Indoor air pollution exposure and early childhood development in the Upstate KIDS Study.

BACKGROUND: Limited human studies have investigated the impact of indoor air pollution on early childhood neurodevelopment among the US population. We aimed to examine the associations between prenatal and postnatal indoor air pollution exposure and early childhood development in a population-based birth cohort. METHODS: This analysis included 4735 mother-child pairs enrolled between 2008 and 2010 in the Upstate KIDS Study. Indoor air pollution exposure from cooking fuels, heating fuels, and passive smoke during pregnancy, and at 12 and 36 months after birth were assessed by questionnaires. Five domains of child development were assessed by the Ages and Stages Questionnaire at 4, 8, 12, 18, 24, 30, and 36 months. Generalized estimating equations were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: Exposure to unclean cooking fuels (natural gas, propane, or wood) throughout the study period was associated with increased odds of failing any development domain (OR = 1.28, 95% CI 1.07, 1.53), the gross motor domain (OR = 1.52, 95% CI: 1.09, 2.13), and the personal-social domain (OR = 1.36, 95% CI: 1.00, 1.85), respectively. Passive smoke exposure throughout the study period increased the odds of failing the problem-solving domain by 71% (OR = 1.71, 95% CI 1.01, 2.91) among children of non-smoking mothers. No association was found between heating fuel use and failing any or specific domains. CONCLUSION: Unclean cooking fuel use and passive smoke exposure during pregnancy and early life were associated with developmental delays in this large prospective birth cohort.

Changes in arachidonic acid (AA)- and linoleic acid (LA)-derived hydroxy metabolites and their interplay with inflammatory biomarkers in response to drastic changes in air pollution exposure.

BACKGROUND: Untargeted metabolomics analyses have indicated that fatty acids and their hydroxy derivatives may be important metabolites in the mechanism through which air pollution potentiates diseases. This study aimed to use targeted analysis to investigate how metabolites in arachidonic acid (AA) and linoleic acid (LA) pathways respond to short-term changes in air pollution exposure. We further explored how they might interact with markers of antioxidant enzymes and systemic inflammation. METHODS: This study included a subset of participants (n = 53) from the Beijing Olympics Air Pollution (BoaP) study in which blood samples were collected before, during, and after the Beijing Olympics. Hydroxy fatty acids were measured by liquid chromatography/mass spectrometry (LC/MS). Native total fatty acids were measured as fatty acid methyl esters (FAMEs) using gas chromatography. A set of chemokines were measured by ELISA-based chemiluminescent assay and antioxidant enzyme activities were analyzed by kinetic enzyme assays. Changes in levels of metabolites over the three time points were examined using linear mixed-effects models, adjusting for age, sex, body mass index (BMI), and smoking status. Pearson correlation and repeated measures correlation coefficients were calculated to explore the relationships of metabolites with levels of serum chemokines and antioxidant enzymes. RESULTS: 12-hydroxyeicosatetraenoic acid (12-HETE) decreased by 50.5% (95% CI: -66.5, -34.5; p < 0.0001) when air pollution dropped during the Olympics and increased by 119.4% (95% CI: 36.4, 202.3; p < 0.0001) when air pollution returned to high levels after the Olympics. In contrast, 13-hydroxyoctadecadienoic acid (13-HODE) elevated significantly (p = 0.023) during the Olympics and decreased nonsignificantly after the games (p = 0.104). Interleukin 8 (IL-8) correlated with 12-HETE (r = 0.399, BH-adjusted p = 0.004) and 13-HODE (r = 0.342, BH-adjusted p = 0.014) over the three points; it presented a positive and moderate correlation with 12-HETE during the Olympics (r = 0.583, BH-adjusted p = 0.002) and with 13-HODE before the Olympics (r = 0.543, BH-adjusted p = 0.008). CONCLUSION: AA- and LA-derived hydroxy metabolites are associated with air pollution and might interact with systemic inflammation in response to air pollution exposure.

Evaluation of occupational pesticide exposure on Egyptian male adolescent cognitive and motor functioning.

