Biomarkers of chlorpyrifos exposure and effect in Egyptian cotton field workers

Background

Chlorpyrifos (CPF), a widely used organophosphorus pesticide (OP), is metabolized to CPF-oxon, a potent cholinesterase (ChE) inhibitor, and trichloro-2-pyridinol (TCPy). Urinary TCPy is often used as a biomarker for CPF exposure, whereas blood ChE activity is considered an indicator of CPF toxicity. However, whether these biomarkers are dose related has not been studied extensively in populations with repeated daily OP exposures.

Objective

We sought to determine the relationship between blood ChE and urinary TCPy during repeated occupational exposures to CPF.

Methods

Daily urine samples and weekly blood samples were collected from pesticide workers (n = 38) in Menoufia Governorate, Egypt, before, during, and after 9–17 consecutive days of CPF application to cotton fields. We compared blood butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activities with the respective urinary TCPy concentrations in each worker.

Results

Average TCPy levels during the middle of a 1- to 2-week CPF application period were significantly higher in pesticide applicators (6,437 μg/g creatinine) than in technicians (184 μg/g) and engineers (157 μg/g), both of whom are involved in supervising the application process. We observed a statistically significant inverse correlation between urinary TCPy and blood BuChE and AChE activities. The no-effect level (or inflection point) of the exposure–effect relationships has an average urinary TCPy level of 114 μg/g creatinine for BuChE and 3,161 μg/g creatinine for AChE.

Conclusions

Our findings demonstrate a dose–effect relationship between urinary TCPy and both plasma BuChE and red blood cell AChE in humans exposed occupationally to CPF. These findings will contribute to future risk assessment efforts for CPF exposure.     

Population Physiologically Based Pharmacokinetic Modeling for the Human Lactational Transfer of PCB-153 with Consideration of Worldwide Human Biomonitoring Results

Background

One of the most serious human health concerns related to environmental contamination with polychlorinated biphenyls (PCBs) is the presence of these chemicals in breast milk.

Objectives

We developed a physiologically based pharmacokinetic model of PCB-153 in women, and predict its transfer via lactation to infants. The model is the first human, population-scale lactational model for PCB-153. Data in the literature provided estimates for model development and for performance assessment.

Methods

We used physiologic parameters from a cohort in Taiwan and reference values given in the literature to estimate partition coefficients based on chemical structure and the lipid content in various body tissues. Using exposure data from Japan, we predicted acquired body burden of PCB-153 at an average childbearing age of 25 years and compared predictions to measurements from studies in multiple countries. We attempted one example of reverse dosimetry modeling using our PBPK model for possible exposure scenarios in Canadian Inuits, the population with the highest breast milk PCB-153 level in the world.

Results

Forward-model predictions agree well with human biomonitoring measurements, as represented by summary statistics and uncertainty estimates.

Conclusion

The model successfully describes the range of possible PCB-153 dispositions in maternal milk, suggesting a promising option for back-estimating doses for various populations.     

Silver Impairs Neurodevelopment: Studies in PC12 Cells

Background

Exposure to silver is increasing because of silver nanoparticles in consumer products.

Objectives and methods

Many biological effects of silver entail actions of Ag⁺ (monovalent silver ions), so we used neuronotypic PC12 cells to evaluate the potential for silver to act as a developmental neurotoxicant, using chlorpyrifos (CPF), a pesticide known to evoke developmental neurotoxicity, as a positive control for comparison.

Results

In undifferentiated cells, a 1-hr exposure to 10 μM Ag⁺ inhibited DNA synthesis more potently than did 50 μM CPF; it also impaired protein synthesis but to a lesser extent than its effect on DNA synthesis, indicating a preferential effect on cell replication. Longer exposures led to oxidative stress, loss of viability, and reduced numbers of cells. With the onset of cell differentiation, exposure to 10 μM Ag⁺ evoked even greater inhibition of DNA synthesis and more oxidative stress, selectively impaired neurite formation without suppressing overall cell growth, and preferentially suppressed development into the acetylcholine phenotype in favor of the dopamine phenotype. Lowering the exposure to 1 μM Ag⁺ reduced the net effect on undifferentiated cells. However, in differentiating cells, the lower concentration produced an entirely different pattern, enhancing cell numbers by suppressing ongoing cell death and impairing differentiation in parallel for both neurotransmitter phenotypes.

