Environmental Chemical Exposures Research Articles

Influence of body mass index status on urinary creatinine and specific gravity for epidemiological study of children

In epidemiological studies, urinary biomonitoring is a valid approach to assess the association between environmental chemical exposure and children's health. Many clinical biomarkers (e.g., endogenous metabolites) are also based on analysis of urine. Considering the variability in urinary output, urinary concentrations of chemicals are commonly adjusted by creatinine and specific gravity (SG). However, there is a lack of systematic evaluation of their appropriateness for children. Furthermore, urinary SG and creatinine excretion could be influenced by body mass index (BMI), but the effect of BMI status on the two correction factors is unknown. We measured SG and creatinine concentrations of repeated first morning urine samples collected from 243 primary school children (8-11 years) over 5 consecutive weekdays. Urinary SG presented a higher temporal consistency compared with creatinine. Urinary SG was associated with sex (p < 0.001), whereas sex (p =0.034) and BMI (p = 00.008) were associated with urinary creatinine levels. Inter-day collection time was not associated with SG or creatinine after excluding the effect of Monday as a confounder. When stratified by BMI status, none of the factors were associated with creatinine among the overweight and obese children. Generally, SG is preferable for correcting the variability in urinary output for children although creatinine correction may also perform well in overweight and obese children. SG correction is recommended for epidemiological exposure analysis in children based on urinary levels of exogenous or endogenous metabolites.

English

Maternal environmental exposures to certain specific chemicals during early pregnancy, including pesticides, air pollutants and others, are known to increase the incidence of autism and autism spectrum disorder in offspring. The prevalence of these diseases can be reduced by taking steps to reduce environmental chemical exposures. Obstetricians and family practice physicians typically counsel patients on good health practices during pregnancy, including proper nutrition, the need for exercise, weight control, avoidance of drugs and other safeguards. It is proposed here that physician counseling of patients include information about the identification and avoidance of exposures to environmental neurotoxins that have been identified as causative agents for autism and autism spectrum disorder and that such counseling will lead to a decrease in the incidence of these diseases.

Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study.

BackgroundThere are several suspected environmental risk factors for non-Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical exposures have typically been evaluated for individual chemicals (i.e., one-by-one).ObjectivesWe determined the association between a mixture of 27 correlated chemicals measured in house dust and NHL risk.MethodsWe conducted a population-based case–control study of NHL in four National Cancer Institute–Surveillance, Epidemiology, and End Results centers—Detroit, Michigan; Iowa; Los Angeles County, California; and Seattle, Washington—from 1998 to 2000. We used weighted quantile sum (WQS) regression to model the association of a mixture of chemicals and risk of NHL. The WQS index was a sum of weighted quartiles for 5 polychlorinated biphenyls (PCBs), 7 polycyclic aromatic hydrocarbons (PAHs), and 15 pesticides. We estimated chemical mixture weights and effects for study sites combined and for each site individually, and also for histologic subtypes of NHL.ResultsThe WQS index was statistically significantly associated with NHL overall [odds ratio (OR) = 1.30; 95% CI: 1.08, 1.56; p = 0.006; for one quartile increase] and in the study sites of Detroit (OR = 1.71; 95% CI: 1.02, 2.92; p = 0.045), Los Angeles (OR = 1.44; 95% CI: 1.00, 2.08; p = 0.049), and Iowa (OR = 1.76; 95% CI: 1.23, 2.53; p = 0.002). The index was marginally statistically significant in Seattle (OR = 1.39; 95% CI: 0.97, 1.99; p = 0.071). The most highly weighted chemicals for predicting risk overall were PCB congener 180 and propoxur. Highly weighted chemicals varied by study site; PCBs were more highly weighted in Detroit, and pesticides were more highly weighted in Iowa.ConclusionsAn index of chemical mixtures was significantly associated with NHL. Our results show the importance of evaluating chemical mixtures when studying cancer risk.CitationCzarnota J, Gennings C, Colt JS, De Roos AJ, Cerhan JR, Severson RK, Hartge P, Ward MH, Wheeler DC. 2015. Analysis of environmental chemical mixtures and non-Hodgkin lymphoma risk in the NCI-SEER NHL Study. Environ Health Perspect 123:965–970; http://dx.doi.org/10.1289/ehp.1408630

The impact of prenatal parental tobacco smoking on risk of diabetes mellitus in middle-aged women.

