Showing papers in "Environmental Health in 2015"

Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment

Abstract: Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships with endocrine disruptors. Fifty-one experimental studies that investigated various effects associated with endocrine disruption elicited by many substances were selected. Scoring criteria were applied by adaptation of an approach previously used for identification of hormesis-type dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were categorized with this method as having a “moderate” to “high” level of plausibility for various effects. Numerous modes of action described in the literature can explain such phenomena. NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation. A stepwise decision tree was developed as a tool to standardize the analysis of NMDR relationships observed in the literature with the final aim to use these results in a Risk Assessment purpose. This decision tree was finally applied to studies focused on the effects of bisphenol A.

Bisphenol A and the risk of cardiometabolic disorders: a systematic review with meta-analysis of the epidemiological evidence

Abstract: Bisphenol A (BPA) is suspected to be associated with several chronic metabolic diseases. The aim of the present study was to review the epidemiological literature on the relation between BPA exposure and the risk of cardiometabolic disorders. PubMed and Embase databases were searched up to August 2014 by two independent investigators using standardized subject terms. We included observational studies (cohort, case–control and cross-sectional studies) carried out in children or adults, measuring urinary BPA (uBPA), including at least 100 participants and published in English. The health outcomes of interest were diabetes, hyperglycemia, measures of anthropometry, cardiovascular disease (CVD) and hypertension. Data were extracted and meta-analyzed when feasible, using a random-effects model. Thirty-three studies with sample size ranging from 239 to 4811 met the inclusion criteria, including five with a prospective design. Twelve studies reported on diabetes or hyperglycemia, 16 on anthropometry, 6 on CVD and 3 on hypertension. Evidence for a positive association between uBPA concentrations and diabetes, overweight, obesity, elevated waist circumference (WC), CVD and hypertension was found in 7/8, 2/7, 6/7, 5/5, 4/5 and 2/3 of the cross-sectional studies, respectively. We were able to conduct outcome-specific meta-analyses including 12 studies. When comparing the highest vs. the lowest uBPA concentrations, the pooled ORs were 1.47 (95 % CI: 1.21–1.80) for diabetes, 1.21 (95 % CI: 0.98–1.50) for overweight, 1.67 (95 % CI: 1.41–1.98) for obesity, 1.48 (95 % CI: 1.25–1.76) for elevated WC, and 1.41 (95 % CI: 1.12–1.79) for hypertension. Moreover, among the five prospective studies, 3 reported significant findings, relating BPA exposure to incident diabetes, incident coronary artery disease, and weight gain. To conclude, there is evidence from the large body of cross-sectional studies that individuals with higher uBPA concentrations are more likely to suffer from diabetes, general/abdominal obesity and hypertension than those with lower uBPA concentrations. Given the potential importance for public health, prospective cohort studies with proper adjustment for dietary characteristics and identification of critical windows of exposure are urgently needed to further improve knowledge about potential causal links between BPA exposure and the development of chronic disease.

Occupational exposure to wood dust and risk of lung cancer in two population-based case-control studies in Montreal, Canada.

Abstract: Wood dust is one of the oldest and one of the most common occupational exposures in the world. The present analyses examine the effect of lifetime exposure to wood dust in diverse occupational settings on lung cancer risk. We conducted two population-based case–control studies in Montreal: Study I (1979–1986) included 857 cases and two sets of controls (533 population and 1349 cancer controls), and Study II (1996–2001) comprised 736 cases and 894 population controls. Detailed job histories were obtained by interview and each job was evaluated by expert chemist–hygienists to estimate the likelihood and level of exposure to many substances, one of which was wood dust. Odds ratios (ORs) were computed in relation to different indices of exposure to wood dust, adjusting for several covariates including smoking. Three datasets were analysed: Study I with population controls, Study I with cancer controls, and Study II. The most frequently exposed occupations in our study population were in construction, timber and furniture making industries. We found increased risks of lung cancer for substantial cumulative exposure to wood dust in Study I with cancer controls, (OR = 1.4: 95% confidence interval 1.0;-2.0) and in Study II (OR = 1.7: 95% confidence interval 1.1-2.7). There were no excess risks of lung cancer in any of the three datasets among workers whose cumulative exposure was not substantial. These tendencies held equally within strata of low smokers and heavy smokers. There was evidence of increased risk of lung cancer among workers with substantial cumulative exposure to wood dust.

Long-term exposure to fine particulate matter and incidence of type 2 diabetes mellitus in a cohort study: effects of total and traffic-specific air pollution

Abstract: Studies investigating the link between long-term exposure to air pollution and incidence of diabetes are still scarce and results are inconsistent, possibly due to different compositions of the particle mixture. We investigate the long-term effect of traffic-specific and total particulate matter (PM) and road proximity on cumulative incidence of diabetes mellitus (mainly type 2) in a large German cohort. We followed prospectively 3607 individuals without diabetes at baseline (2000–2003) from the Heinz Nixdorf Recall Study in Germany (mean follow-up time 5.1 years). Mean annual exposures to total as well as traffic-specific PM10 and PM2.5 at residence were estimated using a chemistry transport model (EURAD, 1 km2 resolution). Effect estimates for an increase of 1 μg/m3 in PM were obtained with Poisson regression adjusting for sex, age, body mass index, lifestyle factors, area-level and individual-level socio-economic status, and city. 331 incident cases developed. Adjusted RRs for total PM10 and PM2.5 were 1.05 (95 %-CI: 1.00;1.10) and 1.03 (95 %-CI: 0.95;1.12), respectively. Markedly higher point estimates were found for local traffic-specific PM with RRs of 1.36 (95 %-CI: 0.98;1.89) for PM10 and 1.36 (95 %-CI: 0.97;1.89) for PM2.5. Individuals living closer than 100 m to a busy road had a more than 30 % higher risk (1.37;95 %-CI: 1.04;1.81) than those living further than 200 m away. Long-term exposure to total PM increases type two diabetes risk in the general population, as does living close to a major road. Local traffic-specific PM was related to higher risks for type two diabetes than total PM.