BACKGROUND: Chronic low-level exposure to organophosphorus pesticides is associated with adverse health effects, including a decline in neurological functioning and long-term impairment. These negative effects may be more detrimental in children and adolescents due to their critical stage in development. Little work has investigated the effects of chronic exposure to pesticides, specifically chlorpyrifos (CPF) during the adolescent period. OBJECTIVES: To examine effects of CPF exposure over a year-long period within a group of male adolescents in Egypt (N = 242, mean age = 17.36), including both pesticide applicators and non-applicators. METHODS: Associations between average CPF exposure (measured via urinary metabolite levels of 3,5,6-trichloro-2-pyridinol [TCPy]) and neurobehavioral functioning were examined in a 1-year longitudinal study. Given previous literature, higher levels of TCPy were expected to be associated with worse neurobehavioral functioning. RESULTS: Using mixed effects linear regression, average TCPy exposure predicted deficits in more complex neurobehavioral tasks (Benton visual retention, digit span reverse, match to sample, serial digit learning, and alternating tapping) with estimates of effects ranging from -0.049 to 0.031. Age (effects ranging from 0.033 to 0.090) and field station (effects ranging from -1.266 to -0.278) were significantly predictive of neurobehavioral functioning over time. An interaction effect was found for field station and TCPy across several neurobehavioral domains. DISCUSSION: Results show that occupational exposure to pesticides may have particularly deleterious effects on complex neurobehavioral domains. Additionally, differences across field stations and the age at which individuals are exposed may be important factors to investigate in future research.

Telomeres as targets for the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) in rats.

Telomere length (TL) can be affected by various factors, including age and oxidative stress. Changes in TL have been associated with chronic disease, including a higher risk for several types of cancer. Environmental exposure of humans to PCBs and dioxins has been associated with longer or shorter leukocyte TL. Relative telomere length (RTL) may serve as a biomarker associated with neoplastic and/or non-neoplastic responses observed with chronic exposures to TCDD and PCBs. RTL was measured in DNA isolated from archived frozen liver and lung tissues from the National Toxicology Program (NTP) studies conducted in female Harlan Sprague Dawley rats exposed for 13, 30, and 52 weeks to TCDD, dioxin-like (DL) PCB 126, non-DL PCB 153, and a mixture of PCB 126 and PCB 153. RTL was assessed by quantitative polymerase chain reaction (qPCR). Consistent with literature, decreased liver and lung RTL was seen with aging. Relative to time-matched vehicle controls, RTL was increased in both the liver and lung tissues of rats exposed to TCDD, PCB 126, PCB 153, and the mixture of PCB 126 and PCB 153, which is consistent with most epidemiological studies that found PCB exposures were associated with increased leukocyte RTL. Increased RTL was observed at doses and/or time points where little to no pathology was observed. In addition to serving as a biomarker of exposure to these compounds in rats and humans, increases in RTL may be an early indicator of neoplastic and non-neoplastic responses that occur following chronic exposure to TCDD and PCBs.

Increased cancer burden among pesticide applicators and others due to pesticide exposure.

A growing number of well-designed epidemiological and molecular studies provide substantial evidence that the pesticides used in agricultural, commercial, and home and garden applications are associated with excess cancer risk. This risk is associated both with those applying the pesticide and, under some conditions, those who are simply bystanders to the application. In this article, the epidemiological, molecular biology, and toxicological evidence emerging from recent literature assessing the link between specific pesticides and several cancers including prostate cancer, non-Hodgkin lymphoma, leukemia, multiple myeloma, and breast cancer are integrated. Although the review is not exhaustive in its scope or depth, the literature does strongly suggest that the public health problem is real. If we are to avoid the introduction of harmful chemicals into the environment in the future, the integrated efforts of molecular biology, pesticide toxicology, and epidemiology are needed to help identify the human carcinogens and thereby improve our understanding of human carcinogenicity and reduce cancer risk.

Risk perception and behavior in Egyptian adolescent pesticide applicators: an intervention study.

