that act through the endocrine system. Methods: We assessed exposure to polybrominated diphenyl ethers, organochlorine pesticides, metals, and perfluoroalkyl substances in blood and urine samples collected two weeks prior to delivery in 166 non-smoking pregnant women, and subsequent birth weight, length, and head circumference of neonates who were part of the Australian Maternal Exposures to Toxic Substances (AMETS) study. We used Bayesian structured additive regression models with spike–slab priors to estimate mixture effects, identify important exposures, and model non-linearity in exposure–response relationships. Results: An increase in cesium exposure measured in whole blood from the 10th to 90th percentile was associated with a reduction in both birth weight (-236.5 g, 90% credible interval: -458.1 to -6.5 g) and the proportion of optimal birth weight (-8.6%, 90% credible interval: -14.8 to -0.4%), after adjusting for potential confounders. We identified several other chemicals and mixtures that may be associated with fetal growth, some non-linearly; however, 90% credible intervals contained the null. Conclusions: Using a Bayesian penalised regression method that is robust to multicollinearity, we assessed the shapes of exposure–response relationships, controlled for confounding by co-exposure, and estimated the single and combined effects of a large mixture of correlated environmental chemicals on fetal growth. While exposure concentrations in the AMETS study were generally low, our findings suggest that cesium exposure is associated with a reduction in birth weight. The potential for non-monotonic relationships between environmental chemicals and fetal growth outcomes warrants further study.

Early-life exposure to multiple persistent organic pollutants and metals and birth weight: Pooled analysis in four Flemish birth cohorts

Background and aimsPrenatal chemical exposure has frequently been associated with reduced fetal growth although results have been inconsistent. Most studies associate single pollutant exposure to this health outcome, even though this does not reflect real life situations as humans are exposed to many pollutants during their life time. The objective of this study is to investigate the association between prenatal exposure to a mixture of persistent environmental chemicals and birth weight using multipollutant models. MethodsWe combined exposure biomarker data measured in cord blood samples of 1579 women from four Flemish birth cohorts collected over a 10 years’ time period. The common set of available and detectable exposure measures in these cohorts are three polychlorinated biphenyls (PCB) congeners (138, 153 and 180), hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (p,p’-DDE) and the metals cadmium and lead. Multiple linear regression (MLR), Bayesian Information Criterion (BIC), penalized regression using minimax concave penalty (MCP) and Bayesian Adaptive Sampling (BAS) were applied to assess the influence of multiple pollutants in a single analysis on birth weight, adjusted for a priori selected covariates. ResultsIn the pooled dataset, a median (P25-P75) birth weight and gestational age of 3420 (3140–3700) grams and 39 (39–40) weeks was observed respectively. The median contaminant levels in cord blood were: 15.8, 26.5, 18.0, 16.9 and 91.5 ng/g lipid for PCB 138, PCB 153, PCB 180, HCB and p,p’-DDE, respectively, 0.075 µg/L for cadmium and 9.7 µg/L for lead. According to the applied statistical methods for multipollutant assessment, p,p’-DDE and PCB 180 were most consistently associated with birth weight. In addition, PCB 153 was selected when applying MCP and BAS. An inverse association with birth weight was found for the PCB congeners, while an increased birth weight was observed for elevated levels of p,p’-DDE. ConclusionsAssessing the health risk of combinations of exposure biomarkers reflects better real-world situations and thereby allows more effective risk assessment. Our results add to the existing evidence based on detrimental effects of PCBs on birth weight and indicate a possible increase in birth weight due to p,p’-DDE (while correcting for PCBs).

Association between prenatal exposure to perfluoroalkyl substances and asthma in 5-year-old children in the Odense Child Cohort

