Multiple Chemical Exposures Research Articles

The Implementation of the Food Quality Protection Act (FQPA) in Increasing the Safety Standards for New Pesticides Used on Foods

This paper examines the Food Quality Protection Act (FQPA) and its impact on enhancing safety standards for pesticides used on food in the United States. Initially, the study explores the Delaney Clause—a strict standard prohibiting carcinogenic food additives—which FQPA replaced with a more flexible "reasonable certainty of no harm" criterion. This shift allows the Environmental Protection Agency (EPA) to assess pesticide risk with consideration of potential benefits, even if a substance is carcinogenic at high doses. The paper also critiques the EPA's implementation challenges, including reliance on quantitative risk assessment (QRA) and cumulative risk assessment, which quantify risks of multiple chemical exposures but face informational and regulatory limitations. Recommendations focus on refining judicial review and integrating cumulative risk assessment to strengthen the FQPA’s capacity to safeguard public health, especially for vulnerable populations such as children. This study underscores the importance of regulatory clarity and rigorous assessment methods in pesticide management.

Elucidation of endogenous and exogenous chemicals in maternal serum using high-resolution mass spectrometry

The increasing exposure to environmental chemicals calls for comprehensive non-targeted analysis to detect unrecognized substances in human samples. We examined human serum samples to classify compounds as endogenous or exogenous using public databases and to explore the relationships between exposure markers and metabolic patterns. Serum samples from 84 pregnant women at 32 weeks gestation were analyzed using LC-QToFMS. Using the PubChemLite for Exposomics database, we annotated and classified 106 compounds (51 endogenous, 55 exogenous). The compound patterns were analyzed using three dimensional reduction methods: Principal Component Analysis (PCA), regularized Generalized Canonical Correlation Analysis (rGCCA), and Uniform Manifold Approximation and Projection (UMAP). OPTICS clustering applied to these methods revealed two distinct clusters, with 89 % of significant compounds overlapping between clusters. The detected exogenous compounds included dietary substances, phthalates, nitrogenous compounds, and parabens. Pathway enrichment analysis showed that chemical exposure was linked to changes in amino acid metabolism, protein and mineral transport, and energy metabolism. While we found associations between exposure and metabolite changes, we could not establish causality. Our approach of analyzing both exogenous and endogenous chemicals from the same dataset using PubChemLite database presents a new method for exposome research, despite limitations in sample size and peak annotation accuracy. These findings contribute to understanding multiple chemical exposures and their metabolic effects in human biomonitoring.

Impact of polyfluoroalkyl chemicals and volatile organic compounds exposure on lung function of American adults

BackgroundEnvironmental chemicals, such as Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and volatile organic compounds (VOCs), and the association between the combined exposure of these chemicals and human lung function remains unclear. This study aimed to explore the effects of mixed exposure to PFAS and VOCs on lung function in the general population of the United States and investigate their potential mechanisms. MethodsData from 30442 respondents were selected for analysis during the US National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2012. Linear models, weighted quantile (WQS) regression, quantile g calculation (QGC), and Bayesian kernel machine regression (BKMR) were used to evaluate the contribution of individual components. Moreover, the interactions between substances in the dose-response relationship mixture of multiple environmental chemical exposures and lung function were also evaluated. The Benjamini-Hochberg method was used to correct multiple tests. FindingsUnivariate analysis showed that nitromethane was negatively correlated with FEV1 (β =−0.052), FVC (β =−0.056), and PEF (β =−0.065), while perfluorohexanesulfonic acid was positively associated with FEV1 (β = 0.026), FVC (β = 0.024), FEF25-75% (β = 0.012), and PEF (β = 0.029). Multivariate analysis showed that chloroform and perfluorohexane sulfonic acid were positively associated with lung function (P <0.05), and perfluorohexane sulfonic acid contributed the most. Nitromethane and perfluorodecanoic acid were negatively associated with lung function (P < 0.05), and perfluorodecanoic acid contributed the highest weight in the negative direction. When all chemicals were in the 50th percentile, the environmental chemical mixture had no significant consistent effect or dose-response on lung function. There were interactions among various environmental chemicals within the mixture except for 2-N-methyl-PFOSA acetate and bromodichloromethane. InterpretationThese results suggest that environmental mixture exposure is associated with abnormal lung function in American adults, and the interaction of various substances in the mixture affects its physiological and chemical effects.

