Gene Target Prediction of Environmental Chemicals Using Coupled Matrix-Matrix Completion.

Human exposure to toxic chemicals presents a huge health burden. Key to understanding chemical toxicity is knowledge of the molecular target(s) of the chemicals. Because a comprehensive safety assessment for all chemicals is infeasible due to limited resources, a robust computational method for discovering targets of environmental exposures is a promising direction for public health research. In this study, we implemented a novel matrix completion algorithm named coupled matrix-matrix completion (CMMC) for predicting direct and indirect exposome-target interactions, which exploits the vast amount of accumulated data regarding chemical exposures and their molecular targets. Our approach achieved an AUC of 0.89 on a benchmark data set generated using data from the Comparative Toxicogenomics Database. Our case studies with bisphenol A and its analogues, PFAS, dioxins, PCBs, and VOCs show that CMMC can be used to accurately predict molecular targets of novel chemicals without any prior bioactivity knowledge. Our results demonstrate the feasibility and promise of computationally predicting environmental chemical-target interactions to efficiently prioritize chemicals in hazard identification and risk assessment.

Cancer mortality and premature deaths among hairdressers in Brazil.

Hairdresser is an occupation classified by the International Agency for Research on Cancer as probably carcinogenic (Group 2A) for lung and bladder cancer, but evidence is accumulating on its association with other cancer types. To our knowledge, this is the first study aimed to compare the cancer mortality and premature mortality between hairdressers and other workers in Brazil. METHODS: In this exploratory study, information on deaths by selected cancers that occurred in Brazil, from 1996 to 2020, among workers aged 20-70y, with identified occupation was gathered from the Brazilian Mortality Information System. Sociodemographic characteristics, sex-specific mortality ratio, and Years of Potential Life Lost (YPLL) were compared between hairdressers, service workers, and general workers. We used logistic regression models to estimate crude (ORC) and adjusted (ORADJ) odds ratios. Models were adjusted by age, educational level, and ethnicity. We also used Poisson regression models to compare the YPLL rates across the occupational groups. RESULTS: From 1996 to 2020, 23 557 deaths occurred among hairdressers, 576 428 among service workers, and 13 332 996 among general workers in Brazil. Higher mortality ORs and YPLL were observed for several types of cancer among hairdressers, compared to service and general workers, especially for women. Hairdressers' mortality was significantly higher among whites, women, younger workers, and those who completed high school. Female hairdressers had significantly higher odds of dying from cancer of the digestive, respiratory, reproductive, urinary, and hematological systems, both in crude and adjusted models. For male hairdressers, higher odds were found only for urinary tract and bladder cancer, while other significant associations indicated lower mortality than the comparison groups. YPLL analyses revealed significant premature deaths among Brazilian hairdressers. In women, this was more evident among those who died of neoplasms of salivary glands, bones and articular cartilages, and acute lymphoid leukemia; in men, tongue, pharynx, and thyroid. CONCLUSIONS: Our results suggest that Brazilian female hairdressers are more likely to die from several cancers, with potential consequences on premature deaths. Causal associations to occupational risks, such as exposure to chemicals, should be investigated by observational epidemiologic studies. Meanwhile, it is important to promote public policies, regulations, and Occupational Safety and Health (OSH) strategies to protect hairdressers' health, mitigate occupational risks, and ensure safe workplaces.

Chemical exposome and children health: Identification of dose-response relationships from meta-analyses and epidemiological studies.