Growing evidence indicates that parental smoking is associated with risk of offspring obesity. The purpose of this study was to identify whether parental tobacco smoking during gestation was associated with risk of diabetes mellitus. This is a prospective study of 44- to 54-year-old daughters (n = 1801) born in the Child Health and Development Studies pregnancy cohort between 1959 and 1967. Their mothers resided near Oakland California, were members of the Kaiser Foundation Health Plan and reported parental tobacco smoking during an early pregnancy interview. Daughters reported physician diagnoses of diabetes mellitus and provided blood samples for hemoglobin A1C measurement. Prenatal maternal smoking had a stronger association with daughters' diabetes mellitus risk than prenatal paternal smoking, and the former persisted after adjustment for parental race, diabetes and employment (aRR = 2.4 [95% confidence intervals 1.4-4.1] P < 0.01 and aRR = 1.7 [95% confidence intervals 1.0-3.0] P = 0.05, respectively). Estimates of the effect of parental smoking were unchanged when further adjusted by daughters' birth weight or current body mass index (BMI). Maternal smoking was also significantly associated with self-reported type 2 diabetes diagnosis (2.3 [95% confidence intervals 1.0-5.0] P < 0.05). Having parents who smoked during pregnancy was associated with an increased risk of diabetes mellitus among adult daughters, independent of known risk factors, providing further evidence that prenatal environmental chemical exposures independent of birth weight and current BMI may contribute to adult diabetes mellitus. While other studies seek to confirm our results, caution toward tobacco smoking by or proximal to pregnant women is warranted in diabetes mellitus prevention efforts.

Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy.

To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM). Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine phthalate metabolites and creatinine were measured at the US Centers for Disease Control and Prevention. Associations between tertiles of phthalate metabolites concentrations and blood glucose levels were estimated using linear regression. Compared to pregnant women in the lowest concentration tertile, women with the highest urinary concentrations (≥ 3 rd tertile) of mono-iso-butyl phthalate (tertile: ≥ 15.3 μg/l, β = -18.3, 95% CI: -35.4, -1.2) and monobenzyl phthalate (tertile: ≥ 30.3 μg/l, β = -17.3, 95% CI: -34.1, -0.4) had lower blood glucose levels at the time of GDM screening after adjustment for urinary creatinine and demographic covariates. Because maternal glucose levels increase during pregnancy to provide adequate nutrition for fetal growth and development, these findings may have implications for fetal health. However, given the limitations of our study, findings should be interpreted cautiously.

Statistical methods for modeling repeated measures of maternal environmental exposure biomarkers during pregnancy in association with preterm birth.

BackgroundIt is of critical importance to evaluate the role of environmental chemical exposures in premature birth. While a number of studies investigate this relationship, most utilize single exposure measurements during pregnancy in association with the outcome. The studies with repeated measures of exposure during pregnancy employ primarily cross-sectional analyses that may not be fully leveraging the power and additional information that the data provide.MethodsWe examine 9 statistical methods that may be utilized to estimate the relationship between a longitudinal exposure and a binary, non-time-varying outcome. To exemplify these methods we utilized data from a nested case–control study examining repeated measures of urinary phthalate metabolites during pregnancy in association with preterm birth.ResultsThe methods summarized may be useful for: 1) Examining sensitive windows of exposure in association with an outcome; 2) Summarizing repeated measures to estimate the relationship between average exposure and an outcome; 3) Identifying acute exposures that may be relevant to the outcome; and 4) Understanding the contribution of temporal patterns in exposure levels to the outcome of interest. In the study of phthalates, changes in urinary metabolites over pregnancy did not appear to contribute significantly to preterm birth, making summary of average exposure across gestation optimal given the current design.ConclusionsThe methods exemplified may be of great use in future epidemiologic research projects intended to: 1) Elucidate the complex relationships between environmental chemical exposures and preterm birth; 2) Investigate biological mechanisms in prematurity using repeated measures of maternal factors throughout pregnancy; and 3) More generally, address the relationship between a longitudinal predictor and a binary, non-time-varying outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-069X-14-9) contains supplementary material, which is available to authorized users.