Associations between exposure to multiple environmental chemicals and metabolic syndrome: A mixture analysis

Exposure to environmental chemicals is prevalent. While previous studies reported associations between multiple chemical exposures and metabolic syndrome (MetS), they did not comprehensively account for correlations among exposures. We used machine learning methods including Boruta algorithm and least absolute shrinkage and selection operator (LASSO) regression, combined with weighted quartiles sum (WQS) regression to investigate the associations of phenols, polycyclic aromatic hydrocarbons (PAHs), metals, and phthalates with MetS and its components. Data were drawn from the 2005–2012 National Health and Nutrition Examination Survey (NHANES). The mean (standard deviation (SD)) age of 2596 participants was 48.4 (17.9) years. After adjusting for age, sex, body mass index, race/ethnicity, marital status, education, poverty income ratio, physical activity, smoking, and alcohol, higher 2-Phenanthrene (2-PHE) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) concentrations were associated with a higher odds of the MetS (odds ratio (OR) = 4.26, 95 % confidence interval (CI) 2.40–7.58 per ng/mL, and 3.24, 1.75–6.02 per ng/L, respectively). WQS index for environmental chemicals was positively associated with the MetS (OR = 1.31, 95 % CI 1.09–1.57). Moreover, we observed consistent and stronger positive associations with MetS (OR = 1.54, 95 % CI 1.04–2.30) in current smokers. Exposure to phenols, PAHs, metals, and phthalates was positively associated with an increase in metabolic syndrome and its components, which was more pronounced in current smokers.

Cumulative Health Risk from Exposure Load (CHREL): Looking at multi-chemical exposures through the lens of biomonitoring guidance values

Exposure load (EL) is an indicator of multiple chemical exposures based on human biomonitoring data. We used EL methodology and human biomonitoring health-based guidance values (HB2GVs) as exposure thresholds to create a new metric called Cumulative Health Risk from Exposure Load (CHREL). HB2GVs are derived by calculating the concentration of a biomarker consistent with a health protective exposure guidance value. CHREL analysis was conducted using Canadian Health Measures Survey (CHMS) cycle 3 and 4 biomonitoring data. Based on 18 chemicals, more than half of the Canadian population had an estimated CHRELTOTAL of 1 or more, indicative of chemical exposures potentially above selected exposure guidance values. Females had a significantly lower CHRELTOTAL compared to males, 12–19 year olds had a lower CHRELTOTAL compared to older age groups (significant compared to 40–59 year olds), and nonsmokers had a significantly lower CHRELTOTAL than smokers. Small segments of the population had a CHRELLIVER or a CHRELNERV of 1 or more, indicating exposures potentially above guideline levels for chemicals affecting the liver or nervous system. CHRELCANC was calculated based on 6 chemicals with HB2GVs derived for cancer endpoints. At the 10−5 risk level, most people had an estimated CHRELCANC of 3, indicative of multiple chemicals that may exceed negligible cancer risk. The most important contributors to exposures above HB2GVs were inorganic arsenic, mercury, acrylamide, xylenes, benzene and triclosan. Keeping certain assumptions, uncertainties and limitations in mind, the CHREL indicator can be used to obtain a picture of potential cumulative health risks from combined chemical exposures in a population, and as a comparative measure between subpopulations, including vulnerable subgroups.

Breast cancer risk and prevention in 2024: An overview from the Breast Cancer UK - Breast Cancer Prevention Conference.