Conclusions

Our results show that silver has the potential to evoke developmental neurotoxicity even more potently than known neurotoxicants, such as CPF, and that the spectrum of effects is likely to be substantially different at lower exposures that do not show signs of outright toxicity.     

Effect of Organic Diet Intervention on Pesticide Exposures in Young Children Living in Low-Income Urban and Agricultural Communities

Background

Recent organic diet intervention studies suggest that diet is a significant source of pesticide exposure in young children. These studies have focused on children living in suburban communities.

Objectives

We aimed to determine whether consuming an organic diet reduced urinary pesticide metabolite concentrations in 40 Mexican-American children, 3–6 years of age, living in California urban and agricultural communities.

Methods

In 2006, we collected urine samples over 16 consecutive days from children who consumed conventionally grown food for 4 days, organic food for 7 days, and then conventionally grown food for 5 days. We measured 23 metabolites, reflecting potential exposure to organophosphorous (OP), pyrethroid, and other pesticides used in homes and agriculture. We used linear mixed-effects models to evaluate the effects of diet on urinary metabolite concentrations.

Results

For six metabolites with detection frequencies > 50%, adjusted geometric mean concentrations during the organic phase were generally lower for all children, and were significant for total dialkylphosphates (DAPs) and dimethyl DAPs (DMs; metabolites of OP insecticides) and 2,4-D (2,4-dichlorophenoxyacetic acid, a herbicide), with reductions of 40%, 49%, and 25%, respectively (p < 0.01). Chemical-specific metabolite concentrations for several OP pesticides, pyrethroids, and herbicides were either infrequently detected and/or not significantly affected by diet. Concentrations for most of the frequently detected metabolites were generally higher in Salinas compared with Oakland children, with DMs and metolachlor at or near significance (p = 0.06 and 0.03, respectively).

Conclusion

An organic diet was significantly associated with reduced urinary concentrations of nonspecific dimethyl OP insecticide metabolites and the herbicide 2,4-D in children. Additional research is needed to clarify the relative importance of dietary and non-dietary sources of pesticide exposures to young children.

Citation

Bradman A, Quirós-Alcalá L, Castorina R, Aguilar Schall R, Camacho J, Holland NT, Barr DB, Eskenazi B. 2015. Effect of organic diet intervention on pesticide exposures in young children living in low-income urban and agricultural communities. Environ Health Perspect 123:1086–1093; http://dx.doi.org/10.1289/ehp.1408660     

Biomonitoring Data for 2,4-Dichlorophenoxyacetic Acid in the United States and Canada: Interpretation in a Public Health Risk Assessment Context Using Biomonitoring Equivalents

Background

Several extensive studies of exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) using urinary concentrations in samples from the general population, farm applicators, and farm family members are now available. Reference doses (RfDs) exist for 2,4-D, and Biomonitoring Equivalents (BEs; concentrations in urine or plasma that are consistent with those RfDs) for 2,4-D have recently been derived and published.

Objective

We reviewed the available biomonitoring data for 2,4-D from the United States and Canada and compared them with BE values to draw conclusions regarding the margin of safety for 2,4-D exposures within each population group.

Data sources

Data on urinary 2,4-D excretion in general and target populations from recent published studies are tabulated and the derivation of BE values for 2,4-D summarized.

Data synthesis

The biomonitoring data indicate margins of safety (ratio of BE value to biomarker concentration) of approximately 200 at the central tendency and 50 at the extremes in the general population. Median exposures for applicators and their family members during periods of use appear to be well within acute exposure guidance values.

Conclusions

Biomonitoring data from these studies indicate that current exposures to 2,4-D are below applicable exposure guidance values. This review demonstrates the value of biomonitoring data in assessing population exposures in the context of existing risk assessments using the BE approach. Risk managers can use this approach to integrate the available biomonitoring data into an overall assessment of current risk management practices for 2,4-D.     

