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Determining biomarkers of responses to environmental exposures and evaluating whether they predict respiratory outcomes may help optimize environmental and medical approaches to childhood asthma. Relative mitochondrial (mt) DNA abundance and other potential mitochondrial indicators of oxidative stress may provide a sensitive metric of the child's shifting molecular responses to its changing environment. We leveraged two urban childhood cohorts (Environmental Control as Add-on Therapy in Childhood Asthma (ECATCh); Columbia Center for Children's Environmental Health (CCCEH)) to ascertain whether biomarkers in buccal mtDNA associate with airway inflammation and altered lung function over 6 months of time and capture biologic responses to multiple external stressors such as indoor allergens and fine particulate matter (PM 2.5 ). Relative mtDNA content was amplified by qPCR and methylation of transfer RNA phenylalanine/rRNA 12S (TF/RNR1), cytochrome c oxidase (CO1), and carboxypeptidase O (CPO) was measured by pyrosequencing. Data on residential exposures and respiratory outcomes were harmonized between the two cohorts. Repeated measures and multiple regression models were utilized to assess relationships between mitochondrial biomarkers, respiratory outcomes, and residential exposures (PM 2.5 , allergens), adjusted for potential confounders and time-varying asthma. We found across the 6 month visits, a 0.64 fold higher level of TF/RNR1 methylation was detected among those with asthma in comparison to those without asthma ((parameter estimate (PE) 0.64, standard error 0.28, p = 0.03). In prospective analyses, CPO methylation was associated with subsequent reduced forced vital capacity (FVC; PE -0.03, standard error 0.01, p = 0.02). Bedroom dust mouse allergen, but not indoor PM 2.5 , was associated with higher methylation of TF/RNR1 (PE 0.015, standard error 0.006, p = 0.01). Select mtDNA measures in buccal cells may indicate children's responses to toxic environmental exposures and associate selectively with asthma and lung function., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Rachel Miller reports financial support was provided by National Institutes of Health. Elizabeth Matsui reports financial support was provided by National Institutes of Health. Janelle RIvera reports financial support was provided by National Institutes of Health. Usha Govindarajulu reports financial support was provided by National Institutes of Health. Kyung Hwa Jung reports financial support was provided by National Institutes of Health. Stephanie Lovinsky-Desir reports financial support was provided by National Institutes of Health. Matthew Perzanowski reports financial support was provided by National Institutes of Health., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation., Methods: 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test., Results: Median follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77)., Conclusions: The risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer., Competing Interests: Declaration of competing interest Dr. Whelan has received in-kind funding from Exact Sciences for work not related to this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Polybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size., Methods: The sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (<80th percentile) and high (>80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity., Results: Adjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (-0.25, 95% CI: -0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (-0.55, 95% CI: -0.98, -0.12). There was a negative association between the overall PBDE mixture and birth length z-score (-0.10, 95% CI: -0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity., Conclusions: These results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Assessments of health and environmental effects of clean air and climate policies have revealed substantial health benefits due to reductions in air pollution, but have included few pediatric outcomes or assessed benefits at the neighborhood level., Objectives: We estimated benefits across a suite of child health outcomes in 42 New York City (NYC) neighborhoods under the proposed regional Transportation and Climate Initiative. We also estimated their distribution across racial/ethnic and socioeconomic groups., Methods: We estimated changes in ambient fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) concentrations associated with on-road emissions under nine different predefined cap-and-invest scenarios. Health outcomes, including selected adverse birth, respiratory, and neurodevelopmental outcomes, were estimated using a program similar to the U.S. EPA BenMAP program. We stratified the associated monetized benefits across racial/ethnic and socioeconomic groups., Results: The benefits varied widely over the different cap-and-investment scenarios. For a 25% reduction in carbon emissions from 2022 to 2032 and a strategy prioritizing public transit investments, NYC would have an estimated 48 fewer medical visits for childhood asthma, 13,000 avoided asthma exacerbations not requiring medical visits, 640 fewer respiratory illnesses unrelated to asthma, and 9 avoided adverse birth outcomes (infant mortality, preterm birth, and term low birth weight) annually, starting in 2032. The total estimated annual avoided costs are $22 million. City-wide, Black and Hispanic children would experience 1.7 times the health benefits per capita than White and Non-Hispanic White children, respectively. Under the same scenario, neighborhoods experiencing the highest poverty rates in NYC would experience about 2.5 times the health benefits per capita than the lowest poverty neighborhoods., Conclusion: A cap-and-invest strategy to reduce carbon emissions from the transportation sector could provide substantial health and monetized benefits to children in NYC through reductions in criteria pollutant concentrations, with greater benefits among Black and Hispanic children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prenatal air pollution exposure is associated with reductions in self-regulation and academic achievement. Self-regulation has been separately linked with academic achievement. Understudied, however, are the contributions of pollution exposure to inhibitory control, a facet of self-regulation, and whether pollution-related inhibitory control deficits are associated with impairment in academic achievement., Methods: Participants were recruited from a prospective birth cohort. Measures of prenatal airborne polycyclic aromatic hydrocarbons (PAH) during the third trimester of pregnancy, inhibitory control (NEPSY Inhibition) at mean age = 10.4 years, and Woodcock-Johnson Tests of Achievement-III at mean age = 13.7 were available for N = 200 participants. Multiple linear regression examined sex-dependent and sex independent associations among prenatal PAH, childhood inhibitory control, and academic achievement during adolescence, and whether childhood inhibitory control mediated associations between prenatal PAH and academic achievement during adolescence, controlling for ethnicity, maternal country of birth, language of prenatal interview, maternal marital status, maternal years of education, material hardship, quality of home caregiving environment, and early life stress., Results: Across all participants, higher prenatal PAH was significantly associated with worse spelling skills (WJ-III Spelling, β = -0.16, 95%Confidence Interval [CI]: 0.30, -0.02, p = .02). Trend level associations between higher prenatal PAH and worse reading comprehension (WJ-III Passage Comprehension, β = -0.13, 95%CI: 0.28, 0.01, p = .07) and math skills (WJ-III Broad Math, β = -0.11, 95%CI: 0.25, 0.03, p = .11) were detected. Across all participants, higher PAH was significantly associated with worse inhibitory control (β = -0.15, 95%CI: 0.29,-0.01 p = .03). Better inhibitory control was significantly associated with better reading comprehension (WJ-III Passage Comprehension, β = 0.22, 95%CI: 0.09, 0.36, p < .002) and math skills (WJ-III Broad Math Index, β = 0.32, 95%CI: 0.19, 0.45, p < .001), and trend level associations with better spelling skills (WJ-III Spelling, β = 0.12, 95%CI: 0.02, 0.26, p = .10). Inhibitory control significantly mediated PAH-related achievement effects for Passage Comprehension (β = -0.61, 95%CI: 1.49, -0.01) and Broad Math Index (β = -1.09, 95%CI: 2.36, -0.03)., Conclusions: Higher prenatal PAH exposure and lower childhood inhibitory control were associated with worse spelling, passage comprehension, and math in adolescence. Notably, childhood inhibitory control mediated PAH exposure-related effects on achievement in adolescents. Identifying these potential exposure-related phenotypes of learning problems may promote interventions that target inhibitory control deficits rather than content specific deficits., (Copyright © 2021. Published by Elsevier Inc.)