BACKGROUND: Adolescents are engaged in agricultural work, including pesticide application, around the world. Adolescent pesticide applicators are more likely to be exposed to pesticides than their adult counterparts because of their application practice and hygiene habits surrounding pesticide use. There is a need for low-cost interventions to reduce pesticide exposure. We evaluated a theoretically-based educational intervention to change perceptions about the risk of pesticide use and hygiene habits during and after pesticide application for adolescent and young adult pesticide applicators in Egypt. METHODS: Young adult and adolescent male pesticide applicators were given a one-hour educational intervention to inform them about the risk of pesticide use and how to reduce pesticide exposure. The median age of participants was 18 years old. Changes in perceived susceptibility and effectiveness were measured with a survey pre and post-intervention (n = 119) on the same day. The same survey (n = 95) was given 8-months post-intervention to identify sustained effects. Observational checklists of pesticide application practice were also completed during application seasons before and after the intervention. RESULTS: There was an increase in the proportion of individuals who viewed pesticides as being a long-term health risk (74.7% pre-intervention to 97.9% post-intervention, McNemar test p < 0.001). This change remained significant when surveyed at the 8-month follow-up (90.5%, p < 0.001). There was also a sustained improvement regarding participants' views of proper hygiene practice surrounding pesticide application. Applicators were observed wearing goggles, shoes, and masks more frequently post-intervention. CONCLUSION: This theoretically-based intervention is an example of a low-cost solution that can improve adolescents' and young adults' practices regarding pesticide application and personal hygiene practices during and after pesticide application. The intervention can be applied in other countries with similar safety culture surrounding pesticide application.

Active and secondhand smoke exposure throughout life and DNA methylation in breast tumors.

PURPOSE: Tobacco smoke exposure has been associated with altered DNA methylation. However, there is a paucity of information regarding tobacco smoke exposure and DNA methylation of breast tumors. METHODS: We conducted a case-only analysis using breast tumor tissue from 493 postmenopausal and 225 premenopausal cases in the Western New York Exposures and Breast Cancer (WEB) study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A, CCND2, BRCA1, FHIT, and SYK) was measured with pyrosequencing. Participants reported their secondhand smoke (SHS) and active smoking exposure for seven time periods. Unconditional logistic regression was used to estimate odds ratios (OR) of having methylation higher than the median. RESULTS: SHS exposure was associated with tumor DNA methylation among postmenopausal but not premenopausal women. Active smoking at certain ages was associated with increased methylation of GSTP1, FHIT, and CDKN2A and decreased methylation of SCGB3A1 and BRCA1 among both pre- and postmenopausal women. CONCLUSION: Exposure to tobacco smoke may contribute to breast carcinogenesis via alterations in DNA methylation. Further studies in a larger panel of genes are warranted.

Responses of serum chemokines to dramatic changes of air pollution levels, a panel study.

Background: Despite the in vitro and in vivo evidence, studies are limited in evaluating whether chemokines are potential inflammatory mediators in response to air pollution exposure in humans. Methods: We conducted a panel study coinciding with the Beijing Olympics, when temporary air pollution controls were implemented. We measured a suite of serum chemokines among healthy adults before, during and after the Olympics, respectively. Linear mixed-effect models were used to evaluate changes in chemokine levels over the three time periods. Results: In response to the 50% drop in air pollution levels during the games, levels of RANTES, MCP-2, and TARC decreased by 25.8%, 20.9% and 35.3%, respectively (p < 0.001) from pre-Olympics, and then increased by 45.8%, 34.9% and 61.5%, respectively (p < 0.001) after the games when air pollution levels went up again. Similar patterns were observed in subgroup analyses by sex, age, smoking and body mass index. GRO-α and IL-8 decreased significantly during the games (22.5% and 30.4%), and increased non-significantly after the games. Eotaxin-1 only increased significantly from during- to post-games. Conclusions: The strongest associations with air pollution levels were observed among RANTES, TARC and MCP-2. Those chemokines may play important roles in the air pollution-induced inflammatory pathway.

Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors.

BACKGROUND: We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors. METHODS: We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status. RESULTS: Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23-0.99) and higher methylation of SYK (OR = 1.86, 95% CI: 1.03-3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05-5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26-0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p < 0.01). CONCLUSIONS: We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.

Consumption of Lake Ontario sport fish and the incidence of colorectal cancer in the New York State Angler Cohort Study (NYSACS).