Assessing Children’s Dietary Pesticide Exposure: Direct Measurement of Pesticide Residues in 24-Hr Duplicate Food Samples

Background

The data presented here are a response to calls for more direct measurements of pesticide residues in foods consumed by children and provide an opportunity to compare direct measures of pesticide residues in foods representing actual consumption with those reported by the U.S. Department of Agriculture Pesticide Data Program.

Objective

We measured pesticide residues in 24-hr duplicate food samples collected from a group of 46 young children participating in the Children’s Pesticide Exposure Study (CPES).

Methods

Parents were instructed to collect 24-hr duplicate food samples of all conventional fruits, vegetables, and fruit juices equal to the quantity consumed by their children, similarly prewashed/prepared, and from the same source or batch. Individual or composite food items were analyzed for organophosphate (OP) and pyrethroid insecticide residues.

Results

We collected a total of 239 24-hr duplicate food samples collected from the 46 CPES children. We found 14% or 5% of those food samples contained at least one OP or pyrethroid insecticide, respectively. We measured a total of 11 OP insecticides, at levels ranging from 1 to 387 ng/g, and three pyrethroid insecticides, at levels ranging from 2 to 1,133 ng/g, in children’s food samples. We found that many of the food items consumed by the CPES children were also on the list of the most contaminated food commodities reported by the Environmental Working Group.

Conclusions

The frequent consumption of food commodities with episodic presence of pesticide residues that are suspected to cause developmental and neurological effects in young children supports the need for further mitigation.     

Depression and Pesticide Exposures among Private Pesticide Applicators Enrolled in the Agricultural Health Study

Background

We evaluated the relationship between diagnosed depression and pesticide exposure using information from private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997 in Iowa and North Carolina.

Methods

There were 534 cases who self-reported a physician-diagnosed depression and 17,051 controls who reported never having been diagnosed with depression and did not feel depressed more than once a week in the past year. Lifetime pesticide exposure was categorized in three mutually exclusive groups: low (< 226 days, the reference group), intermediate (226–752 days), and high (> 752 days). Two additional measures represented acute high-intensity pesticide exposures: an unusually high pesticide exposure event (HPEE) and physician-diagnosed pesticide poisoning. Logistic regression analyses were performed relating pesticide exposure to depression.

Results

After adjusting for state, age, education, marital status, doctor visits, alcohol use, smoking, solvent exposure, not currently having crops or animals, and ever working a job off the farm, pesticide poisoning was more strongly associated with depression [odds ratio (OR) = 2.57; 95% confidence interval (CI), 1.74–3.79] than intermediate (OR = 1.07; 95% CI, 0.87–1.31) or high (OR = 1.11; 95% CI, 0.87–1.42) cumulative exposure or an HPEE (OR = 1.65; 95% CI, 1.33–2.05). In analysis of a subgroup without a history of acute poisoning, high cumulative exposure was significantly associated with depression (OR = 1.54; 95% CI, 1.16–2.04).

Conclusion

These findings suggest that both acute high-intensity and cumulative pesticide exposure may contribute to depression in pesticide applicators. Our study is unique in reporting that depression is also associated with chronic pesticide exposure in the absence of a physician-diagnosed poisoning.     

Pesticide Exposure and Hypertensive Disorders During Pregnancy

Background

Hypertensive disorders of pregnancy, including pregnancy-induced hypertension (PIH) and preeclampsia (PE), complicate 2–8% of pregnancies. Few studies have examined environmental risk factors in relation to these conditions.

Objectives

Our goal was to examine whether pesticide exposure during pregnancy was associated with hypertensive disorders of pregnancy.

Methods

We analyzed self-reported data from 11,274 wives of farmers enrolled in the Agricultural Health Study (AHS) between 1993 and 1997. Using logistic regression models, we estimated the adjusted odds ratios (AORs) for PIH and PE associated with pesticide-related activities during the first trimester of pregnancy.

Results

First-trimester residential and agricultural activities with potential exposure to pesticides were associated with both PIH [residential AOR = 1.27; 95% confidence interval (CI), 1.02–1.60; agricultural AOR = 1.60; 95% CI, 1.05–2.45] and PE (residential AOR = 1.32; 95% CI, 1.02–1.70; agricultural AOR = 2.07; 95% CI, 1.34–3.21).