Background: Improved understanding of how prenatal exposure to environmental mixtures influences birth weight or other adverse outcomes is essential in protecting child health., Objective: We illustrate a novel exposure continuum mapping (ECM) framework that combines the self-organizing map (SOM) algorithm with generalized additive modeling (GAM) in order to integrate spatially-correlated learning into the study mixtures of environmental chemicals. We demonstrate our method using biomarker data on chemical mixtures collected from a diverse mother-child cohort., Methods: We obtained biomarker concentrations for 16 prevalent endocrine disrupting chemicals (EDCs) collected in the first-trimester from a large, ethnically/racially diverse cohort of healthy pregnant women (n = 604) during 2009-2012. This included 4 organochlorine pesticides (OCPs), 4 polybrominated diphenyl ethers (PBDEs), 4 polychlorinated biphenyls (PCBs), and 4 perfluoroalkyl substances (PFAS). We applied a two-stage exposure continuum mapping (ECM) approach to investigate the combined impact of the EDCs on birth weight. First, we analyzed our EDC data with SOM in order to reduce the dimensionality of our exposure matrix into a two-dimensional grid (i.e., map) where nodes depict the types of EDC mixture profiles observed within our data. We define this map as the 'exposure continuum map', as the gridded surface reflects a continuous sequence of exposure profiles where adjacent nodes are composed of similar mixtures and profiles at more distal nodes are more distinct. Lastly, we used GAM to estimate a joint-dose response based on the coordinates of our ECM in order to capture the relationship between participant location on the ECM and infant birth weight after adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index (BMI), education, serum cotinine, total plasma lipids, and infant sex. Single chemical regression models were applied to facilitate comparison., Results: We found that an ECM with 36 mixture profiles retained 70% of the total variation in the exposure data. Frequency analysis showed that the most common profiles included relatively low concentrations for most EDCs (~10%) and that profiles with relatively higher concentrations (for single or multiple EDCs) tended to be rarer (~1%) but more distinct. Estimation of a joint-dose response function revealed that lower birth weights mapped to locations where profile compositions were dominated by relatively high PBDEs and select OCPs. Higher birth weights mapped to locations where profiles consisted of higher PCBs. These findings agreed well with results from single chemical models., Conclusions: Findings from our study revealed a wide range of prenatal exposure scenarios and found that combinations exhibiting higher levels of PBDEs were associated with lower birth weight and combinations with higher levels of PCBs and PFAS were associated with increased birth weight. Our ECM approach provides a promising framework for supporting studies of other exposure mixtures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: While animal data support an association between prenatal exposure to endocrine disrupting chemicals (EDCs) and altered mammary gland development and tumorigenesis, epidemiologic studies have only considered a few classes of EDCs in association with pubertal growth and development in girls. Polycyclic aromatic hydrocarbons (PAH) are a class of EDCs that have not been rigorously evaluated in terms of prenatal exposure and pubertal growth and development in girls., Objective: In a New York City birth cohort of Black and Hispanic girls (n = 196; recruited 1998-2006), we examined associations of prenatal PAH exposure with self-reported age at growth spurt onset, breast development onset and menarche, and clinical measures of adolescent body composition including body mass index, waist-to-hip ratio, and body fat measured at ages 11-20 years., Methods: We measured prenatal exposure to PAH using personal air monitoring data collected from backpacks worn by mothers during the third trimester of pregnancy (data available for all 196 girls) and biomarkers of benzo[α]pyrene-DNA adducts in umbilical cord blood (data available for 106 girls). We examined associations of prenatal PAH with the timing of pubertal milestones and adolescent body composition (11-20 years) using multivariable linear regression models adjusted for race/ethnicity, household public assistance status at birth, and age at outcome assessment. We also fit models further adjusted for potential mediators, including birthweight and childhood body size (BMI-for-age z-score measured at 6-8 years)., Results: Girls in the highest versus lowest tertile of ambient exposure to PAH, based on a summary measure of eight carcinogenic higher-molecular weight non-volatile PAH compounds (Σ8 PAH), had a 0.90 year delay in growth spurt onset (95% confidence interval (CI) = 0.25, 1.55; n = 196), a 0.35 year delay in breast development onset (95% CI = -0.26, 0.95; n = 193), and a 0.59 year delay in menarche (95% CI = 0.06, 1.11; n = 191) in models adjusted for race/ethnicity and household public assistance at birth. The statistically significant associations for age at growth spurt onset and menarche were not impacted by adjustment for birthweight or childhood body size. No differences in BMI-for-age z-score, waist-to-hip ratio, or percent body fat were found between girls in the highest versus lowest tertile of ambient Σ8 PAH. Results were similar when we evaluated benzo[α]pyrene-DNA adduct levels., Discussion: Our results suggest that prenatal exposure to PAH might delay pubertal milestones in girls, but findings need to be replicated in other cohorts using prospectively collected data on pubertal outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Air pollution exposure is ubiquitous with demonstrated effects on morbidity and mortality. A growing literature suggests that prenatal air pollution exposure impacts neurodevelopment. We posit that the Environmental influences on Child Health Outcomes (ECHO) program will provide unique opportunities to fill critical knowledge gaps given the wide spatial and temporal variability of ECHO participants., Objectives: We briefly describe current methods for air pollution exposure assessment, summarize existing studies of air pollution and neurodevelopment, and synthesize this information as a basis for recommendations, or a blueprint, for evaluating air pollution effects on neurodevelopmental outcomes in ECHO., Methods: We review peer-reviewed literature on prenatal air pollution exposure and neurodevelopmental outcomes, including autism spectrum disorder, attention deficit hyperactivity disorder, intelligence, general cognition, mood, and imaging measures. ECHO meta-data were compiled and evaluated to assess frequency of neurodevelopmental assessments and prenatal and infancy residential address locations. Cohort recruitment locations and enrollment years were summarized to examine potential spatial and temporal variation present in ECHO., Discussion: While the literature provides compelling evidence that prenatal air pollution affects neurodevelopment, limitations in spatial and temporal exposure variation exist for current published studies. As >90% of the ECHO cohorts have collected a prenatal or infancy address, application of advanced geographic information systems-based models for common air pollutant exposures may be ideal to address limitations of published research., Conclusions: In ECHO we have the opportunity to pioneer unifying exposure assessment and evaluate effects across multiple periods of development and neurodevelopmental outcomes, setting the standard for evaluation of prenatal air pollution exposures with the goal of improving children's health., (Copyright © 2020 Elsevier Inc. All rights reserved.)

