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Exposure to traffic-related pollutants, including diesel exhaust, is associated with increased risk of cardiopulmonary disease and mortality; however, the precise biochemical pathways underlying these effects are not known. To investigate biological response mechanisms underlying exposure to traffic related pollutants, we used an integrated molecular response approach that included high-resolution metabolomic profiling and peripheral blood gene expression to identify biological responses to diesel exhaust exposure. Plasma samples were collected from 73 non-smoking males employed in the US trucking industry between February 2009 and October 2010, and analyzed using untargeted high-resolution metabolomics to characterize metabolite associations with shift- and week-averaged levels of elemental carbon (EC), organic carbon (OC) and particulate matter with diameter ≤ 2.5 μm (PM2.5). Metabolic associations with EC, OC and PM2.5 were evaluated for biochemical processes known to be associated with disease risk. Annotated metabolites associated with exposure were then tested for relationships with the peripheral blood transcriptome using multivariate selection and network correlation. Week-averaged EC and OC levels, which were averaged across multiple shifts during the workweek, resulted in the greatest exposure-associated metabolic alterations compared to shift-averaged exposure levels. Metabolic changes associated with EC exposure suggest increased lipid peroxidation products, biomarkers of oxidative stress, thrombotic signaling lipids, and metabolites associated with endothelial dysfunction from altered nitric oxide metabolism, while OC exposures were associated with antioxidants, oxidative stress biomarkers and critical intermediates in nitric oxide production. Correlation with whole blood RNA gene expression provided additional evidence of changes in processes related to endothelial function, immune response, inflammation, and oxidative stress. We did not detect metabolic associations with PM2.5. This study provides an integrated molecular assessment of human exposure to traffic-related air pollutants that includes diesel exhaust. Metabolite and transcriptomic changes associated with exposure to EC and OC are consistent with increased risk of cardiovascular diseases and the adverse health effects of traffic-related air pollution.

Given the complex exposures from both exogenous and endogenous sources that an individual experiences during life, exposome-wide association studies that interrogate levels of small molecules in biospecimens have been proposed for discovering causes of chronic diseases. We conducted a study to explore associations between environmental chemicals and endogenous molecules using Gaussian graphical models (GGMs) of non-targeted metabolomics data measured in a cohort of California women firefighters and office workers. GGMs revealed many exposure-metabolite associations, including that exposures to mono-hydroxyisononyl phthalate, ethyl paraben and 4-ethylbenzoic acid were associated with metabolites involved in steroid hormone biosynthesis, and perfluoroalkyl substances were linked to bile acids—hormones that regulate cholesterol and glucose metabolism—and inflammatory signaling molecules. Some hypotheses generated from these findings were confirmed by analysis of data from the National Health and Nutrition Examination Survey. Taken together, our findings demonstrate a novel approach to discovering associations between chemical exposures and biological processes of potential relevance for disease causation.

Given the complex exposures from both exogenous and endogenous sources that an individual experiences during life, exposome-wide association studies that interrogate levels of small molecules in biospecimens have been proposed for discovering causes of chronic diseases. We conducted a study to explore associations between environmental chemicals and endogenous molecules using Gaussian graphical models (GGMs) of non-targeted metabolomics data measured in a cohort of California women firefighters and office workers. GGMs revealed many exposure-metabolite associations, including that exposures to mono-hydroxyisononyl phthalate, ethyl paraben and 4-ethylbenzoic acid were associated with metabolites involved in steroid hormone biosynthesis, and perfluoroalkyl substances (PFAS) were linked to bile acids – hormones that regulate cholesterol and glucose metabolism – and inflammatory signaling molecules. Some hypotheses generated from these findings were confirmed by analysis of data from the National Health and Nutrition Examination Survey (NHANES). Taken together, our findings demonstrate a novel approach to discovering associations between chemical exposures and biological processes of potential relevance for disease causation.

Nearly all Americans have detectable concentrations of endocrine disrupting chemicals from consumer products in their bodies, and expert panels recommend reducing exposures. To inform exposure reduction, we investigated whether consumers who are trying to avoid certain chemicals in consumer products have lower exposures than those who are not. We also aimed to make exposure biomonitoring more widely available. We enrolled 726 participants in a crowdsourced biomonitoring study. We targeted phenolic compounds-specifically parabens, bisphenol A (BPA) and analogs bisphenol F (BPF) and bisphenol S (BPS), the UV filter benzophenone-3, the anti-microbial triclosan, 2,4-dichlorophenol, and 2,5-dichlorophenol-and collected survey data on consumer products, cleaning habits, and efforts to avoid related chemicals. We investigated associations between 68 self-reported exposure behaviors and urine concentrations of ten chemicals, and evaluated whether associations were modified by intention to avoid exposures. A large majority (87%) of participants reported taking steps to limit exposure to specific chemicals, and, overall, participants achieved lower concentrations than the general U.S. population for parabens, BPA, triclosan, and benzophenone-3 but not BPF and BPS. Participants who reported avoiding all four ingredient groups-parabens, triclosan, bisphenols, and fragrances-were twice as likely as others to be in the lowest quartile of cumulative exposure. Avoiding certain products and reading ingredient labels to avoid chemicals was most effective for parabens, triclosan, and benzophenone-3. Avoiding BPA was not effective for reducing bisphenol exposures. Avoiding certain chemicals in products was generally associated with reduced exposure for chemicals listed on labels. Greater ingredient transparency will help consumers who read labels to reduce their exposure to a wider range of potentially harmful chemicals. In order to more equitably address public health, labeling policies should be complemented by regulations that exclude harmful chemicals from consumer products.