BACKGROUND: Health impact assessment studies quantifying the impact of the chemical exposome on children's health generally consider a small fraction of the exposome. Synthetizing available dose-response relationships is an essential step to fill this gap. We reviewed the literature for dose-response relationships relating the chemical exposome with children health. METHOD: We focused on 78 substance-outcome pairs for which the level of evidence had previously been classified as 'likely' or 'very likely'. We searched for dose-response relationships for these pairs from meta-analyses and, if none was available, from single epidemiological studies, from which we conducted meta-analyses whenever possible. RESULTS: We identified dose-response relationships for 50 of the 78 prioritized substance-outcome pairs (64%). Dose-response relationships stemmed from meta-analyses for 21 pairs, from de novo meta-analyses for 1 pair and single studies for 28 pairs. Dose-response relationships were available for tobacco (fetal and infant death, congenital heart defects, birth outcomes, orofacial clefts, respiratory health), lead (asthma, cognition, delayed puberty onset and iron deficiency anaemia), polychlorobiphenyls (PCBs) (cognition, respiratory infections and birth outcomes), bisphenol A (cognition), hexachlorobenzene (HCB) (respiratory health), Polybrominated diphenyl ethers (neurodevelopment), DDT (hypospadias, cryptorchidism, miscarriage), pesticides (neurodevelopment), methylmercury (cognition), PFAS (immune system, birth weight, behavior, miscarriage), arsenic (cognition, birth weight, death, respiratory health), cadmium (cognition, birth weight), manganese (behavior), sodium (blood pressure) and thallium (birth weight). For 28 of the 78 substance-outcome pairs (36%), no dose-response relationship was available from epidemiological studies in children. CONCLUSIONS: We identified dose-response relationships for 50 substance-outcome pairs, corresponding to 20 chemicals and 17 health outcomes. These can be used to perform more comprehensive quantitative health impact assessment of the exposome on child health. We also identified 28 substance-outcome pairs corresponding to 'likely' or 'very likely' effects for which research generating dose-response functions in children would be relevant.

Immediate dry decontamination using efficient absorbent materials is beneficial following skin exposure to low-volatile toxic chemicals.

In a chemical mass casualty incident requiring skin decontamination, dry removal using absorbent materials may be beneficial to enable immediate decontamination. The efficacy of absorbent materials has therefore been evaluated, alone or procedures including both dry and wet decontamination, following skin exposure to two low volatile toxic chemicals using an in vitro human skin penetration model. Additionally, removal using active carbon wipes was evaluated with or without the Dahlgren Decon solution. All dry decontamination procedures resulted in a significantly decreased skin penetration rate of the industrial chemical 2-butoxyethanol compared to the control without decontamination. Wet decontamination following dry absorption significantly improved the efficacy compared to dry removal alone. Dry decontamination post-exposure to the chemical warfare nerve agent VX showed no decontamination efficacy. However, dry and wet decontamination resulted in a decreased agent skin penetration rate during the last hour of the experiment. At -15°C, significantly reduced VX skin penetration rates were demonstrated for both dry decontamination alone and the dry and wet decontamination procedure. The Dahlgren Decon solution significantly reduced the amount of VX penetrating the skin, but the active carbon wipe alone did not impact the skin penetration rate. In conclusion, absorbent materials are beneficial for the removal of low-volatile chemicals from the skin, but the degree of efficacy varies between chemicals. Despite the variability, immediate dry decontamination using available absorbent materials prior to wet decontamination is recommended as a general procedure for skin decontamination. The procedure should also be prioritized in cold-weather conditions to prevent patient hypothermia.

Heavy metals and diminished ovarian reserve: single-exposure and mixture analyses amongst women consulting in French fertility centres.

RESEARCH QUESTION: Do heavy metals affect the risk of diminished ovarian reserve (DOR) in women of reproductive age? DESIGN: A total of 139 cases and 153 controls were included between 2016 and 2020. The participants were aged between 18 and 40 years and attended consultations for couple infertility in one of four fertility centres in western France. Cases of DOR were defined as women with an antral follicle count less than 7, anti-Müllerian hormone levels 1.1 ng/ml or less, or both. Controls were frequency matched on age groups and centres, and were women with normal ovarian reserve evaluations, no malformations and menstrual cycles between 26 and 35 days. Heavy metals (lead, mercury, cadmium and chromium) were measured in whole blood at inclusion. Single-exposure associations were examined with multivariable logistic regressions adjusted on potential confounders. Mixture effects were investigated with quantile g-computation and Bayesian kernel machine regression (BKMR). RESULTS: Chromium as a continuous exposure was significantly associated with DOR in unadjusted models (OR 2.07, 95% CI 1.04 to 4.13) but the association was no longer significant when confounders were controlled for (adjusted OR 2.75, 95% CI 0.88 to 8.60). Similarly, a statistically significant association was observed for the unadjusted second tercile of cadmium exposure (OR 1.87, 95% CI 1.06 to 3.30); however, this association was no longer statistically significant after adjustment. None of the other associations tested were statistically significant. Quantile g-computation and BKMR both yielded no significant change of risk of DOR for the mixture of metals, with no evidence of interaction. CONCLUSIONS: Weak signals that some heavy metals could be associated with DOR were detected. These findings should be replicated in other studies.