The Breast Cancer UK-Breast Cancer Prevention Conference addressed risk from environmental pollutants and health behaviour-related breast-cancer risk. Epidemiological studies examining individual chemicals and breast cancer risk have produced inconclusive results including endocrine disrupting chemicals (EDCs) Bisphenol A, per- and polyfluorinated alkyl substances as well as aluminium. However, laboratory studies have shown that multiple EDCs, can work together to exhibit effects, even when combined at levels that alone are ineffective. The TEXB-α/β assay measures total estrogenic load, and studies have provided evidence of a link between multiple-chemical exposures and breast cancer. However, prospective studies using TEXB-α/β are needed to establish a causative link. There is also a need to assess real-life exposure to environmental-chemical mixtures during pregnancy, and their potential involvement in programming adverse foetal health outcomes in later life. Higher rates of breast cancer have occurred alongside increases in potentially-modifiable risk factors such as obesity. Increasing body-mass index is associated with increased risk of developing postmenopausal breast cancer, but with decreased risk of premenopausal breast cancer. In contrast, lower rates of breast cancer in Asian compared to Western populations have been linked to soya/isoflavone consumption. Risk is decreased by breastfeeding, which is in addition to the decrease in risk observed for each birth and a young first-birth. Risk is lower in those with higher levels of self-reported physical activity. Current evidence suggests breast-cancer survivors should also avoid weight gain, be physically active, and eat a healthy diet for overall health. A broad scientific perspective on breast cancer risk requires focus on both environmental exposure to chemicals and health behaviour-related risk. Research into chemical exposure needs to focus on chemical mixtures and prospective epidemiological studies in order to test the effects on breast cancer risk. Behaviour-related research needs to focus on implementation as well as deeper understanding of the mechanisms of cancer prevention.

From primers to pipettes: An immersive course introducing high school students to qPCR for quantifying chemical defense gene expression.

We created a 2-week, dual-module summer course introducing high school students to environmental toxicology by teaching them quantitative polymerase chain reaction (qPCR) as a way to quantify gene expression of chemical defense proteins in response to exposure to environmental pollutants. During the course, students are guided through the various stages of a successful qPCR experiment: in silico primer design and quality control, total RNA extraction and isolation, cDNA conversion, primer test PCR, and evaluation of results via agarose gel electrophoresis or UV/Vis spectra. The course combines lectures, discussions, and demonstrations with dry and wet laboratory sections to give students a thorough understanding of the scope, utility, and chemical principles of qPCR. At the end of the course, the students are taught how to analyze qPCR data and are encouraged to discuss their findings with other classmates to evaluate their hypotheses and assess possible sources of error. This course was designed to be easily adaptable to multiple test species, chemical exposures, and genes of interest. To explore both terrestrial and aquatic toxicology, the students use honey bees (Apis mellifera) and mosquitofish (Gambusia affinis) as test organisms, as well as ABC-type efflux transporters, antioxidant enzymes, and cytochrome P450 enzymes as endpoints for assessing gene expression. We share this course setup and applied protocols to encourage others to design and offer similar courses that give high school students a hands-on introduction to a broad swath of environmental toxicology research and an opportunity to develop scientific skills necessary for university-level research.

Challenges in health risk assessment of multiple chemical exposures in epidemiological studies.

Challenges in health risk assessment of multiple chemical exposures in epidemiological studies.

Detecting Shape-Based Interactions Among Environmental Chemicals Using an Ensemble of Exposure-Mixture Regression and Interpretable Machine Learning Tools