Parma consensus statement on metabolic disruptors

Abstract: A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16–18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as “metabolic disruptors”, in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

Drinking well water and occupational exposure to Herbicides is associated with chronic kidney disease, in Padavi-Sripura, Sri Lanka

Abstract: The chronic kidney disease of unknown etiology (CKDu) among paddy farmers in was first reported in 1994 and has now become most important public health issue in dry zone of Sri Lanka. The objective was to identify risk factors associated with the epidemic in an area with high prevalence. A case control study was carried out in Padavi-Sripura hospital in Trincomalee district. CKDu patients were defined using health ministry criteria. All confirmed cases (N = 125) fulfilling the entry criteria were recruited to the study. Control selection (N = 180) was done from people visiting the hospital for CKDu screening. Socio-demographic and data related to usage of applying pesticides and fertilizers were studied. Drinking water was also analyzed using ICP-MS and ELISA to determine the levels of metals and glyphosate. Majority of patients were farmers (N = 107, 85.6%) and were educated up to ‘Ordinary Level’ (N = 92, 73.6%). We specifically analyzed for the effect modification of, farming by sex, which showed a significantly higher risk for male farmers with OR 4.69 (95% CI 1.06-20.69) in comparison to their female counterparts. In the multivariable analysis the highest risk for CKDu was observed among participants who drank well water (OR 2.52, 95% CI 1.12-5.70) and had history of drinking water from an abandoned well (OR 5.43, 95% CI 2.88-10.26) and spray glyphosate (OR 5.12, 95% CI 2.33-11.26) as a pesticide. Water analysis showed significantly higher amount of hardness, electrical conductivity and glyphosate levels in abandoned wells. In addition Ca, Mg, Ba, Sr, Fe, Ti, V and Sr were high in abandoned wells. Surface water from reservoirs in the endemic area also showed contamination with glyphosate but at a much lower level. Glyphosate was not seen in water samples in the Colombo district. The current study strongly favors the hypothesis that CKDu epidemic among farmers in dry zone of Sri Lanka is associated with, history of drinking water from a well that was abandoned. In addition, it is associated with spraying glyphosate and other pesticides in paddy fields. Farmers do not use personnel protective equipments and wears scanty clothing due to heat when spraying pesticides.

Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure

Abstract: Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH, such as Roundup, pose a particular health risk to liver and kidneys although low environmentally relevant doses have not been examined. To address this issue, a 2-year study in rats administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked increased incidence of anatomorphological and blood/urine biochemical changes was indicative of liver and kidney structure and functional pathology. In order to confirm these findings we have conducted a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 transcript clusters (a group of probes corresponding to a known or putative gene) were found to be altered respectively in liver and kidney (p < 0.01, q < 0.08). Changes in gene expression varied from −3.5 to 3.7 fold in liver and from −4.3 to 5.3 in kidneys. Among the 1319 transcript clusters whose expression was altered in both tissues, ontological enrichment in 3 functional categories among 868 genes were found. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. Pathway analysis suggests a modulation of the mTOR and phosphatidylinositol signalling pathways. Gene disturbances associated with the chronic administration of ultra-low dose Roundup reflect a liver and kidney lipotoxic condition and increased cellular growth that may be linked with regeneration in response to toxic effects causing damage to tissues. Observed alterations in gene expression were consistent with fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with and thus confirm observations of pathology made at an anatomical, histological and biochemical level. Our results suggest that chronic exposure to a GBH in an established laboratory animal toxicity model system at an ultra-low, environmental dose can result in liver and kidney damage with potential significant health implications for animal and human populations.

Association of pyrethroid pesticide exposure with attention-deficit/hyperactivity disorder in a nationally representative sample of U.S. children

Abstract: Pyrethroid pesticides cause abnormalities in the dopamine system and produce an ADHD phenotype in animal models, with effects accentuated in males versus females. However, data regarding behavioral effects of pyrethroid exposure in children is limited. We examined the association between pyrethroid pesticide exposure and ADHD in a nationally representative sample of US children, and tested whether this association differs by sex. Data are from 8–15 year old participants (N = 687) in the 2001–2002 National Health and Nutrition Examination Survey. Exposure was assessed using concurrent urinary levels of the pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). ADHD was defined by either meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria on the Diagnostic Interview Schedule for Children (DISC) or caregiver report of a prior diagnosis. ADHD symptom counts were determined via the DISC. Multivariable logistic regression examined the link between pyrethroid exposure and ADHD, and poisson regression investigated the link between exposure and ADHD symptom counts. Children with urinary 3-PBA above the limit of detection (LOD) were twice as likely to have ADHD compared with those below the LOD (adjusted odds ratio [aOR] 2.42; 95 % confidence interval [CI] 1.06, 5.57). Hyperactive-impulsive symptoms increased by 50 % for every 10-fold increase in 3-PBA levels (adjusted count ratio 1.50; 95 % CI 1.03, 2.19); effects on inattention were not significant. We observed possible sex-specific effects: pyrethroid biomarkers were associated with increased odds of an ADHD diagnosis and number of ADHD symptoms for boys but not girls. We found an association between increasing pyrethroid pesticide exposure and ADHD which may be stronger for hyperactive-impulsive symptoms compared to inattention and in boys compared to girls. Given the growing use of pyrethroid pesticides, these results may be of considerable public health import.