Machine Learning Assisted Discovery of Interactions between Pesticides, Phthalates, Phenols, and Trace Elements in Child Neurodevelopment.

A growing body of literature suggests that developmental exposure to individual or mixtures of environmental chemicals (ECs) is associated with autism spectrum disorder (ASD). However, investigating the effect of interactions among these ECs can be challenging. We introduced a combination of the classical exposure-mixture Weighted Quantile Sum (WQS) regression and a machine-learning method termed Signed iterative Random Forest (SiRF) to discover synergistic interactions between ECs that are (1) associated with higher odds of ASD diagnosis, (2) mimic toxicological interactions, and (3) are present only in a subset of the sample whose chemical concentrations are higher than certain thresholds. In a case-control Childhood Autism Risks from Genetics and Environment (CHARGE) study, we evaluated multiordered synergistic interactions among 62 ECs measured in the urine samples of 479 children in association with increased odds for ASD diagnosis (yes vs no). WQS-SiRF identified two synergistic two-ordered interactions between (1) trace-element cadmium (Cd) and the organophosphate pesticide metabolite diethyl-phosphate (DEP); and (2) 2,4,6-trichlorophenol (TCP-246) and DEP. Both interactions were suggestively associated with increased odds of ASD diagnosis in the subset of children with urinary concentrations of Cd, DEP, and TCP-246 above the 75th percentile. This study demonstrates a novel method that combines the inferential power of WQS and the predictive accuracy of machine-learning algorithms to discover potentially biologically relevant chemical-chemical interactions associated with ASD.

Associations between the chemical exposome and pregnancy induced hypertension.

Exposure to environmental chemicals has been linked to an increased risk of pregnancy-induced hypertension (PIH). This prospective cohort study examined the associations between PIH and maternal chemical exposure to four classes of chemicals (i.e., phthalates, bisphenols, perfluoroalkyl acids, non-essential metals and trace minerals). Participants included 420 pregnant women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort who had data available on diagnosed PIH and environmental chemical exposure. Twelve phthalate metabolites, two bisphenols, eight perfluoroalkyl acids and eleven non-essential metals or trace minerals were quantified in maternal urine or blood samples collected in the second trimester of pregnancy. Associations between the urinary and blood concentrations of these chemicals and PIH were assessed using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. Thirty-five (8.3%) participants were diagnosed with PIH. In single chemical exposure models, two phthalate metabolites, mono-methyl phthalate (MMP) and monoethyl phthalate (MEP), three perfluoroalkyl acids, perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), and one metal, manganese, were associated with increased odds of PIH. The metabolites of di (2-ethylhexyl) phthalate (DEHP) and the molar sum of these metabolites, as well as antimony, displayed trend associations (p < 0.10). In multi-chemical exposure models using LASSO penalized regressions and double-LASSO regressions, MEP (AOR: 1.43, 95% CI: 1.09-1.88, p = 0.009) and PFNA (AOR: 2.03, 95% CI: 1.01-4.07, p = 0.04) were selected as the chemicals most highly associated with PIH. These findings suggest that maternal levels of phthalates and perfluoroalkyl acids may be associated with the diagnosis on PIH. Future research should consider both individual and multi-chemical exposures when examining predictors of PIH and other maternal cardiometabolic health disorders, such as preeclampsia, eclampsia, HELLP syndrome, and gestational diabetes.