BackgroundAsthma is the most common non-communicable disease in children. Prenatal exposure to perfluoroalkyl substances (PFASs), a group of persistent environmental chemicals with endocrine disrupting abilities, has been associated with immunomodulation and may contribute to the aetiology of asthma. We investigated the associations between prenatal exposure to five PFASs and asthma in 5-year-old children.MethodsWe studied 981 mother-child pairs within the Odense Child Cohort (OCC), Denmark. We measured perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in maternal serum donated in early pregnancy. A standardized questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC) was used to assess wheeze, self-reported asthma and doctor-diagnosed asthma among children at age 5 years. Associations were examined using logistic regression analyses adjusting for parity, maternal educational level, maternal pre-pregnancy BMI, asthma predisposition and child sex.ResultsAmong the 5-year-old children 18.6% reported wheeze and 7.1% reported asthma. We found no association between prenatal exposure to PFAS and doctor-diagnosed asthma or wheeze. Prenatal PFAS exposure was associated with self-reported asthma, although only significant for PFNA (OR = 1.84, 95% CI 1.03,3.23).ConclusionOur findings support the suggested immunomodulatory effects of PFASs, however, additional studies are warranted. In order to verify our findings, it is important to re-examine the children with postnatal measurements of serum PFAS concentrations and additional clinical diagnostic testing at an older age where an asthma diagnosis is more valid.

Early-life exposure to multiple environmental contaminants and birth outcomes

OPS 16: Chemical exposures and birth outcomes, Room 114, Floor 1, August 28, 2019, 10:30 AM - 12:00 PM Background/Aim: Prenatal chemical exposure has frequently been associated with reduced fetal growth although results have been inconsistent. Most studies associate single pollutant exposure to these health outcomes, even though this does not reflect real life situations as humans are exposed to thousands pollutants during their life time. The objective of this study is to investigate the association between prenatal exposure to a mixture of persistent environmental chemicals and birth weight. Methods: We combined exposure biomarker data obtained from cord blood samples of 1579 women from three Flemish birth cohorts (FLEHS I, II & III) and a regional birth cohort (3xG). The common set of available and detectable exposure measures are three polychlorinated biphenyls (PCB) congeners (138, 153 and 180), hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (p,p’-DDE), cadmium and lead. Multiple linear regression (MLR), Bayesian Information Criterion (BIC), Elastic net (ENET) and Bayesian Adaptive Sampling (BAS) were applied to assess the influence of multiple pollutants on birth weight, adjusted for a priori selected covariates. Results: In the pooled database, birth weight ranged from 1245 to 5575 grams with a median of 3430 grams. The median contaminant levels in cord blood were: 15.8, 26.5, 18.0, 16.9 and 91.5 ng/g lipid for PCB 138, PCB 153, PCB 180, HCB and p,p’-DDE, respectively, 0.075 µg/L for cadmium and 9.7 µg/L for lead. Based on the four applied multipollutant statistical methods, p,p’-DDE and PCB 180 were most consistently associated to birth weight. Additionally, PCB 153 was selected when applying ENET and BAS. An inverse association with birth weight was found for the PCB congeners, while an increased birth weight was observed for elevated levels of p,p’-DDE. Conclusions: Assessing health risk of combinations of exposure biomarkers reflects better real-world situations. The findings allow more effective risk assessment as addressing the critical chemical in a mixture of pollutants is pivotal.

Multiple Persistent Environmental Chemicals at Low Concentrations Differentially Regulates Fatty Acids/Lipids in Wild Type and PPARAa−/− Mice

Many chemicals are detected in the environment at very low levels, they were viewed as being incapable of causing harm. Their risks to human health and associated environment are now emerging. But effects of their multiple interactions at cellular and molecular levels is unknown. We have investigated the effects of treatment of wild type and PPARα knockout mice on fatty acid contents in different organs. Mice were treated with low concentrations of multiple persistent environmental chemicals: atrazine, dieldrin, endrin, endosulfan and anthracene (1–100ng/L) in drinking water for six weeks and brain, liver, kidney, heart and spleen were collected, processed for fatty acid/lipid contents determination by GC/MS. The percentage changes in the levels of the fatty acid following treatment were calculated for wild type (WT) and PPARα −/− (KO). The changes (WT and KO) were compared to find the effects of treatment and the genetic (PPARα) influence on the regulation of fatty acid levels. Our results show differential presence of fatty acids: hexadecanoic acid, hexadecanoic acid methyl ester, hexadecanamide, 9‐octadecanemaide, pentadecanoic acid, octadecanoid acid, arachidonic acid, and cholesterol in the different organs as well as their differential regulation in the WT and KO. Results are summarized in Tables 1 and 2. Briefly, treatment increased 9‐octadecanemaide by 145% (WT) and 38% (KO) in the heart, reduced in the kidney 17% (WT), 29% (KO); hexadecanoic acid, octadecanoic acid was increased 0% (WT) but by 178% and 110% respectively (KO) (kidney), octadecanoic acid went up by 334% (KO) with not change in WT, hexadecanamide increased by 92% in KO Liver with 5% in WT. Generally, more perturbations in the regulation of the levels of fatty acid species in the KO than in the WT. These results indicate that multiple persistent environmental chemicals at low concentrations have limited effects on fatty acid dynamics in the WT but enhanced possible dysregulations in the PPARAα−/− mice.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Combined effects of pentachlorophenol and its byproduct hexachlorobenzene on endocrine and reproduction in zebrafish