Human and Environmental Toxicity of Sodium Lauryl Sulfate (SLS): Evidence for Safe Use in Household Cleaning Products.

Environmental chemical exposure is a major concern for consumers of packaged goods. The complexity of chemical nomenclature and wide availability of scientific research provide detailed information but lends itself to misinterpretation by the lay person. For the surfactant sodium lauryl sulfate (SLS), this has resulted in a misunderstanding of the environmental health impact of the chemical and statements in the media that are not scientifically supported. This review demonstrates how scientific works can be misinterpreted and used in a manner that was not intended by the authors, while simultaneously providing insight into the true environmental health impact of SLS. SLS is an anionic surfactant commonly used in consumer household cleaning products. For decades, this chemical has been developing a negative reputation with consumers because of inaccurate interpretations of the scientific literature and confusion between SLS and chemicals with similar names. Here, we review the human and environmental toxicity profiles of SLS and demonstrate that it is safe for use in consumer household cleaning products.

Role of Environmental Chemical Insult in Neuronal Cell Death and Cytoskeleton Damage.

Environmental influences, such as chemical exposure, have long been considered potential risk factors for neurodegenerative disorders, including neuromuscular diseases. However, no definitive links between environmental chemical exposure and a pathogenic mechanism of neurodegenerative disease has yet been established. In this study, we describe that exposure to arsenic, an environmental pollutant naturally found in drinking water, induces neuronal cell death and alteration of morphology, particularly neurite outgrowth and in the cytoskeleton of neurons. Since progressive cell loss accompanied by the alteration of neuronal structures and cytoskeleton is considered the major pathologic feature of neurodegenerative disorders, arsenic-induced neurotoxicity might contribute to an etiologic mechanism of some neurodegenerative diseases. Further, we discuss the importance of in vitro assay, particularly an embryonic toxicity test, for assessing the neurotoxicity of chemicals, because most of chemicals found in our environment remain to be evaluated regarding their neurotoxicity risk for neurodegenerative diseases.

Can exposure to environmental chemicals increase the risk of diabetes type 1 development?

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged.

Evaluating geographically weighted regression models for environmental chemical risk analysis.

In the evaluation of cancer risk related to environmental chemical exposures, the effect of many correlated chemicals on disease is often of interest. The relationship between correlated environmental chemicals and health effects is not always constant across a study area, as exposure levels may change spatially due to various environmental factors. Geographically weighted regression (GWR) has been proposed to model spatially varying effects. However, concerns about collinearity effects, including regression coefficient sign reversal (ie, reversal paradox), may limit the applicability of GWR for environmental chemical risk analysis. A penalized version of GWR, the geographically weighted lasso, has been proposed to remediate the collinearity effects in GWR models. Our focus in this study was on assessing through a simulation study the ability of GWR and GWL to correctly identify spatially varying chemical effects for a mixture of correlated chemicals within a study area. Our results showed that GWR suffered from the reversal paradox, while GWL overpenalized the effects for the chemical most strongly related to the outcome.

Assessment of weighted quantile sum regression for modeling chemical mixtures and cancer risk.

In evaluation of cancer risk related to environmental chemical exposures, the effect of many chemicals on disease is ultimately of interest. However, because of potentially strong correlations among chemicals that occur together, traditional regression methods suffer from collinearity effects, including regression coefficient sign reversal and variance inflation. In addition, penalized regression methods designed to remediate collinearity may have limitations in selecting the truly bad actors among many correlated components. The recently proposed method of weighted quantile sum (WQS) regression attempts to overcome these problems by estimating a body burden index, which identifies important chemicals in a mixture of correlated environmental chemicals. Our focus was on assessing through simulation studies the accuracy of WQS regression in detecting subsets of chemicals associated with health outcomes (binary and continuous) in site-specific analyses and in non-site-specific analyses. We also evaluated the performance of the penalized regression methods of lasso, adaptive lasso, and elastic net in correctly classifying chemicals as bad actors or unrelated to the outcome. We based the simulation study on data from the National Cancer Institute Surveillance Epidemiology and End Results Program (NCI-SEER) case–control study of non-Hodgkin lymphoma (NHL) to achieve realistic exposure situations. Our results showed that WQS regression had good sensitivity and specificity across a variety of conditions considered in this study. The shrinkage methods had a tendency to incorrectly identify a large number of components, especially in the case of strong association with the outcome.