There is growing interest in discovering interactions between multiple environmental chemicals associated with increased adverse health effects. However, most existing approaches (1) either use a projection or product of multiple chemical exposures, which are difficult to interpret and (2) cannot simultaneously handle multi-ordered interactions. Therefore, we develop and validate a method to discover shape-based interactions that mimic usual toxicological interactions. We developed the Multi-ordered explanatory interaction (Moxie) algorithm by merging the efficacy of Extreme Gradient Boosting with the inferential power of Weighted Quantile Sum regression to extract synergistic interactions associated with the outcome/odds of disease in an adverse direction. We evaluated the algorithm’s performance through simulations and compared it with the currently available gold standard, the signed-iterative random forest algorithm. We used the 2017–18 US-NHANES dataset (n = 447 adults) to evaluate interactions among nine per- and poly-fluoroalkyl substances and five metals measured in whole blood in association with serum low-density lipoprotein cholesterol. In simulations, the Moxie algorithm was highly specific and sensitive and had very low false discovery rates in detecting true synergistic interactions of 2nd, 3rd, and 4th order through moderate (n = 250) to large (n = 1000) sample sizes. In NHANES data, we found a two-order synergistic interaction between cadmium and lead detected in people with whole-blood cadmium concentrations and lead above 0.605 ug/dL and 1.485 ug/dL, respectively. Our findings demonstrate a novel validated approach in environmental epidemiology for detecting shape-based toxicologically mimicking interactions by integrating exposure-mixture regression and machine learning methods.

Continuous surface and air decontamination technologies: Current concepts and controversies

Effective and safe continuous surface and air decontamination technologies could be a useful adjunct to routine cleaning and disinfection in health care settings. Continuously active quaternary ammonium disinfectants that provide residual antimicrobial activity on undisturbed surfaces for up to 24.ßhours have been shown to reduce the recovery of clinically important pathogens in some but not all real-world studies. Although quaternary ammonium-based supplemental coatings have been reported to provide prolonged residual efficacy in patient care settings, there is concern that some of these products may be removed by routine cleaning and disinfection. To address this concern, the Environmental Protection Agency has recently issued updated guidance requiring demonstration of efficacy after multiple abrasion and chemical exposures for registration of supplemental residual antimicrobial coatings. Far-ultraviolet-C and direct irradiation below exposure limits are promising technologies for continuous air and surface decontamination in occupied spaces, but additional studies are needed to evaluate their long-term safety and efficacy. Given the increasing use of electronic air cleaning technologies in community and health care settings, there is a need for studies to assess real-world efficacy and safety.

Levels of persistent organic pollutants in breast milk samples representing Finnish and Danish boys with and without hypospadias

Hypospadias is a congenital malformation of penile urethra with unknown etiology in most cases. Persistent organic pollutant (POP) exposure may disrupt endocrine function during a critical window of development of male genitalia. In animal studies, POPs have been associated with male reproductive disorders, including hypospadias, but only few studies have assessed this relationship in humans. The aim of this study is to investigate the association between hypospadias and POP concentration levels in breast milk, as a proxy for prenatal exposure. This is a nested case-control study of Danish and Finnish mother-son pairs. Maternal breast milk samples were collected between 1997 and 2002, and they represent infant boys born with hypospadias [n = 33 (n = 22 Danish and n = 11 Finnish)] and their 1:1 matched controls. Breast milk samples were analyzed for six classes of POPs [including dioxins, polychlorinated biphenyls, flame retardants and perfluorinated alkylated substances (PFAS)]. We estimated odds ratios (ORs) and 95% confidence intervals (CI) for each chemical class using conditional logistic regression. In addition, a composite exposure score system was used to explore the effect of a POP mixture (four chemical classes): The composite score was categorized as low, moderate, or high exposure, and differences between cases and controls were tested with conditional logistic regression. No statistically significant associations were observed between the sums of the chemical classes and hypospadias in either country. The composite score was unable to detect differences in the risk of hypospadias between the tertiles of POP exposure. Levels of PFAS were significantly higher in Danish than in Finnish breast milk samples. This small study does not provide evidence for an association between hypospadias and exposure to POPs but adds information on quantitative exposures. Further development of multi-exposure models is needed for assessing the potential mixture effect associated with multiple chemical exposures.