New York City (NYC) experienced a sharp decline in air pollution during the COVID-19 shutdown period (March 15, 2020 to May 15, 2020)-albeit at high social and economic costs. It provided a unique opportunity to simulate a scenario in which the city-wide air quality improvement during the shutdown were sustained over the five-year period, 2021 through 2025, allowing us to estimate the potential public health benefits to children and adults and their associated economic benefits. We focused on fine particulate matter (PM 2.5 ) and modeled potential future health benefits to children and adults. The analysis considered outcomes in children that have not generally been accounted for in clean air benefits assessments, including preterm birth, term low birthweight, infant mortality, child asthma incidence, child asthma hospital admissions and emergency department visits, autism spectrum disorder, as well as adult mortality. We estimated a city-wide 23% improvement in PM 2.5 levels during the COVID-19 shutdown months compared to the average level for those months in 2015-2018 (the business as usual period). Based on the data for 2020, we extrapolated the ambient levels of PM 2.5 for the following five-year period. The estimated cumulative benefits for 2021-2025 included thousands of avoided cases of illness and death, with associated economic benefits from $31.8 billion to $77 billion. This "natural experiment," tragic though the cause, has provided a hypothetical clean air scenario that can be considered aspirational-one that could be achieved through transportation, climate, and environmental policies that support robust economic recovery with similarly reduced emissions., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Impacts on children's health are under-represented in benefits assessments of policies related to ambient air quality and climate change. To complement our previous compilation of concentration-response (C-R) functions for a number of children's health outcomes associated with air pollution, we provide per-case monetary estimates of the same health outcomes., Objectives: Our goal was to establish per-case monetary estimates for a suite of prevalent children's health outcomes (preterm birth, low birth weight, asthma, autism spectrum disorder, attention-deficit/hyperactivity disorder, and IQ reduction) that can be incorporated into benefits assessments of air pollution regulations and climate change mitigation policies., Methods: We conducted a systematic review of the literature published between January 1, 2000 and June 30, 2018 to identify relevant economic costs for these six adverse health outcomes in children. We restricted our literature search to studies published in the U.S., with a supplemental consideration of studies from the U.K. and prioritized literature reviews with summary cost estimates and papers that provided lifetime cost of illness estimates., Results: Our literature search and evaluation process reviewed 1065 papers and identified 12 most relevant papers on per-case monetary estimates for preterm birth, low birth weight, asthma, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Details are presented in full. We separately identified estimates of the lost lifetime earnings associated with the loss of a single IQ point. The final per-case cost estimates for each outcome were selected based on the most robust evidence. These estimates range from $23,573 for childhood asthma not persisting into adulthood to $3,109,096 for a case of autism with a concurrent intellectual disability., Conclusion: To our knowledge, this is the first time that the child-specific health outcomes of preterm birth, low birth weight, asthma, autism spectrum disorder, attention-deficit/hyperactivity disorder, and IQ reduction have been systematically valued and presented in one place. This is an important addition to the body of health-related valuation literature as these outcomes have substantial economic costs that are not considered in most assessments of the benefits of air pollution and climate mitigation policies. In general, however, the available per-case estimates presented here did not incorporate the broad societal and long-term costs and are likely underestimates. Although our context has been air pollution and climate policies, the per-case monetary estimates presented here can be applied to other environmental exposures. Fuller assessments of health benefits to children and their corresponding economic gains will improve decision-making on environmental policy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

There is evidence that exposures to polycyclic aromatic hydrocarbons (PAH) and fine particles in air pollution are associated with higher childhood body mass index (BMI). Birth cohort analyses of prenatal exposures to PAH and child BMI Z-scores from age 5-14 years were conducted. African-American and Hispanic children born in the Bronx or Northern Manhattan, New York (1998-2006), whose mothers underwent personal air monitoring for airborne PAH exposure during pregnancy, were followed up with measurements of height and weight at approximate ages 5, 7, 9, 10, 11, 12.5 and 13.5 years. Multivariable generalized estimating equation analyses were used to relate prenatal airborne PAH exposures to child BMI Z-scores through time. The analyses adjusted for many known risk factors for childhood obesity and included interactions terms between age and exposure tertiles and age squared and exposure tertiles. In total, 535 children had at least one height and weight measure during follow-up. The prevalence of obesity was 20.6% at age 5 and increased across follow-ups until age 11 when it was 33.0%. At age 5, BMI Z-scores were significantly greater for children in the third tertile of exposure relative to the first tertile (0.35 Z-score units, 95% CI 0.09, 0.61, p = 0.007) and were non-significantly higher for the second tertile of exposure compared to the first tertile (0.25 Z-score units, 95% CI -0.02, 0.52, P = 0.075). The trajectories of BMI Z-scores by tertiles of exposure converged as the children aged, such that by age 11 years the estimated mean BMI Z-scores associated with each tertile of exposure were not different. Prenatal exposures to airborne PAH were associated with higher childhood BMI Z-scores at a young age, but growth trajectories converged by age 11 years. Accordingly, highly exposed children spend a greater proportion of their childhood with higher BMI Z-scores., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Fossil fuel combustion by-products, including particulate matter (PM 2.5 ), polycyclic aromatic hydrocarbons (PAH), nitrogen dioxide (NO 2 ) and carbon dioxide (CO 2 ), are a significant threat to children's health and equality. Various policies to reduce emissions have been implemented to reduce air pollution and mitigate climate change, with sizeable estimated health and economic benefits. However, only a few adverse outcomes in children have been considered, resulting in an undercounting of the benefits to this vulnerable population., Objectives: Our goal was to expand the suite of child health outcomes