The impact of low-level lead toxicity on school performance among children in the Chicago Public Schools: a population-based retrospective cohort study

Abstract: Environmental lead exposure poses a risk to educational performance, especially among poor, urban children. Previous studies found low-level lead exposure was a risk factor for diminished academic abilities, however, this study is distinct because of the very large sample size and because it controlled for very low birth weight and early preterm birth–two factors closely associated with lower academic performance. In this study we examined the association between lead concentration in whole blood (B-Pb) of Chicago Public School (CPS) children and their performance on the 3rd grade Illinois Standard Achievement Tests (ISAT) reading and math scores. We examined 58,650 children born in Chicago between 1994 and 1998 who were tested for blood lead concentration between birth and 2006 and enrolled in the 3rd grade at a CPS school between 2003 and 2006. We linked the Chicago birth registry, the Chicago Blood Lead Registry, and 3rd grade ISAT scores to examine associations between B-Pb and school performance. After adjusting for other predictors of school performance including poverty, race/ethnicity, gender, maternal education and very low birth weight or preterm-birth, we found that B-Pbs below 10 μg/dL were inversely associated with reading and math scores in 3rd grade children. For a 5 μg/dL increase in B-Pb, the risk of failing increased by 32% for reading (RR = 1.32, 95%CI = 1.26, 1.39) and math (RR = 1.32, 95%CI = 1.26, 1.39). The effect of lead on reading was non-linear with steeper failure rates at lower B-Pbs. We estimated that 13% of reading failure and 14.8% of math failure can be attributed to exposure to blood lead concentrations of 5 to 9 vs. 0 to 4 μg/dL in Chicago school children. Early childhood lead exposure is associated with poorer achievement on standardized reading and math tests in the third grade, even at very low B-Pbs. Preventing lead exposure in early childhood is critical to improving school performance.

Urban-rural differences in daily time-activity patterns, occupational activity and housing characteristics

Abstract: There is evidence that rural residents experience a health disadvantage compared to urban residents, associated with a greater prevalence of health risk factors and socioeconomic differences. We examined differences between urban and rural Canadians using data from the Canadian Human Activity Pattern Survey (CHAPS) 2. Data were collected from 1460 respondents in two rural areas (Haldimand-Norfolk, Ontario and Annapolis Valley-Kings County, Nova Scotia) and 3551 respondents in five urban areas (Vancouver, Edmonton, Toronto, Montreal, and Halifax) using a 24-h recall diary and supplementary questionnaires administered using computer-assisted telephone interviews. We evaluated differences in time-activity patterns, occupational activity, and housing characteristics between rural and urban populations using multivariable linear and logistic regression models adjusted for design as well as demographic and socioeconomic covariates. Taylor linearization method and design-adjusted Wald tests were used to test statistical significance. After adjustment for demographic and socioeconomic covariates, rural children, adults and seniors spent on average 0.7 (p < 0.05), 1.2 (p < 0.001), and 0.9 (p < 0.001) more hours outdoors per day respectively than urban counterparts. 23.1 % (95 % CI: 19.0–27.2 %) of urban and 37.8 % (95 % CI: 31.2–44.4 %) of rural employed populations reported working outdoors and the distributions of job skill level and industry differed significantly (p < 0.001) between urban and rural residents. In particular, 11.4 % of rural residents vs. 4.9 % of urban residents were employed in unskilled jobs, and 11.5 % of rural residents vs. <0.5 % of urban residents were employ in primary industry. Rural residents were also more likely than urban residents to report spending time near gas or diesel powered equipment other than vehicles (16.9 % vs. 5.2 %, p < 0.001), more likely to report wood as a heating fuel (9.8 % vs. <0.1 %; p < 0.001 for difference in distribution of heating fuels), less likely to have an air conditioner (43.0 % vs. 57.2 %, p < 0.001), and more likely to smoke (29.1 % vs. 19.0 %, p < 0.001). Private wells were the main water source in rural areas (68.6 %) in contrast to public water systems (97.6 %) in urban areas (p < 0.001). Despite these differences, no differences in self-reported health status were observed between urban and rural residents. We identified a number of differences between urban and rural residents, which provide evidence pertinent to the urban–rural health disparity.

The association of long-term exposure to PM2.5 on all-cause mortality in the Nurses’ Health Study and the impact of measurement-error correction

Abstract: Long-term exposure to particulate matter less than 2.5 μm in diameter (PM2.5) has been consistently associated with risk of all-cause mortality. The methods used to assess exposure, such as area averages, nearest monitor values, land use regressions, and spatio-temporal models in these studies are subject to measurement error. However, to date, no study has attempted to incorporate adjustment for measurement error into a long-term study of the effects of air pollution on mortality. We followed 108,767 members of the Nurses’ Health Study (NHS) 2000–2006 and identified all deaths. Biennial mailed questionnaires provided a detailed residential address history and updated information on potential confounders. Time-varying average PM2.5 in the previous 12-months was assigned based on residential address and was predicted from either spatio-temporal prediction models or as concentrations measured at the nearest USEPA monitor. Information on the relationships of personal exposure to PM2.5 of ambient origin with spatio-temporal predicted and nearest monitor PM2.5 was available from five previous validation studies. Time-varying Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 percent confidence intervals (95%CI) for each 10 μg/m3 increase in PM2.5. Risk-set regression calibration was used to adjust estimates for measurement error. Increasing exposure to PM2.5 was associated with an increased risk of mortality, and results were similar regardless of the method chosen for exposure assessment. Specifically, the multivariable adjusted HRs for each 10 μg/m3 increase in 12-month average PM2.5 from spatio-temporal prediction models were 1.13 (95%CI:1.05, 1.22) and 1.12 (95%CI:1.05, 1.21) for concentrations at the nearest EPA monitoring location. Adjustment for measurement error increased the magnitude of the HRs 4-10% and led to wider CIs (HR = 1.18; 95%CI: 1.02, 1.36 for each 10 μg/m3 increase in PM2.5 from the spatio-temporal models and HR = 1.22; 95%CI: 1.02, 1.45 from the nearest monitor estimates). These findings support the large body of literature on the adverse effects of PM2.5, and suggest that adjustment for measurement error be considered in future studies where possible.