Innovative exposure measurement methods are needed for large environmental health studies, particularly for semivolatile organic compounds (SVOCs). Active air sampling methods are costly to implement, but passive air sampling presents a viable method. To expand and improve the use of passive air samplers (PAS) for indoor SVOC monitoring, we designed a unique, compact sampler using commercially available polyurethane foam (PUF) disks housed within durable, easy-to-setup, low-profile enclosures. We evaluated the new design using co-located active air samplers (AAS) and analyzed for SVOCs. Most of the targeted SVOCs found using active sampling (27 of 33) were also detected using passive sampling. We found good agreement (R2 = 0.88) between active and passive sampling methods for characterizing the relative abundance of each chemical, and the measured active sampler concentrations and passive sampler masses were significantly positively correlated for 14 of 21 chemicals, for which correlations could be estimated. We found that measurements of many SVOCs originating from consumer products and typically found in the gas-phase (log KOA

Background Personal care products are a source of exposure to endocrine disrupting and asthma-associated chemicals. Because use of hair products differs by race/ethnicity, these products may contribute to exposure and disease disparities. Objective This preliminary study investigates the endocrine disrupting and asthma-associated chemical content of hair products used by U.S. Black women. Methods We used gas chromatography/mass spectrometry (GC/MS) to test 18 hair products in 6 categories used by Black women: hot oil treatment, anti-frizz/polish, leave-in conditioner, root stimulator, hair lotion, and relaxer. We tested for 66 chemicals belonging to 10 chemical classes: ultraviolet (UV) filters, cyclosiloxanes, glycol ethers, fragrances, alkylphenols, ethanolamines, antimicrobials, bisphenol A, phthalates, and parabens. Results The hair products tested contained 45 endocrine disrupting or asthma-associated chemicals, including every targeted chemical class. We found cyclosiloxanes, parabens, and the fragrance marker diethyl phthalate (DEP) at the highest levels, and DEP most frequently. Root stimulators, hair lotions, and relaxers frequently contained nonylphenols, parabens, and fragrances; anti-frizz products contained cyclosiloxanes. Hair relaxers for children contained five chemicals regulated by California's Proposition 65 or prohibited by EU cosmetics regulation. Targeted chemicals were generally not listed on the product label. Conclusions Hair products used by Black women and children contained multiple chemicals associated with endocrine disruption and asthma. The prevalence of parabens and DEP is consistent with higher levels of these compounds in biomonitoring samples from Black women compared with White women. These results indicate the need for more information about the contribution of consumer products to exposure disparities. A precautionary approach would reduce the use of endocrine disrupting chemicals in personal care products and improve labeling so women can select products consistent with their values.

Health disparities in low-income communities may be linked to residential exposures to chemicals infiltrating from the outdoors and characteristics of and sources in the home. Indoor sources comprise those introduced by the occupant as well as releases from building materials. To examine the impact of renovation on indoor pollutants levels and to classify chemicals by predominant indoor sources, we collected indoor air and surface wipes from newly renovated “green” low-income housing units in Boston before and after occupancy. We targeted nearly 100 semivolatile organic compounds (SVOCs) and volatile organic compounds (VOCs), including phthalates, flame retardants, fragrance chemicals, pesticides, antimicrobials, petroleum chemicals, chlorinated solvents, and formaldehyde, as well as particulate matter. All homes had indoor air concentrations that exceeded available risk-based screening levels for at least one chemical. We categorized chemicals as primarily influenced by the occupant or as having building-related sources. While building-related chemicals observed in this study may be specific to the particular housing development, occupant-related findings might be generalizable to similar communities. Among 58 detected chemicals, we distinguished 25 as primarily occupant-related, including fragrance chemicals 6-acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran (HHCB). The pre- to post-occupancy patterns of the remaining chemicals suggested important contributions from building materials for some, including dibutyl phthalate and xylene, whereas others, such as diethyl phthalate and formaldehyde, appeared to have both building and occupant sources. Chemical classification by source informs multi-level exposure reduction strategies in low-income housing. Keywords: Semivolatile organic compounds (SVOCs), Volatile organic compounds (VOCs), Indoor air, Surface wipes, Consumer products, Building materials

BackgroundEnvironmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential biomarker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA.MethodsWe measured serum concentrations of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters (N = 84) and office workers (N = 79) who participated in the 2014–15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length.ResultsRegression results revealed significant positive associations between perfluorooctanoic acid (PFOA) and telomere length and perfluorooctanesulfonic acid (PFOS) and telomere length among the whole cohort. Models stratified by occupation showed stronger and more significant associations among firefighters as compared to office workers. Among firefighters in models adjusted for age, we found positive associations between telomere length and log-transformed PFOA (β(95%CI) = 0.57(0.12, 1.02)), PFOS (0.44 (0.05, 0.83)), and perfluorodecanoic acid (PFDA) (0.43 (0.02, 0.84)). Modeling PFAS as categories of exposure showed significant associations between perfluorononanoic acid (PFNA) and telomere length among firefighters. Significant associations between OPFR metabolites and telomere length were seen for bis (1,3-dichloro-2-propyl) phosphate (BDCPP) and telomere length among office workers (0.21(0.03, 0.40)) and bis (2-chloroethyl) phosphate (BCEP) and telomere length among firefighters (− 0.14(− 0.28, − 0.01)). For OPFRs, the difference in the direction of effect by occupational group may be due to the disparate detection frequencies and concentrations of exposure between the two groups and/or potential unmeasured confounding.ConclusionOur findings suggest positive associations between PFAS and telomere length in women workers, with larger effects seen among firefighters as compared to office workers. The OPFR metabolites BDCPP and BCEP are also associated with telomere length in firefighters and office workers. Associations between chemical exposures and telomere length reported here and by others suggest mechanisms by which these chemicals may affect carcinogenesis and other adverse health outcomes.