Assessment of personal care product use and perceptions of use in a sample of US adults affiliated with a university in the Northeast.

Evidence supports unequal burdens of chemical exposures from personal care products (PCPs) among some groups, namely femme-identifying and racial and ethnic minorities. In this study, we implemented an online questionnaire to assess PCP purchasing and usage behaviors and perceptions of use among a sample of US adults recruited at a Northeastern university. We collected PCP use across seven product categories (hair, beauty, skincare, perfumes/colognes, feminine hygiene, oral care, other), and behaviors, attitudes, and perceptions of use and safety across sociodemographic factors to evaluate relationships between sociodemographic factors and the total number of products used within the prior 24-48 h using multivariable models. We also summarized participants' perceptions and attitudes. Among 591 adults (20.0% Asian American/Pacific Islander [AAPI], 5.9% Hispanic, 9.6% non-Hispanic Black [NHB], 54.6% non-Hispanic White [NHW], and 9.9% multiracial or other), the average number of PCPs used within the prior 24-48 h was 15.6 ± 7.7. PCP use was greater among females than males (19.0 vs. 7.9, P < 0.01) and varied by race and ethnicity among females. Relative to NHWs, AAPI females used fewer hair products (2.5 vs. 3.1) and more feminine hygiene products (1.5 vs. 1.1), NHB females used more hair products (3.8 vs. 3.1), perfumes (1.0 vs. 0.6), oral care (2.3 vs. 1.9), and feminine hygiene products (1.8 vs. 1.1), and multiracial or other females used more oral care (2.2 vs. 1.9) and feminine hygiene products (1.5 vs. 1.1) (P-values <0.05). Generally, study participants reported moderate concern about exposures and health effects from using PCPs, with few differences by gender, race, and ethnicity. These findings add to the extant literature on PCP use across sociodemographic characteristics. Improving the understanding of patterns of use for specific products and their chemical ingredients is critical for developing interventions to reduce these exposures, especially in vulnerable groups with an unequal burden of exposure.

Responsibility for chemical exposures: perspectives from small beauty salons and auto shops in southern metropolitan Tucson.

BACKGROUND: Throughout the United States, low-wage, minority workers are disproportionately affected by occupational illnesses and injuries. Chronic exposure to hazardous chemicals at work can lead to serious illnesses, contributing to health inequities. In this article, we expand on theories of 'responsibilization' in an occupational health context to reveal how responsibilities for workplace chemical exposures are negotiated by workers and owners in Latinx-owned small businesses. METHODS: We conducted semi-structured interviews with a total of 22 workers and owners in auto repair shops and beauty salons - two high-risk industries - in Southern Metropolitan Tucson. Participants were asked about their insights into workplace chemical exposures and health. A qualitative analysis team with representation from all study partner organizations collectively coded and reviewed the interview data in QSR International's NVivo 11 and identified overarching themes across the interviews. RESULTS: We identified three primary themes: 1) ambivalence toward risks in the workplace; 2) shifting responsibilities for exposure protection at work; and 3) reflections on the system behind chemical exposure risks. Participants discussed the complexities that small businesses face in reducing chemical exposures. CONCLUSIONS: Through our analysis of the interviews, we examine how neoliberal occupational and environmental policies funnel responsibility for controlling chemical exposures down to individuals in small businesses with limited resources, obscuring the power structures that maintain environmental health injustices. We conclude with a call for upstream policy changes that more effectively regulate and hold accountable the manufacturers of chemical products used daily by small business workers.

Self-reported and objectively measured occupational exposures, health, and safety concerns among fishermen: A cross-sectional Fishing Industry Safety and Health (FISH) pilot study.

