The relationship between prenatal PCB exposure and intelligence (IQ) in 9-year-old children

Background

Several epidemiologic studies have demonstrated relationships between prenatal exposure to polychlorinated biphenyls (PCBs) and modest cognitive impairments in infancy and early childhood. However, few studies have followed cohorts of exposed children long enough to examine the possible impact of prenatal PCB exposure on psychometric intelligence in later childhood. Of the few studies that have done so, one in the Great Lakes region of the United States reported impaired IQ in children prenatally exposed to PCBs, whereas another found no association.

Objectives

This study was designed to determine whether environmental exposure to PCBs predicts lower IQ in school-age children in the Great Lakes region of the northeastern United States.

Methods

We measured prenatal exposure to PCBs and IQ at 9 years of age in 156 subjects from Oswego, New York. We also measured > 50 potential predictors of intelligence in children, including repeated measures of the home environment [Home Observation for Measurement of the Environment (HOME)], socioeconomic status (SES), parental IQ, alcohol/cigarette use, neonatal risk factors, and nutrition.

Results

For each 1-ng/g (wet weight) increase in PCBs in placental tissue, Full Scale IQ dropped by three points (p = 0.02), and Verbal IQ dropped by four points (p = 0.003). The median PCB level was 1.50 ng/g, with a lower quartile of 1.00 ng/g and an upper quartile of 2.06 ng/g. Moreover, this association was significant after controlling for many potential confounders, including prenatal exposure to methylmercury, dichlorodiphenyldichloroethylene, hexachlorobenzene, and lead.

Conclusions

These results, in combination with similar results obtained from a similar study in the Great Lakes conducted 10 years earlier, indicate that prenatal PCB exposure in the Great Lakes region is associated with lower IQ in children.     

Using Systematic Reviews and Meta-Analyses to Support Regulatory Decision Making for Neurotoxicants: Lessons Learned from a Case Study of PCBs

Background

Epidemiologic weight-of-evidence reviews to support regulatory decision making regarding the association between environmental chemical exposures and neurodevelopmental outcomes in children are often complicated by lack of consistency across studies.

Objective

We examined prospective cohort studies evaluating the relation between prenatal and neonatal exposure to polychlorinated biphenyls (PCBs) and neurodevelopment in children to assess the feasibility of conducting a meta-analysis to support decision making.

Data extraction/synthesis

We described studies in terms of exposure and end point categorization, statistical analysis, and reporting of results. We used this evaluation to assess the feasibility of grouping studies into reasonably uniform categories.

Results

The current literature includes 11 cohorts of children for whom effects from prenatal or neonatal PCB exposures were assessed. The most consistently used tests included Brazelton’s Neonatal Behavioral Assessment Scale, the neurologic optimality score in the neonatal period, the Bayley Scales of Infant Development at 5–8 months of age, and the McCarthy Scales of Children’s Abilities in 5-year-olds. Despite administering the same tests at similar ages, the studies were too dissimilar to allow a meaningful quantitative examination of outcomes across cohorts.

Conclusions

These analyses indicate that our ability to conduct weight-of-evidence assessments of the epidemiologic literature on neurotoxicants may be limited, even in the presence of multiple studies, if the available study methods, data analysis, and reporting lack comparability. Our findings add support to previous calls for establishing consensus standards for the conduct, analysis, and reporting of epidemiologic studies in general, and for those evaluating the effects of potential neurotoxic exposures in particular.     

Investigating intergenerational differences in human PCB exposure due to variable emissions and reproductive behaviors

Background

Reproductive behaviors—such as age of childbearing, parity, and breast-feeding prevalence—have changed over the same historical time period as emissions of polychlorinated biphenyls (PCB) and may produce intergenerational differences in human PCB exposure.

Objectives

Our goal in this study was to estimate prenatal, postnatal, and lifetime PCB exposures for women at different ages according to year of birth, and to evaluate the impact of reproductive characteristics on intergenerational differences in exposure.

Methods

We used the time-variant mechanistic model CoZMoMAN to calculate human bioaccumulation of PCBs, assuming both hypothetical constant and realistic time-variant emissions.

Results

Although exposure primarily depends on when an individual was born relative to the emission history of PCBs, reproductive behaviors can have a significant impact. Our model suggests that a mother’s reproductive history has a greater influence on the prenatal and postnatal exposures of her children than it does on her own cumulative lifetime exposure. In particular, a child’s birth order appears to have a strong influence on their prenatal exposure, whereas postnatal exposure is determined by the type of milk (formula or breast milk) fed to the infant.

Conclusions

Prenatal PCB exposure appears to be delayed relative to the time of PCB emissions, particularly among those born after the PCB production phaseout. Consequently, the health repercussions of environmental PCBs can be expected to persist for several decades, despite bans on their production for > 40 years.     

Lead and PCBs as Risk Factors for Attention Deficit/Hyperactivity Disorder

Objectives

Attention deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed neurobehavioral disorder of childhood, yet its etiology is not well understood. In this review we present evidence that environmental chemicals, particularly polychlorinated biphenyls (PCBs) and lead, are associated with deficits in many neurobehavioral functions that are also impaired in ADHD.