Pentachlorophenol (PCP) and its byproduct hexachlorobenze (HCB) are two co-existing persistent environmental chemicals, but their combined toxicity remains unclear. In this study, adult zebrafish were exposed to 5 (low dose) and 25 μg·L−1 (high dose) of PCP, HCB or their combination for 21 days, and the impact on endocrine and reproduction was investigated. Results showed that combined exposure to 25 μg·L−1 PCP and 25 μg· L−1 HCB significantly increased the plasma estradiol (E2) and testosterone (T) levels, altered the expressions of genes along the hypothalamic-pituitary-gonadal-liver (HPGL) axis, inhibited gonadal development, and eventually lead to decreased egg production of F0 zebrafish as well as inhibited development of F1 eggs/larvae. Compared to the combined exposure of high doses, significantly lower levels of plasma E2 and T were observed for either the high PCP or high HCB alone exposure, indicating a synergistic effect of the two chemicals on endocrine disruption after combination. Furthermore, the high PCP alone exposure inhibited the gonadal development in both the males and females, while the HCB alone exposure did not. Comparison of exposure effects indicated a greater decrease of mature gametes levels and egg production in the high combined group when compared to the high HCB alone group, but no significant difference was observed between the high combined group and the high PCP alone group. Taken together, the results suggested that combined exposure to PCP and HCB may synergistically affect endocrine of zebrafish, and result in reproduction impairments, with PCP being the primary contributor.

Prenatal Exposure to Perfluoroalkyl Substances and Isomers Link to Depressed Toxoid Antibody Responses in Early Childhood: Guangzhou Birth Cohort Study

Background/Aim: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are ubiquitous and persistent environmental chemicals and are suggested to have immunosuppressive effects. Studies indicate that prenatal exposure to PFAS may lead to suppressed immune responses in early life. However, human studies of immune effects are inconsistent. In this study, we aim to assess the association between prenatal exposure of PFASs with isomers and serum antibody concentrations against measles, coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) toxoids in newborn and infant at 3 months. Methods: We recruited 295 pairs of mothers and their infants in Guangzhou Birth Cohort Study, China from July to October 2013. Measles IgG antibody was examined using ELISA assay, neutralizing antibodies titers against CA16, EV71 toxoids were performed in cord blood serum and infant aged 3 months, respectively. A PFAS isomer-specific analysis method based on high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) was applied to determine the PFASs and isomers concentration in cord blood serum. Results: For measles antibody, PFOA showed the strongest negative correlations with toxoid antibody concentration in newborn and 3-month infant. A doubling of lnPFOA level (ng/ml) increasing among newborn and 3-m infant was associated with a difference of -24.4% (95% CI: -30.7, -17.5) and -33.3% (95% CI: --43.9, -20.6) in measles antibody concentration, respectively. A doubling ln-unit (ng/ml) increase in total branch PFOS isomers in 3-month infant was associated with higher odds ratio of 1.70 (95%: 1.03, 2.79) and 2.49 (95%, 1.45, 4.28) than that with linear PFOS for falling below a clinically protection level (&lt;1_8 titers) for CA16 and EV71 antibody, respectively. This association was more obvious in boys than in girls. Interestingly, we observed that long-chain PFASs, such as perflouorotetradodecanoic acid (PFDoDA) and perfluoroundecanoic acid (PFUnDA) exposure were negatively associated with measles, CA16 and EV71 antibody level in both newborn and 3-month infant. Conclusions: Elevated prenatal exposures to PFASs, including long-chain PFASs were associated with depressed toxoid antibody response in newborn and infant. Branch isomer shows higher impact on CA16 and EV71 antibody level in 3-month infant for bellowing clinical protection.

Univariate predictors of maternal concentrations of environmental chemicals: The MIREC study.