Selecting spatial scale of covariates in regression models of environmental exposures.

Environmental factors or socioeconomic status variables used in regression models to explain environmental chemical exposures or health outcomes are often in practice modeled at the same buffer distance or spatial scale. In this paper, we present four model selection algorithms that select the best spatial scale for each buffer-based or area-level covariate. Contamination of drinking water by nitrate is a growing problem in agricultural areas of the United States, as ingested nitrate can lead to the endogenous formation of N-nitroso compounds, which are potent carcinogens. We applied our methods to model nitrate levels in private wells in Iowa. We found that environmental variables were selected at different spatial scales and that a model allowing spatial scale to vary across covariates provided the best goodness of fit. Our methods can be applied to investigate the association between environmental risk factors available at multiple spatial scales or buffer distances and measures of disease, including cancers.

Environmental chemical exposure may contribute to uterine cancer development: studies with tetrabromobisphenol A.

Tetrabromobisphenol A (TBBPA), a widely used flame retardant, caused uterine tumors in rats. In this study, TBBPA was administered to male and female Wistar Han rats and B6C3F1/N mice by oral gavage in corn oil for 2 years at doses up to 1,000 mg/kg. TBBPA induced uterine epithelial tumors including adenomas, adenocarcinomas, and malignant mixed Müllerian tumors (MMMTs). In addition, endometrial epithelial atypical hyperplasia occurred in TBBPA-treated rats. Also found to be related to TBBPA treatment, but at lower incidence and at a lower statistical significance, were testicular tumors in rats, and hepatic tumors, hemangiosarcomas (all organs), and intestinal tumors in male mice. It is hypothesized that the TBBPA uterine tumor carcinogenic mechanisms involve altered estrogen levels and/or oxidative damage. TBBPA treatment may affect hydroxysteroid-dehydrogenase-17β (HSD17β) and/or sulfotransferases, enzymes involved in estrogen homeostasis. Metabolism of TBBPA may also result in the formation of free radicals. The finding of TBBPA-mediated uterine cancer in rats is of concern because TBBPA exposure is widespread and endometrial tumors are a common malignancy in women. Further work is needed to understand TBBPA cancer mechanisms.

Evolution of DOHaD: the impact of environmental health sciences.

Environmental exposures have a significant influence on the chronic health conditions plaguing children and adults. Although the Developmental Origins of Health and Disease (DOHaD) paradigm historically has focused on nutrition, an expanding body of research specifically communicates the effects of chemical exposures on early-life development and the propagation of non-communicable disease across the lifespan. This paper provides an overview of 20 years of research efforts aimed at identifying critical windows of susceptibility to environmental exposures and the signaling changes and epigenetic influences associated with disease progression. DOHaD grants funded by the National Institute of Environmental Health Sciences (NIEHS) in 1991, 2001 and 2011 are identified by grant-analysis software, and each portfolio is analyzed for exposures, disease endpoints, windows of exposure, study design and impact on the field based on publication data. Results show that the 1991 and 2001 portfolios comprised metals, PCBs and air pollutants; however, by 2011, the portfolio has evolved to include or expand the variety of endocrine disruptors, pesticides/persistent organic pollutants and metals. An assortment of brain-health endpoints is most targeted across the portfolios, whereas reproduction and cancer increase steadily over the same time period, and new endpoints like obesity are introduced by 2011. With mounting evidence connecting early-life exposures to later-life disease, we conclude that it is critical to expand the original DOHaD concept to include environmental chemical exposures, and to continue a research agenda that emphasizes defining sensitive windows of exposure and the mechanisms that cause disease.