Conclusions

Exposure to pesticides during pregnancy may increase the risk of hypertensive disorders of pregnancy. Laboratory research may provide insights into relationships between pesticide exposure and hypertensive diseases of pregnancy.     

Population Toxicokinetic Modeling of Cadmium for Health Risk Assessment

Background

Cadmium is a widespread environmental pollutant that has been shown to exert toxic effects on kidney and bones in humans after long-term exposure. Urinary cadmium concentration is considered a good biomarker of accumulated cadmium in kidney, and diet is the main source of cadmium among nonsmokers.

Objective

Modeling the link between urinary cadmium and dietary cadmium intake is a key step in the risk assessment of long-term cadmium exposure. There is, however, little knowledge on how this link may vary, especially for susceptible population strata.

Methods

We used a large population-based study (the Swedish Mammography Cohort), with repeated dietary intake data covering a period of 20 years, to compare estimated dietary cadmium intake with urinary cadmium concentrations on an individual basis. A modified version of the Nordberg-Kjellström model and a one-compartment model were evaluated in terms of their predictions of urinary cadmium. We integrated the models and quantified the between-person variability of cadmium half-life in the population. Finally, sensitivity analyses and Monte Carlo simulations were performed to illustrate how the latter model could serve as a robust tool supporting the risk assessment of cadmium in humans.

Results

The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability. We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability.

Conclusions

Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.     

Arsenic Exposure within the Korean Community (United States) Based on Dietary Behavior and Arsenic Levels in Hair,Urine, Air,and Water

Background

Determining arsenic exposure in groups based on geographic location, dietary behaviors, or lifestyles is important, as even moderate exposures may lead to health concerns.

Objectives/Methods

The Korean community in Washington State, represents a group warranting investigation, as they consume foods (e.g., shellfish, rice, finfish, and seaweed) known to contain arsenic. As part of the Arsenic Mercury Intake Biometric Study, we examined the arsenic levels in hair and urine along with the diets of 108 women of childbearing age from within this community. Arsenic levels in indoor air and drinking water were also investigated, and shellfish commonly consumed were collected and analyzed for total and speciated arsenic.

Results

The six shellfish species analyzed (n = 667) contain total arsenic (range, 1–5 μg/g) but are a small source of inorganic arsenic (range, 0.01–0.12 μg/g). Six percent of the individuals may have elevated urinary inorganic arsenic levels (> 10 μg/L) due to diet. Seaweed, rice, shellfish, and finfish are principal sources for total arsenic intake/excretion based on mass balance estimates. Rice consumption (163 g/person/day) may be a significant source of inorganic arsenic. Air and water are not significant sources of exposure. Hair is a poor biometric for examining arsenic levels at low to moderate exposures.

Conclusions

We conclude that a portion of this community may have dietary inorganic arsenic exposure resulting in urine levels exceeding 10 μg/L. Although their exposure is below that associated with populations exposed to high levels of arsenic from drinking water (> 100 μg/L), their exposure may be among the highest in the United States.     

Variability and predictors of urinary bisphenol A concentrations during pregnancy

Background

Prenatal bisphenol A (BPA) exposure may be associated with developmental toxicity, but few studies have examined the variability and predictors of urinary BPA concentrations during pregnancy.

Objective

Our goal was to estimate the variability and predictors of serial urinary BPA concentrations taken during pregnancy.

Methods

We measured BPA concentrations during pregnancy and at birth in three spot urine samples from 389 women. We calculated the intraclass correlation coefficient (ICC) to assess BPA variability and estimated associations between log₁₀-transformed urinary BPA concentrations and demographic, occupational, dietary, and environmental factors, using mixed models.

Results

Geometric mean (GM) creatinine-standardized concentrations (micrograms per gram) were 1.7 (16 weeks), 2.0 (26 weeks), and 2.0 (birth). Creatinine-standardized BPA concentrations exhibited low reproducibility (ICC = 0.11). By occupation, cashiers had the highest BPA concentrations (GM: 2.8 μg/g). Consuming canned vegetables at least once a day was associated with higher BPA concentrations (GM = 2.3 μg/g) compared with those consuming no canned vegetables (GM = 1.6 μg/g). BPA concentrations did not vary by consumption of fresh fruits and vegetables, canned fruit, or store-bought fresh and frozen fish. Urinary high-molecular-weight phthalate and serum tobacco smoke metabolite concentrations were positively associated with BPA concentrations.