BackgroundOccupational exposures to flame retardants (FR), which are suspected endocrine disrupting compounds, may be of particular concern for firefighters as they are commonly found in consumer products and have been detected in fire station dust and firefighter gear.ObjectivesThe Women Workers Biomonitoring Collaborative is a community based participatory research study that sought to measure environmental chemicals relevant to firefighting and evaluate their effects on thyroid hormone levels.MethodsWe measured 10 FR or their metabolites in urine of female firefighters and office workers from San Francisco: bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBuP), dibenzyl phosphate (DBzP), di-p-cresyl phosphate (DpCP), di-o-cresyl phosphate (DoCP), 2,3,4,5-tetrabromobenzoic acid (TBBA), tetrabromobisphenol-A (TBBPA), 5-OH-BDE 47, and 5-OH-BDE 100. We assessed potential predictors of exposure levels and the association between FR exposures and thyroxine (T4) and thyroid stimulating hormone (TSH).ResultsBDCPP, BCEP, and DBuP were the most commonly detected FRs, among all study participants, with intermediate BMI and college educated women having the highest levels, and Black women having higher BDCPP levels than White women. Firefighters had higher detection frequencies (DF) and exposure levels compared to office workers; median BDCPP levels were five times higher in firefighters than in office workers. Among firefighters, occupational activities were not significantly associated with FR levels, although position (i.e. officer and firefighter versus driver), being on-duty (versus off-duty) and assigned to the airport suggested a positive association with FR levels. Among firefighters, a doubling of BDCPP was associated with a 2.88% decrease (95%CI −5.28,-0.42) in T4. We did not observe significant associations between FR and T4 among office workers.DiscussionFirefighters had significantly higher exposures to FR compared to office workers, and we observed a negative association between BDCPP and thyroxine in firefighters. Future research should elucidate occupational sources of FR exposure and opportunities for exposure reduction.

BackgroundWomen firefighters are exposed to recognized and probable carcinogens, yet there are few studies of chemical exposures and associated health concerns, such as breast cancer. Biomonitoring often requires a priori selection of compounds to be measured, and so may not detect important, lesser known, exposures.ObjectivesThe Women Firefighters Biomonitoring Collaborative (WFBC) created a biological sample archive and conducted a general suspect screen (GSS) to address this data gap.MethodsUsing liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) we sought to identify candidate chemicals of interest in serum samples from 83 women firefighters (FF) and 79 office workers (OW) in San Francisco. Through the GSS approach we identified chemical peaks by matching accurate mass from serum samples against a custom chemical database of 740 slightly polar phenolic and acidic compounds, including many of relevance to firefighting or breast cancer etiology. We then selected chemicals for confirmation based on a priori criteria: 1) detection frequency or peak area differences between OW and FF; 2) evidence of mammary carcinogenicity, estrogenicity, or genotoxicity; and 3) not currently measured in large biomonitoring studies.ResultsWe detected 620 chemicals that matched 300 molecular formulas in the WFBC database, including phthalate metabolites, phosphate flame retardant metabolites, phenols, pesticides, nitro-and nitroso-compounds, and per- and polyfluoroalkyl substances. The average number of chemicals from the database that were detected in participants was 72 and 70 in FF and OW, respectively. We confirmed 8 of the 20 prioritized suspect chemicals –including two alkylphenols, ethyl paraben, BPF, PFOSAA, benzophenone-3, benzyl p-hydroxybenzoate, and triphenyl phosphate--by running a matrix spike of the reference standards and using m/z, retention time and the confirmation of at least two fragment ions as criteria for matching.ConclusionGSS provides a powerful high-throughput approach to identify and prioritize novel chemicals for biomonitoring and health studies.

Domestic drinking water wells serve 44 million people in the US and are common globally. They are often located in areas served by onsite wastewater treatment systems, including septic systems, which can be sources of biological and chemical pollutants to groundwater. In this study we tested 20 domestic drinking water wells in a sand and gravel aquifer on Cape Cod, Massachusetts, USA, for 117 organic wastewater compounds (OWCs) and for inorganic markers of septic system impact. We detected 27 OWCs, including 12 pharmaceuticals, five per- and polyfluoroalkyl substances (PFASs), four organophosphate flame retardants, and an artificial sweetener (acesulfame). Maximum concentrations of several PFASs and pharmaceuticals were relatively high compared to public drinking water supplies in the US. The number of detected OWCs and total concentrations of pharmaceuticals and of PFASs were positively correlated with nitrate, boron, and acesulfame and negatively correlated with well depth. These wells were all located in areas served exclusively by onsite wastewater treatment systems, which are likely the main source of the OWCs in these wells, although landfill leachate may also be a source. Our results suggest that current regulations to protect domestic wells from pathogens in septic system discharges do not prevent OWCs from reaching domestic wells, and that nitrate, a commonly measured drinking water contaminant, is a useful screening tool for OWCs in domestic wells. Nitrate concentrations of 1mg/L NO3-N, which are tenfold higher than local background and tenfold lower than the US federal drinking water standard, were associated with wastewater impacts from OWCs in this study.