The developing fetus and pregnant woman can be exposed to a variety of environmental chemicals that may adversely affect their health. Moreover, environmental exposure and risk disparities are associated with different social determinants, including socioeconomic status (SES) and demographic indicators. Our aim was to investigate whether and how maternal concentrations of a large panel of persistent and non-persistent environmental chemicals vary according to sociodemographic and lifestyle characteristics in a large pregnancy and birth cohort. Data were analyzed from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a cohort of pregnant women (N=2001) recruited over four years (2008-2011) in 10 cities across Canada. In all, 1890 urine and 1938 blood samples from the first trimester (1st and 3rd trimester for metals) were analysed and six sociodemographic and lifestyle indicators were assessed: maternal age, household income, parity, smoking status, country of birth and pre-pregnancy body mass index (BMI). We found these indicators to be significantly associated with many of the chemicals measured in maternal blood and urine. Women born outside Canada had significantly higher concentrations of di-2-ethylhexyl and diethyl phthalate metabolites, higher levels of all metals except cadmium (Cd), as well as higher levels of polychlorinated biphenyls (PCBs) and legacy organochlorine pesticides (OCPs). Nulliparity was associated with higher concentrations of dialkyl phosphates (DAPs), arsenic, dimethylarsinic acid (DMAA), perfluoroalkyl substances (PFASs) and many of the persistent organic pollutants. Smokers had higher levels of bisphenol A, Cd and perfluorohexane sulfonate, while those women who had never smoked had higher levels of triclosan, DMAA, manganese and some OCPs. Our results demonstrated that inequitable distribution of exposure to chemicals among populations within a country can occur. Sociodemographic and lifestyle factors are an important component of a thorough risk assessment as they can impact the degree of exposure and may modify the individual's susceptibility to potential health effects due to differences in lifestyle, cultural diets, and aging.

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis.

BACKGROUNDMore than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders.OBJECTIVE AND RATIONALEThe aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism.SEARCH METHODSA systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data.OUTCOMESThe literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74). The data did not indicate that this increased risk was driven by any specific disorder.WIDER IMPLICATIONSThe current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure–response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure–outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.

Philippe Grandjean is the 2015 BCPT Nordic Prize Awardee.

Philippe Grandjean is the 2015 BCPT Nordic Prize Awardee.

Paternal exposures to environmental chemicals and time-to-pregnancy: overview of results from the LIFE study.

Published findings from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study regarding the relation between environmental chemicals and couple fecundity, as measured by time-to-pregnancy (TTP), are reviewed with a particular focus on role of the male partner. The LIFE Study recruited 501 couples from 16 counties in two U.S. states upon discontinuing contraception for purposes of becoming pregnant. Upon enrollment, couples provided a blood and urine sample for the quantification of persistent and non-persistent environmental chemicals, respectively, and then completed daily journals until pregnant or up to one year of trying. Female partners used fertility monitors to aid the timing of intercourse relative to ovulation, and digital home pregnancy test kits on the day of expected menses. Chemical classes included: metals, persistent organic pollutants, environmental phenols, and phthalates that were quantified using inductively coupled plasma mass spectrometry or isotope dilution high-resolution or tandem mass spectrometry. Time-to-pregnancy (TTP) was defined as the number of prospectively observed menstrual cycles required for pregnancy. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for each chemical and partner after adjusting for potential confounders and accounting for right censoring and time off contraception. FORs<1 are suggestive of diminished fecundity or a longer TTP. Significant reductions (ranging from 17-31%) in couple fecundity were observed for male partners' concentration of lead (0.83; 0.70, 0.98), 2,2',4,4'-tetrahydroxybenzophenone (0.69; 0.49, 0.97), monobenzyl (0.80; 0.67, 0.97), and monomethyl (0.81; 0.70, 0.94) phthalates after adjusting for the female partners' concentrations. Seven PCB congeners quantified in men's serum were associated with a 17-29% reduction in couple fecundity. Our findings underscore the importance of a couple-based exposure design, inclusive of the male partner, when assessing couple-dependent outcomes such as TTP to avoid misinterpretation of results based only upon the female partner.

Organochlorine pesticide levels in maternal blood and placental tissue with reference to preterm birth: a recent trend in North Indian population.