Conclusions

These results suggest numerous sources of BPA exposure during pregnancy. Etiological studies may need to measure urinary BPA concentrations more than once during pregnancy and adjust for phthalates and tobacco smoke exposures.     

Neurobehavioral Deficits and Increased Blood Pressure in School-Age Children Prenatally Exposed to Pesticides

Background

The long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable.

Objectives

In northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children’s neurobehavioral functions at 6–8 years of age.

Methods

We examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children’s current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity.

Results

Of 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with prenatal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5–2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m². Inclusion of the pilot data strengthened these results.

Conclusions

These findings support the notion that prenatal exposure to pesticides—at levels not producing adverse health outcomes in the mother—can cause lasting adverse effects on brain development in children. Pesticide exposure therefore may contribute to a “silent pandemic” of developmental neurotoxicity.     

Effectiveness of an Integrated Pest Management Intervention in Controlling Cockroaches,Mice, and Allergens in New York City Public Housing

Background

Cockroaches and mice, which are common in urban homes, are sources of allergens capable of triggering asthma symptoms. Traditional pest control involves the use of scheduled applications of pesticides by professionals as well as pesticide use by residents. In contrast, integrated pest management (IPM) involves sanitation, building maintenance, and limited use of least toxic pesticides.

Objectives

We implemented and evaluated IPM compared with traditional practice for its impact on pests, allergens, pesticide use, and resident satisfaction in a large urban public housing authority.

Methods

We assigned IPM or control status to 13 buildings in five housing developments, and evaluated conditions at baseline, 3 months, and 6 months in 280 apartments in Brooklyn and Manhattan, in New York City (New York). We measured cockroach and mouse populations, collected cockroach and mouse urinary protein allergens in dust, and interviewed residents. All statistical models controlled for baseline levels of pests or allergens.

Results

Compared with controls, apartments receiving IPM had significantly lower counts of cockroaches at 3 months and greater success in reducing or sustaining low counts of cockroaches at both 3 and 6 months. IPM was associated with lower cockroach allergen levels in kitchens at 3 months and in beds and kitchens at 6 months. Pesticide use was reduced in IPM relative to control apartments. Residents of IPM apartments also rated building services more positively.

Conclusions

In contrast to previous IPM studies, which involved extensive cleaning, repeat visits, and often extensive resident education, we found that an easily replicable single IPM visit was more effective than the regular application of pesticides alone in managing pests and their consequences.     

Long-Term Effects on Hypothalamic Neuropeptides after Developmental Exposure to Chlorpyrifos in Mice

Background

Increasing evidence from animal and human studies indicates that chlorpyrifos (CPF), similar to other organophosphorus insecticides still widely used, is a developmental neurotoxicant. Developmental exposure to CPF in rodents induces sex-dimorphic behavioral changes at adulthood, including social and agonistic responses, which suggests that CPF may interfere with maturation of neuroendocrine mechanisms.

Objectives

We assessed the hypothesis that CPF affects the levels of neurohypophyseal hormones acting as modulators of social behavior in mammals, such as oxytocin (OT), arginine vasopressin (AVP), and prolactin (PRL).

Methods

Pregnant female mice were orally administered with either vehicle (peanut oil) or 3 or 6 mg/kg CPF on gestational day (GD) 15 to GD18, and offspring were treated subcutaneously with either vehicle or 1 or 3 mg/kg CPF on postnatal days (PNDs) 11 to PND14. Dose levels were chosen to avoid systemic toxicity and inhibition of brain acetylcholinesterase. Offspring were sacrificed at 5 months of age, and expression of OT, AVP, and PRL was analyzed in the hypothalamus by Western blot or enzyme-linked immunosorbent assay (ELISA) analysis.

Results

Both male and female mice showed dose-related enhancement of OT expression, with males presenting the more intense effect. AVP expression was significantly reduced in male mice at the higher prenatal and postnatal dose. We observed no significant effect on PRL expression in either sex. Overall, outcomes were mainly attributable to fetal exposure, whereas postnatal doses appeared to potentiate the prenatal effects.