addressed by programs to assess health and economic benefits, such as the Environmental Protection Agency (EPA) Benefits Mapping and Analysis Program (BenMAP), by identifying concentration-response (C-R) functions for six outcomes related to PM 2.5 , NO 2 , PAH, and/or PM 10 : preterm birth (PTB), low birthweight (LBW), autism, attention deficit hyperactivity disorder, IQ reduction, and the development of childhood asthma., Methods: We conducted a systematic review of the literature published between January 1, 2000 and April 30, 2018 to identify relevant peer-reviewed case-control and cohort studies and meta-analyses. In some cases meta-analyses were available that provided reliable C-R functions and we assessed their consistency with subsequent studies. Otherwise, we reviewed all eligible studies published between our search dates., Results: For each pollutant and health outcome, we present the characteristics of each selected study. We distinguish between C-R functions for endpoints having a causal or likely relationship (PTB, LBW, autism, asthma development) with the pollutants for incorporation into primary analyses and endpoints having a suggestive causal relationship with the pollutants (IQ reduction, ADHD) for secondary analyses., Conclusion: We have identified C-R functions for a number of adverse health outcomes in children associated with air pollutants largely from fossil fuel combustion. Their incorporation into expanded assessments of health benefits of clean air and climate mitigation policies will provide an important incentive for preventive action., (Copyright © 2018. Published by Elsevier Inc.)

Personal air pollution monitoring in research studies should not interfere with usual patterns of behavior and bias results. In an urban pediatric cohort study we tested whether wearing an air monitor impacted activity time based on continuous watch-based accelerometry. The majority (71%) reported that activity while wearing the monitor mimicked normal activity. Correspondingly, variation in activity while wearing versus not wearing the monitor did not differ greatly from baseline variation in activity (P = 0.84)., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Prior research has demonstrated inverse associations between maternal prenatal urinary phthalate metabolite concentrations and cognitive development assessed in preschool and school-aged children. While there are a limited number of studies that evaluated these associations during infancy, no study has evaluated whether these associations exist when using the Fagan Test of Infant Intelligence (FTII), which captures novelty preference as a function of visual recognition memory., Objective: We evaluated associations between phthalate metabolite concentrations in maternal prenatal urine and cognition in infancy using the FTII at 27 weeks and determine if these associations are sex-specific., Methods: Mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), mono-ethyl phthalate (MEP), mono-3-carboxypropyl phthalate (MCPP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in urine samples collected from 168 minority women living in urban neighborhoods during their third trimester of pregnancy. The FTII was administered to infants at 27 weeks to measure visual recognition memory and was recorded as the novelty preference score., Results: There were no associations between prenatal phthalate metabolite concentrations and novelty preference score in the full sample. However, there was evidence of effect modification by infant sex. Sex-stratified models demonstrated that compared to girls in the lowest tertile of MBzP concentrations, girls in tertiles 2 and 3 had, on average, 3.98 and 4.65 points lower novelty preference scores (p-value=0.04 and 0.03, respectively). The relationship was similar for ΣDEHP, MiBP, and MEP. Effects among boys were inconsistent and generally not significant., Conclusion: Maternal prenatal exposure to some phthalates was negatively associated with visual recognition memory as measured by the FTII among girls at age 27 weeks., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Experimental and epidemiological studies suggest that gestational exposure to Bisphenol A (BPA), an ubiquitous endocrine disrupting chemical, may lead to neurobehavioral problems in childhood; however, not all results have been consistent. We previously reported a positive association between prenatal BPA exposure and symptoms of anxiety/depression reported by the mother at child age 7-9 years in boys, but not girls., Objectives: Here, in the same birth cohort, we investigated the association of prenatal BPA exposure with symptoms of depression and anxiety self-reported by the 10-12 year olds, hypothesizing that we would observe sex-specific differences in anxiety and depressive symptoms., Methods: African-American and Dominican women living in Northern Manhattan and their children were followed from mother's pregnancy through children's age 10-12 years. BPA was quantified in maternal urine collected during the third trimester of pregnancy and in child urine collected at ages 3 and 5 years. Children were evaluated using the Revised Children's Manifest Anxiety Scale (RCMAS) and Children's Depression Rating Scale (CDRS). We compared the children in the highest tertile of BPA concentration to those in the lower two tertiles. Associations between behavior and prenatal (maternal) BPA concentration or postnatal (child) BPA concentration were assessed in regression models stratified by sex., Results: Significant positive associations between prenatal BPA and symptoms of depression and anxiety were observed among boys. Postnatal BPA exposure was not significantly associated with outcomes. There was substantial co-occurrence of anxiety and depressive symptoms in this sample., Conclusion: These results provide evidence that prenatal BPA exposure is associated with more symptoms of anxiety and depression in boys but not in girls at age 10-12 years., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Within a New York City (NYC) birth cohort, we assessed the associations between polycyclic aromatic hydrocarbon (PAH) and other aromatic DNA adducts and brain derived neurotrophic factor (BDNF) concentrations in umbilical cord blood, and neurodevelopment at age 2 years and whether BDNF is a mediator of the associations between PAH/aromatic-DNA adducts and neurodevelopment., Methods: PAH/aromatic-DNA adduct concentrations in cord blood were measured in 505 children born to nonsmoking African-American and Dominican women residing in NYC, and a subset was assessed for neurodevelopment at 2 years using the Bayley Scales of Infant Development Mental Development Index (MDI). A spectrum of PAH/aromatic-DNA adducts was measured using the (32)P-postlabeling assay; DNA adducts formed by benzo[a]pyrene (B[a]P), a representative PAH, were measured by High Performance Liquid Chromatography (HPLC)/fluorescence. BDNF mature protein in cord blood plasma was quantified by an ELISA. Multivariate regression analysis, adjusting for potential confounders, was conducted., Results: PAH/aromatic-DNA adduct concentration measured by