BACKGROUND: Fishing industry workers are exposed to hazardous working conditions, engage in strenuous labor, and work long hours in variable weather conditions. Despite these known employment challenges, little is known of their perceived occupational health and safety concerns. In this pilot study, we: (1) describe fishermen's perceptions on worker- and organizational-level characteristics that impact occupational health and safety; and (2) estimate environmental exposure to polycyclic aromatic hydrocarbons (PAHs) encountered during fishing activities. METHODS: We collected both qualitative and quantitative data from Mississippi and Florida fishermen. Using an ethnographic approach, the study team conducted 1-h key informant interviews, administered a one-page demographic survey, and collected objective measurements to PAHs using silicone-based passive sampling wristbands. RESULTS: Study participants (n = 17) had a mean age of 50.9 years (SD = 11.7), 88.2% were male, 94.1% white, 100.0% non-Hispanic/Latino, and 52.9% were married. Approximately, 87.5% reported fishing as their primary job, with a mean of 26.4 years in the industry (SD = 15.3). Four broad themes describing the culture of the fishing industry, common workplace exposures that impact fishermen's safety and health, and facilitators and barriers to safety while working in the fishing industry were documented. Deckhands had the lowest mean exposure to PAHs (8.3 ppb), followed by crew members (11.0 ppb), captains (82.64 ppb), and net makers (208.1 ppb). CONCLUSIONS: Gulf coast fishermen expressed specific occupational health and safety concerns and were exposed to carcinogenic PAHs during regular work. Opportunities exist and strategies are needed for health protection and health promotion interventions among Gulf fishermen.

Effects of firefighting hood design, laundering and doffing on smoke protection, heat stress and wearability.

Firefighter hoods must provide protection from elevated temperatures and products of combustion (e.g. particulate) while simultaneously being wearable (comfortable and not interfering with firefighting activities). The purpose of this study was to quantify the impact of (1) hood design (traditional knit hood vs particulate-blocking hood), (2) repeated laundering, and (3) hood removal method (traditional vs overhead doffing) on (a) protection from soot contamination on the neck, (b) heat stress and (c) wearability measures. Using a fireground exposure simulator, 24 firefighters performed firefighting activities in realistic smoke and heat conditions using a new knit hood, new particulate-blocking hood and laundered particulate-blocking hood. Overall, soot contamination levels measured from neck skin were lower when wearing the laundered particulate-blocking hoods compared to new knit hoods, and when using the overhead hood removal process. No significant differences in skin temperature, core temperature, heart rate or wearability measures were found between the hood conditions. Practitioner Summary: The addition of a particulate-blocking layer to firefighters' traditional two-ply hood was found to reduce the PAH contamination reaching the neck but did not affect heat stress measurements or thermal perceptions. Modifying the process for hood removal resulted in a larger reduction in neck skin contamination than design modification. Abbreviations: ANOVA: analysis of variance; B: new particulate-blocking hood and PPE (PPE configuration); FES: fireground exposure simulator; GI: gastrointestinal; K: new knit hood and PPE (PPE configuration); L: laundered particulate-blocking hood and PPE (PPE configuration); LOD: limit of detection; MLE: maximum likelihood estimation; NFPA: National fire protection association; PAH: polycyclic aromatic hydrocarbon; PPE: personal protective equipment; SCBA: self-contained breathing apparatus; THL: total heat loss; TPP: thermal protective performance.

VOC sources and exposures in nail salons: a pilot study in Michigan, USA.

PURPOSE: Exposures of nail salon technicians have received attention due to the potentially toxic materials used in nail products, which include volatile organic compounds (VOCs) such as formaldehyde and methyl methacrylate (MMA). This study characterized area and personal concentrations and other indoor air parameters in 17 nail salons in fall and winter seasons in three areas of Michigan. METHODS: VOC samples were analyzed using thermal desorption, gas chromatography and mass spectroscopy, and the VOC composition of 35 nail products (e.g., polish, top coat, base coat) was measured using headspace sampling. Ventilation rates were derived using CO2 concentrations, occupancy and building information, and VOC sources were apportioned by a novel application of chemical mass balance models. RESULTS: We detected ethyl acetate, propyl acetate, butyl acetate, MMA, n-heptane and toluene in most salons, and benzene, D-limonene, formaldehyde, and ethyl methacrylate in some salons. While MMA was not measured in the consumer and professional products, and the use of pure MMA in salons has been not been permitted since the 1970s, MMA was found in air at concentrations from 100 to 36,000 µg/m3 in 15 of 17 salons; thus its use appears to be commonplace in the industry. Personal measurements, representing exposures to workers and clients, were about twice those of the area measurements for many VOCs. CONCLUSION: This study identifies the products responsible for emissions, shows the widespread presence of MMA, and documents low ventilation rates in some salons. It also demonstrates that "informal" short-term sampling approaches can evaluate chemical exposures in nail salons, providing measurements that can be used to protect a potentially susceptible and vulnerable population. Additional controls, including restrictions on the VOC compositions and improved ventilation, can reduce exposures to salon workers and clients.

A screening questionnaire for occupational and hobby exposures during pregnancy.

BACKGROUND: Occupational and environmental exposures during the prenatal period may be associated with adverse pregnancy outcomes and lifelong health effects. Yet, identification and evaluation of these potential hazards is lacking in routine obstetric care. AIMS: To assess the feasibility of incorporating a self-administered occupational and environmental exposure questionnaire into obstetric clinics. METHODS: A cross-sectional survey assessed prenatal clinic patients at a public hospital who were currently employed and <20 weeks gestation. Questionnaires evaluated job characteristics, workplace and hobby exposures, protective equipment use and symptoms during pregnancy. RESULTS: Of 69 participants (96% response rate), 46% were predominantly Spanish-speaking. Primary occupations were caregiver (16%), cleaner (14%) and administrative assistant (14%). Overall, 93% were exposed to a workplace hazard, with most participants reporting physical stressors (82%) or organic solvent exposure (78%). Most women (74%) used some personal protective equipment. Nearly half (54%) reported at least one non-pregnancy symptom, and 52% were referred for follow-up with an occupational medicine practitioner. Household and hobby-related chemical exposures were common in our sample (91%). We observed moderate consistency between job task and chemical use responses: 67-99% of intentionally redundant questions were fully or partially matched. Closed- compared to open-ended activity questions identified a higher proportion of physical stressors (82% versus 12%) and cleaning product (76% versus 30%) exposures. CONCLUSIONS: A self-administered questionnaire is an effective screening tool for identifying women with occupational and hobby-related exposures during pregnancy. Consistent incorporation of exposure assessment into prenatal care can improve clinical communications and early interventions for at-risk pregnant women.

Heavy metal toxicity from the leather industry in Bangladesh: a case study of human exposure in Dhaka industrial area.

Activities in the Bangladeshi leather industries have the potential to cause chemical pollutions thereby deteriorating the working environments, the surrounding residential areas, or even foodstuffs. Therefore, it is important to determine the chemical exposures among the industry workers and residents of the surrounding areas who may be directly or indirectly impacted by the contaminated environment. This study focused on evaluating the hazard arising from exposure to metals due to industrial contamination. Tissue samples of hair and nails were collected from both the leather industry workers and residents in the vicinity of the industries. Using chromium as an indicator of contamination/exposure from the leather industry, it was the most significant metal contaminant for industry workers ranging from 21.85 to 483 mg/kg and for industry-neighboring residents at 6.01 to 296.16 mg/kg. Both the workers and neighboring residents were found to be excessively exposed (P < 0.05) to chromium compared with the investigated control group of people living in a distant village area which had no industrial establishments.

Latent class analysis to model multiple chemical exposures among children.