Fish consumption is hypothesized to reduce the risk of colorectal cancer. Nonetheless, consuming sport fish from the Great Lakes increases exposure to certain persistent organic pollutants, namely polychlorinated biphenyls (PCBs) and organochlorine insecticides, which may increase the risk of cancer. Evidence that exposure to persistent organic pollutants is associated with colorectal cancer is sparse. We examined colorectal cancer incidence in the New York State Angler Cohort Study (NYSACS), a prospective cohort of 17,110 anglers and spouses age 18-40 years at enrollment. In 1991, participants completed a mailed self-administered questionnaire that ascertained the number of years that fish from Lake Ontario were consumed, as well as potential confounders. Forty-one histologically confirmed first primary incident colorectal cancers diagnosed as of December 31, 2008 were identified via the New York State Cancer Registry. Vital status was ascertained by linkage with the Social Security Administration Death File. Rate ratios (RR) and 95% confidence intervals (CI) were calculated with Poisson regression, adjusting for age, pack-years of smoking, and sex. Compared with never consumers, colorectal cancer incidence was statistically non-significantly lower among consumers of Lake Ontario sport fish (RR=0.66; 95% CI: 0.35; 1.24). Incidence of colon cancer was lower among Lake Ontario sport fish consumers (RR=0.45, 95%CI: 0.20; 1.00). We did not observe any evidence of effect measure modification by sex or age. Although consumption of Lake Ontario sport fish may have an inverse association with colorectal cancer risk, inferences are complicated by a small number of cases and a lack of information regarding potential confounders including other dietary factors. However, our results do not provide support for the hypothesis that consumption of contaminated sport fish increases the risk of colorectal cancer.

The impact of repeated organophosphorus pesticide exposure on biomarkers and neurobehavioral outcomes among adolescent pesticide applicators.

Egyptian adolescents are hired as seasonal workers to apply pesticides to the cotton crop and may perform this occupation for several years. However, few studies examined the effects of repeated pesticide exposure on health outcomes The goal of this study was to determine the impact of repeated pesticide exposure on neurobehavioral (NB) performance and biomarkers of exposure (urinary metabolite) and effect (cholinesterase activity). Eighty-four adolescents from two field stations in Menoufia, Egypt, were examined four times: before and during pesticide application season in 2010 and again before and during application season in 2011. At each of the four time points, participants completed a questionnaire, performed an NB test battery, and were assessed for urinary levels of the chlorpyrifos metabolite TCPy (3,5,6-trichloro-2-pyridinol) and blood cholinesterase activity. Following the study cohort over two consecutive pesticide application seasons revealed that TCPy levels significantly increased following exposure, and returned to baseline levels following the end of the application season. Blood butyryl cholinesterase activity exhibited a similar pattern. Although NB outcomes displayed learning and practice effects over time, deficits in performance were significantly associated with increased TCPy levels with reduction in the number of NB measures showing improvement over time. Biomarkers of exposure and effect demonstrated changes associated with pesticide application and recovery after application ended. Deficits in NB performance were correlated with elevated pesticide exposure. Data demonstrated that repeated pesticide exposure may exert a long-term adverse impact on human health.

Urinary Cadmium and Risk of Invasive Breast Cancer in the Women's Health Initiative.

Cadmium is a widespread heavy metal pollutant that may act as an exogenous estrogenic hormone. Environmental cadmium exposure has been associated with risk of breast cancer in retrospective studies. We prospectively assessed the relationship between cadmium exposure, evaluated by creatinine-normalized urinary cadmium concentration, and invasive breast cancer among 12,701 postmenopausal women aged ≥50 years in a Women's Health Initiative study of bone mineral density. After a median of 13.2 years of follow-up (1993-2010), 508 cases of invasive breast cancer and 1,050 comparison women were identified for a case-cohort analysis. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. Risk of breast cancer was not associated with urinary cadmium parameterized either in quartiles (comparing highest quartile with lowest, hazard ratio = 0.80, 95% confidence interval: 0.56, 1.14; P for trend = 0.20) or as a log-transformed continuous variable (per 2-fold higher urinary cadmium concentration, hazard ratio = 0.94, 95% confidence interval: 0.86, 1.03). We did not observe an association between urinary cadmium and breast cancer risk in any subgroup examined, including never smokers and women with body mass index (weight (kg)/height (m)(2)) less than 25. Results were consistent in both estrogen receptor-positive and estrogen receptor-negative tumors. Our results do not support the hypothesis that environmental cadmium exposure is associated with risk of postmenopausal breast cancer.

Polychlorinated biphenyls and omega-3 fatty acid exposure from fish consumption, and thyroid cancer among New York anglers.