Prenatal exposure to mixtures of replacement flame retardant chemicals and children’s neuro-behavioral outcomes in a sample of children from socioeconomically disadvantaged communities

BACKGROUND. Organophosphate ester flame retardants (OPFRs) are persistent organic chemicals that are commercially applied to a wide variety of consumer products including electronics, building materials, foam-based furniture and children’s clothing that have individually been shown to adversely impact neurodevelopmental outcomes including hyperactivity symptoms, working memory, IQ and depressive symptoms. METHODS. We quantified nine prenatal OPFR urinary metabolites [DPHP, DNBP+DIBP, BDCIPP, BCEP, BBOEP, BCIPP, BMPP, BEHP and DPRP] by HPLC-MS/MS in samples from participants in the MADRES cohort--an ongoing pregnancy cohort in urban Los Angeles. Detection frequencies ranged from 99.8% for DPHP to 24.2% for DPRP. Specific-gravity adjusted OPFR metabolites detected in 60% or greater samples [DPHP, DNBP+DIBP, BDCIPP, BCEP, and BBOEP] were modeled continuously and log transformed, and values &amp;#x2264; LOD were imputed as LOD/√2. The remaining four metabolites were modeled as detect/non-detect [BCIPP, BMPP, BEHP, and DPRP]. We assessed prenatal OPFR exposure associations with neurodevelopmental outcomes from the Child Behavior Checklist 1.5/5 in 151 predominantly Hispanic/Latino (~78%) children at age 3 years. RESULTS. We found significant associations between several OPFR metabolite concentrations and neurobehavioral outcomes in single metabolite adjusted models [e.g., a 10% increase in DNBP+DIBP concentration was associated with a 3.3% (95% CI 0.02%-6.49%) increase in internalizing symptoms score and a 4.8% (0.82%-8.95%) increase in DSM pervasive symptoms score]. However, exposure to a particular compound does not occur in isolation; thus it is critical that multiple exposures be considered jointly in human studies. We will discuss various analytical approaches to quantify the effects of environmental mixtures and apply them to understand multiple OPFR chemical exposure effects on early childhood neurobehavioral outcomes in a highly exposed, socioeconomically disadvantaged population. CONCLUSIONS. The application of mixtures methods will yield important insight into the conditional associations of co-exposures and enhance health risk assessment for child neurodevelopmental outcomes. KEYWORDS. Neurodevelopment, children, chemical mixtures

Job and demographic risk factors influencing cellular mediated hypersensitivity among Nigerian Laboratory University workers in multiple chemical exposures

Background: Chemicals from laboratories represent a significant risk in cellular mediated hypersensitivity (CMH) and chemo-induced skin injury due to chemical agents present under human skin layers absorbed from the surface. This study aimed to determine the occupational and socio-demographic characteristics of the laboratory workers associated with CMH in multiple chemical exposures. Design: This was a cross-sectional study on a population-based sample of Nigerian laboratory university workers. Methods: Data were collected using the erythema index meter. The study included 287 laboratory workers. Results: The results showed that the number of positive with CMH was 176 (61.3%) with 99 (56.3%) of them were male with AOR 0.31 (95%CI: 0.12, 0.77; p=0.011). Dark-skinned participants with CMH had adjusted odd ration, AOR 0.49 (95%CI: 0.21, 081; p =0.001). Most of the respondents have college education and have been exposed for 4-5hrs in the laboratory with AOR 2.42 (95%CI: 1.10, 5.38; p = 0.049) and 3.11 (95%CI: 1.77, 9.23; p =0.001) respectively. The use of personal protective equipment (PPE) was 60% less likely to be significantly induced with CMH with AOR 0.40 (95%CI: 0.22, 0.77; p =0.011). The Permissible exposure limit (PEL) of chemical was less but have an induced CMH with AOR 4.22 (95%CI: 2.88, 12.11; p =0.004). Conclusion: Results revealed that sex, skin color, working experience, educational level, PPE, PEL, and time of exposure were the probable predictive factors associated with the development of CMH. This study has shown that CMH was significantly associated with occupational and demographic factors. Better educational knowledge and attitude of hazards and safety in the laboratory would lead to a reduced rate of new cases.