Organochlorine pesticides (OCPs) have been widely used in public health and agriculture programs in developed as well as developing countries, including India. Being xenoestrogenic in nature, OCPs may act as endocrine disruptors leading to preterm birth (PTB) through disturbance of normal estrogen-progesterone ratio. PTB is the leading cause of neonatal deaths worldwide. Therefore, the present study is aimed to determine the extent to which persistent environmental chemicals may accumulate in pregnant women and placenta and ascertain possible associations between exposure level and period of gestation (POG), baby weight, and/or placental weight in PTB cases. Maternal blood and placenta samples of PTB cases (n = 50) and subjects of term delivery as controls (n = 50) were collected. OCP residue levels were estimated by the gas chromatography system equipped with an electron capture detector. Significantly higher levels of α-hexachlorocyclohexane (α-HCH), β-hexachlorocyclohexane (β-HCH), dichlorodiphenyldichloroethane (DDD), and dichlorodiphenyldichloroethylene (DDE) were found in maternal blood of PTB cases as compared to control. Significantly higher levels of DDE and dichlorodiphenyltrichloroethane (DDT) were also found in placental tissue of PTB cases as compared to control group. There was a statistically significant negative correlation between maternal blood level of α-HCH and birth-weight (r = -0.299) and POG (r = -0.234). γ-Hexachlorocyclohexane (γ-HCH) and dieldrin had a negative correlation with placental weight (r = -0.401 and -0.256, respectively), and DDE and β-HCH had a negative correlation with POG (r = -0.251 and -0.229, respectively). The presence of OCPs in maternal blood and placental tissue represents prenatal exposure hazard for fetuses due to chronic bioaccumulation and poor elimination with possible deleterious effect on health.

Maternal and paternal serum concentrations of perfluoroalkyl and polyfluoroalkyl substances and the secondary sex ratio

Select persistent environmental chemicals have been associated with a reduction in the secondary sex ratio (SSR), or the ratio of male to female live births. We evaluated preconception maternal, paternal, and couple serum concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in relation to the SSR, given the absence of previous investigation. Two hundred thirty-three couples from Michigan and Texas were enrolled prior to conception and prospectively followed through delivery of a singleton birth, 2005–2009. Maternal and paternal serum concentrations (ngmL−1) were measured at baseline for seven PFASs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a male birth, after adjusting for potential confounders. When maternal and paternal PFAS concentrations were modeled jointly, five of the seven PFASs, including the two most prominent PFASs, perfluorooctane sulfonic acid and perfluorooctanoic acid, were not significantly associated with the SSR. However, paternal N-methyl-perfluorooctane sulfonamidoacetic acid (MeFOSAA) and perfluorononanoic acid (2nd versus 1st tertile, OR, 0.43, 95% CI, 0.21–0.88) were significantly associated with an excess of female births. Meanwhile, a dose–response relation was observed only for paternal MeFOSAA (2nd versus 1st tertile, OR, 0.53, 95% CI, 0.26–1.10; 3rd versus 1st tertile, OR, 0.34, 95% CI, 0.13–0.89). This study suggests a possible dose–response relation between a less prevalent PFAS and a reversal in the SSR, though the underlying mechanisms remain unknown and the findings await corroboration to eliminate other explanations including chance.

Pediatric Exposures to Persistent Environmental Chemicals

Traditional risk factors are responsible for about 70% of the population attributable risk of Cardiovascular Disease (CVD).1 Common environmental exposures are known to be responsible for some portion of the remaining 30%. Therefore, it is important to study chemicals like the class known as Perfluoroalkyl Chemicals (PFCs) or Perfluoroalkyl Substances (PSASs). Two of the most highly studied PFCs are Perfluorooctanoic Acid (PFOA or C8) and Perfluorooctane Sulfonate (PFOS or C8S). PFCs are persistent in the environment and associations have been shown with a whole host of negative health outcomes in laboratory animals, including endocrine-disrupting properties as well as developmental effects.2 To make matters worse, PFCs have been detected in the blood of >98% of the US population3 and epidemiological studies have demonstrated associations between PFOA and PFOS, and many negative health outcomes such as cancer,4 CVD,5 osteoarthritis,6 hyperuricemia,7 pregnancy-induced hypertension,8 endocrine disruption,9 dyslipidemia,10,11 and reproductive effects,12,13 often times even at baseline levels typical of the general population’s exposure level.