Conclusions

Our data indicate that developmental exposure to CPF may permanently interfere with specific key signaling proteins of the hypothalamic peptidergic system, with time-, dose-, and sex-related effects still evident at adulthood.     

Dietary Intake of Methionine,Cysteine, and Protein and Urinary Arsenic Excretion in Bangladesh

Background

In Bangladesh, millions of people are exposed to arsenic in drinking water; arsenic is associated with increased risk of cancer. Once ingested, arsenic is metabolized via methylation and excreted in urine. Knowledge about nutritional factors affecting individual variation in methylation is limited.

Objectives

The purpose of this study was to examine associations between intakes of protein, methionine, and cysteine total urinary arsenic in a large population-based sample.

Methods

The study subjects were 10,402 disease-free residents of Araihazar, Bangladesh, who participated in the Health Effects of Arsenic Longitudinal Study (HEALS). Food intakes were assessed using a validated food frequency questionnaire developed for the study population. Nutrient composition was determined by using the U.S. Department of Agriculture National Nutrient Database for Standard Reference. Generalized estimating equations were used to examine association between total urinary arsenic across quintiles of nutrient intakes while controlling for arsenic exposure from drinking water and other predictors of urinary arsenic.

Results

Greater intakes of protein, methionine, and cysteine were associated with 10–15% greater total urinary arsenic excretion, after controlling for total energy intake, body weight, sex, age, tobacco use, and intake of some other nutrients.

Conclusions

Given previously reported risks between lower rates of arsenic excretion and increased rates of cancer, these findings support the role of nutrition in preventing arsenic-related disease.     

Urinary Porphyrin Excretion in Neurotypical and Autistic Children

Background

Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).

Objectives

This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.

Methods

This exploratory study enrolled 278 children 2–12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.

Results

Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.

Conclusions

These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.     

A Review of Nonoccupational Pathways for Pesticide Exposure in Women Living in Agricultural Areas

Background

Women living in agricultural areas may experience high pesticide exposures compared with women in urban or suburban areas because of their proximity to farm activities.

Objective

Our objective was to review the evidence in the published literature for the contribution of nonoccupational pathways of pesticide exposure in women living in North American agricultural areas.

Methods

We evaluated the following nonoccupational exposure pathways: paraoccupational (i.e., take-home or bystander exposure), agricultural drift, residential pesticide use, and dietary ingestion. We also evaluated the role of hygiene factors (e.g., house cleaning, shoe removal).

Results

Among 35 publications identified (published 1995–2013), several reported significant or suggestive (p < 0.1) associations between paraoccupational (n = 19) and agricultural drift (n = 10) pathways and pesticide dust or biomarker levels, and 3 observed that residential use was associated with pesticide concentrations in dust. The 4 studies related to ingestion reported low detection rates of most pesticides in water; additional studies are needed to draw conclusions about the importance of this pathway. Hygiene factors were not consistently linked to exposure among the 18 relevant publications identified.

Conclusions

Evidence supported the importance of paraoccupational, drift, and residential use pathways. Disentangling exposure pathways was difficult because agricultural populations are concurrently exposed to pesticides via multiple pathways. Most evidence was based on measurements of pesticides in residential dust, which are applicable to any household member and are not specific to women. An improved understanding of nonoccupational pesticide exposure pathways in women living in agricultural areas is critical for studying health effects in women and for designing effective exposure-reduction strategies.

Citation

Deziel NC, Friesen MC, Hoppin JA, Hines CJ, Thomas K, Beane Freeman LE. 2015. A review of nonoccupational pathways for pesticide exposure in women living in agricultural areas. Environ Health Perspect 123:515–524; http://dx.doi.org/10.1289/ehp.1408273     

Cancer Incidence among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study

Background

Permethrin is a synthetic pyrethroid insecticide widely used in agriculture, in public health, and in many U.S. homes and gardens.

Objective

In this study we evaluated the incidence of cancer among pesticide applicators exposed to permethrin in the Agricultural Health Study (AHS).