Fish from the Great Lakes contain polychlorinated biphenyls (PCBs) which have been shown to disrupt endocrine function and mimic thyroid hormones, but they also contain beneficial omega-3 fatty acids that may offer protection against endocrine cancers. The purpose of this study was to examine the effects of Lake Ontario fish consumption and the estimated consumption of PCBs and omega-3 fatty acids on the risk of thyroid cancer in a group of sport fishermen. Anglers from the New York State Angler Cohort Study were followed for cancer incidence from 1991-2008. Twenty-seven cases of incident thyroid cancer and 108 controls were included in the analyses. Total estimated fish consumption, estimated omega-3 fatty acid consumption, and estimated PCB consumption from Lake Ontario fish were examined for an association with the incidence of thyroid cancer, while matching on sex, and controlling for age and smoking status. Results from logistic regression indicate no significant associations between fish consumption, short-term estimated omega-3 fatty acids, or estimated PCB consumption from Great Lakes fish and the development of thyroid cancer, but it was suggested that long-term omega-3 fatty acid from Great Lakes fish may be protective of the development of thyroid cancer. In conclusion, fish consumption, with the possible concomitant PCBs, from the Great Lakes does not appear to increase the risk of thyroid cancer in New York anglers. Further research is needed in order to separate the individual health effects of PCBs from omega-3 fatty acids contained within the fish.

Peak expiratory flow, breath rate and blood pressure in adults with changes in particulate matter air pollution during the Beijing Olympics: a panel study.

OBJECTIVES: This study aims to examine whether changes in short-term exposures to particulate matter are associated with changes in lung function, breath rate, and blood pressure among healthy adults and whether smoking status modifies the association. METHODS: We took advantage of the artificially controlled changes in air pollution levels that occurred during the 2008 Olympic Games in Beijing, China and conducted a panel study of 201 Beijing residents. Data were collected before, during, and after the Olympics, respectively. Linear mixed-effect models and generalized estimating equation models were used to compare measurements of peak expiratory flow, breath rate and blood pressure across three time points. RESULTS: The mean values of peak expiratory flow were 346.0 L/min, 399.3 L/min, and 364.1L/min over the three study periods. Peak expiratory flow levels increased in 78% of the participants when comparing the during- with pre- Olympics time points, while peak expiratory flow levels decreased in 80% of participants for the post- and during-Olympic periods comparison. In subgroup analyses comparing the during-Olympic to pre-Olympic time points, we found a larger percentage change in peak expiratory flow (+17%) among female, younger and non-smoking participants than among male, elderly and smoking participants (+12%). The percentage of participants with a fast breath rate (>20/min) changed from 9.7% to 4.9% to 30.1% among females, and from 7.9% to 2.6% to 27.3% among males over the three time points. The changes in blood pressure over the three study periods were not very clear, although there is an increase in diastolic pressure and a decrease in pulse pressure among males during the games. CONCLUSIONS: The results suggest that exposure to different air pollution levels has significant effects on respiratory function. Smoking, age and gender appear to modify participants' biological response to changes in air quality.

Impact of chlorpyrifos exposure on lung function in Egyptian adolescent agriculture workers.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide that has been linked to detrimental health effects that range from neurological impacts to respiratory disease. The objective of this study was to assess respiratory symptoms associated with CPF exposure throughout the application season. Urine samples were collected from Egyptian adolescent applicators (n = 206) and non-applicators (n = 72) to assess 3,5,6-trichloro-2-pyridinol (TCPy), a biomarker for CPF exposure, along with spirometry measures to determine lung ventilatory function. Samples were collected over 7 months in 2016. Logistic regression was used to model the odds of reporting wheeze symptoms based on urinary TCPy concentrations while controlling for age and smoking in the household. Ordinal multinomial logistic regression was used to model the percent reference for forced expiratory volume in one second (rFEV1) based on urinary TCPy concentration (µg/g creatinine). Wheezing increased with increasing pesticide exposure (OR = 1.74 (1.32 - 2.31)). There was no statistically significant relationship between rFEV1 and TCPy concentration. Efforts to reduce pesticide exposure should be implemented to prevent the potential onset or exacerbation of any linked respiratory complications in adolescents.

Clustering of place of birth for women with breast cancer: differences by tumor characteristics.