Leading edge development of food safety

Food safety in China has been significantly improved since the melamine crisis in 2008 and the promulgation of the first Food Safety Law in 2009. However, food safety is a long standing issue in China due to the backward productive structure of agriculture and food business. In order to further improve the food safety in China, it is critical to reach a consensus on the leading edge concept of food safety and the identification of priority areas based on the concept. The leading edge concept of food safety aims to prevent potential issues and deal with current issues based on the risk, i.e. risk-based approach, as opposed to the concept based on the hazard, i.e. hazard-based approach. Practice is to determine the key problems that need to be solved first according to the concept. This paper expounds the different food safety management strategies and measures caused by the two concepts, and lists several key food safety problems (importance and solutions) determined according to the concept of "risk-based". These examples include foodborne diseases caused by pathogenic microorganisms, antimicrobial resistance, food allergen control, risk assessment of multiple chemical hazards exposure and alternative methods in food toxicology.

Identification of occupations susceptible to high exposure and risk associated with multiple toxicants in an observational study: National Health and Nutrition Examination Survey 1999-2014.

Occupational exposures to toxicants are estimated to cause over 370 000 premature deaths annually. The risks due to multiple workplace chemical exposures and those occupations most susceptible to the resulting health effects remain poorly characterized. The aim of this study is to identify occupations with elevated toxicant biomarker concentrations and increased health risk associated with toxicant exposures in a diverse working US population. For this observational study of 51 008 participants, we used data from the 1999–2014 National Health and Nutrition Examination Survey. We characterized differences in chemical exposures by occupational group for 131 chemicals by applying a series of generalized linear models with the outcome as biomarker concentrations and the main predictor as the occupational groups, adjusting for age, sex, race/ethnicity, poverty income ratio, study period, and biomarker of tobacco use. For each occupational group, we calculated percentages of participants with chemical biomarker levels exceeding acceptable health-based guidelines. Blue-collar workers from “Construction,” “Professional, Scientific, Technical Services,” “Real Estate, Rental, Leasing,” “Manufacturing,” and “Wholesale Trade” have higher biomarker levels of toxicants such as several heavy metals, acrylamide, glycideamide, and several volatile organic compounds (VOCs) compared with their white-collar counterparts. Moreover, blue-collar workers from these industries have toxicant concentrations exceeding acceptable levels: arsenic (16%–58%), lead (1%–3%), cadmium (1%–11%), glycideamide (3%–6%), and VOCs (1%–33%). Blue-collar workers have higher toxicant levels relative to their white-collar counterparts, often exceeding acceptable levels associated with noncancer effects. Our findings identify multiple occupations to prioritize for targeted interventions and health policies to monitor and reduce toxicant exposures.

Imputation of Below Detection Limit Missing Data in Chemical Mixture Analysis with Bayesian Group Index Regression.

There is growing scientific interest in identifying the multitude of chemical exposures related to human diseases through mixture analysis. In this paper, we address the issue of below detection limit (BDL) missing data in mixture analysis using Bayesian group index regression by treating both regression effects and missing BDL observations as parameters in a model estimated through a Markov chain Monte Carlo algorithm that we refer to as pseudo-Gibbs imputation. We compare this with other Bayesian imputation methods found in the literature (Multiple Imputation by Chained Equations and Sequential Full Bayes imputation) as well as with a non-Bayesian single-imputation method. To evaluate our proposed method, we conduct simulation studies with varying percentages of BDL missingness and strengths of association. We apply our method to the California Childhood Leukemia Study (CCLS) to estimate concentrations of chemicals in house dust in a mixture analysis of potential environmental risk factors for childhood leukemia. Our results indicate that pseudo-Gibbs imputation has superior power for exposure effects and sensitivity for identifying individual chemicals at high percentages of BDL missing data. In the CCLS, we found a significant positive association between concentrations of polycyclic aromatic hydrocarbons (PAHs) in homes and childhood leukemia as well as significant positive associations for polychlorinated biphenyls (PCBs) and herbicides among children from the highest quartile of household income. In conclusion, pseudo-Gibbs imputation addresses a commonly encountered problem in environmental epidemiology, providing practitioners the ability to jointly estimate the effects of multiple chemical exposures with high levels of BDL missingness.

Combined chemical exposure using exposure loads on human biomonitoring data of the 4th Flemish Environment and Health Study (FLEHS-4).

To improve our understanding of internal exposure to multiple chemicals, the concept exposure load (EL) was used on human biomonitoring (HBM) data of the 4th FLEHS (Flemish Environment and Health Study; 2016-2020). The investigated chemicals were per- and polyfluoroalkyl substances (PFASs), bisphenols, phthalates and alternative plasticizers, flame retardants, pesticides, toxic metals, organochlorine compounds and polycyclic aromatic hydrocarbons (PAHs). The EL calculates "the number of chemicals to which individuals are internally exposed above a predefined threshold". In this study, the 50th and 90th percentile of each of the 45 chemicals were applied as thresholds for the EL calculations for 387 study participants. Around 20% of the participants were exposed to >27 chemicals above the P50 and to >6 chemicals above the P90 level. This shows that participants can be internally exposed to multiple chemicals in relatively high concentrations. When the chemical composition of the EL was considered, the variability between individuals was driven by some chemicals more than others. The variability of the chemical profiles at high exposure loads (EL-P90) was somewhat dominated by e.g. organochlorine chemicals, PFASs, phthalates, PAHs, organophosphate flame retardants, bisphenols (A & F), pesticides, metals, but to a lesser extent by brominated flame retardants, the organophosphorus flame retardants TCIPP & TBOEP, naphthalene and benzene, bisphenols S, B & Z, the pesticide 2,4-D, the phthalate DEP and alternative plasticizer DINCH. Associations between the EL and exposure determinants suggested determinants formerly associated with fat soluble chemicals, PFASs, bisphenols, and PAHs. This information adds to the knowledge needed to reduce the exposure by policymakers and citizens. However, a more in depth study is necessary to explore in detail the causes for the higher EL in some individuals. Some limitations in the EL concept are that a binary number is used for exposure above or below a threshold, while toxicity and residence time in the body are not accounted for and the sequence of exposure in different life stages is unknown. However, EL is a first useful step to get more insight in multiple chemical exposure in higher exposed subpopulations (relative to the rest of the sampled population).

Exposure to phthalates and environmental phenols in association with chronic kidney disease (CKD) among the general US population participating in multi-cycle NHANES (2005–2016)

Exposure to consumer chemicals has been associated with chronic kidney disease (CKD) among humans, but their associations with estimated glomerular filtration rate (eGFR) are inconsistent. Such observations may be due to potential bias caused by the method of urine dilution adjustment and lack of consideration for multiple chemical exposure in the association models. This study aimed to identify major urinary chemicals associated with CKD by applying an alternative adjustment method of urine dilution ('novel' covariate-adjusted creatinine adjustment vs 'traditional' creatinine adjustment) and with a mixture exposure concept in the association model. For this purpose, the adult participants of US National Health and Nutrition Examination Survey (NHANES) 2005–2016 (n = 9008) were used, and the associations of urinary exposure biomarkers of major consumer chemicals, e.g., phthalates, bisphenol A, benzophenone-3, and parabens, with CKD related parameters of eGFR and albumin-to-creatinine ratio (ACR), were assessed. The use of the novel covariate-adjusted creatinine standardization resulted in significant inverse associations with eGFR for most measured chemicals, unlike the results with the use of the conventional creatinine adjustment. Phthalate metabolites, such as monobutyl phthalate (MBP) and mono-benzyl phthalate (MBzP), were positively associated with ACR. Even in mixture exposure models using weighted quantile sum (WQS) regression, MBzP, metabolites of di-(2-ethylhexyl) phthalate (DEHP), and bisphenol A (BPA) were revealed as major drivers of the association with eGFR or ACR. Results of sensitivity analyses with the subpopulation with normal eGFR range (n = 7041) were generally similar. Our observation suggests that exposure to benzyl butyl phthalate (BBP), DEHP, and BPA may be responsible for declined eGFR and increased ACR even at the exposure levels occurring among general adults.