BACKGROUND: Children are exposed to multiple potentially harmful chemicals simultaneously. Efforts to understand the patterns and consequences of these exposures have been hampered by statistical limitations in estimations of higher order interactions. OBJECTIVES: The current study uses latent class analysis, a form of person-centered modeling to identify unobservable subgroups within populations and examine relationships between latent classes and measures of immune function. METHODS: Data from the National Health and Nutrition Examination Survey 2011-2012 were analyzed. A sample of 721 children aged 6-19 years were included who provided data on 47 chemicals of interest representing six chemical classes. Groups were identified using latent class analysis controlling for race/ethnicity, age, sex and poverty status. RESULTS: Two alternative approaches to identifying latent classes each resulted in similar three class solutions, including one group of children characterized by low co-exposures across chemicals, a group with moderate co-exposure levels, and a group characterized by high co-occurring levels of polycyclic aromatic hydrocarbons, volatile organic compounds, phenols and phthalates. Under one of the approaches, latent classes were significantly associated with immune function as measured by lymphocyte and neutrophil counts. CONCLUSIONS: Latent class analysis offers a potential approach to measuring and understanding interactions among multiple co-occurring chemical stressors. However, additional work is needed to test the ability of latent classes to predict health variables.

Neural autoantibodies in patients with neurological symptoms and histories of chemical/mold exposures.

A number of studies have linked exposures to industrial and household chemicals and biological toxins to increased risk of autoimmunity in general and elevated levels of autoantibodies to neural antigens specifically. Elevated neural autoantibodies are biomarkers for many diseases such as multiple sclerosis and Parkinson's disease. Our study reports levels of six types of neural autoantibodies in a group of 24 toxicant-exposed patients. The patients were exposed to a variety of toxicants including contaminated drinking water (four patients), building water/mold damage (eight patients), pesticides (four patients), and other assorted toxic chemicals (eight patients). Levels of all six neural autoantibodies were significantly elevated in most patients and in the patient group at large, with mean antibody levels for the 24 chemically exposed patients (relative to a healthy control population), in descending order: 475% for tau proteins, 391% for microtubule associated proteins-2, 334% for neurofilament proteins (NFP), 302% for myelin basic protein, 299% for glial fibrillary acidic proteins, and 225% for tubulin. Tau protein autoantibodies were significantly elevated in the patient groups with peripheral neuropathy, muscle and joint pain, asthma, and chemical sensitivity. Autoantibodies to tubulin were significantly higher in the chemical sensitivity and asthma patients, autoantibodies to NFP were significantly higher in the patients with sleep apnea, whereas S-100B autoantibodies were significantly increased in patients with muscle/joint pain, asthma, and apnea/insomnia. In patients exposed to environmental toxicants, measurements of autoantibodies may be useful for prevention, diagnosis, and treatment. This study adds to the scientific literature the ability of a broad spectrum of environmental triggers adversely affecting the nervous system through the process of autoimmunity, which may explain the increasing incidence of neurodegenerative diseases.

Chemical exposures and risk of acute myeloid leukemia and myelodysplastic syndromes in a population-based study.

Benzene exposure is one of the few well-established risk factors for myeloid malignancy. Exposure to other chemicals has been inconsistently associated with hematologic malignancies. We evaluated occupational and residential chemical exposures as risk factors for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) using population-based data. AML and MDS cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota driver's license/identification card list. Chemical exposures were measured by self-report. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). We included 265 MDS cases, 420 AML cases and 1388 controls. We observed significant associations between both MDS and AML and benzene (OR = 1.77, 95% CI 1.19, 2.63 and OR = 2.10, 95% CI 1.35, 3.28, respectively) and vinyl chlorides (OR = 2.05, 95% CI 1.15, 3.63 and OR = 2.81, 95% CI 1.14, 6.92). Exposure to soot, creosote, inks, dyes and tanning solutions and coal dust were associated with AML (range ORs = 2.68-4.03), while no association was seen between these exposures and MDS (range ORs = 0.57-1.68). Pesticides and agricultural chemicals were not significantly associated with AML or MDS. Similar results were observed in analyses stratified by sex. In addition to providing risk estimates for benzene from a population-based sample, we also identified a number of other occupational and residential chemicals that were significantly associated with AML; however, all exposures were reported by only a small percentage of cases (≤10%). While chemical exposures play a clear role in the etiology of myeloid malignancy, these exposures do not account for the majority of cases.