Editorial Effect of Epi-drugs on Epigenetic Modifications Induced by Environmental Pollutants: Implications for the Pathophysiology of Cancer and Endocrine/metabolic Diseases.

It is my pleasure to be the guest editor for the special issue focused on “Effect of epi-drugs on epigenetic modifications induced by environmental pollutants: implications for the pathophysiology of cancer and endocrine/metabolic diseases”. We are now living in the “epigenomic era” and are faced with a growing number of information about all the DNA-external factors that control gene expression of regulatory proteins. Most epimutations, including changes in DNA methylation, histone modifications, and microRNA levels, translate into either up-regulation or silencing of gene expression which, in turn, may predispose the organism to mutational events, reduced ability to repair DNA damage, increased genomic instability, altered cellular response, and reduced apoptosis. Over the last decades, rapidly increasing evidence has connected environmental pollutants with epigenetic variations that may occur in a wide spectrum of diseases, including a variety of tumors and metabolic disorders. For these reasons, several clinical trials employing epi-drugs are underway or planned especially in areas exposed to environmental contaminants. Agents regulating histone deacetylases (HDACs), DNA methyltransferases (DNMTs), or miRNA expression profiles are proving to represent a good alternative for treating pollutant-induced diseases. This special thematic issue takes into account: i) the epigenetic alterations induced by environmental chemical exposures and the underlying mechanisms; ii) their impact on human health; iii) the association with carcinogenesis, deregulation of cell cycle and apoptosis, altered mitochondrial function, energy metabolism, and impairment of the development process; iv) the biomarkers relevant in establishing the environmental health risk and response to treatment. The data reported in this issue will give opportunities, challenges and future directions for epidemiology research in environmental epigenomics coupled to neoplastic, metabolic, and developmental diseases. Understanding the nature and the role of environmental pollutants on the epigenetic interactions and assessing correctly the risk of incidence of severe conditions that threaten the health and life expectancy represent a major challenge for basic and translational research. These acquisitions will further strengthen the precondition for the development of therapeutic strategies aimed at reversing the epigenetic damage induced by environmental pollutants.

Differential environmental exposure among non-Indigenous Canadians as a function of sex/gender and race/ethnicity variables: a scoping review.

To determine the extent, range and types of studies of differential environmental chemical exposures among non-Indigenous Canadians as a function of sex/gender and race/ethnicity. Computerized database searches were performed from November to December 2013 using Medline, Embase, CAB Abstracts, Proquest and Scopus to identify relevant studies of environmental exposures among non-Indigenous adults aged ≥18 years in Canada published between 1993 and 2013. Articles were identified for full-text review based on a screening of titles and abstracts and were excluded during this initial review if they focused on environmental exposures in the following populations: 1) Indigenous populations, 2) individuals &lt;15 years of age, 3) pregnant women and associated negative birth outcomes, or 4) non-Canadian populations. Articles were also excluded if the primary focus was on exposures to environmental tobacco smoke, non-chemical occupational hazards, infectious diseases, noise and/or radiation. A full-text review of 78 identified articles systematically assessed how sex/gender and race/ethnicity were considered. Although 59% of studies stratified results by sex, less than half of these offered any explanation of differential exposures. Eighteen of the 78 studies (23%) used terms related to race/ethnicity in their participant descriptions. Of the studies that conducted subgroup analyses of exposure results by race/ethnicity (n=15), a total of 8 also included subgroup analysis by sex. Overall, 3 of the 78 (3%) articles reviewed analyzed environmental exposures as a function of sex/gender and race/ethnicity. The role of sex/gender and race/ethnicity in influencing environmental exposure levels among non-Indigenous Canadians has not been adequately addressed to date.