The association between maternal urinary phthalate concentrations and blood pressure in pregnancy: The HOME Study.

Abstract: Exposure to phthalates, a class of endocrine disrupting chemicals, is ubiquitous. We examined the association of urinary phthalate metabolite concentrations during pregnancy with maternal blood pressure and risk of pregnancy-induced hypertensive diseases. We used data from the Health Outcomes and Measures of the Environment Study, a prospective birth cohort of low-risk pregnant women recruited between March 2003 and January 2006. We analyzed maternal urine samples collected at 16 and 26 weeks gestation for 9 phthalate monoester metabolites reflecting exposure to 6 phthalate diesters. Outcomes included maternal blood pressure at <20 and ≥20 weeks gestation and pregnancy induced hypertensive diseases (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome). Data were available for 369 women who gave birth to singleton, live-born infants without congenital anomalies. Of the phthalate metabolites evaluated, only mono-benzyl phthalate (MBzP) concentrations were significantly associated with maternal diastolic blood pressure at <20 weeks gestation. Women in the third MBzP tercile at 16 weeks gestation had diastolic blood pressure 2.2 (95 % CI: 0.5–3.9) mm Hg higher at <20 weeks gestation and 2.8 (95 % CI: 0.9–4.7) mm Hg higher at ≥20 weeks gestation compared to women in the first tercile. Compared to women in the first tercile, women in the top MBzP tercile at 16 weeks had an increased risk of developing pregnancy-induced hypertensive diseases (RR = 2.92, 95 % CI 1.15–7.41, p-value for trend = 0.01). MBzP concentrations at 26 weeks gestation were not as strongly associated with blood pressure at ≥20 weeks gestation or risk of pregnancy-induced hypertensive diseases. This study suggests that maternal urinary MBzP concentrations may be associated with increased diastolic blood pressure and risk of pregnancy-induced hypertensive diseases.

The associations between daily spring pollen counts, over-the-counter allergy medication sales, and asthma syndrome emergency department visits in New York City, 2002-2012

Abstract: Many types of tree pollen trigger seasonal allergic illness, but their population-level impacts on allergy and asthma morbidity are not well established, likely due to the paucity of long records of daily pollen data that allow analysis of multi-day effects. Our objective in this study was therefore to determine the impacts of individual spring tree pollen types on over-the-counter allergy medication sales and asthma emergency department (ED) visits. Nine clinically-relevant spring tree pollen genera (elm, poplar, maple, birch, beech, ash, sycamore/London planetree, oak, and hickory) measured in Armonk, NY, were analyzed for their associations with over-the-counter allergy medication sales and daily asthma syndrome ED visits from patients’ chief complaints or diagnosis codes in New York City during March 1st through June 10th, 2002-2012. Multi-day impacts of pollen on the outcomes (0-3 days and 0-7 days for the medication sales and ED visits, respectively) were estimated using a distributed lag Poisson time-series model adjusting for temporal trends, day-of-week, weather, and air pollution. For asthma syndrome ED visits, age groups were also analyzed. Year-to-year variation in the average peak dates and the 10th-to-90th percentile duration between pollen and the outcomes were also examined with Spearman’s rank correlation. Mid-spring pollen types (maple, birch, beech, ash, oak, and sycamore/London planetree) showed the strongest significant associations with both outcomes, with cumulative rate ratios up to 2.0 per 0-to-98th percentile pollen increase (e.g., 1.9 [95 % CI: 1.7, 2.1] and 1.7 [95 % CI: 1.5, 1.9] for the medication sales and ED visits, respectively, for ash). Lagged associations were longer for asthma syndrome ED visits than for the medication sales. Associations were strongest in children (ages 5-17; e.g., a cumulative rate ratio of 2.6 [95 % CI: 2.1, 3.1] per 0-to-98th percentile increase in ash). The average peak dates and durations of some of these mid-spring pollen types were also associated with those of the outcomes. Tree pollen peaking in mid-spring exhibit substantive impacts on allergy, and asthma exacerbations, particularly in children. Given the narrow time window of these pollen peak occurrences, public health and clinical approaches to anticipate and reduce allergy/asthma exacerbation should be developed.

Assessing dose–response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity

Abstract: The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose–response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts’ knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions.

Association between perfluoroalkyl acids and kidney function in a cross-sectional study of adolescents

Abstract: Perfluoroalkyl acids are synthetic compounds widely used in industrial and commercial applications. Laboratory studies suggest that these persistent and bioaccumulative chemicals produce oxidant stress and damage glomerular endothelial cells, raising concern regarding the impact of these compounds on renal function. We performed cross-sectional analyses of data 1960 participants aged 12–19 years of the 2003–2010 National Health and Nutrition Examination Surveys. PFAA exposure was assessed using levels of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid, and perfluorohexane sulfonic acid. Primary study outcomes were estimated glomerular filtration rate (eGFR) and serum uric acid. While adjusting for demographics, cotinine, prehypertension, insulin resistance, body mass index, and hypercholesterolemia, adolescents in the highest PFOA and PFOS quartile had a lower eGFR, 6.84 mL/min/1.73 m2 (95 % CI: 2.19 to 11.48) and 9.69 mL/min/1.73 m2 (95 % CI: -4.59 to 14.78), respectively, compared to the lowest quartile. Highest PFOA and PFOS quartiles were also associated with 0.21 mg/dL (95 % CI: 0.056 to 0.37) and 0.19 mg/dL (95 % CI: 0.032 to 0.34) increases in uric acid, respectively. PFAAs are associated with a reduction in kidney function and increased uric acid levels in otherwise healthy adolescents. Reverse causation and residual confounding could explain the results. Our study results confirm and amplify previous findings, though longitudinal studies examining prenatal and childhood biomarkers in relationship with robust measures of childhood renal function are needed.

The effect of heat waves on mortality in susceptible groups: a cohort study of a mediterranean and a northern European City

Abstract: Background: Climate change is projected to increase the number and intensity of extreme weather events, for example heat waves. Heat waves have adverse health effects, especially for the elderly, since chronic diseases are more frequent in that group than in the population overall. The aim of the study was to investigate mortality during heat waves in an adult population aged 50 years or over, as well as in susceptible subgroups of that population in Rome and Stockholm during the summer periods from 2000 to 2008. Methods: We collected daily number of deaths occurring between 15th May and 15th September each year for the population above 50 as well as the susceptible subgroups. Heat wave days were defined as two or more days exceeding the city specific 95th percentile of maximum apparent temperature (MAT). The relationship between heat waves and all-cause non-accidental mortality was investigated through time series modelling, adjusting for time trends. Results: The percent increase in daily mortality during heat waves as compared to normal summer days was, in the 50+ population, 22% (95% Confidence Interval (CI): 18-26%) in Rome and 8% (95% CI: 3-12%) in Stockholm. Subgroup specific increase in mortality in Rome ranged from 7% (95% CI:–17-39%) among survivors of myocardial infarction to 25% in the COPD (95% CI:9-43%) and diabetes (95% CI:14-37%) subgroups. In Stockholm the range was from 10% (95% CI: 2-19%) for congestive heart failure to 33% (95% CI: 10-61%) for the psychiatric subgroup. Conclusions: Mortality during heat waves increased in both Rome and Stockholm for the 50+ population as well as in the considered subgroups. It should be evaluated if protective measures should be directed towards susceptible groups, rather than the population as a whole.

Analytical studies assessing the association between extreme precipitation or temperature and drinking water-related waterborne infections: a review

Abstract: Determining the role of weather in waterborne infections is a priority public health research issue as climate change is predicted to increase the frequency of extreme precipitation and temperature events. To document the current knowledge on this topic, we performed a literature review of analytical research studies that have combined epidemiological and meteorological data in order to analyze associations between extreme precipitation or temperature and waterborne disease. A search of the databases Ovid MEDLINE, EMBASE, SCOPUS and Web of Science was conducted, using search terms related to waterborne infections and precipitation or temperature. Results were limited to studies published in English between January 2001 and December 2013. Twenty-four articles were included in this review, predominantly from Asia and North-America. Four articles used waterborne outbreaks as study units, while the remaining articles used number of cases of waterborne infections. Results presented in the different articles were heterogeneous. Although most of the studies identified a positive association between increased precipitation or temperature and infection, there were several in which this association was not evidenced. A number of articles also identified an association between decreased precipitation and infections. This highlights the complex relationship between precipitation or temperature driven transmission and waterborne disease. We encourage researchers to conduct studies examining potential effect modifiers, such as the specific type of microorganism, geographical region, season, type of water supply, water source or water treatment, in order to assess how they modulate the relationship between heavy rain events or temperature and waterborne disease. Addressing these gaps is of primary importance in order to identify the areas where action is needed to minimize negative impact of climate change on health in the future.

Cyanobacteria blooms and non-alcoholic liver disease: evidence from a county level ecological study in the United States

Abstract: Background Harmful cyanobacterial blooms present a global threat to human health. There is evidence suggesting that cyanobacterial toxins can cause liver damage and cancer. However, because there is little epidemiologic research on the effects of these toxins in humans, the excess risk of liver disease remains uncertain. The purpose of this study is to estimate the spatial distribution of cyanobacterial blooms in the United States and to conduct a Bayesian statistical analysis to test the hypothesis that contamination from cyanobacterial blooms is a potential risk factor for non-alcoholic liver disease.

Phthalate concentrations in house dust in relation to autism spectrum disorder and developmental delay in the CHildhood Autism Risks from Genetics and the Environment (CHARGE) study

Abstract: Phthalates are endocrine-disrupting chemicals that influence thyroid hormones and sex steroids, both critical for brain development. We studied phthalate concentrations in house dust in relation to the risks of developing autism spectrum disorder (ASD) or developmental delay (DD). Participants were a subset of children from the CHARGE (CHildhood Autism Risks from Genetics and the Environment) case–control study. ASD and DD cases were identified through the California Department of Developmental Services system or referrals; general population controls were randomly sampled from state birth files and frequency-matched on age, sex, and broad geographic region to ASD cases. All children (50 ASD, 27 DD, 68 typically developing (TD)) were assessed with Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales (VABS) and Aberrant Behavior Checklist. We measured 5 phthalates in dust collected in the child’s home using a high volume small surface sampler. None of the phthalates measured in dust was associated with ASD. After adjustment, we observed greater di(2-ethylhexyl) phthalate (DEHP) and butylbenzyl phthalate (BBzP) concentrations in indoor dust from homes of DD children: Odds ratios (OR) were 2.10 (95 % confidence interval (CI); 1.10; 4.09) and 1.40 (95 % CI; 0.97; 2.04) for a one-unit increase in the ln-transformed DEHP and BBzP concentrations, respectively. Among TD children, VABS communication, daily living, and adaptive composite standard scores were lower, in association with increased diethyl phthalate (DEP) concentrations in dust. Participants with higher dibutyl phthalate (DBP) concentrations in house dust also trended toward reduced performance on these subscales. Among ASD and DD boys, higher indoor dust concentrations of DEP and DBP were associated with greater hyperactivity-impulsivity and inattention. House dust levels of phthalates were not associated with ASD. The inability to distinguish past from recent exposures in house dust and the fact that house dust does not capture exposure from all sources, limit the interpretation of both positive and null findings and further work is needed. However, the associations observed for DEP and DBP with impairments in several adaptive functions and greater hyperactivity, along with evidence for increased risk of DD raise concerns that these chemicals may affect neurodevelopment in children.

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

Abstract: Background: It 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. Methods: We 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. Results: The 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. Conclusions: The 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.

A nested case-control study indicating heavy metal residues in meconium associate with maternal gestational diabetes mellitus risk

Abstract: Environmental pollutant exposure may play certain roles in the pathogenesis and progression of diabetes mellitus including gestational diabetes mellitus (GDM). We hypothesize that heavy metal exposure may trigger GDM during pregnancy. The objective of this study was to investigate the possible associations between selected heavy metal exposure and GDM risk. This investigation is a retrospective case–control study nested within a cohort of 1359 pregnant women. These participants were recruited in Xiamen Maternity and Child Care Hospital, China, during June to July, 2012. All their newborns’ meconium samples were collected. By reviewing the antenatal care records, 166 GDM mothers were screened out from the 1359 participants; 137 of 166 GDM mothers offered their newborns’ meconium samples for the metal analysis. Those 137 mothers were set as the case group. Similarly, 294 healthy mothers without any gestational complication were initially screened out from the rest 1193 non-GDM mothers. 190 of the 294 healthy mothers offered their newborns’ meconium samples for the metal analysis. Those 190 mothers were set as the control group. Arsenic (As), mercury (Hg), lead (Pb), cadmium (Cd), and chromium (Cr) levels in these case–control meconium samples were measured by inductively coupled plasma mass spectrometry. The possible association between the metal levels and maternal GDM risk of studied subjects was assessed by binary logistic regression. GDM prevalence of 12.21% was observed in the investigated 1359 participants. The concentrations of As, Hg, Cr and Cd in studied cases were significantly higher (p < 0.05) than those of controls. After adjustments for maternal age, pre-pregnant body mass index, gravidity, parity, hepatitis B virus infection, and newborn sex, As, Cd and Cr were found to be positively associated with GDM prevalence in dose-dependent manners. Among them, As was detected in all samples and its levels associated the maternal GDM with the adjusted odds ratios of 3.28 [95% CI 1.24, 8.71], 3.35 [95% CI 1.28, 8.75] and 5.25 [95% CI 1.99, 13.86] for the 2nd, 3rd and 4th quartiles, respectively. The present work implies that exposure to some of the selected metals (noticeably As) may contribute to maternal GDM risk during pregnancy.

Parental urinary biomarkers of preconception exposure to bisphenol A and phthalates in relation to birth outcomes

Abstract: Bisphenol A (BPA) and phthalates are ubiquitous non-persistent endocrine disrupting chemicals whose relation with infant birth size is not clearly understood. We examined associations between maternal and paternal preconception urinary concentrations of total BPA and 14 phthalate metabolites and birth size for 233 infants. Multiple linear regression models were used to estimate parental quartiles of BPA and phthalates in relation to birth weight, length, head circumference, and ponderal index with separate models run for each parent adjusting for age, smoking, body mass index, education, alcohol, parity, and creatinine. Models also included an interaction term for each chemical and infant sex and were further adjusted to include the other partner’s chemical concentrations. In maternal models adjusted for partner’s exposure and covariates, reductions in birth weight (range: 178-215 g; p < 0.05) were observed for the 2nd quartile of maternal monomethyl phthalate, mono-[(2-carboxymethyl) hexyl] phthalate and mono-n-octyl phthalate when compared with the 1st quartiles. The 3rd quartile of monoethylhexyl phthalate (mEHP) was also associated with a 200.16 g (95 % CI: -386.90, -13.42) reduction. Similar reductions in birth weight were observed for the 2nd quartile of paternal mEHP (β = -191.93 g; 95 % CI: -381.61, -2.25). Additionally, select maternal urinary metabolites were associated with decreased head circumference, birth length and gestational age. However, paternal concentrations were generally associated with increased birth length and gestational age. We observed some suggestion that preconception maternal and paternal urinary concentration of BPA and specific phthalate metabolites may be associated with smaller birth size and increased gestational age, though the findings appeared to be parent and chemical specific.

Projections of temperature-attributable premature deaths in 209 U.S. cities using a cluster-based Poisson approach

Abstract: A warming climate will affect future temperature-attributable premature deaths. This analysis is the first to project these deaths at a near national scale for the United States using city and month-specific temperature-mortality relationships. We used Poisson regressions to model temperature-attributable premature mortality as a function of daily average temperature in 209 U.S. cities by month. We used climate data to group cities into clusters and applied an Empirical Bayes adjustment to improve model stability and calculate cluster-based month-specific temperature-mortality functions. Using data from two climate models, we calculated future daily average temperatures in each city under Representative Concentration Pathway 6.0. Holding population constant at 2010 levels, we combined the temperature data and cluster-based temperature-mortality functions to project city-specific temperature-attributable premature deaths for multiple future years which correspond to a single reporting year. Results within the reporting periods are then averaged to account for potential climate variability and reported as a change from a 1990 baseline in the future reporting years of 2030, 2050 and 2100. We found temperature-mortality relationships that vary by location and time of year. In general, the largest mortality response during hotter months (April – September) was in July in cities with cooler average conditions. The largest mortality response during colder months (October–March) was at the beginning (October) and end (March) of the period. Using data from two global climate models, we projected a net increase in premature deaths, aggregated across all 209 cities, in all future periods compared to 1990. However, the magnitude and sign of the change varied by cluster and city. We found increasing future premature deaths across the 209 modeled U.S. cities using two climate model projections, based on constant temperature-mortality relationships from 1997 to 2006 without any future adaptation. However, results varied by location, with some locations showing net reductions in premature temperature-attributable deaths with climate change.

Associations between air pollution and perceived stress: the Veterans Administration Normative Aging Study

Abstract: Background: There is mixed evidence suggesting that air pollution may be associated with increased risk of developing psychiatric disorders We aimed to investigate the association between air pollution and non-specific perceived stress, often a precursor to development of affective psychiatric disorders Methods: This longitudinal analysis consisted of 987 older men participating in at least one visit for the Veterans Administration Normative Aging Study between 1995 and 2007 (n = 2,244 visits) At each visit, participants were administered the 14-item Perceived Stress Scale (PSS), which quantifies stress experienced in the previous week Scores ranged from 0–56 with higher scores indicating increased stress Differences in PSS score per interquartile range increase in moving average (1, 2, and 4-weeks) of air pollution exposures were estimated using linear mixed-effects regression after adjustment for age, race, education, physical activity, anti-depressant medication use, seasonality, meteorology, and day of week We also evaluated effect modification by season (April-September and March-October for warm and cold season, respectively) Results: Fine particles (PM25), black carbon (BC), nitrogen dioxide, and particle number counts (PNC) at moving averages of 1, 2, and 4-weeks were associated with higher perceived stress ratings The strongest associations were observed for PNC; for example, a 15,997 counts/cm 3 interquartile range increase in 1-week average PNC was associated with a 32 point (95%CI: 21-43) increase in PSS score Season modified the associations for specific pollutants; higher PSS scores in association with PM25, BC, and sulfate were observed mainly in colder months Conclusions: Air pollution was associated with higher levels of perceived stress in this sample of older men, particularly in colder months for specific pollutants

Temperature, ozone, and mortality in urban and non-urban counties in the northeastern United States

Abstract: Most health effects studies of ozone and temperature have been performed in urban areas, due to the available monitoring data. We used observed and interpolated data to examine temperature, ozone, and mortality in 91 urban and non-urban counties. Ozone measurements were extracted from the Environmental Protection Agency’s Air Quality System. Meteorological data were supplied by the National Center for Atmospheric Research. Observed data were spatially interpolated to county centroids. Daily internal-cause mortality counts were obtained from the National Center for Health Statistics (1988–1999). A two-stage Bayesian hierarchical model was used to estimate each county’s increase in mortality risk from temperature and ozone. We examined county-level associations according to population density and compared urban (≥1,000 persons/mile2) to non-urban (<1,000 persons/mile2) counties. Finally, we examined county-level characteristics that could explain variation in associations by county. A 10 ppb increase in ozone was associated with a 0.45% increase in mortality (95% PI: 0.08, 0.83) in urban counties, while this same increase in ozone was associated with a 0.73% increase (95% PI: 0.19, 1.26) in non-urban counties. An increase in temperature from 70°F to 90°F (21.2°C 32.2°C) was associated with a 8.88% increase in mortality (95% PI: 7.38, 10.41) in urban counties and a 8.08% increase (95% PI: 6.16, 10.05) in non-urban counties. County characteristics, such as population density, percentage of families living in poverty, and percentage of elderly residents, partially explained the variation in county-level associations. While most prior studies of ozone and temperature have been performed in urban areas, the impacts in non-urban areas are significant, and, for ozone, potentially greater. The health risks of increasing temperature and air pollution brought on by climate change are not limited to urban areas.

Air toxics and the risk of autism spectrum disorder: the results of a population based case–control study in southwestern Pennsylvania

Abstract: Autism spectrum disorders (ASD) constitute a major public health problem affecting one in 68 children. There is little understanding of the causes of ASD despite its serious social impact. Air pollution contains many toxicants known to have adverse effects on the fetus. We conducted a population based case–control study in southwestern Pennsylvania to estimate the association between ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30 neurotoxicants. A total of 217 ASD cases born between 2005 and 2009 were recruited from local ASD diagnostic and treatment centers. There were two different control groups: 1) interviewed controls (N = 224) frequency matched by child’s year of birth, sex and race with complete residential histories from prior to pregnancy through the child’s second birthday, and 2) 5,007 controls generated from a random sample of birth certificates (BC controls) using residence at birth. We used logistic regression analysis comparing higher to first quartile of exposure to estimate odds ratios (ORs) and 95 % confidence intervals (CI), adjusting for mother’s age, education, race, smoking status, child’s year of birth and sex. Comparing fourth to first quartile exposures for all births, the adjusted OR for styrene was 2.04 (95 % CI = 1.17–3.58, p = 0.013) for the interviewed case–control analysis and 1.61 (95 % CI = 1.08-2.40, p = 0.018) for the BC analysis. In the BC comparison, chromium also exhibited an elevated OR of 1.60 (95 % CI = 1.08-2.38, p = 0.020), which was similarly elevated in the interviewed analysis (OR = 1.52, 95 % CI = 0.87–2.66). There were borderline significant ORs for the BC comparison for methylene chloride (OR = 1.41, 95 % CI = 0.96–2.07, p = 0.082) and PAHs (OR = 1.44, 95 % CI = 0.98–2.11, p = 0.064). Living in areas with higher levels of styrene and chromium during pregnancy was associated with increased risk of ASD, with borderline effects for PAHs and methylene chloride. These results are consistent with other studies. It is unclear, however, whether these chemicals are risk factors themselves or if they reflect the effect of a mixture of pollutants. Future work should include improved spatiotemporal estimates of exposure to air toxics, taking into account the dynamic movement of individuals during daily life.

Vaginal douching and racial/ethnic disparities in phthalates exposures among reproductive-aged women: National Health and Nutrition Examination Survey 2001–2004

Abstract: Diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) are industrial chemicals found in consumer products that may increase risk of adverse health effects. Although use of personal care/beauty products is known to contribute to phthalate exposure, no prior study has examined feminine hygiene products as a potential phthalate source. In this study, we evaluate whether vaginal douching and other feminine hygiene products increase exposure to phthalates among US reproductive-aged women. We conducted a cross-sectional study on 739 women (aged 20–49) from the National Health and Nutrition Examination Survey 2001–2004 to examine the association between self-reported use of feminine hygiene products (tampons, sanitary napkins, vaginal douches, feminine spray, feminine powder, and feminine wipes/towelettes) with urinary concentrations of monoethyl phthalate (MEP) and mono-n-butyl phthalate (MnBP), metabolites of DEP and DnBP, respectively. A greater proportion of black women than white and Mexican American women reported use of vaginal douches, feminine spray, feminine powder, and wipes/towelettes in the past month whereas white women were more likely than other racial/ethnic groups to report use of tampons (p < 0.05). Douching in the past month was associated with higher concentrations of MEP but not MnBP. No other feminine hygiene product was significantly associated with either MEP or MnBP. We observed a dose–response relationship between douching frequency and MEP concentrations (ptrend < 0.0001); frequent users (≥2 times/month) had 152.2 % (95 % confidence intervals (CI): (68.2 %, 278.3 %)) higher MEP concentrations than non-users. We also examined whether vaginal douching mediates the relationship between race/ethnicity and phthalates exposures. Black women had 48.4 % (95 % CI: 16.8 %, 88.6 %; p = 0.0002) higher MEP levels than white women. Adjustment for douching attenuated this difference to 26.4 % (95 % CI:−0.9 %, 61.2 %; p = 0.06). Mediation effects of douching were statistically significant for black-white differences (z = 3.71, p < 0.001) but not for differences between Mexican Americans and whites (z = 1.80, p = 0.07). Vaginal douching may increase exposure to DEP and contribute to racial/ethnic disparities in DEP exposure. The presence of environmental chemicals in vaginal douches warrants further examination.

Exposure to fluoridated water and attention deficit hyperactivity disorder prevalence among children and adolescents in the United States: an ecological association.

Abstract: Epidemiological and animal-based studies have suggested that prenatal and postnatal fluoride exposure has adverse effects on neurodevelopment. The aim of this study was to examine the relationship between exposure to fluoridated water and Attention-Deficit Hyperactivity Disorder (ADHD) prevalence among children and adolescents in the United States. Data on ADHD prevalence among 4-17 year olds collected in 2003, 2007 and 2011 as part of the National Survey of Children’s Health, and state water fluoridation prevalence from the Centers for Disease Control and Prevention (CDC) collected between 1992 and 2008 were utilized. State prevalence of artificial water fluoridation in 1992 significantly positively predicted state prevalence of ADHD in 2003, 2007 and 2011, even after controlling for socioeconomic status. A multivariate regression analysis showed that after socioeconomic status was controlled each 1% increase in artificial fluoridation prevalence in 1992 was associated with approximately 67,000 to 131,000 additional ADHD diagnoses from 2003 to 2011. Overall state water fluoridation prevalence (not distinguishing between fluoridation types) was also significantly positively correlated with state prevalence of ADHD for all but one year examined. Parents reported higher rates of medically-diagnosed ADHD in their children in states in which a greater proportion of people receive fluoridated water from public water supplies. The relationship between fluoride exposure and ADHD warrants future study.

Endocrine disruptors alter social behaviors and indirectly influence social hierarchies via changes in body weight

Abstract: In humans, the causal link between socioeconomic status (SES) and body weight (BW) is bidirectional, as chronic stress associated with low SES may increase risk of obesity and excess weight may worsen career opportunities resulting in lower SES. We hypothesize that environmental factors affecting BW and/or social stress might reprogram physiological and social trajectories of individuals. To analyze interactions between BW and social behaviors in mice perinatally exposed to one of several environmental endocrine disruptors. CD-1 mice were fed 0.2 mg/kg BW/day tetrabromobisphenol-A (TBBPA), 2,2,4,4-tetrabromodiphenyl ether (BDE-47), bisphenol S (BPS), or oil (vehicle) from pregnancy day 8 through postpartum day 21. Three male offspring (triad) from each litter were housed together until week 15 and subjected to a Sociability Test and Tube Tests. Cages were then rearranged so that animals of the same social rank from the four exposure groups were housed together in tetrads. Social hierarchy in tetrads was again analyzed by Tube Tests. In Sociability Tests, the mean velocity of all exposed animals increased when they encountered a stranger mouse and less time was spent with conspecifics. BW and social dominance of animals in triads and tetrads were inversely associated. BDE-47 and BPS caused transient decreases in BW. Developmental exposure to environmental xenobiotics shifted behavior towards increased anxiety and decreased interest in social interactions. Our mouse model reproduces negative associations between social hierarchy status and BW. These results suggest that manipulation of BW by endocrine disruptors may affect social ranking.

Urgent need to reevaluate the latest World Health Organization guidelines for toxic inorganic substances in drinking water

Abstract: The World Health Organization (WHO) has established guidelines for drinking-water quality that cover biological and chemical hazards from both natural and anthropogenic sources. In the most recent edition of Guidelines for Drinking-water Quality (2011), the WHO withdrew, suspended, did not establish, or raised guidelines for the inorganic toxic substances manganese, molybdenum, nitrite, aluminum, boron, nickel, uranium, mercury, and selenium. In this paper, we review these changes to the WHO drinking-water guidelines, examining in detail the material presented in the WHO background documents for each of these toxic substances. In some cases, these WHO background documents use literature reviews that do not take into account scientific research published within the last 10 or more years. In addition, there are instances in which standard WHO practices for deriving guidelines are not used; for example, rounding and other mathematical errors are made. According to published meeting reports from the WHO Chemical Aspects Working Group, the WHO has a timetable for revising some of its guidelines for drinking-water quality, but for many of these toxic substances the planned changes are minimal or will be delayed for as long as 5 years. Given the limited nature of the planned WHO revisions to the inorganic toxic substances and the extended timetable for these revisions, we suggest that governments, researchers, and other stakeholders might establish independent recommendations for inorganic toxic substances and possibly other chemicals to proactively protect public health, or at the very least, revert to previous editions of the Guidelines for Drinking-water Quality, which were more protective of public health.