Bayesian Group Index Regression for Modeling Chemical Mixtures and Cancer Risk.

There has been a growing interest in the literature on multiple environmental risk factors for diseases and an increasing emphasis on assessing multiple environmental exposures simultaneously in epidemiologic studies of cancer. One method used to analyze exposure to multiple chemical exposures is weighted quantile sum (WQS) regression. While WQS regression has been demonstrated to have good sensitivity and specificity when identifying important exposures, it has limitations including a two-step model fitting process that decreases power and model stability and a requirement that all exposures in the weighted index have associations in the same direction with the outcome, which is not realistic when chemicals in different classes have different directions and magnitude of association with a health outcome. Grouped WQS (GWQS) was proposed to allow for multiple groups of chemicals in the model where different magnitude and direction of associations are possible for each group. However, GWQS shares the limitation of WQS of a two-step estimation process and splitting of data into training and validation sets. In this paper, we propose a Bayesian group index model to avoid the estimation limitation of GWQS while having multiple exposure indices in the model. To evaluate the performance of the Bayesian group index model, we conducted a simulation study with several different exposure scenarios. We also applied the Bayesian group index method to analyze childhood leukemia risk in the California Childhood Leukemia Study (CCLS). The results showed that the Bayesian group index model had slightly better power for exposure effects and specificity and sensitivity in identifying important chemical exposure components compared with the existing frequentist method, particularly for small sample sizes. In the application to the CCLS, we found a significant negative association for insecticides, with the most important chemical being carbaryl. In addition, for children who were born and raised in the home where dust samples were taken, there was a significant positive association for herbicides with dacthal being the most important exposure. In conclusion, our approach of the Bayesian group index model appears able to make a substantial contribution to the field of environmental epidemiology.

Exposure Load: Using biomonitoring data to quantify multi-chemical exposure burden in a population.

People are often concurrently exposed to numerous chemicals. Here we sought to leverage existing large biomonitoring datasets to improve our understanding of multi-chemical exposures in a population. Using nationally-representative data from the 2012-2015 Canadian Health Measures Survey (CHMS), we developed Exposure Load, a metric that counts the number of chemicals measured in people above a defined concentration threshold. We calculated Exposure Loads based on five concentration thresholds: the analytical limit of detection (LOD) and the 50th, 75th, 90th and 95th percentiles. Our analysis considered 44 analyte biomarkers representing 26 chemicals from the 2012-2015 CHMS; complete biomarker data were available for 1858 participants aged 12-79 years following multiple imputation of results that were missing due to sample loss. Chemicals may have one or more biomarkers, and for the purposes of Exposure Load calculation, participants were considered to be exposed to a chemical if at least one biomarker was above the threshold. Distributions of Exposure Loads are reported for the total population, as well as by age group, sex and smoking status. Canadians had an Exposure Load between 9 and 21 (out of 26) when considering LOD as the threshold, with the majority between 13 and 18. At higher thresholds, such as the 95th percentile, the majority of Canadians had an Exposure Load between 0 and 3, although some people had an Exposure Load of up to 15, indicating high exposures to multiple chemicals. Adolescents aged 12-19 years had significantly lower Exposure Loads than adults aged 40-79yearsat all thresholds and adults aged 20-39yearsat the 50th and 75th percentiles. Smokers had significantly higher Exposure Loads than nonsmokers at all thresholds except the LOD, which was expected given that tobacco smoke is a known source of certain chemicals included in our analysis. No differences in Exposure Loads were observed between males and females at any threshold. These findings broadly suggest that Canadians are concurrently exposed to many chemicals at lower concentrations and to fewer chemicals at high concentrations. They should assist in identifying vulnerable subpopulations disproportionately exposed to numerous chemicals at high concentrations. Future work will use Exposure Loads to identify prevalent chemical combinations and their link with adverse health outcomes in the Canadian population. The Exposure Load concept can be applied to other large datasets, through collaborative efforts in human biomonitoring networks, in order to further improve our understanding of multiple chemical exposures in different populations.