Windows of sensitivity to toxic chemicals in the motor effects development.

Many chemicals currently used are known to elicit nervous system effects. In addition, approximately 2000 new chemicals introduced annually have not yet undergone neurotoxicity testing. This review concentrated on motor development effects associated with exposure to environmental neurotoxicants to help identify critical windows of exposure and begin to assess data needs based on a subset of chemicals thoroughly reviewed by the Agency for Toxic Substances and Disease Registry (ATSDR) in Toxicological Profiles and Addenda. Multiple windows of sensitivity were identified that differed based on the maturity level of the neurological system at the time of exposure, as well as dose and exposure duration. Similar but distinct windows were found for both motor activity (GD 8-17 [rats], GD 12-14 and PND 3-10 [mice]) and motor function performance (insufficient data for rats, GD 12-17 [mice]). Identifying specific windows of sensitivity in animal studies was hampered by study designs oriented towards detection of neurotoxicity that occurred at any time throughout the developmental process. In conclusion, while this investigation identified some critical exposure windows for motor development effects, it demonstrates a need for more acute duration exposure studies based on neurodevelopmental windows, particularly during the exposure periods identified in this review.

The life course model as a framework for post-conflict health analysis: reflections on the Gulf War critical period.

In the Kuwait context, from January 1991 to December 1991, there were a series of chemical and psychological Gulf War-era exposures that left persistent, long-term damage. Extreme stress from a critical event speeds up the usual disease latency period, and may be part of a synergistic effect that leads to higher disease rates over a shorter period of time. I am interested in the impact of armed conflict on health outcomes over the life course in Kuwait, and particularly the pathways through which armed conflict causes changes in health on a population level. In this paper, I propose a culturally sensitive, post-conflict socio-ecological model that informs a three-pronged health study. I propose a macro-micro mix that includes an ecological study, a case-control study and a qualitative study to investigate Kuwait's post-conflict health concerns. Thus, I revise the concept of 'post-conflict health' as a trajectory that is mediated through different, complex social levels and develops over time during the latency period. The main advantage of a macro-micro mix approach for post-conflict health is that it contextualizes the Gulf War as an environmental health issue.

Advancing Understanding of Chemical Exposures and Maternal-child Health Through the U.S. Environmental Influences on Child Health Outcomes (ECHO) Program: A Scoping Review.

PURPOSE OF REVIEW: Environmental chemical exposures may disrupt child development, with long-lasting health impacts. To date, U.S. studies of early environmental exposures have been limited in size and diversity, hindering power and generalizability. With harmonized data from over 60,000 participants representing 69 pregnancy cohorts, the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Program is the largest study of U.S. children's health. Here, we: (1) review ECHO-wide studies of chemical exposures and maternal-child health; and (2) outline opportunities for future research using ECHO data. RECENT FINDINGS: As of early 2024, in addition to over 200 single-cohort (or award) papers on chemical exposures supported by ECHO, ten collaborative multi-cohort papers have been made possible by ECHO data harmonization and new data collection. Multi-cohort papers have examined prenatal exposure to per- and polyfluoroalkyl substances (PFAS), phthalates, phenols and parabens, organophosphate esters (OPEs), metals, melamine and aromatic amines, and emerging contaminants. They have primarily focused on describing patterns of maternal exposure or examining associations with maternal and infant outcomes; fewer studies have examined later child outcomes (e.g., autism) although follow up of enrolled ECHO children continues. The NICHD's Data and Specimen Hub (DASH) database houses extensive ECHO data including over 470,000 chemical assay results and complementary data on priority outcome areas (pre, peri-, and postnatal, airway, obesity, neurodevelopment, and positive health), making it a rich resource for future analyses. ECHO's extensive data repository, including biomarkers of chemical exposures, can be used to advance our understanding of environmental influences on children's health. Although few published studies have capitalized on these unique harmonized data to date, many analyses are underway with data now widely available.