PURPOSE: There is increasing evidence that exposures in early life affect breast cancer risk, and that breast cancer etiology differs by tumor subtype. If environmental exposures in early life contribute to risk, it is expected that there would be clustering of women with breast cancer by their place of birth, and that clustering might differ by subtype. We examined spatial associations between place of birth and breast cancer by subtype, using hormone receptor status and molecular profiles of breast tumors. METHODS: Data were drawn from the Western New York Exposures and Breast Cancer study, a population-based case-control study of incident, pathologically confirmed breast cancer (1996-2001) in Erie and Niagara Counties. Included were women born in the study area (579 cases and 931 controls). Clustering of breast cancer subgroups relative to controls was examined by the k-function method in groups stratified by estrogen receptor (ER), progesterone receptor (PR), and HER2 status, and by DNA methylation status and p53 mutation status, and the k-function difference was used to compare relative spatial aggregation and spatial range of the difference between case subgroups and controls. RESULTS: We found a tendency to cluster among ER positive, PR positive, and HER2 negative cases (i.e., luminal A subtype), especially among premenopausal women, but not among the other groups defined by hormonal receptor status, or by either methylation or p53 mutation status. CONCLUSIONS: While our findings cannot rule out clustering of cases by birth place because of shared behaviors related to residence location, they also suggest that early life environmental exposures may affect subsequent breast cancer risk, and that premenopausal breast tumors of the luminal A subtype may be more affected by these early life exposures than other subtypes.

Exposure to traffic emissions: associations with biomarkers of antioxidant status and oxidative damage.

BACKGROUND: Oxidative stress has been implicated as a possible mechanism for adverse health effects associated with traffic emissions. We examined the association of an estimate of traffic emissions with blood biomarkers of antioxidant capacity (glutathione, glutathione peroxidase, trolox-equivalent antioxidant capacity) and oxidative damage (thiobarbituric acid-reactive substances (TBARS)) among 1810 healthy women, randomly selected from Erie and Niagara Counties in Western New York. METHODS: A geographic traffic emission and meteorological dispersion model was used to estimate annual polycyclic aromatic hydrocarbon (PAH) exposure from traffic emissions for each woman based on her residence at the time of study. Associations of traffic-related PAH exposure with measures of oxidative stress and antioxidant capacity were examined in multiple regression analyses with adjustment for potential confounders. RESULTS: Higher traffic-related PAH exposure was associated with decreased glutathione and increased glutathione peroxidase. Stronger associations between traffic-related PAH exposure and levels of glutathione and glutathione peroxidase were suggested among nonsmoking women without secondhand smoke exposure, especially among premenopausal nonsmoking women. Associations were also stronger for measurements made in warmer months. CONCLUSIONS: These findings suggest that PAHs or other components of traffic emissions may impact anti-oxidative capacity among healthy women, particularly premenopausal non-smokers without secondhand smoke exposure.

Evaluating how occupational exposure to organophosphates and pyrethroids impacts ADHD severity in Egyptian male adolescents.

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in attention and hyperactivity/impulsivity that cause impairments to daily living. An area of long-standing concern is understanding links between environmental toxicants, including pesticides, and the development or worsening of ADHD. OBJECTIVES: The present study evaluated associations between occupational pesticide exposure, specifically organophosphate (OP) pesticides, chlorpyrifos (CPF) and the pyrethroids (PYR) alpha-cypermethrin (αCM) and lambda-cyhalothrin (λCH), and symptoms of ADHD in a longitudinal study among Egyptian adolescent males. METHODS: Participants (N = 226, mean age = 17) were Egyptian adolescent males who either applied pesticides or were non-applicators. Urinary trichloro-2-pyridinol (TCPy) was measured as a specific metabolite biomarker of exposure to chlorpyrifos. Urinary 3-phenoxybenzoic acid (3-PBA) was measured as a general metabolite biomarker of exposure to pyrethroids, while urinary cis-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA) was measured as a specific biomarker of exposure to αCM and lambda cyhalothric acid (λCH acid) measured as a specific biomarker of exposure to λCH. Ordinal logistic regression models controlling for age were used to determine the likelihood of ADHD development (measured via parent-reported ADHD symptoms) as the level of biomarkers of pesticide exposure increased. RESULTS: Cis-DCCA was the only biomarker associated with higher likelihood ADHD symptoms (> 0.60 vs. 0-0.17 µg/g creatinine; OR = 2.82, 95% CI: 1.29-6.14). All participants reported clinical levels of ADHD symptoms when compared to national norms used in the United States. TCPy, trans-DCCA and λCH acid were not associated with risk of ADHD symptoms after controlling for levels of cis-DCCA. No other metabolites were associated with the number of ADHD symptoms. There were no interaction effects found for exposure to both OPs and Pyrethroids. DISCUSSION: The results suggest that exposure to the pyrethroid αCM is associated with more ADHD symptoms. Methodological and cultural considerations in need of further study are discussed.

PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos.

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n=120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P≤0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P≤0.05) and PON1 192 (P≤0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal.