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BackgroundHigh ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, the incidence is increasing, and in the United States it disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood ALL.MethodsWe used data from California birth records (1982-2015) and California Cancer Registry (1988-2015) to identify ALL cases diagnosed FindingsOur study included 6,258 ALL cases and 307,579 controls. The peak association between ambient temperature and risk of ALL was observed in gestational week 8, where a 5 °C increase was associated with an odds ratio of 1.09 (95% confidence interval 1.04-1.14) and 1.05 (95% confidence interval 1.00-1.11) among Latino and non-Latino White children, respectively. The sensitivity analyses supported this.InterpretationOur findings suggest an association between high ambient temperature in early pregnancy and risk of childhood ALL. Further replication and investigation of mechanistic pathways may inform mitigation strategies.

Health studies report associations between metrics of residential proximity to unconventional oil and gas (UOG) development and adverse health endpoints. We investigated whether exposure through household groundwater is captured by existing metrics and a newly developed metric incorporating groundwater flow paths. We compared metrics with detection frequencies/concentrations of 64 organic and inorganic UOG-related chemicals/groups in residential groundwater from 255 homes (Pennsylvania n = 94 and Ohio n = 161). Twenty-seven chemicals were detected in ≥20% of water samples at concentrations generally below U.S. Environmental Protection Agency standards. In Pennsylvania, two organic chemicals/groups had reduced odds of detection with increasing distance to the nearest well: 1,2-dichloroethene and benzene (Odds Ratio [OR]: 0.46, 95% confidence interval [CI]: 0.23–0.93) and m- and p-xylene (OR: 0.28, 95% CI: 0.10–0.80); results were consistent across metrics. In Ohio, the odds of detecting toluene increased with increasing distance to the nearest well (OR: 1.48, 95% CI: 1.12–1.95), also consistent across metrics. Correlations between inorganic chemicals and metrics were limited (all |ρ| ≤ 0.28). Limited associations between metrics and chemicals may indicate that UOG-related water contamination occurs rarely/episodically, more complex metrics may be needed to capture drinking water exposure, and/or spatial metrics in health studies may better reflect exposure to other stressors.

Few studies have evaluated the validity of self-report of work activities because of challenges in obtaining objective measures. In this study, farmers’ recall of the previous day’s agricultural activities was compared to activities observed by field staff during air monitoring. Recall was assessed in 32 farmers from the Biomarkers of Exposure and Effect in Agriculture Study, a subset of a prospective cohort study. The farmers participated in 56 visits that comprised air monitoring the day before an interview. The answers for 14 agricultural activities were compared to activities observed by field staff during air monitoring (median duration 380 minutes, range 129–486). For each task, evaluated as yes/no, overall agreement, sensitivity, specificity, and kappa were calculated. Median prevalence of the 14 activities was 8% from observation and 13% from participants (range: 2–54%). Agreement was generally good to perfect, with a median overall agreement of 95% (range: 89–100%), median sensitivity of 84% (50–100%), median specificity of 95% (88–100%), and median kappa of 0.65 (0.31–1.0). Reasons for disagreement included activities occurring when the field staff was not present (i.e., milking cows), unclear timing notes that made it difficult to determine whether the activity occurred the day of and/or day before the interview, definition issues (i.e., participant included hauling in the definition of harvesting), and difficulty in observing details of an activity (i.e., whether hay was moldy). This study provides support for accurate participant recall the day after activities.

Oil and gas development has led to environmental hazards and community concerns, particularly in relation to water supply issues. Filing complaints with state agencies enables citizens to register concerns and seek investigations. We evaluated associations between county-level socio-economic and demographic factors, oil and gas drilling, and three outcomes in Pennsylvania between 2004-2016: number of oil and gas complaints filed, and both the number and proportion of state investigations of water supply complaints yielding a confirmed water supply impairment (i.e., "positive determination"). We used hierarchical Bayesian Poisson and binomial regression analyses. From 2004-2016, 9,404 oil and gas-related complaints were filed, of which 4,099 were water supply complaints. Of those, 3,906 received investigations, and 215 yielded positive determinations. We observed a 47% increase in complaints filed per $10,000 increase in annual median household income (MHI) (Rate Ratio [RR]: 1.47, 95% credible interval [CI]: 1.09-1.96) and an 18% increase per 1% increase in educational attainment (RR: 1.18, 95% CI: 1.11-1.26). While the number of complaints filed did not vary by race/ethnicity, the odds of a complaint yielding a positive determination were 0.81 times lower in counties with a higher proportion of marginalized populations (Odds Ratio [OR]: 0.81 per 1% increase in percent Black, Asian, and Native American populations combined, 95% CI: 0.64-0.99). The odds of positive determinations were also lower in areas with higher income (OR per $10,000 increase in MHI: 0.35, 95% CI: 0.09-0.96). Our results suggest these relationships are complex and may indicate potential environmental and procedural inequities, warranting further investigation.

Background: Thyroid cancer incidence is the most rapidly increasing malignancy; rates are three times higher in women than men. Thyroid hormone–disrupting flame-retardant chemicals, including polybrominated diphenyl ethers (PBDE) and polybrominated biphenyls (PBB), may contribute to this trend. Methods: We investigated the relationship between PBDE/PBB exposure and papillary thyroid cancer (PTC) in 250 incident female papillary thyroid cancer cases and 250 female controls frequency-matched on age. Interviews and postdiagnostic serum samples were collected from 2010 to 2013. Serum samples were analyzed for 11 congeners. We calculated ORs and 95% confidence intervals (95% CI) using single-pollutant logistic regression models for continuous and categorical lipid-adjusted serum concentrations of PBDE/PBB, adjusted for age, alcohol consumption, and education. We applied three multi-pollutant approaches [standard multipollutant regression models, hierarchical Bayesian logistic regression modeling (HBLR), principal components analysis (PCA)] to investigate associations with PBDE/PBB mixtures. Results: In single-pollutant models, a decreased risk was observed at the highest (>90th percentile) versus lowest ( Conclusions: Our results using single- and multi-pollutant modeling do not generally support a positive association with PBDE/PBB and PTC risk. Impact: Prospective studies with more advanced statistical approaches to analyze mixtures and populations with higher exposures could reveal new insights.