Environmental Chemical Exposure in the Neonatal Intensive Care Unit

Introduction: Preterm infants admitted to the neonatal intensive care unit (NICU) are exposed to the chemical-laden hospital environment during a developmentally sensitive time period. Epidemiologic studies show an association between in utero exposure to common organic chemicals and suboptimal intrauterine growth. Animal studies show an association between exposure to organic chemicals and poor growth in infancy. Hypothesis: Environmental chemical exposure in the NICU is associated with poor growth velocity during the NICU hospitalization. Method: We conducted a pilot prospective observational study of 20 preterm infants admitted to a tertiary care NICU. Data on 61 more subjects are pending analyses. We collected serial urine specimens and compared biomarkers of 25 organic chemicals to growth parameters from birth to discharge (22-131days, median 49). We fitted a multivariable-adjusted functional mixed model with penalized splines for each chemical to identify the effect on growth during the NICU hospitalization. Result: Biomarkers of methyl-paraben and monoethyl phthalate were inversely associated with weight gain. This effect was seen even at low urinary biomarker levels (median (ng/mL) = 14.98; 11.52). As with nutritional growth restriction, height and head circumference were not impacted. Conclusion: Our findings indicate an inverse association between phthalate and paraben exposure and growth in hospitalized preterm neonates. As weight gain during infancy is an important predictor of neurodevelopmental outcome, these findings have potential implications to NICU care.

Mediation of the Relationship between Phthalate Exposure and Preterm Birth by Oxidative Stress

Mediation of the Relationship between Phthalate Exposure and Preterm Birth by Oxidative StressAbstract Number:2475 Kelly Ferguson*, Thomas McElrath, Yin-Hsiu Chen, Bhramar Mukherjee, John Meeker Kelly Ferguson* University of Michigan, United States, E-mail Address: [email protected] Search for more papers by this author , Thomas McElrath Brigham and Women's Hospital, United States, E-mail Address: [email protected] Search for more papers by this author , Yin-Hsiu Chen University of Michigan, United States, E-mail Address: [email protected] Search for more papers by this author , Bhramar Mukherjee University of Michigan, United States, E-mail Address: [email protected] Search for more papers by this author , and John Meeker University of Michigan, United States, E-mail Address: [email protected] Search for more papers by this author AbstractPhthalate exposure has been linked to preterm birth in a number of studies, but the underlying mechanism remains unclear. We examined the role of oxidative stress as a mediator in the relationship between phthalate exposure across pregnancy and preterm birth in a nested case-control study of women selected from a prospective birth cohort at Brigham and Women’s Hospital in Boston, MA (N=130 cases, 352 controls). Phthalate metabolites were measured in urine samples collected from multiple study visits (median 3.5 samples per subject). Oxidative stress was assessed by 8-isoprostane, a marker of lipid peroxidation, also measured in repeated urine samples. Subject-specific averages of phthalate metabolites and of 8-isoprostane were created for more stable measures of phthalate exposure and oxidative stress during pregnancy. Preterm birth was defined as delivery before 37 weeks, and we also examined spontaneous preterm births alone, as phthalate exposure was more strongly associated with this subset of cases. We established that: 1) phthalate metabolite levels were associated with increased odds of preterm birth; 2) phthalate metabolite levels were associated with increased 8- isoprostane during pregnancy; and 3) 8-isoprostane concentrations were associated with increased odds of preterm birth after adjustment for phthalate metabolite in the same model. We performed a mediation analysis to estimate the proportion of the phthalate- preterm relationship that was mediated by 8-isoprostane. Associations between di-2- ethylhexyl phthalate (DEHP) metabolites and overall preterm birth were 21-29% mediated by 8-isoprostane. Mediation was stronger for phthalate associations with spontaneous preterm birth (ranging between 24-46% for DEHP metabolites). This study is the first to identify through mediation analysis a mechanism between an environmental chemical exposure and preterm birth, and future use of this analysis may be particularly useful as animal models of prematurity are poor.