Over 200 chemicals have been associated with altered mammary gland development and cancer in rodent studies, yet the molecular mechanisms by which this diverse set of chemicals affect the breast remain poorly understood. We examined gene expression profiles of eight known and suspected mammary toxicants using the TempO-Seq platform and a targeted gene expression panel, Breast Carcinogen Screen (BCScreen). The BCScreen panel has 500 genes with at least 30 genes strongly associated with each of the 14 biologic processes relevant to breast cancer and mammary gland development. We compared gene expression profiles in MCF-7 cells treated for 24hrs with four concentrations (1 nM to 10 uM) of the following chemicals: three estrogenic chemicals (genistein, bisphenol A, butyl benzyl phthalate); the selective estrogen receptor modulator, tamoxifen (TAM); 1,4 benzoquinone (BQ), a genotoxic metabolite of the rodent mammary carcinogen benzene; perfluorooctanoic acid (PFOA), a persistent pollutant that alters mammary gland development; and two closely related perfluorinated chemicals that have not been evaluated for mammary toxicity/effects (PFHXA, PFNA). We identified expression patterns activated by mammary toxicants with known ER agonist activity (genistein, BPA, BBP). Some of these genes were suppressed by PFOA and BQ and TAM, mammary toxicants with antagonist or no known direct ER activity. The known weak estrogens genistein, BPA, and BBP had similar gene expression profiles and were enriched for genes associated with cell cycle and DNA repair, particularly at higher doses. Notably, PFOA, Tam, and BQ had greater gene expression changes at lowest (1nM) vs. higher doses and were enriched for genes associated with cell cycle. For context, serum PFOA levels in the general US population are generally five to ten times higher than the 1 nM dose where we observed these changes (i.e., > 0.4 micrograms/L). PFOA profiles were enriched for several transcription factors including E2F1 and E2F4, which regulate cell cycle genes and important processes in mammary development and tumor progression. Utilizing the BCScreen gene panel, we have identified mechanistic targets relevant to breast cancer that are perturbed by mammary toxicants. Citation Format: Vanessa Y. De La Rosa, Erik Lehnert, Marko Milanovic, Chris Vulpe, Ruthann A. Rudel. Targeted expression profiling identifies mechanisms of potential breast carcinogens [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A52.

Background Low-income and minority communities often face disproportionately high pollutant exposures. The lead crisis in Flint, Michigan, has sparked concern about broader socioeconomic disparities in exposures to drinking water contaminants. Nitrate is commonly found in drinking water, especially in agricultural regions, and epidemiological evidence suggests elevated risk of cancer and birth defects at levels below U.S. EPA’s drinking water standard (10 mg/L NO3-N). However, there have been no nationwide assessments of socioeconomic disparities in exposures to nitrate or other contaminants in U.S. drinking water. The goals of this study are to identify determinants of nitrate concentrations in U.S. community water systems (CWSs) and to evaluate disparities related to wealth or race/ethnicity. Methods We compiled nitrate data from 39,466 U.S. CWSs for 2010–2014. We used EPA’s Safe Drinking Water Information System (SDWIS) to compile CWS characteristics and linked this information with both city- and county-level demographic data gathered from the U.S. Census Bureau. After applying multiple imputation methods to address censored nitrate concentration data, we conducted mixed-effects multivariable regression analyses at national and regional scales. Results 5.6 million Americans are served by a CWS that had an average nitrate concentration ≥ 5 mg/L NO3-N between 2010 and 2014. Extent of agricultural land use and reliance on groundwater sources were significantly associated with nitrate. The percent of Hispanic residents served by each system was significantly associated with nitrate even after accounting for county-level cropland and livestock production, and CWSs in the top quartile of percent Hispanic residents exceeded 5 mg/L nearly three times as often as CWSs serving the lowest quartile. By contrast, the percent of residents living in poverty and percent African American residents were both inversely associated with nitrate. Conclusions Epidemiological evidence for health effects associated with drinking water above 5 mg/L NO3-N raises concerns about increased risk for the 5.6 million Americans served by public water supplies with average nitrate concentrations above this level. The associations we observed between nitrate concentrations and proportions of Hispanic residents support the need for improved efforts to assist vulnerable communities in addressing contamination and protecting source waters. Future studies can extend our methods to evaluate disparities in exposures to other contaminants and links to health effects. Electronic supplementary material The online version of this article (10.1186/s12940-018-0442-6) contains supplementary material, which is available to authorized users.

Male reproductive alterations found in animals and humans following in utero phthalate exposure include decreased anogenital distance (AGD) and other reproductive-tract malformations. The aim of this investigation was to conduct systematic reviews of human and animal evidence of the effect of in utero exposure to diethylhexyl phthalate (DEHP) on anogenital distance (AGD) in males. PubMed, Embase, and Toxline were searched for relevant human and experimental animal studies on August 15, 2016. Search results were screened for relevance, and studies that met the inclusion criteria were evaluated for quality and data extracted for analysis. Confidence in the human and animal bodies of evidence was assessed and hazard conclusions reached by integrating evidence streams. The search yielded 6 relevant human studies and 19 animal studies. Meta-analysis of 5 human observational prospective cohort studies showed that increased maternal urinary concentrations of DEHP metabolites were associated with decreased AGD in boys (−4.07 [CI, −6.49 to −1.66] % decrease per log10 rise in DEHP metabolites). Meta-analysis and meta-regression of the 19 experimental animal studies found reduced AGD with DEHP treatment, with a dose-response gradient, and with heterogeneity explained by species and strain. There is a moderate level of evidence from human investigations and a high level of data from animal studies that in utero exposure to DEHP decreases AGD. Based upon the available human and animal evidence, and consideration of mechanistic data, DEHP is presumed to be a reproductive hazard to humans on the basis of effects on AGD.

A recent systematic review (SR) and meta-analysis of human studies found an association between prenatal serum polybrominated diphenyl ethers (PBDE) concentrations and a decrease in the IQ of children. A SR of experimental developmental animal PBDE-mediated neurotoxicity studies was performed in the present study. Outcomes assessed included measures related to learning, memory, and attention, which parallel the intelligence-related outcomes evaluated in the human studies SR. PubMed, Embase, and Toxline were searched for relevant experimental non-human mammalian studies. Evaluation of risk of bias (RoB) and overall body of evidence followed guidance developed by the National Toxicology Program. Animal studies using varying designs and outcomes were available for BDEs 47, 99, 153, 203, 206, and 209 and the technical mixture DE-71. Study reporting of methods and results was often incomplete leading to concerns regarding RoB. A meta-analysis of 6 Morris water maze studies showed evidence of a significant increase in last trial latency (effect size of 25.8 [CI, 20.3 to 31.2]) in PBDE-exposed animals with low heterogeneity. For most endpoints, there were unexplained inconsistencies across studies and no consistent evidence of a dose-response relationship. There is a "moderate" level of evidence that exposure to BDEs 47, 99, and 209 affects learning. For other PBDEs and other endpoints, the level of evidence was "low" or "very low". The meta-analysis led to stronger conclusions than that based upon a qualitative review of the evidence. The SR also identified RoB concerns that might be remedied by better study reporting.

Furniture flammability standards are typically met with chemical flame retardants (FRs). FRs can migrate out of products into dust and are linked to cancer, neurological impairment, and endocrine disruption. We collected 95 dust samples from dormitory common areas and student rooms on two U.S. college campuses adhering to two different furniture flammability standards: Technical Bulletin 117 (TB117) and Technical Bulletin 133 (TB133). Because TB133 requires furniture to withstand a much-more-demanding test flame than TB117, we hypothesized that spaces with TB133 furniture would have higher levels of FRs in dust. We found all 47 targeted FRs, including 12 polybrominated diphenyl ether (PBDE) congeners, 19 other brominated FRs, 11 phosphorus FRs (PFRs), 2 Dechlorane-Plus (DP) isomers, and 3 hexabromocyclododecane (HBCDD) isomers in the 95 dust samples. We measured the highest reported U.S. concentrations for a number of FRs, including BDE 209 (up to 990 000 ng/g), which may be used to meet the TB133 standard. We prioritized 16 FRs and analyzed levels in relation to flammability standard as well as presence and age of furniture and electronics. Adherence to TB133 was associated with higher concentrations of BDE 209, decabromodiphenylethane (DBDPE), DPs, and HBCDD compared to adherence to TB117 in univariate models (p < 0.05). Student dormitory rooms tended to have higher levels of some FRs compared to common rooms, likely a result of the density of furniture and electronics. As flammability standards are updated, it is critical to understand their impact on exposure and health risks.

© 2014 American Chemical Society. Residential exposure can dominate total exposure for commercial chemicals of health concern; however, despite the importance of consumer exposures, methods for estimating household exposures remain limited. We collected house dust and indoor air samples in 49 California homes and analyzed for 76 semivolatile organic compounds (SVOCs)-phthalates, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and pesticides. Sixty chemicals were detected in either dust or air and here we report 58 SVOCs detected in dust for the first time. In dust, phthalates (bis(2-ethylhexyl) phthalate, benzyl butyl phthalate, di-n-butyl phthalate) and flame retardants (PBDE 99, PBDE 47) were detected at the highest concentrations relative to other chemicals at the 95th percentile, while phthalates were highest at the median. Because SVOCs are found in both gas and condensed phases and redistribute from their original source over time, partitioning models can clarify their fate indoors. We use empirical data to validate air-dust partitioning models and use these results, combined with experience in SVOC exposure assessment, to recommend residential exposure measurement strategies. We can predict dust concentrations reasonably well from measured air concentrations (R2= 0.80). Partitioning models and knowledge of chemical Koaelucidate exposure pathways and suggest priorities for chemical regulation. These findings also inform study design by allowing researchers to select sampling approaches optimized for their chemicals of interest and study goals. While surface wipes are commonly used in epidemiology studies because of ease of implementation, passive air sampling may be more standardized between homes and also relatively simple to deploy. Validation of passive air sampling methods for SVOCs is a priority.

Owing to their toxicity, phthalate plasticizers are currently being replaced with terephthalates in many consumer products. Nevertheless, data on human exposure to and toxicity of terephthalates are still scarce. In this study, we developed a robust analytical method for the measurement of six terephthalate metabolites (TPhMs) in human urine through their successful separation from phthalate metabolites (PhMs). Target analytes were identified, using commercially available standards, and quantified with isotopically labeled internal standards (IS). The limit of quantification (LOQ) of TPhMs were in the range of 0.12 to 0.4 ng/mL, with the exception of 2.8 ng/mL for terephthalic acid (TPA) and 3.75 ng/mL for mono-(2-ethylhexyl) terephthalate (mEHTP), which were found in procedural blanks at notable levels. The method developed in this study showed excellent accuracy (recoveries: 86–117%) and precision (RSD: 0.6–12.2%) for TPhMs. The method was successfully applied for the analysis of 30 human urine samples collected from individuals with no known history of occupational exposure. The detection frequencies (df %) of TPhMs in urine ranged between 26.6 and 100%. This is one of the first studies that report a method for the analysis of emerging class of environmental chemicals in human specimens.