Unconventional oil and gas development (UOGD) expanded rapidly in the United States between 2004-2019 with resultant industrial change to landscapes and new environmental exposures. By 2019, West Texas' Permian Basin accounted for 35% of domestic oil production. We conducted an online survey of 566 Texans in 2019 to examine the implications of UOGD using three measures from the Environmental Distress Scale (EDS): perceived threat of environmental issues, felt impact of environmental change, and loss of solace when valued environments are transformed ("solastalgia"). We found increased levels of environmental distress among respondents living in counties in the Permian Basin who reported a 2.75% increase in perceived threat of environmental issues (95% CI = -1.14, 6.65) and a 4.21% increase in solastalgia (95% CI = 0.03, 8.40). In our subgroup analysis of women, we found higher EDS subscale scores among respondents in Permian Basin counties for perceived threat of environmental issues (4.08%, 95% CI= -0.12, 8.37) and solastalgia (7.09%, 95% CI= 2.44, 11.88). In analysis restricted to Permian Basin counties, we found exposure to at least one earthquake of magnitude ≥ 3 was associated with increases in perceived threat of environmental issues (4.69%, 95% CI = 0.15, 9.23), and that county-level exposure to oil and gas injection wells was associated with increases in felt impact (4.38%, 95% CI = -1.77, 10.54) and solastalgia (4.06%, 95% CI = 3.02, 11.14). Our results indicate increased environmental distress in response to UOGD-related environmental degradation among Texans and highlight the importance of considering susceptible sub-groups.

Background Most methods for treating left-censored data assume the analyte is present but not quantified. Biased estimates may result if the analyte is absent such that the unobserved data represents a mixed exposure distribution with an unknown proportion clustered at zero. Objective We used semi-continuous models to identify time and industry trends in 52,457 OSHA inspection lead sample results. Method The first component of the semi-continuous model predicted the probability of detecting concentrations ≥ 0.007 mg/m3 (highest estimated detection limit, 62% of measurements). The second component predicted the median concentration of measurements ≥ 0.007 mg/m3. Both components included a random-effect for industry and fixed-effects for year, industry group, analytical method, and other variables. We used the two components together to predict median industry- and time-specific lead concentrations. Results The probabilities of detectable concentrations and the median detected concentrations decreased with year; both were also lower for measurements analyzed for multiple (vs. one) metals and for those analyzed by inductively-coupled plasma (vs. atomic absorption spectroscopy). The covariance was 0.30 (standard error = 0.06), confirming the two components were correlated. Significance We identified determinants of exposure in data with over 60% left-censored, while accounting for correlated relationships and without assuming a distribution for the censored data.

The Pacific Island nation of Samoa is marked by prevalent obesity and an increasing dependence on packaged foods likely to contain the endocrine disruptor bisphenol-A (BPA). We evaluated participant- and household-level characteristics associated with estimated dietary BPA exposure in Samoan mothers and their children and examined associations between dietary BPA exposure and body mass index (BMI) and abdominal circumference (AC). Dietary BPA exposure indices were estimated for 399 mother–child pairs by combining information from dietary questionnaires and relative concentrations of BPA measured in foods/beverages. We observed moderate to strong correlation between mother–child daily BPA indices (Spearman’s rho = 0.7, p < 0.0001). In mothers, we observed lower daily BPA indices in those who were less physically active (p = 0.0004) and living in homes with higher income (p = 0.00001). In children, we observed lower daily BPA indices in those living in homes with higher income (p = 0.0003) and following a less modern dietary pattern (p = 0.002), and higher daily BPA indices in those who were less physically active (p = 0.02). No significant associations were observed between daily BPA indices and BMI or AC. Despite this, the application of the daily BPA index identified factors associated with dietary BPA exposure and warrants further examination in Samoa and other understudied populations.

Systematic review (SR) is a rigorous methodology applied to synthesize and evaluate a body of scientific evidence to answer a research or policy question. Effective use of systematic-review methodology enables use of research evidence by decision makers. In addition, as reliance on systematic reviews increases, the required standards for quality of evidence enhances the policy relevance of research. Authoritative guidance has been developed for use of SR to evaluate evidence in the fields of medicine, social science, environmental epidemiology, toxicology, as well as ecology and evolutionary biology. In these fields, SR is typically used to evaluate a cause-effect relationship, such as the effect of an intervention, procedure, therapy, or exposure on an outcome. However, SR is emerging to be a useful methodology to transparently review and integrate evidence for a wider range of scientifically informed decisions and actions across disciplines. As SR is being used more broadly, there is growing consensus for developing resources, guidelines, ontologies, and technology to make SR more efficient and transparent, especially for handling large amounts of diverse data being generated across multiple scientific disciplines. In this article, we advocate for advancing SR methodology as a best practice in the field of exposure science to synthesize exposure evidence and enhance the value of exposure studies. We discuss available standards and tools that can be applied and extended by exposure scientists and highlight early examples of SRs being developed to address exposure research questions. Finally, we invite the exposure science community to engage in further development of standards and guidance to grow application of SR in this field and expand the opportunities for exposure science to inform environment and public health decision making.

Timing of breast development (or thelarche) and its endogenous and exogenous determinants may underlie global variation in breast cancer incidence. The study objectives were to characterize endogenous estrogen levels and bisphenol A (BPA) exposure using a migrant study of adolescent girls and test whether concentrations explained differences in thelarche by birthplace and growth environment. Estrogen metabolites (EM) and BPA-glucuronide (BPA-G) were quantified in urine spot samples using liquid chromatography tandem mass spectrometry (LC-MS/MS) from a cross-sectional study of Bangladeshi, first- and second-generation Bangladeshi migrants to the UK, and white British girls aged 5&ndash, 16 years (n = 348). Thelarche status at the time of interview was self-reported and defined equivalent to Tanner Stage &ge, 2. We compared geometric means (and 95% confidence interval (CIs)) of EM and BPA-G using linear regression and assessed whether EM and BPA-G explained any of the association between exposure to the UK and the age at thelarche using hazard ratios and 95% confidence intervals. Average EM decreased with exposure to the UK, whereas BPA-G increased and was significantly higher among white British (0.007 ng/mL, 95% CI: 0.0024&ndash, 0.0217) and second-generation British-Bangladeshi girls (0.009 ng/mL, 95% CI: 0.0040&ndash, 0.0187) compared to Bangladeshi girls (0.002 ng/mL, 95% CI: 0.0018&ndash, 0.0034). Two of four EM ratios (16-pathway/parent and parent/all pathways) were significantly associated with thelarche. The relationship between exposure to the UK and thelarche did not change appreciably after adding EM and BPA-G to the models. While BPA-G is often considered a ubiquitous exposure, our findings suggest it can vary based on birthplace and growth environment, with increasing levels for girls who were born in or moved to the UK. Our study did not provide statistically significant evidence that BPA-G or EM concentrations explained earlier thelarche among girls who were born or raised in the UK.

Background Perfluoroalkyl substances (PFAS) are suggested to interfere with thyroid hormone during pregnancy and influence fetal neurodevelopment. Epidemiological evidence regarding behavioral difficulties in childhood associated with prenatal PFAS exposure has been inconclusive. Objective We evaluated the association between prenatal PFAS exposure and behavioral difficulties at 7 and 11 years, and investigated the potential mediating role of maternal thyroid hormones. Methods Using pooled samples in the Danish National Birth Cohort established between 1996 and 2002, we estimated the associations between concentrations of six types of PFAS in maternal plasma (median, 8 gestational weeks) and child behavioral assessments from the Strength and Difficulties Questionnaire (SDQ), reported by parents at 7 years (n = 2421), and by parents (n = 2070) and children at 11 years (n = 2071). Behavioral difficulties were defined as having a composite SDQ score above the 90th percentile for total difficulties and externalizing or internalizing behaviors. We used logistic regression to estimate the adjusted Odds Ratio (OR) by doubling increase of prenatal PFAS (ng/ml). The possible mediating effect of maternal thyroid function classified based on thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were evaluated. Results Prenatal perfluorononanoic acid (PFNA) was consistently associated with total and externalizing behavioral difficulties in all three SDQ measures reported by parents (OR = 1.40, 95% CI: 1.14–1.73 for age 7; OR = 1.27, 95% CI: 1.05–1.53 for age 11) or children (OR = 1.32, 95% CI: 1.11–1.58) while no consistent associations were observed for other types of PFAS. A small magnitude of natural indirect effects via maternal thyroid dysfunction (ORs ranged from 1.01 to 1.03) of several PFAS were observed for parent-reported total and externalizing behaviors at 7 years only. Discussion Prenatal PFNA exposure was associated with externalizing behavioral difficulties in childhood in repeated SDQ measures at 7 and 11 years. The slight mediating effects of maternal thyroid hormones in early gestation warrant further evaluation.

Residents of agricultural areas experience pesticide exposures from sources other than direct agricultural work. We developed a quantitative, active ingredient-specific algorithm for cumulative (adult, married lifetime) non-occupational pesticide exposure intensity for spouses of farmers who applied pesticides in the Agricultural Health Study (AHS). The algorithm addressed three exposure pathways: take-home, agricultural drift, and residential pesticide use. Pathway-specific equations combined (i) weights derived from previous meta-analyses of published pesticide exposure data and (ii) information from the questionnaire on frequency and duration of pesticide use by applicators, home proximity to treated fields, residential pesticide usage (e.g., termite treatments), and spouse's off-farm employment (proxy for time at home). The residential use equation also incorporated a published probability matrix that documented the likelihood active ingredients were used in home pest treatment products. We illustrate use of these equations by calculating exposure intensities for the insecticide chlorpyrifos and herbicide atrazine for 19,959 spouses. Non-zero estimates for ≥1 pathway were found for 78% and 77% of spouses for chlorpyrifos and atrazine, respectively. Variability in exposed spouses' intensity estimates was observed for both pesticides, with 75th to 25th percentile ratios ranging from 7.1 to 7.3 for take-home, 6.5 to 8.5 for drift, 2.4 to 2.8 for residential use, and 3.8 to 7.0 for the summed pathways. Take-home and drift estimates were highly correlated (≥0.98), but were not correlated with residential use (0.01‒0.02). This algorithm represents an important advancement in quantifying non-occupational pesticide relative exposure differences and will facilitate improved etiologic analyses in the AHS spouses. The algorithm could be adapted to studies with similar information.

Emerging studies have provided evidence on the carcinogenicity of radiofrequency radiation (RFR) from cell phones. This study aims to test the genetic susceptibility on the association between cell phone use and thyroid cancer. Population-based case-control study was conducted in Connecticut between 2010 and 2011 including 440 thyroid cancer cases and 465 population-based controls with genotyping information for 823 single nucleotide polymorphisms (SNPs) in 176 DNA genes. We used multivariate unconditional logistic regression models to estimate the genotype-environment interaction between each SNP and cell phone use and to estimate the association with cell phone use in populations according to SNP variants. Ten SNPs had P 0.01 for interaction in all thyroid cancers. In the common homozygote groups, no association with cell phone use was observed. In the variant group (heterozygotes and rare homozygotes), cell phone use was associated with an increased risk for rs11070256 (odds ratio (OR): 2.36, 95% confidence interval (CI): 1.30-4.30), rs1695147 (OR: 2.52, 95% CI: 1.30-4.90), rs6732673 (OR: 1.59, 95% CI: 1.01-2.49), rs396746 (OR: 2.53, 95% CI: 1.13-5.65), rs12204529 (OR: 2.62, 95% CI: 1.33-5.17), and rs3800537 (OR: 2.64, 95% CI: 1.30-5.36) with thyroid cancers. In small tumors, increased risk was observed for 5 SNPs (rs1063639, rs1695147, rs11070256, rs12204529 and rs3800537), In large tumors, increased risk was observed for 3 SNPs (rs11070256, rs1695147, and rs396746). Our result suggests that genetic susceptibilities modify the associations between cell phone use and risk of thyroid cancer. The findings provide more evidence for RFR carcinogenic group classification.

The widespread distribution of unconventional oil and gas (UO&G) wells and other facilities in the United States potentially exposes millions of people to air and water pollutants, including known or suspected carcinogens. Childhood leukemia is a particular concern because of the disease severity, vulnerable population, and short disease latency. A comprehensive review of carcinogens and leukemogens associated with UO&G development is not available and could inform future exposure monitoring studies and human health assessments. The objective of this analysis was to assess the evidence of carcinogenicity of water contaminants and air pollutants related to UO&G development. We obtained a list of 1177 chemicals in hydraulic fracturing fluids and wastewater from the U.S. Environmental Protection Agency and constructed a list of 143 UO&G-related air pollutants through a review of scientific papers published through 2015 using PubMed and ProQuest databases. We assessed carcinogenicity and evidence of increased risk for leukemia/lymphoma of these chemicals using International Agency for Research on Cancer (IARC) monographs. The majority of compounds (>80%) were not evaluated by IARC and therefore could not be reviewed. Of the 111 potential water contaminants and 29 potential air pollutants evaluated by IARC (119 unique compounds), 49 water and 20 air pollutants were known, probable, or possible human carcinogens (55 unique compounds). A total of 17 water and 11 air pollutants (20 unique compounds) had evidence of increased risk for leukemia/lymphoma, including benzene, 1,3-butadiene, cadmium, diesel exhaust, and several polycyclic aromatic hydrocarbons. Though information on the carcinogenicity of compounds associated with UO&G development was limited, our assessment identified 20 known or suspected carcinogens that could be measured in future studies to advance exposure and risk assessments of cancer-causing agents. Our findings support the need for investigation into the relationship between UO&G development and risk of cancer in general and childhood leukemia in particular.

This study examines critical issues in accounting for urinary dilution in peri-implantation samples used to assess environmental exposures. Early pregnancy could impact creatinine excretion, which could bias biomarker measurement and interpretation when creatinine adjustment is used. We compared creatinine levels pre-implantation with levels soon after implantation at 3–6 weeks gestation. Using data and urine specimens from 145 women who conceived, we used linear mixed models to estimate the effect of pregnancy on creatinine concentrations. We also studied whether creatinine adjustment is biased when using pooled, within-person samples rather than averaging individually-adjusted results. For this, we grouped 2,655 daily urinary estrogen metabolite and associated creatinine measures into 762 mathematically-constructed sample pools, and compared averaged individual measures with pooled measures using weighted kappa coefficients and t-tests. Urinary creatinine concentration declined an average of 14% (95% CI: −19%, −11%) from pre- to post-implantation. While there was strong correlation between results based on the two creatinine adjustment methods, adjustment based on pooled specimens introduced a small 3% (95% CI: 2%, 4%) underestimation of the analyte compared to averaging individually-adjusted samples. Post-implantation creatinine declines could introduce errors in biomonitoring results when comparing exposure measures from pre- and post-implantation. Though pooled creatinine adjustment underestimated adjusted analyte concentrations, the bias was small and agreement excellent between pooled and averaged individually-adjusted assessments.

Background Thyroid cancer incidence has increased substantially over the past decades, and environmental risk factors have been suggested to play a role. Polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) are established thyroid hormone disruptors, but their relationship to thyroid cancer is not known. Methods We investigated the relationship between serum PCB and OCP concentrations and papillary thyroid cancer (PTC) in 250 incident female PTC cases and 250 female controls frequency-matched on age, all residing in Connecticut. Interviews and serum samples were collected from 2010 to 2013. Samples were analyzed for 32 different chemicals using gas chromatography with isotope dilution high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using single pollutant logistic regression models for concentrations (per interquartile range) of individual PCB/OCP and summed groups of structurally or biologically similar PCB/OCP, adjusted for education, family history of cancer, alcohol consumption, age, and body mass index. Sub-analyses included stratification by tumor size (≤ and >1 cm) and birth before or during peak PCB production (born in 1960 or earlier and born after 1960), as exposures during early life may be important. We also applied three multi-pollutant approaches (standard multi-pollutant regression, hierarchical Bayesian modeling, principal components regression analysis) to investigate associations with co-exposures to multiple PCB/OCPs. Results No PCB/OCPs were positively associated with PTC in primary analyses. Statistically significant associations were observed for 9 of the 32 chemicals and 3 summed groups of similar chemicals in the those born during peak production based on single-pollutant models. Multi-pollutant analyses suggested null associations overall. Conclusions Our results using single and multi-pollutant modeling do not generally support an association between PCB or OCP exposure and PTC, but some associations in those born during peak production suggest that additional investigation into early-life exposures and subsequent thyroid cancer risk may be warranted.

Background Dioxins are persistent organic pollutants generated from industrial combustion processes such as waste incineration. To date, results from epidemiologic studies of dioxin exposure and breast cancer risk have been mixed. Objectives To prospectively examine the association between ambient dioxin exposure using a nationwide spatial database of industrial dioxin-emitting facilities and invasive breast cancer risk in the Nurses’ Health Study II (NHSII). Methods NHSII includes female registered nurses in the US who have completed self-administered biennial questionnaires since 1989. Incident invasive breast cancer diagnoses were self-reported and confirmed by medical record review. Dioxin exposure was estimated based on residential proximity, duration of residence, and emissions from facilities located within 3, 5, and 10 km around geocoded residential addresses updated throughout follow-up. Cox regression models adjusted for breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results From 1989 to 2013, 3840 invasive breast cancer cases occurred among 112,397 participants. There was no association between residential proximity to any dioxin facilities (all facilities combined) and breast cancer risk overall. However, women who resided within 10 km of any municipal solid waste incinerator (MSWI) compared to none had increased breast cancer risk (adjusted HR = 1.15, 95% CI: 1.03, 1.28), with stronger associations noted for women who lived within 5 km (adjusted HR = 1.25, 95% CI: 1.04, 1.52). Positive associations were also observed for longer duration of residence and higher dioxin emissions from MSWIs within 3, 5, and 10 km. There were no clear differences in patterns of association for ER + vs. ER-breast cancer or by menopausal status. Discussion Results from this study support positive associations between dioxin exposure from MSWIs and invasive breast cancer risk.

Currently, there are >11,000 synthetic turf athletic fields in the United States and >13,000 in Europe. Concerns have been raised about exposure to carcinogenic chemicals resulting from contact with synthetic turf fields, particularly the infill material (“crumb rubber”), which is commonly fabricated from recycled tires. However, exposure data are scant, and the limited existing exposure studies have focused on a small subset of crumb rubber components. Our objective was to evaluate the carcinogenic potential of a broad range of chemical components of crumb rubber infill using computational toxicology and regulatory agency classifications from the United States Environmental Protection Agency (US EPA) and European Chemicals Agency (ECHA) to inform future exposure studies and risk analyses. Through a literature review, we identified 306 chemical constituents of crumb rubber infill from 20 publications. Utilizing ADMET Predictor™ , a computational program to predict carcinogenicity and genotoxicity, 197 of the identified 306 chemicals met our a priori carcinogenicity criteria. Of these, 52 chemicals were also classified as known, presumed or suspected carcinogens by the US EPA and ECHA. Of the remaining 109 chemicals which were not predicted to be carcinogenic by our computational toxicology analysis, only 6 chemicals were classified as presumed or suspected human carcinogens by US EPA or ECHA. Importantly, the majority of crumb rubber constituents were not listed in the US EPA (n = 207) and ECHA (n = 262) databases, likely due to an absence of evaluation or insufficient information for a reliable carcinogenicity classification. By employing a cancer hazard scoring system to the chemicals which were predicted and classified by the computational analysis and government databases, several high priority carcinogens were identified, including benzene, benzidine, benzo(a)pyrene, trichloroethylene and vinyl chloride. Our findings demonstrate that computational toxicology assessment in conjunction with government classifications can be used to prioritize hazardous chemicals for future exposure monitoring studies for users of synthetic turf fields. This approach could be extended to other compounds or toxicity endpoints.

Phthalates are plastic softeners that have been linked to several adverse health outcomes. The relative contributions of different sources to phthalate exposure in populations in different regions and at different life stages is unclear. We examined the relationships between water consumption, consumer product use, and phthalate exposure among 40 adolescents (20 males, 20 females) in Cluj-Napoca, Romania. Interviewers administered a questionnaire about drinking water consumption and use of phthalate-containing consumer products. Four common phthalates were measured in representative samples of participants&rsquo, municipal drinking water and consumed bottled water using gas chromatography-mass spectrometry. Urine samples were collected from participants and analyzed for the corresponding phthalate metabolites. Relationships between different exposure measures were assessed using nonparametric tests (Spearman rank correlation coefficients and the Kruskal&ndash, Wallis test). Diisobutyl phthalate, dibutyl phthalate, and bis(2-ethylhexyl) phthalate were commonly detected in bottled water, but generally not the municipal drinking water samples. Mono-n-butyl phthalate (MnBP) was the most commonly detected urinary metabolite (detected in 92.5% of participants) and had the highest maximum concentration (1139.77 &micro, g/g creatinine). We did not identify any statistically significant associations between water consumption or consumer product use practices and urinary phthalate metabolite concentrations in our adolescent group, and directions of correlation coefficients differed by individual phthalate compound. While phthalate exposure was widespread, these results highlight the challenges in examining phthalate exposure determinants and emphasize the need for further investigation into understanding exposure sources and potential health risks from chronic low-level exposures.

Purpose This study aims to investigate the association between cell phone use and thyroid cancer. Methods A population-based case–control study was conducted in Connecticut between 2010 and 2011 including 462 histologically confirmed thyroid cancer cases and 498 population-based controls. Multivariate unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between cell phone use and thyroid cancer. Results Cell phone use was not associated with thyroid cancer (OR: 1.05, 95% CI: 0.74–1.48). A suggestive increase in risk of thyroid microcarcinoma (tumor size ≤10 mm) was observed for long-term and more frequent users. Compared with cell phone nonusers, several groups had nonstatistically significantly increased risk of thyroid microcarcinoma: individuals who had used a cell phone >15 years (OR: 1.29, 95% CI: 0.83–2.00), who had used a cell phone >2 hours per day (OR: 1.40, 95% CI: 0.83–2.35), who had the most cumulative use hours (OR: 1.58, 95% CI: 0.98–2.54), and who had the most cumulative calls (OR: 1.20, 95% CI: 0.78–1.84). Conclusions This study found no significant association between cell phone use and thyroid cancer. A suggestive elevated risk of thyroid microcarcinoma associated with long-term and more frequent uses warrants further investigation.

Polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) emissions from industrial sources contaminate the surrounding environment. Proximity-based exposure surrogates assume accuracy in the location of PCDD/F sources, but locations are not often verified. We manually reviewed locations (i.e., smokestack geo-coordinates) in a historical database of 4478 PCDD/F-emitting facilities in 2009 and 2016. Given potential changes in imagery and other resources over this period, we re-reviewed a random sample of 5% of facilities (n = 240) in 2016. Comparing the original and re-review of this sample, we evaluated agreement in verification (location confirmed or not) and distances between verified locations (verification error), overall and by facility type. Using the verified location from re-review as a gold standard, we estimated the accuracy of proximity-based exposure metrics and epidemiologic bias. Overall agreement in verification was high (>84%), and verification errors were small (median = 84 m) but varied by facility type. Accuracy of exposure classification (≥1 facility within 5 km) for a hypothetical study population also varied by facility type (sensitivity: 69–96%; specificity: 95–98%). Odds ratios were attenuated 11–69%, with the largest bias for rare facility types. We found good agreement between reviews of PCDD/F source locations, and that exposure prevalence and facility type may influence associations with exposures derived from this database. Our findings highlight the need to consider location error and other contextual factors when using proximity-based exposure metrics.

To investigate the risk of non-Hodgkin lymphoma (NHL) associated with residential carpet dust measurements of polycyclic aromatic hydrocarbons (PAHs). We evaluated the relationship between residential carpet dust PAH concentrations (benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(k)fluoranthene, chrysene, dibenz(a,h)anthracene, and indeno(1,2,3-c,d)pyrene, and their sum) and risk of NHL (676 cases, 511 controls) in the National Cancer Institute Surveillance Epidemiology and End Results multicenter case–control study. As a secondary aim, we investigated determinants of dust PAH concentrations. We computed odds ratios (OR) and 95 % confidence interval (CI) for associations between NHL and concentrations of individual and summed PAHs using unconditional logistic regression, adjusting for age, gender, and study center. Determinants of natural log-transformed PAHs were investigated using multivariate least-squares regression. We observed some elevated risks for NHL overall and B cell lymphoma subtypes in association with quartiles or tertiles of PAH concentrations, but without a monotonic trend, and there was no association comparing the highest quartile or tertile to the lowest. In contrast, risk of T cell lymphoma was significantly increased among participants with the highest tertile of summed PAHs (OR = 3.04; 95 % CI, 1.09–8.47) and benzo(k)fluoranthene (OR = 3.20; 95 % CI, 1.13–9.11) compared with the lowest tertile. Predictors of PAH dust concentrations in homes included ambient air PAH concentrations and the proportion of developed land within 2 km of a residence. Older age, more years of education, and white race were also predictive of higher levels in homes. Our results suggest a potential link between PAH exposure and risk of T cell lymphoma and demonstrate the importance of analyzing risk by NHL histologic type.

Proximity to facilities emitting polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) has been associated with increased risk of non-Hodgkin lymphoma (NHL). There is limited information about whether proximity to industrial sources leads to indoor PCDD/F contamination of homes. We measured carpet dust concentrations (pg/g) of 17 toxic PCDD/F congeners and calculated their toxic equivalence (TEQ) in 100 homes in a population-based case-control study of NHL in Detroit, Los Angeles, Seattle, and Iowa (1998–2000). We took global positioning system readings at residences and obtained coordinates and PCDD/F emissions (ng TEQ/yr) from an Environmental Protection Agency database for 6 facility types: coal-fired electricity generating plants, cement kilns burning non-hazardous waste, hazardous waste incinerators, medical waste incinerators, municipal solid waste incinerators, and sewage sludge incinerators. For each residence, we computed an inverse distance-squared weighted average emission index (AEI [pg TEQ/km2/yr]) for all facilities within 5 km from 1983–2000. We also computed AEIs for each of the 6 facility types. We evaluated relationships between PCDD/F dust concentrations and the all-facility AEI or categories of facility-type AEIs using multivariable linear regression, adjusting for study center, demographics, and home characteristics. A doubling of the all-facility AEI was associated with a 4–8% increase in PCDD/F dust concentrations of 7 of 17 PCDD/F congeners and the TEQ (p-value

Metabolomics studies of the early-life exposome often use maternal urine specimens to investigate critical developmental windows, including the periconceptional period and early pregnancy. During these windows changes in kidney function can impact urine concentration. This makes accounting for differential urinary dilution across samples challenging. Because there is no consensus on the ideal normalization approach for urinary metabolomics data, this study&rsquo, s objective was to determine the optimal post-analytical normalization approach for untargeted metabolomics analysis from a periconceptional cohort of 45 women. Urine samples consisted of 90 paired pre- and post-implantation samples. After untargeted mass spectrometry-based metabolomics analysis, we systematically compared the performance of three common approaches to adjust for urinary dilution&mdash, creatinine adjustment, specific gravity adjustment, and probabilistic quotient normalization (PQN)&mdash, using unsupervised principal components analysis, relative standard deviation (RSD) of pooled quality control samples, and orthogonal partial least-squares discriminant analysis (OPLS-DA). Results showed that creatinine adjustment is not a reliable approach to normalize urinary periconceptional metabolomics data. Either specific gravity or PQN are more reliable methods to adjust for urinary concentration, with tighter quality control sample clustering, lower RSD, and better OPLS-DA performance compared to creatinine adjustment. These findings have implications for metabolomics analyses on urine samples taken around the time of conception and in contexts where kidney function may be altered.

We evaluated predictors of differences in published occupational lead concentrations for activities disturbing material painted with or containing lead in U.S. workplaces to aid historical exposure reconstruction.For the aforementioned tasks, 221 air and 113 blood lead summary results (1960-2010) were extracted from a previously developed database. Differences in the natural log-transformed geometric mean (GM) for year, industry, job, and other ancillary variables were evaluated in meta-regression models that weighted each summary result by its inverse variance and sample size.Air and blood lead GMs declined 5%/year and 6%/year, respectively, in most industries. Exposure contrast in the GMs across the nine jobs and five industries was higher based on air versus blood concentrations. For welding activities, blood lead GMs were 1.7 times higher in worst-case versus non-worst case scenarios.Job, industry, and time-specific exposure differences were identified; other determinants were too sparse or collinear to characterize. Am. J. Ind. Med. 60:189-197, 2017. © 2017 Wiley Periodicals, Inc.

Objectives To assess the associations between occupational exposure to biocides and pesticides and risk of thyroid cancer. Methods Using data from a population-based case–control study involving 462 incident thyroid cancer cases and 498 controls in Connecticut collected in 2010–2011, we examined the association with occupational exposure to biocides and pesticides through a job-exposure matrix. We used unconditional logistic regression models to estimate OR and 95% CI, adjusting for potential confounders. Results Individuals who were occupationally ever exposed to biocides had an increased risk of thyroid cancer (OR=1.65, 95% CI 1.16 to 2.35), and the highest risk was observed for the high cumulative probability of exposure (OR=2.18, 95% CI 1.28 to 3.73). The observed associations were similar when we restricted to papillary thyroid cancer and well-differentiated thyroid cancer. Stronger associations were observed for thyroid microcarcinomas (tumour size ≤1 cm). No significant association was observed for occupational exposure to pesticides. Conclusions Our study provides the first evidence linking occupational exposure to biocides and risk of thyroid cancer. The results warrant further investigation.

Active ingredients in residential and agricultural insecticides have changed over time, due in part to regulatory restrictions. Few studies have evaluated how changes in active ingredients have impacted insecticide levels measured in homes. We measured concentrations of insecticides in one carpet-dust sample from each of 434 homes in California from 2001 to 2006. Analytes included four insecticides sold for indoor home use during our study period (carbaryl, cypermethrin, permethrin, and propoxur) and four that are no longer sold for indoor use including dichlorodiphenyltrichloroethylene (DDT, removed from the market in 1972), chlordane (1988), chlorpyrifos (2001), and diazinon (2004). We considered other potential determinants of concentrations of insecticides in carpet dust, such as home and garden use, occupational exposure, and nearby agricultural applications. We calculated the percentage change in the concentration of each insecticide per year, adjusting for significant determinants. In adjusted models, concentrations of insecticides in carpet dust decreased for three of four insecticides no longer sold for residential use: chlordane (-15% per year), chlorpyrifos (-31%), diazinon (-48%), and propoxur (-34%), which is currently sold for residential use but with increased restrictions since 1997. Concentrations of other insecticides sold for indoor use (carbaryl, cypermethrin, and permethrin) and DDT did not change over time in our study population.

Inconsistent risk estimates for dietary heterocyclic amine (HCA) exposure and cancers may be due to differences in exposure assessment methods and the associated measurement error. We evaluated repeatability and comparability of intake estimates of the HCA 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) among two food frequency questionnaire (FFQ) collections, three diary collections, and three measurements of urinary PhIP and its metabolites in 36 non-smokers in Baltimore, Maryland, during 2004-2005. Collections spanned ∼9 months. Method repeatability was characterised with intraclass correlation coefficients (ICCs). Comparability among methods was assessed with Spearman correlation coefficients. Within-subject variability in PhIP intake was comparably high across all methods (ICCs of 0.20, 0.30, and 0.15 for FFQ, diary, and creatinine-adjusted urinary PhIP, respectively). Mean diary-based PhIP intake and mean urinary PhIP concentration were strongly correlated when restricting the analysis to participants with at least one non-zero diary-based estimate of PhIP intake (n = 15, r = 0.75, p = 0.001), but not in the full study population (n = 36, r = 0.18, p = 0.28). Mean PhIP intake from the FFQ was not associated with that either based on the diary or urinary PhIP separately, but was modestly correlated with a metric that combined the diary- and biomarker-based approaches (r = 0.30, p = 0.08). The high within-subject variability will result in significantly attenuated associations if a single measure is used to estimate exposure within an epidemiologic study. Improved HCA assessment tools, such as a combination of methods or validated biomarkers that capture long term exposure, are needed.

Linzhou, China has one of the highest rates of esophageal squamous cell carcinoma in the world. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), may have a role in this increased risk. To better understand PAH sources, we measured PAHs in the air and food of 20 non-smokers over multiple days and compared the concentrations with a urinary PAH biomarker, 1-hydroxypyrene glucuronide (1-OHPG). Sampling occurred over 4 consecutive days. Kitchen air samples (days 2-3) and duplicate diet samples (days 1-4) were analyzed for 14 or more unique PAHs, including BaP. Daily urine samples (days 1-3) were analyzed for 1-OHPG. Mixed-effects models were used to evaluate the associations between air or food PAH concentrations and urine 1-OHPG concentrations. The median kitchen air BaP concentration was 10.2 ng/m(3) (interquartile range (IQR): 5.1-20.2 ng/m(3)). The median daily food BaP concentration and intake were 0.08 ng/g (IQR=0.04-0.16 ng/g) and 86 ng/day (IQR=41-142 ng/day), respectively. The median 1-OHPG concentration was 3.36 pmol/ml (IQR=2.09-6.98 pmol/ml). In mixed-effects models, 1-OHPG concentration increased with same-day concentration of food BaP (P=0.07). Although PAH concentrations in air were not associated with 1-OHPG concentrations, the high concentrations of PAHs in both air and food suggest that they are both important routes of exposure to PAHs in this population. Further evaluation of the role of PAH exposure from air and food in the elevated rates of esophageal cancer in this region is warranted.

Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001–2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants’ household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs (based on OR per ln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR per ln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI= 0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study.

The reliability and validity of six experts' exposure ratings were evaluated for 64 nickel-exposed and 72 chromium-exposed workers from six Shanghai electroplating plants based on airborne and urinary nickel and chromium measurements. Three industrial hygienists and three occupational physicians independently ranked the exposure intensity of each metal on an ordinal scale (1-4) for each worker's job in two rounds: the first round was based on responses to an occupational history questionnaire and the second round also included responses to an electroplating industry-specific questionnaire. The Spearman correlation (r(s)) was used to compare each rating's validity to its corresponding subject-specific arithmetic mean of four airborne or four urinary measurements. Reliability was moderately high (weighted kappa range=0.60-0.64). Validity was poor to moderate (r(s)=-0.37-0.46) for both airborne and urinary concentrations of both metals. For airborne nickel concentrations, validity differed by plant. For dichotomized metrics, sensitivity and specificity were higher based on urinary measurements (47-78%) than airborne measurements (16-50%). Few patterns were observed by metal, assessment round, or expert type. These results suggest that, for electroplating exposures, experts can achieve moderately high agreement and (reasonably) distinguish between low and high exposures when reviewing responses to in-depth questionnaires used in population-based case-control studies.

Polychlorinated biphenyls (PCBs), banned in the United Sates in the late 1970s, are still found in indoor and outdoor environments. Little is known about the determinants of PCB levels in homes. We measured concentrations of five PCB congeners (105, 138, 153, 170, and 180) in carpet dust collected between 1998 and 2000 from 1187 homes in four sites: Detroit, Iowa, Los Angeles, and Seattle. Home characteristics, occupational history, and demographic information were obtained by interview. We used a geographic information system to geocode addresses and determine distances to the nearest major road, freight route, and railroad; percentage of developed land; number of industrial facilities within 2 km of residences; and population density. Ordinal logistic regression was used to estimate the associations between the covariates of interest and the odds of PCB detection in each site separately. Total PCB levels [all congenersmaximum practical quantitation limit (MPQL) vs at least one congener ≥ MPQL tomedian concentration vs at least one congenermedian concentration] were positively associated with either percentage of developed land [odds ratio (OR) range 1.01-1.04 for each percentage increase] or population density (OR 1.08 for every 1000/mi(2)) in each site. The number of industrial facilities within 2 km of a home was associated with PCB concentrations; however, facility type and direction of the association varied by site. Our findings suggest that outdoor sources of PCBs may be significant determinants of indoor concentrations.

Determinants of levels of polychlorinated dibenzo- p-dioxins and polychlorinated dibenzofurans (PCDD/F) in dust in U.S. homes are not well characterized. We conducted a pilot study to evaluate the relationship between concentrations of PCDD/F in house dust and residential proximity to known sources, including industrial facilities and traffic. Samples from vacuum bag dust from homes of 40 residents of Detroit, Los Angeles, Seattle, or Iowa who participated in a population-based case-control study of non-Hodgkin lymphoma conducted in 1998-2000 were analyzed using high resolution gas chromatography/high resolution mass spectrometry for 7 PCDD and 10 PCDF congeners considered toxic by the U.S. Environmental Protection Agency (EPA). Locations of 10 types of PCDD/F-emitting facilities were obtained from the EPA; however only 4 types were located near study homes (non-hazardous waste cement kilns, coal-fired power plants, sewage sludge incinerators, and medical waste incinerators). Relationships between concentrations of each PCDD/F and proximity to industrial facilities, freight routes, and major roads were evaluated using separate multivariate regression models for each congener. The median (inter-quartile range [IQR]) toxic equivalence (TEQ) concentration of these congeners in the house dust was 20.3. pg/g (IQR. =. 14.3, 32.7). Homes within 3 or 5. km of a cement kiln had 2 to 9-fold higher concentrations of 5 PCDD and 5 PCDF (p.

Different wipe materials and wetting agents have been used to collect pesticide residues from surfaces, but little is known about their comparability. To inform the selection of a wipe for the National Children’s Study, the analytical feasibility, collection efficiency, and precision of Twillwipes wetted with isopropanol (TI), Ghost Wipes (GW), and Twillwipes wetted with water (TW), and were evaluated. Wipe samples were collected from stainless steel surfaces spiked with high and low concentrations of 27 insecticides, including organochlorines, organophosphates, and pyrethroids. Samples were analyzed by GC/MS/SIM. No analytical interferences were observed for any of the wipes. The mean percent collection efficiencies across all pesticides for the TI, GW, and TW were 69.3%, 31.1%, and 10.3% at the high concentration, respectively, and 55.6%, 22.5%, and 6.9% at the low concentration, respectively. The collection efficiencies of the TI were significantly greater than that of GW or TW (p

Background: Inconsistent presence and strength of associations between dietary benzo[a]pyrene (BaP) exposure and cancers may be due to differences in exposure assessment methods. Thus, we determined correlations of usual meat and BaP intake among three methods: food frequency questionnaires (FFQ), diet diaries, and a biomarker. Methods: Thirty-six nonsmokers were recruited in Baltimore, MD during 2004–2005. Meat and BaP intake estimated from baseline and follow-up FFQs combined with a BaP residue database (FFQ-RD), mean meat and BaP intake estimated from three diet diaries coupled with the residue database (Diary-RD), and mean of three urinary 1-hydroxypyrene glucuronide (1-OHPG) measurements were compared using Spearman correlations. Collections spanned approximately nine months. Results: BaP intakes from meat from the baseline [median = 6.4, interquartile range (IQR) = 13.9 ng/d] and follow-up FFQ-RD (median = 7.3, IQR = 35.7 ng/d) were higher than the Diary-RD (median = 1.1, IQR = 7.4 ng/d). Mean 1-OHPG concentration was weakly correlated with mean meat intake (r = 0.33, P = 0.05) and BaP intake from meat (r = 0.27, P = 0.11) from the Diary-RD. Mean BaP intake estimated from the Diary-RD was positively correlated with the follow-up (r = 0.35, P = 0.04) but not baseline (r = 0.20, P = 0.24) FFQ; the converse was true for meat intake. Conclusions: Diary-RD estimates were supported by biomarker measurements, but considerable unexplained variability remained. Limited correlation among the dietary BaP exposure assessment methods could be due to differences in timeframes covered by the assessments, interpersonal variability in metabolism, deficiencies in the residue database, or nondietary exposures to BaP. Impact: Limited correlation in estimated BaP intake among standard methods may contribute to inconsistent epidemiology of BaP and cancer. Cancer Epidemiol Biomarkers Prev; 20(5); 962–70. ©2011 AACR.