postlabeling was inversely associated with BDNF concentration (p=0.02) and with MDI scores at 2 years (p=0.04). BDNF level was positively associated with MDI scores (p=0.003). Restricting to subjects having all three measures (PAH/aromatic-DNA adducts by postlabeling, MDI, and BDNF), results were similar but attenuated (p=0.13, p=0.05, p=0.01, respectively). Associations between B[a]P-DNA adducts and BDNF and B[a]P-DNA adducts and MDI at age 2 years were not significant. At age 3 years, the positive association of BDNF with MDI was not observed., Conclusions: The results at age 2 suggest that prenatal exposure to a spectrum of PAH/aromatic pollutants may adversely affect early neurodevelopment, in part by reducing BDNF levels during the fetal period. However, the same relationship was not seen at age 3., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Polycyclic aromatic hydrocarbons (PAH) exposure from solid fuel burning represents an important public health issue for the majority of the global population. Yet, understanding of individual-level exposures remains limited., Objectives: To develop regionally adaptable chronic personal exposure model to pro-carcinogenic PAH (c-PAH) for the population in Kraków, Poland., Methods: We checked the assumption of spatial uniformity in eight c-PAH using the coefficients of divergence (COD), a marker of absolute concentration differences. Upon successful validation, we developed personal exposure models for eight pro-carcinogenic PAH by integrating individual-level data with area-level meteorological or pollutant data. We checked the resulting model for accuracy and precision against home outdoor monitoring data., Results: During winter, COD of 0.1 for Kraków suggest overall spatial uniformity in the ambient concentration of the eight c-PAH. The three models that we developed were associated with index of agreement approximately equal to 0.9, root mean square error < 2.6 ng/m(3), and 90th percentile of absolute difference ≤ 4 ng/m(3) for the predicted and the observed concentrations for eight pro-carcinogenic PAH., Conclusions: Inexpensive and logistically feasible information could be used to estimate chronic personal exposure to PAH profiles, in lieu of costly and labor-intensive personal air monitoring at wide scale. At the same time, thorough validation through direct personal monitoring and assumption checking are critical for successful model development., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Exposure to air pollutants including polycyclic aromatic hydrocarbons (PAH), and specifically pyrene from combustion of fuel oil, coal, traffic and indoor sources, has been associated with adverse respiratory health outcomes. However, time trends of airborne PAH and metabolite levels detected via repeat measures over time have not yet been characterized. We hypothesized that PAH levels, measured repeatedly from residential indoor and outdoor monitors, and children׳s urinary concentrations of PAH metabolites, would decrease following policy interventions to reduce traffic-related air pollution., Methods: Indoor PAH (particle- and gas-phase) were collected for two weeks prenatally (n=98), at age 5/6 years (n=397) and age 9/10 years (n=198) since 2001 and at all three age-points (n=27). Other traffic-related air pollutants (black carbon and PM2.5) were monitored indoors simultaneous with PAH monitoring at ages 5/6 (n=403) and 9/10 (n=257) between 2005 and 2012. One third of the homes were selected across seasons for outdoor PAH, BC and PM2.5 sampling. Using the same sampling method, ambient PAH, BC and PM2.5 also were monitored every two weeks at a central site between 2007 and 2012. PAH were analyzed as semivolatile PAH (e.g., pyrene; MW 178-206) (∑8PAH(semivolatile): Including pyrene (PYR), phenanthrene (PHEN), 1-methylphenanthrene (1-MEPH), 2-methylphenanthrene (2-MEPH), 3-methylphenanthrene (3-MEPH), 9-methylphenanthrene (9-MEPH), 1,7-dimethylphenanthrene (1,7-DMEPH), and 3,6-dimethylphenanthrene (3,6-DMEPH)) and the sum of eight nonvolatile PAH (∑8PAH(nonvolatile): Including benzo[a]anthracene (BaA), chrysene/iso-chrysene (Chry), benzo[b]fluoranthene (BbFA), benzo[k]fluoranthene (BkFA), benzo[a]pyrene (BaP), indeno[1,2,3-c,d]pyrene (IP), dibenzo[a,h]anthracene (DahA), and benzo[g,h,i]perylene (BghiP); MW 228-278). A spot urine sample was collected from children at child ages 3, 5, 7 and 9 between 2001 and 2012 and analyzed for 10 PAH metabolites., Results: Modest declines were detected in indoor BC and PM2.5 levels between 2005 and 2012 (Annual percent change [APC]=-2.08% [p=0.010] and -2.18% [p=0.059] for BC and PM2.5, respectively), while a trend of increasing pyrene levels was observed in indoor and outdoor samples, and at the central site during the comparable time periods (APC=4.81%, 3.77% and 7.90%, respectively; p<0.05 for all). No significant time trend was observed in indoor ∑8PAH(nonvolatile) levels between 2005 and 2012; however, significant opposite trends were detected when analyzed seasonally (APC=-8.06% [p<0.01], 3.87% [p<0.05] for nonheating and heating season, respectively). Similarly, heating season also affected the annual trends (2005-2012) of other air pollutants: the decreasing BC trend (in indoor/outdoor air) was observed only in the nonheating season, consistent with dominating traffic sources that decreased with time; the increasing pyrene trend was more apparent in the heating season. Outdoor PM2.5 levels persistently decreased over time across the seasons. With the analyses of data collected over a longer period of time (2001-2012), a decreasing trend was observed in pyrene (APC=-2.76%; p<0.01), mostly driven by measures from the nonheating season (APC=-3.54%; p<0.01). In contrast, levels of pyrene and naphthalene metabolites, 1-hydroxypyrene and 2-naphthol, increased from 2001 to 2012 (APC=6.29% and 7.90% for 1-hydroxypyrene and 2-naphthol, respectively; p<0.01 for both)., Conclusions: Multiple NYC legislative regulations targeting traffic-related air pollution may have led to decreases in ∑8PAH(nonvolatile) and BC, especially in the nonheating season. Despite the overall decrease in pyrene over the 2001-2012 periods, a rise in pyrene levels in recent years (2005-2012), that was particularly evident for measures collected during the heating season, and 2-naphthol, indicates the contribution of heating oil combustion and other indoor sources to airborne pyrene and urinary 2-naphthol., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: This study of a birth cohort in the city of Tongliang in Chongqing, China, evaluated the relationship between two prenatal exposures (polycyclic aromatic hydrocarbons(PAH) and environmental tobacco smoke(ETS)) and child intelligence quotient (IQ) as measured by the Wechsler Preschool and Primary Scale of Intelligence at age 5 years. A coal-fired power plant was the major source of ambient PAH in this city. We tested the hypothesis that, after adjusting for potential confounders, prenatal exposure to these pollutants would be associated with lower IQ scores at 5 years of age., Methods: Nonsmoking mothers and children were enrolled before delivery. PAH