Methods

A total of 49,093 pesticide applicators were included in this analysis of the AHS, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed in 1993–1997. Average length of follow-up since applicator enrollment in the cohort was 9.14 years. We used two permethrin exposure metrics: a) lifetime days applicators personally mixed or applied permethrin and b) intensity-weighted lifetime days (lifetime days weighted by estimated intensity of exposure). We used Poisson regression analysis to estimate relative risks (RRs) and 95% confidence intervals (CIs) for malignancies by tertiles of exposure.

Results

We found no associations between permethrin and all malignant neoplasms combined, or between permethrin and melanoma, non-Hodgkin lymphoma, leukemia, or cancers of the colon, rectum, lung, or prostate. We found elevated and statistically significant risks for multiple myeloma in the highest tertiles of both lifetime exposure-days (RR = 5.72; 95% CI, 2.76–11.87) and intensity-weighted lifetime exposure-days (RR = 5.01; 95% CI, 2.41–10.42), compared with applicators reporting they never used permethrin; these results are based on only 15 exposed cases. These findings were similar across a variety of alternative exposure metrics, exposure categories, and reference groups.

Conclusions

This study found no association with most cancers analyzed. Although the suggested association with multiple myeloma was based on a small number of cases, it warrants further evaluation.     

Renal function, bisphenol A, and alkylphenols: results from the National Health and Nutrition Examination Survey (NHANES 2003-2006)

Background

Urinary excretion of bisphenol A (BPA) and alkylphenols (APs) was used as a biomarker in most previous studies, but no study has investigated whether urinary excretion of these environmental phenols differed by renal function.

Objective

We estimated the association between renal function and urinary excretion of BPA and APs.

Methods

Analyses were conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2003–2006. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) Study equation and by the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Regression models were used to calculate geometric means of urinary BPA and APs excretion by eGFR category (≥ 90, 60–90, < 60 mL/min/m²) after adjusting for potential confounding factors.

Results

When we used the MDRD Study equation, participants without known renal disease (n = 2,573), 58.2% (n = 1,499) had mildly decreased renal function or undiagnosed chronic kidney disease. The adjusted geometric means for urinary BPA excretion decreased with decreasing levels of eGFR (p for trend = 0.04). The associations appeared primarily in females (p for trend = 0.03). Urinary triclosan excretion decreased with decreasing levels of eGFR (p for trend < 0.01) for both males and females, and the association primarily appeared in participants < 65 years of age. The association between BPA and eGFR was nonsignificant when we used the CKD-EPI equation.

Conclusions

Urinary excretion of triclosan, and possibly BPA, decreased with decreasing renal function. The associations might differ by age or sex. Further studies are necessary to replicate our results and understand the mechanism.     

Predicting Plasma Concentrations of Bisphenol A in Children Younger Than 2 Years of Age after Typical Feeding Schedules,using a Physiologically Based Toxicokinetic Model

Background

Concerns have recently been raised regarding the safety of potential human exposure to bisphenol A (BPA), an industrial chemical found in some polycarbonate plastics and epoxy resins. Of particular interest is the exposure of young children to BPA via food stored in BPA-containing packaging.

Objectives

In this study we assessed the age dependence of the toxicokinetics of BPA and its glucuronidated metabolite, BPA-Glu, using a coupled BPA–BPA-Glu physiologically based toxicokinetic (PBTK) model.

Methods

Using information gathered from toxicokinetic studies in adults, we built a PBTK model. We then scaled the model to children < 2 years of age based on the age dependence of physiologic parameters relevant for absorption, distribution, metabolism, and excretion.

Results

We estimated the average steady-state BPA plasma concentration in newborns to be 11 times greater than that in adults when given the same weight-normalized dose. Because of the rapid development of the glucuronidation process, this ratio dropped to 2 by 3 months of age. Simulation of typical feeding exposures, as estimated by regulatory authorities, showed a 5-fold greater steady-state BPA plasma concentration in 3- and 6-month-olds compared with adults, reflecting both a reduced capacity for BPA metabolism and a greater weight-normalized BPA exposure. Because of uncertainty in defining the hepatic BPA intrinsic clearance in adults, these values represent preliminary estimates.

Conclusions

Simulations of the differential BPA dosimetry between adults and young children point to the need for more sensitive analytical methods for BPA to define, with greater certainty, the adult hepatic BPA intrinsic clearance, as well as a need for external exposure data in young children.