In a recent Brief Communication, Calafat et al. expressed concern that epidemiological studies inappropriately assess exposure to nonpersistent chemicals such as bisphenol A (BPA) and phthalates by measuring chemical concentrations in serum and tissues. They assert that urine is the most scientifically valid matrix and that accurate measurement of other matrices is difficult due to contamination of samples and assays. We believe their assertions require clarification. The scientifically appropriate matrix is determined by the study objectives. For population studies, we agree urine is an appropriate matrix to initially probe whether exposure to a nonpersistent chemical is associated with a disease or risk factor. However, Calafat et al. appear to target more than population studies. They illustrate the purportedly growing problem of non-urine measurement in epidemiology with a list of 80 studies, cited by PubMed identification numbers (PMIDs), which surprisingly includes pharmacokinetic and experimental studies. Of these 80 studies, 35 arguably required non-urine matrices to achieve study objectives. For example, in five studies (PMIDs 10716589, 10964036, 11604266, 17661831, 23145999) the subjects were dialysis patients—i.e., people without normal capacity to produce urine. One study used a placenta perfusion system to examine phthalate distribution between maternal and fetal circulation (PMID 17049806). A dog study (PMID 23761051) found unmetabolized BPA was rapidly absorbed into circulation following sublingual administration. A human study (PMID 25337790) exposed participants to BPA-containing thermal receipt paper and found a substantial increase of unmetabolized BPA in serum. It seems inconceivable to us that Calafat et al. would consider such studies inherently flawed. For chemicals excreted in urine, the urinary concentration provides an estimate of exposure. However, the bioactive form in serum and tissue is what alters physiology. When a nonpersistent chemical is absorbed via the gut, first-pass metabolism by the liver can dramatically reduce the amount of unmetabolized compound reaching the bloodstream as compared with other routes (Soeborg et al. 2014). Therefore, for chemicals in widespread undocumented use—where route-of-exposure information is unavoidably incomplete—one cannot accurately predict the internal concentrations of the unmetabolized compounds with urine measurements and a model that includes only gut absorption. Such models may grossly underestimate internal bioactive dose from non-gut exposures and incorrectly suggest that measurement of higher-than-predicted serum concentrations is due to contamination. In our view, Calafat et al. suggest that non-urine measurements are invariably contaminated. However, contamination cannot explain the results of the studies by Gayrard et al. (2013) and Hormann et al. (2014), which demonstrated classic pharmacokinetic curves with logical interrelationships between the parent compound and metabolites. Furthermore, the proposition that contamination is unavoidable is contradicted by numerous studies spanning 15 years (vom Saal and Welshons 2014). For example, in a paper coauthored by Calafat (Ye et al. 2013), the authors reported accurately measuring BPA in human serum after identifying and eliminating contamination. Subsequently, Vandenberg et al. (2014) reported a blinded study directed by the National Institutes of Health (NIH) in which several U.S. laboratories accurately measured BPA in human serum spiked by NIH personnel. Arguing that chemical X cannot be measured in tissue Y because of contamination is an odd position to take, given that eliminating sources of contamination is a normal part of the development and validation of any assay—as was clearly described by Ye et al. (2013). In summary, without further clarification, the Brief Communication by Calafat et al. could easily be interpreted as proposing that human environmental studies of any kind must measure nonpersistent chemicals and metabolites only in urine if they are to be funded and published. Such an interpretation would greatly restrict our ability to move from surface-level exposure measures to internal dose, pharmacokinetics, and in vivo pathophysiology. Given the prominence of the authors in environmental health research, this issue needs to be clarified.

Background: Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. Objectives: We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. Methods: We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters. Results: We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels. Conclusions: Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in product composition. Consumers should be able to avoid some target chemicals—synthetic fragrances, BPA, and regulated active ingredients—using purchasing criteria. More complete product labeling would enable consumers to avoid the rest of the target chemicals.

Background: Bisphenol A (BPA) and bis(2-ethylhexyl) phthalate (DEHP) are high-production-volume chemicals used in plastics and resins for food packaging. They have been associated with endocrine di...

Interest in the health effects of potential endocrine-disrupting compounds (EDCs) that are high production volume chemicals used in consumer products has made exposure assessment and source identification a priority. We collected paired indoor and outdoor air samples in 40 nonsmoking homes in urban, industrial Richmond, CA, and 10 in rural Bolinas, CA. Samples were analyzed by GC-MS for 104 analytes, including phthalates (11), alkylphenols (3), parabens (3), polybrominated diphenyl ether (PBDE) flame retardants (3), polychlorinated biphenyls (PCBs) (3), polycyclic aromatic hydrocarbons (PAHs) (24), pesticides (38), and phenolic compounds (19). We detected 39 analytes in outdoor air and 63 in indoor air. For many of the phenolic compounds, alkylphenols, phthalates, and PBDEs, these represent some of the first outdoor measures and the first analysis of the relative importance of indoor and outdoor sources in paired samples. Data demonstrate higher indoor concentrations for 32 analytes, suggesting primarily indoor sources, as compared with only 2 that were higher outdoors. Outdoor air concentrations were higher in Richmond than Bolinas for 3 phthalates, 10 PAHs, and o-phenylphenol, while indoor air levels were more similar between communities, except that differences observed outdoors were also seen indoors. Indoor concentrations of the most ubiquitous chemicals were generally correlated with each other (4-t-butylphenol, o-phenylphenol, nonylphenol, several phthalates, and methyl phenanthrenes; Kendall correlation coefficients 0.2−0.6, p < 0.05), indicating possible shared sources and highlighting the importance of considering mixtures in health studies., Paired indoor and outdoor air concentrations of semivolatile endocrine-disrupting chemicals suggest primarily indoor sources, and the most ubiquitous commercial chemicals are correlated across homes.

Septic systems serve approximately 25% of U.S. households and may be an important source of estrogenic and other organic wastewater contaminants (OWC) to groundwater. We monitored several estrogenic OWC, including nonylphenol (NP), nonylphenol mono- and diethoxycarboxylates (NP1EC and NP2EC), the steroid hormones 17β-estradiol (E2), estrone (E1) and their glucuronide and sulfate conjugates, and other OWC such as methylene blue active substances (MBAS), caffeine and its degradation product paraxanthine, and two fluorescent whitening agents in a residential septic system and in downgradient groundwater. E1 and E2 were present predominantly as free estrogens in groundwater, and near-source groundwater concentrations of all OWC were highest in the suboxic to anoxic portion of the wastewater plume, where concentrations of most OWC were similar to those observed in the septic tank on the same day. NP and NP2EC were up to 6- to 30-fold higher, and caffeine and paraxanthine were each 60-fold lower than septic tan...

In order to characterize typical indoor exposures to chemicals of interest for research on breast cancer and other hormonally mediated health outcomes, methods were developed to analyze air and dust for target compounds that have been identified as animal mammary carcinogens or hormonally active agents and that are used in commercial or consumer products or building materials. These methods were applied to a small number of residential and commercial environments to begin to characterize the extent of exposure to these classes of compounds. Phenolic compounds, including nonylphenol, octylphenol, bisphenol A, and the methoxychlor metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), were extracted, derivatized, and analyzed by gas chromatography/mass spectrometry (GC/MS)-selective ion monitoring (SIM). Selected phthalates, pesticides, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were extracted and analyzed by GC/MS-SIM. Residential and workplace samples showed detectable levels of twelve pesticides in dust and seven in air samples. Phthalates were abundant in dust (0.3-524 micrograms/g) and air (0.005-2.8 micrograms/m3). Nonylphenol and its mono- and di-ethoxylates were prevalent in dust (0.82-14 micrograms/g) along with estrogenic phenols such as bisphenol A and o-phenyl phenol. In this 7-sample pilot study, 33 of 86 target compounds were detected in dust, and 24 of 57 target compounds were detected in air. In a single sample from one home, 27 of the target compounds were detected in dust and 15 in air, providing an indication of chemical mixtures to which humans are typically exposed.

As part of a larger effort to characterize the impacts to Cape Cod drinking water supplies from on-site wastewater disposal, we developed two analytical methods using HPLC and GC/MS for a range of compounds identified as endocrine-disrupting chemicals (EDCs), including the nonionic surfactants alkylphenol polyethoxylates (APEOs) and their degradation products. We analyzed samples for nonylphenol, octylphenol, and their ethoxylates up to the hexaethoxylate using an HPLC method, with detection limits ranging from 2 to 6 μg/L. A set of phenolic compounds including bisphenol A and nonylphenol were derivatized and analyzed by GC/MS with detection limits from 0.001 to 0.02 μg/L. Total APEOs in untreated wastewater and septage samples ranged from 1350 to 11 000 μg/L by the HPLC method. Nonylphenol was detected in all septage samples at concentrations above 1000 μg/L. Phenylphenol and bisphenol A were detected in septage and wastewater at about 1 μg/L. In groundwater downgradient of an infiltration bed for second...

Phthalates are a diverse group of chemicals, including five with production volumes of over 1 million pounds per year in the United States (U.S.). They are used as plasticizers in a variety of plastics including polyvinyl chloride (PVC), medical devices (e.g., intravenous bags and tubing), food contact materials (FCMs), toys, and household goods, and as solvents in fragranced personal care and household products. Although not all phthalates have been evaluated for their toxic effects, many that are in widespread use have displayed endocrine disrupting properties on the developing reproductive system, especially in males, in laboratory, animal, and human studies. Widespread exposure to phthalates has been documented in the U.S. and in European countries, with some examples of unusually high exposures in certain populations, such as neonates with intravenous interventions in hospital settings. For the majority of the population, the primary route of exposure to the endocrine disrupting phthalates produced in the highest volume, bis(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP), is through diet. DEHP is used in food packaging, and also has been found to contaminate food sources directly. Some newer phthalates that have been introduced as alternatives to phthalates with known health concerns are also endocrine disruptors, while others have not been evaluated. Regulatory agencies are considering ways to define phthalates and assess their risk as a group based on chemical structure.

Phosphate flame retardants (PFRs) are abundant and found at the highest concentrations relative to other flame retardant chemicals in house dust; however, little is known about the biological levels of PFRs and their relationship with house dust concentrations. These relationships provide insight into major exposure pathways and potential health risks. We analyzed urine samples from 16 California residents in 2011 for 6 chlorinated and nonchlorinated dialkyl or diaryl phosphates (DAPs), the expected major metabolites of the most prominent PFRs, and qualitatively screened for 18 other metabolites predicted from in vitro studies. We detected all 6 DAPs within the range of previously reported levels, although very few comparisons are available. We found weakly positive nonsignificant correlations between urine and dust concentrations and maxima urine corresponding to maxima dust for the pairs bis(1,3-dichloro-2-propyl) phosphate (BDCIPP)-tris(1,3-dichloro-isopropyl) phosphate (TDCIPP) and bis(2-chloroethyl) phosphate (BCEP)-tris(2-chloroethyl) phosphate (TCEP). Metabolite levels of PFRs were correlated for many PFR combinations, suggesting they commonly co-occur. As far as we know, this is the first study to measure these 6 DAP metabolites simultaneously and to detect other PFR metabolites in US urine samples. We recommend biomonitoring studies include these 6 DAPs as well as several additional compounds detected through qualitative screening and previous ADME studies. PFRs represent a class of poorly studied commercial chemicals with widespread exposure and raise concerns for health effects including carcinogenicity and neurotoxicity.

Exposure to di(2-ethylhexyl) phthalate (DEHP) may be related to adverse health effects including developmental and reproductive disorders, prompting interest in strategies for reducing human exposure. We previously reported a reduction of DEHP metabolite levels in composite urine samples by more than 50% (geometric means) during a 3-day dietary intervention avoiding plastics in food packaging, preparation, and storage. In the present study, we analyzed individual spot urine samples before compositing in order to evaluate temporal variability. There were no meaningful changes in any of the previous findings when using individual rather than composited samples. Individual urine samples, like the composites, showed significant decreases of ≥50% in all three measured DEHP metabolites during the intervention. Compositing urine samples provided sufficient information to observe the effect of the intervention, whereas reducing analytical expenses compared with analyzing multiple samples individually. Low intraclass correlations (ICCs) for samples collected from the same person before the intervention indicate the importance of collecting multiple samples per exposure condition. Substantially larger ICCs during and after the intervention suggest that much of the variability observed in DEHP metabolite levels originates from dietary exposure.

Higher house dust levels of PBDE flame retardants (FRs) have been reported in California than other parts of the world, due to the state's furniture flammability standard. However, changing levels of these and other FRs have not been evaluated following the 2004 U.S. phase-out of PentaBDE and OctaBDE. We analyzed dust collected in 16 California homes in 2006 and again in 2011 for 62 FRs and organohalogens, which represents the broadest investigation of FRs in homes. Fifty-five compounds were detected in at least one sample; 41 in at least 50% of samples. Concentrations of chlorinated OPFRs, including two (TCEP and TDCIPP) listed as carcinogens under California's Proposition 65, were found up to 0.01% in dust, higher than previously reported in the U.S. In 75% of the homes, we detected TDBPP, or brominated "Tris," which was banned in children's sleepwear because of carcinogenicity. To our knowledge, this is the first report on TDBPP in house dust. Concentrations of Firemaster 550 components (EH-TBB, BEH-TEBP, and TPHP) were higher in 2011 than 2006, consistent with its use as a PentaBDE replacement. Results highlight the evolving nature of FR exposures and suggest that manufacturers continue to use hazardous chemicals and replace chemicals of concern with chemicals with uncharacterized toxicity.

Steven Risotto, representing phthalate manufacturers for the American Chemistry Council (ACC), commented on our study that found a 3-day diet with limited food packaging reduced participants’ average bis(2-ethylhexyl) phthalate (DEHP) exposure by > 50% (Rudel et al. 2011).

Chemicals identified as endocrine-disrupting compounds (EDCs) have widespread consumer uses, yet little is known about indoor exposure. We sampled indoor air and dust in 120 homes, analyzing for 89 organic chemicals identified as EDCs. Fifty-two compounds were detected in air and 66 were detected in dust. These are the first reported measures in residential environments for over 30 of the compounds, including several detected at the highest concentrations. The number of compounds detected per home ranged from 13 to 28 in air and from 6 to 42 in dust. The most abundant compounds in air included phthalates (plasticizers, emulsifiers), o-phenylphenol (disinfectant), 4-nonylphenol (detergent metabolite), and 4-tert-butylphenol (adhesive) with typical concentrations in the range of 50-1500 ng/m3. The penta- and tetrabrominated diphenyl ethers (flame retardants) were frequently detected in dust, and 2,3-dibromo-1-propanol, the carcinogenic intermediate of a flame retardant banned in 1977, was detected in air and dust. Twenty-three pesticides were detected in air and 27 were detected in dust, the most abundant being permethrins and the synergist piperonyl butoxide. The banned pesticides heptachlor, chlordane, methoxychlor, and DDT were also frequently detected, suggesting limited indoor degradation. Detected concentrations exceeded government health-based guidelines for 15 compounds, but no guidelines are available for 28 compounds, and existing guidelines do not consider endocrine effects. This study provides a basis for prioritizing toxicology and exposure research for individual EDCs and mixtures and provides new tools for exposure assessment in health studies.

Many substances are active in in vitro tests for estrogenic activity, but data from multigenerational and other toxicity studies are not available for many of those substances. Controversy has arisen, therefore, concerning the likelihood of adverse health effects. Based on a toxic equivalence factor risk assessment approach, some researchers have concluded that exposure to environmental estrogens is not associated with estrogen receptor (ER)-mediated health effects. Their rationale cites the low potency of these compounds in in vitro assays relative to estradiol, and the widespread exposure to pharmaceutical, endogenous, and dietary estrogens. This reasoning relies on two assumptions: that the relative estrogenic potency in in vitro assays is predictive of the relative potency for the most sensitive in vivo estrogenic effect; and that all estrogens act via the same mechanism to produce the most sensitive in vivo estrogenic effect. Experimental data reviewed here suggest that these assumptions may be inappropriate because diversity in both mechanism and effect exists for estrogenic compounds. Examples include variations in ER-ligand binding to estrogen response elements, time course of nuclear ER accumulation, patterns of gene activation, and other mechanistic characteristics that are not reflected in many in vitro assays, but may have significance for ER-mediated in vivo effects. In light of these data, this report identifies emerging methodological issues in risk assessment for estrogenic compounds: the need to address differences in in vivo end points of concern and the associated mechanisms; pharmacokinetics; the crucial role of timing and duration of exposure; interactions; and non-ER-mediated activities of estrogenic compounds.

Epidemiological data relating arsenic ingestion and skin and internal cancers strongly suggest a sublinear or threshold relationship. Physiological saturation of methylation-based arsenic detoxification has been proposed as one explanation for a sublinear response. We have evaluated the molecular bases for sublinearity in light of new data and hypotheses regarding arsenic genotoxicity and chemical carcinogenesis. A review of the dose–response relationships observed in arsenic genotoxicity assays is presented. With the exception of sister chromatid exchanges, sublinear dose–response relationships for arsenic-induced chromosomal aberrations were observed repeatedly in different mammalian and human cell systems. Arsenic also enhanced the clastogenicity and mutagenicity of other DNA damaging agents with a sublinear dose response. Consistent with the dose response of arsenic-induced genetic alterations, arsenic also inhibited DNA ligases I and II, enzymes which play a role in DNA repair, with a sublinear dose response. In some cases, protective effects of relatively low exposures to arsenic have been observed, again consistent with sublinearity. We discuss recent theories on the mechanism of arsenic carcinogenicity and the potential implications for dose–response modeling and risk assessment. Overall, based on available arsenic genotoxicity data, we conclude that it is likely that arsenic indirectly induces genetic damage with a sublinear dose response in humans, thus providing a biological basis for a sublinear dose–response relationship for human cancer. Furthermore, these results suggest that linear dose–response modeling from populations experiencing high arsenic exposures is likely to overpredict cancer risks at relatively low arsenic levels.