exposure was measured by DNA adducts in umbilical cord white blood cells using High-Performance Liquid Chromatography-Fluorescence. Estimated exposure to environmental tobacco smoke was based on personal interview. At age 5 years, scores for verbal, performance, and full scale IQ were obtained. Multiple regression was used to test the main effects of adducts and environmental tobacco smoke on IQ and to explore the interactions between these exposures on IQ., Results: after adjusting for potential confounders, neither DNA adducts nor exposure to environmental tobacco smoke had significant main effects on IQ. However, significant interactions between adducts and environmental tobacco smoke were observed on full scale (p=0.025) and verbal (p=0.029) IQ scores, indicating that the adverse effects of prenatal PAH exposure became greater as exposure to environmental tobacco smoke increased. The interaction on performance IQ score was not significant (p=0.135)., Conclusion: These results suggest that exposure of pregnant women to emissions of PAHs from the coal-burning plant, in combination with prenatal exposure to envrionmental tobacco smoke, may have adversely affected cognitive function of children at age 5. The polluting coal-fired plant has since been closed by the government, with likely important benefits to child health and development., (Copyright © 2012. Published by Elsevier Inc.)

The goal of the study was to test the hypothesis that prenatal Paracetamol exposure increases the risk of developing eczema in early childhood and that this association may be stronger in children who are exposed in fetal period to higher concentrations of fine particulate matter (PM2.5). The study sample consisted of 322 women recruited from January 2001 to February 2004 in the Krakow inner city area who gave birth to term babies and completed 5-year follow-up. Paracetamol use in pregnancy was collected by interviews and prenatal personal exposure to PM2.5 over 48 h was measured in recruited women in the second trimester of pregnancy. After delivery, every three months in the first 24 months of the newborn's life and every 6 months later, a detailed standardized face-to-face interview on the infant's health was administered to each mother by trained interviewers. During the interviews at each of the study periods after birth, a history of eczema was recorded. The incident rate ratio (IRR) for frequency of eczema events over the follow-up was estimated from the Poisson regression model and the overall effect of main exposure variables on eczema was assessed by odds ratios (ORs) by the logistic model. The estimated relative risk of eczema occurring whenever in the follow-up was related significantly neither with prenatal Paracetamol nor higher PM2.5 exposure, however, their joint effect was significant (OR interaction term=6.04; 95%CI: 1.04-35.16). Of potential confounders considered in the analysis only damp/moldy home significantly increased the risk of eczema (OR=1.53; 95%CI: 1.14-2.05). In contrast, there was an inverse significant association between the presence of older siblings and eczema (OR=0.55; 95%CI: 0.35-0.84). The joint effect of the main exposure variables significantly increased frequency of eczema events (IRR=1.78, 95%CI: 1.22-2.61). In conclusion, the findings of the study suggest that Paracetamol use by mothers in pregnancy is not an independent risk factor for eczema in children, however, even very small doses of Paracetamol taken in pregnancy may contribute to the occurrence of allergic symptoms in early childhood if there is prenatal co-exposure to higher airborne fine particulate matter., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines., Objectives: The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood., Material and Methods: The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), child's gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts., Results and Conclusion: In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR=2.25, 95%CI: 1.21-4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Unlabelled: The primary purpose of this study was to assess the relationship between very low-level of prenatal lead exposure measured in the cord blood (<5 microg/dL) and possible gender-specific cognitive deficits in the course of the first three years of life. The accumulated lead dose in infants over the pregnancy period was measured by the cord blood lead level (BLL) and cognitive deficits were assessed by the Bayley Mental Development Index (MDI). The study sample consisted of 457 children born to non-smoking women living in the inner city and the outlying residential areas of Krakow. The relationship between prenatal lead exposure and MDI scores measured at 12, 24 and 36 months of age and adjusted to a set of important covariates (gender of child, maternal education, parity, breastfeeding, prenatal and postnatal environmental tobacco smoke) was evaluated with linear multivariate regression, and the Generalized Estimating Equations (GEE) longitudinal panel model. The median of lead level in cord blood was 1.21 microg/dL with the range of values from 0.44 to 4.60 microg/dL. Neither prenatal BLL (dichotomized by median) nor other covariates affected MDI score at 12 months of age. Subsequent testing of children at 24 months of age showed a borderline significant inverse association of lead exposure and mental function (beta coefficient=-2.42, 95%CI: -4.90 to 0.03), but the interaction term (BLL x male gender) was not significant. At 36 months, prenatal lead exposure was inversely and significantly associated with cognitive function in boys (Spearman correlation coefficient=-0.239, p=0.0007) but not girls (r=-0.058, p=0.432) and the interaction between BLL and male gender was significant (beta coefficient=-4.46; 95%CI: -8.28 to -0.63). Adjusted estimates of MDI deficit in boys at 36 months confirmed very strong negative impact of prenatal lead exposure (BLL>1.67 microg/dL) compared with the lowest quartile of exposure (beta coefficient=-6.2, p=0.002), but the effect in girls was insignificant (beta coefficient=-0.74, p=0.720). The average deficit of cognitive function in the total sample over the first three years of life (GEE model) associated with higher prenatal lead exposure was also significant (beta coefficient=-3.00; 95%CI: -5.22 to -0.70). Beside prenatal lead exposure, presence of older siblings at home and prenatal environmental tobacco smoke had a negative impact on MDI score. Better maternal education showed a strong beneficial effect on the cognitive development of children., Conclusion: the study suggests that there might be no threshold for lead toxicity in children and provides evidence that 3-year old boys are more susceptible than girls to prenatal very low lead exposure. The results of the study should persuade policy makers to consider gender-related susceptibility to lead and possibly to other toxic hazards in setting environmental protection guidelines. To determine whether the cognitive deficit documented in this study persists to older ages, the follow-up of the children over the next several years is to be carried out.

Our primary purpose was to assess sex-specific fetal growth reduction in newborns exposed prenatally to fine particulate matter. Only women 18-35 years of age, who claimed to be non-smokers, with singleton pregnancies, without illicit drug use and HIV infection, free from chronic diseases were eligible for the study. A total of 481 enrolled pregnant women who gave birth between 37 and 43 weeks of gestation were included in the study. Prenatal personal exposure to fine particles over 48 h during the second trimester was measured using personal monitors. To evaluate the relationship between the level of PM(2.5) measured over 48 h in the second trimester of pregnancy with those in the first and the third trimesters, a series of repeated measurements in each trimester was carried out in a random subsample of 85 pregnant women. We assessed the effect of PM(2.5) exposure on the birth outcomes (weight, length and head circumference at birth) by multivariable regression models, controlling for potential confounders (maternal education, gestational age, parity, maternal height and prepregnancy weight, sex of infant, prenatal environmental tobacco smoke, and season of birth). Birth outcomes were associated positively with gestational age, parity, maternal height and prepregnancy weight, but negatively with the level of prenatal PM(2.5) exposure. Overall average increase in gestational period of prenatal exposure to fine particles by about 30 microg/m3, i.e., from 25th percentile (23.4 microg/m3) to 75th percentile (53.1 microg/m3) brought about an average birth weight deficit of 97.2g (95% CI: -201, 6.6) and length at birth of 0.7 cm (95% CI: -1.36, -0.04). The corresponding exposure lead to birth weight deficit in male newborns of 189 g (95% CI: -34.2, -343) in comparison to 17g in female newborns; the deficit of length at birth in male infants amounted to 1.1cm (95% CI: -0.11, -2.04). We found a significant interrelationship between self-reported ETS and PM(2.5), however, none of the models showed a significant interaction of both variables. The joint effect of various levels of PM(2.5) and ETS on birth outcomes showed the significant deficit only for the categories of exposure with higher component of PM(2.5). Concluding, the results of the study suggest that observed deficits in birth outcomes are rather attributable to prenatal PM(2.5) exposure and not to environmental tobacco smoke. The study also provided evidence that male fetuses are more sensitive to prenatal PM(2.5) exposure and this should persuade policy makers to consider birth outcomes by gender separately while setting air pollution guidelines.

Purpose: The aim of the study is to assess the cognitive and psychomotor status of 1-year-old infants whose mothers were exposed to low, but varying, amounts of mercury during pregnancy., Methods: Mercury levels in cord and maternal blood at delivery were used to assess prenatal environmental exposure to mercury. Bayley Scales of Infant Development were used to assess neurobehavioral health outcomes. The cohort consisted of 233 infants who were born at 33 to 42 weeks of gestation between January 2001 and March 2003 to mothers attending ambulatory prenatal clinics in the first and second trimesters of pregnancy. Enrollment included only nonsmoking women with singleton pregnancies between the ages of 18 and 35 years who were free from chronic diseases., Results: The geometric mean (GM) for maternal blood mercury level for the group of infants with normal neurocognitive performance was lower (GM = 0.52 mug/L; 95% confidence interval [CI], 0.46-0.58) than that observed in the group with delayed performance (GM = 0.75 mug/L; 95% CI, 0.59-0.94), and this difference was significant (p = 0.010). The GM of cord blood mercury level in the normal group also was lower (GM = 0.85 mug/L; 95% CI, 0.78-0.93) than that observed in the group with delayed performance (GM = 1.05 mug/L; 95% CI, 0.87-1.27), and this difference was of borderline significance (p = 0.070). The relative risk (RR) for delayed performance increased more than threefold (RR = 3.58; 95% CI, 1.40-9.14) if cord blood mercury level was greater than 0.80 mug/L. Risk for delayed performance in the group of infants with greater maternal mercury levels (>0.50 mug/L) also was significantly greater (RR = 2.82; 95% CI, 1.17-6.79) compared with children whose mothers had mercury levels less than 0.50 mug/L., Conclusions: The results may be of public health importance because delayed psychomotor or mental performance in infants is assumed to be an indicator of later neurocognitive development in children, which may persist into adult life.

Although the etiology of the majority of human breast cancers is unknown, environmental carcinogens are suspected to play a role. In this study, we investigated polycyclic aromatic hydrocarbon-DNA adducts in 78 breast cancer patients and benign breast disease patients with lifetime environmental exposure to polycyclic aromatic hydrocarbon (PAH) compounds. Adducts were detected in paraffin sections by immunoperoxidase method using polyclonal antiserum and were quantitated by the image-analyzing system. A significantly higher level of adducts was found in benign breast disease as compared to cancer patients (P < .001; Mann-Whitney U test). Neither smoking nor genetic polymorphisms in glutathione S-transferase and cytochrome P450 influenced the level of adducts. This exploratory study demonstrates the usefulness of the immunoperoxidase method to detect PAH-DNA adducts in stored breast tissue and suggests further research on a larger population, including patients from both high- and low-pollution environments.

New concepts of cancer risk estimation have been developed during the past decade. Short-term bioassays dealing with mutagenicity and carcinogenicity of environmental samples are being replaced by more relevant molecular epidemiology studies. The general idea of using a battery of bioassays remains unchanged while the origin of tested samples is different. Instead of testing samples collected from the environment, body fluids or human cells from exposed populations are under investigation. This paper reviews the collaborative study on cancer risk assessment in highly polluted industrial region of Silesia in which both approaches had been employed during the 1985-1995 period. A potent carcinogenic activity of airborne pollutants was indicated in a battery of in vitro and in vivo short-term assays. These studies were followed by the molecular epidemiology study performed on human populations inhabiting the region of Silesia. An elevated damage of genetic material on the chromosome and/or DNA levels was observed in the Silesian populations as compared with proper rural controls.

Coal tar treated psoriasis patients were used as a model population to evaluate a panel of immunoassays for monitoring exposure to benzo[a]pyrene (BP) and related polycyclic aromatic hydrocarbons (PAH). The assays included measurement of PAH diol epoxide-DNA adducts in white blood cells by competitive enzyme-linked immunosorbent assay (ELISA) with fluorescence endpoint detection, PAH-albumin adducts by competitive ELISA with color endpoint detection and serum levels of antibodies recognizing BP diol epoxide-DNA adducts by noncompetitive color ELISA. PAH-DNA adducts by ELISA were elevated in patients (mean 6.77 +/- 12.05/10(8)) compared to controls (4.90 +/- 8.81/10(8), p = 0.12). There was no difference in PAH-albumin adducts between patients (mean 0.61 +/- 0.31 fmol/micrograms) and controls (0.63 +/- 0.30 fmol/micrograms). Glutathione S-transferase M1 genotype was also determined but no relationship was found between presence of the gene and either DNA or protein adduct levels. About 30% of both patients and controls had measurable titer of antibodies recognizing BPDE-I-DNA adducts. Measurement of white blood cell DNA adducts by ELISA was the most sensitive method for detecting PAH exposure in coal tar-treated psoriasis patients.

The level of sister-chromatid exchanges (SCE), high-frequency cells (HFC), chromosomal aberrations (CA) as well as the proliferation rate index (PRI) were measured in peripheral blood lymphocytes from three groups of volunteers. The environmentally exposed donors were residents from the vicinity of a coke factory; the occupationally exposed persons were cokery workers, while rural region inhabitants served as a control group. Compared with the control group, statistically significant increases of SCE and HFC, as well as decreased cell kinetics (PRI) were observed for both occupationally and environmentally exposed groups. The effect was especially pronounced when only smokers were taken into account. A statistically significant increase of CA was observed in the environmentally exposed group when CA including gaps (CA + G) were evaluated. The proportion of HFC was found to be the most sensitive method to detect genetic effects on the tested human population. This study demonstrates the usefulness of all 4 biomarkers (SCE, HFC, CA and PRI) in monitoring populations exposed to ambient pollution and clearly indicates effects from residential as well as occupational exposure to industrial air pollutants.

14 fiberglass-reinforced plastics (FRP) boatbuilders were compared with 9 unexposed controls with respect to several chemical specific and nonspecific biomarkers measured in peripheral blood. Biomarkers included styrene-hemoglobin adducts (styrene-Hb), sister-chromatid exchanges (SCEs), micronuclei (MN), single-strand breaks (SSBs) and N-acetoxy-2-acetylaminofluorene-induced DNA binding (NA-AAF binding) as a measure of susceptibility to DNA damage. Workers' exposures averaged 11 ppm (8-h TWA; geometric mean) and ranged from 0.6 to 44 p.p.m. Mandelic acid levels were measured in end-of-shift urine samples and reflected an average styrene exposure equivalent to 15 p.p.m. There was a large though not significant difference in levels of styrene-Hb adducts among exposed workers and controls, largely the consequence of a single heavily-exposed individual with an extremely high level of adducts. Significant differences between biomarker levels in exposed workers and controls were observed with MN, SSBs and NA-AAF binding. No significant differences were seen in mean levels of SCEs nor in the incidence of cells with a high frequency of SCEs. The data suggest that exposure to levels of styrene in occupational settings near or below the current OSHA standard (50 p.p.m.) can induce damage at the cellular/molecular level. Appropriately-selected panels of biomarkers can be useful in identifying potentially harmful exposures.

A review of recent studies of biologic markers in populations with model exposures to carcinogens (cigarette smoke and polycyclic aromatic hydrocarbons) illustrates their potential role in cancer prevention. Data on macromolecular adducts and oncogene activation from cross-sectional, serial sampling and case-control studies demonstrate the usefulness of biologic markers in signalling a potential carcinogenic risk and in estimating the magnitude of interindividual variation within exposed groups. Recommendations for future research include nested case-control studies to establish the relationship between markers of biologic dose and effect (e.g., adducts, gene mutation, oncogene activation) and cancer risk.

Should federal agencies use separate, less stringent guidelines for regulating epigenetic or nongenotoxic carcinogens on the assumption that thresholds are likely to exist for these agents? This article reviews recent initiatives by the Environmental Protection Agency that either propose or informally adopt this approach in light of responses from the scientific community and a review of the recent literature. Relevant background is provided by current research concerning the role of chromosomal damage and oncogene activation in carcinogenesis along with findings that classical promoters or "epigenetic" agents can induce both DNA damage and chromosomal rearrangements. The conclusion is that such a revision of cancer policy is not now supported by available scientific data concerning chemical carcinogenesis.