Environmental Chemical Exposures and Autism Spectrum Disorders: A Review of the Epidemiological Evidence

In the past decade, the number of epidemiological publications addressing environmental chemical exposures and autism has grown tremendously. These studies are important because it is now understood that environmental factors play a larger role in causing autism than previously thought and because they address modifiable risk factors that may open up avenues for the primary prevention of the disability associated with autism. In this review, we covered studies of autism and estimates of exposure to tobacco, air pollutants, volatile organic compounds and solvents, metals (from air, occupation, diet, dental amalgams, and thimerosal-containing vaccines), pesticides, and organic endocrine-disrupting compounds such as flame retardants, non-stick chemicals, phthalates, and bisphenol A. We included studies that had individual-level data on autism, exposure measures pertaining to pregnancy or the 1st year of life, valid comparison groups, control for confounders, and adequate sample sizes. Despite the inherent error in the measurement of many of these environmental exposures, which is likely to attenuate observed associations, some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates. Whether any of these play a causal role requires further study. Given the limited scope of these publications, other environmental chemicals cannot be ruled out, but have not yet been adequately studied. Future research that addresses these and additional environmental chemicals, including their most common routes of exposures, with accurate exposure measurement pertaining to several developmental windows, is essential to guide efforts for the prevention of the neurodevelopmental damage that manifests in autism symptoms.

Human biomonitoring to assess environmental chemical exposures: work towards a UK framework.

PHE's Centre for Radiation, Chemical and Environmental Hazards (CRCE) provides advice, develops guidance and is involved in research in order to advance understanding on radiation, chemical and environmental hazards at international, national, regional and local levels. As part of PHE's responsibility to protect the public from chemical hazards, CRCE provides toxicological advice on exposures to chemicals, poisons and environmental toxins, and engages with international initiatives to coordinate information acquisition, regulation and management of these exposures. A useful tool to assess human exposure to existing and emerging environmental substances and in some cases, their potential health risks, is human biomonitoring (HBM).HBM involves the collection of biological samples, such as urine, blood and hair, from volunteers to measure markers of exposure to (or the effects of) chemicals known as biomarkers.1 The UK does not have a national study for HBM so PHE plans to develop national protocols and a national framework. Evaluating human exposure in this way will support the elaboration of background levels and guidance values, which will facilitate, for example, the identification of potential high exposure populations or subpopulations and lead to policy interventions and focused research projects.In order to help develop a national framework and to ensure useful comparisons with other studies, PHE has been involved in two sister European research consortia, which were formed after the European Environment and Health Action Plan 2004-2010 called for the development of a coherent approach to biomonitoring in Europe (Action 3).2 The Consortium to Perform Human biomonitoring on a European Scale (COPHES) developed a European Union (EU) HBM framework to enable the collection of comparable biomonitoring data throughout Europe and DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale), a collaborative pilot study, which demonstrated/tested the protocols produced by COPHES by measuring biomarkers of cadmium, mercury, phthalates and environmental tobacco smoke in the general public. For the first time in the EU, a common approach for HBM surveys has been tested by the twin consortia COPHES/DEMOCOPHES. A brief overview of the results from the studies was presented at the PHE conference in September 2013.THE CONSORTIUM TO PERFORM HUMAN BIOMONITORING ON A EUROPEAN SCALE (COPHES)Funded by the European Community's Seventh Framework Programme, COPHES developed an EU HBM framework that will allow for cross-boundary evaluation of human exposure and can also be used to enable the integration of human biomarker data with environmental and health information, elaborate background levels and guidance values and ultimately support the evaluation of environment and health policy. The approach for designing and conducting the study and implementing the fieldwork procedures is detailed elsewhere.3 The harmonized study protocols included recruitment, fieldwork, sampling, chemical analysis, as well as guidance on the ethical aspects specific for the collection and storage of human material and biomarker data, a training and capacity building programme and an extended communication strategy.4When the harmonized protocols were tested, in collaboration with DEMOCOPHES, the laboratories analysing the samples were selected through a strict quality assurance process, comprising Inter-laboratory Comparison Investigations (ICI) and External Quality Assessment Schemes (EQUAS) run by COPHES.5 In addition to statistical analysis and interpretation of the results from each country, COPHES analysed the data at EU level in compliance with data protection rules and regulations for each country. Support, including a help desk and training, was provided by COPHES to all participating countries.DEMONSTRATION OF A STUDY TO COORDINATE AND PERFORM HUMAN BIOMONITORING ON A EUROPEAN SCALE (DEMOCOPHES)The pilot study assessed the levels of cadmium, cotinine and five phthalate metabolites in urine samples and mercury in hair samples. …