Data sources

Human and animal studies of developmental PCB or lead exposures that assessed specific functional domains shown to be impaired in ADHD children were identified via searches of PubMed using “lead” or “PCB exposure” in combination with key words, including “attention,” “working memory,” “response inhibition,” “executive function,” “cognitive function,” “behavior,” and “ADHD.”

Data synthesis

Children and laboratory animals exposed to lead or PCBs show deficits in many aspects of attention and executive function that have been shown to be impaired in children diagnosed with ADHD, including tests of working memory, response inhibition, vigilance, and alertness. Studies conducted to date suggest that lead may reduce both attention and response inhibition, whereas PCBs may impair response inhibition to a greater degree than attention. Low-level lead exposure has been associated with a clinical diagnosis of ADHD in several recent studies. Similar studies of PCBs have not been conducted.

Conclusions

We speculate that exposures to environmental contaminants, including lead and PCBs, may increase the prevalence of ADHD.     

Serum Concentrations of Antibodies Against Vaccine Toxoids in Children Exposed Perinatally to Immunotoxicants

Background

Polychlorinated biphenyls (PCBs) may cause immunotoxic effects, but the detailed dose–response relationship and possible vulnerable time windows of exposure are uncertain. In this study we applied serum concentrations of specific antibodies against childhood vaccines as sentinels of immunotoxicity.

Objectives

The main objective was to assess the possible dependence of antibody concentrations against diphtheria and tetanus toxoids in children with regard to prenatal and postnatal PCB exposures.

Methods

From a cohort of 656 singleton births formed in the Faroe Islands during 1999–2001, children were invited for examination with assessment of serum antibody concentrations at 5 years (before and after a booster vaccination) and at 7 years of age. Total PCB concentrations were determined in serum from ages 5 and 7 years, and data were also available on PCB concentrations in maternal pregnancy serum, maternal milk, and, for a subgroup, the child’s serum at 18 months of age.

Results

A total of 587 children participated in the examinations at ages 5 and/or 7 years. At age 5 years, before the booster vaccination, the antidiphtheria antibody concentration was inversely associated with PCB concentrations in milk and 18-month serum. Results obtained 2 years later showed an inverse association of concentrations of antibodies against both toxoids with PCB concentrations at 18 months of age. The strongest associations suggested a decrease in the antibody concentration by about 20% for each doubling in PCB exposure. At age 5 years, the odds of an antidiphtheria antibody concentration below a clinically protective level of 0.1 IU/L increased by about 30% for a doubling in PCB in milk and 18-month serum.

Conclusions

Developmental PCB exposure is associated with immunotoxic effects on serum concentrations of specific antibodies against diphtheria and tetanus vaccinations. The immune system development during the first years of life appears to be particularly vulnerable to this exposure.     

Polychlorinated Biphenyls Disrupt Intestinal Integrity via NADPH Oxidase-Induced Alterations of Tight Junction Protein Expression

Background

Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants that contribute to numerous disease states. The main route of exposure to PCBs is through the gastrointestinal tract; however, little is known about the effects of PCBs on intestinal epithelial barrier functions.

Objective

The aim of the present study was to address the hypothesis that highly chlorinated PCBs can disrupt gut integrity at the level of tight junction (TJ) proteins.

Methods

Caco-2 human colon adenocarcinoma cells were exposed to one of the following PCB congeners: PCB153, PCB118, PCB104, and PCB126. We then assessed NAD(P)H oxidase (NOX) activity and expression and the barrier function of Caco-2 cells. In addition, the integrity of intestinal barrier function and expression of TJ proteins were evaluated in C57BL/6 mice exposed to individual PCBs by oral gavage.

Results

Exposure of Caco-2 cells to individual PCB congeners resulted in activation of NOX and increased permeability of fluorescein isothiocyanate (FITC)-labeled dextran (4 kDa). Treatment with PCB congeners also disrupted expression of TJ proteins zonula occludens-1 (ZO-1) and occludin in Caco-2 cells. Importantly, inhibition of NOX by apocynin significantly protected against PCB-mediated increase in epithelial permeability and alterations of ZO-1 protein expression. Exposure to PCBs also resulted in alterations of gut permeability via decreased expression of TJ proteins in an intact physiological animal model.

Conclusions

These results suggest that oral exposure to highly chlorinated PCBs disrupts intestinal epithelial integrity and may directly contribute to the systemic effects of these toxicants.     

Allergy and Sensitization during Childhood Associated with Prenatal and Lactational Exposure to Marine Pollutants

Background

Breast-feeding may affect the risk of developing allergy during childhood and may also cause exposure to immunotoxicants, such as polychlorinated biphenyls (PCBs), which are of concern as marine pollutants in the Faroe Islands and the Arctic region.

Objectives

The objective was to assess whether sensitization and development of allergic disease is associated with duration of breast-feeding and prenatal or postnatal exposures to PCBs and methylmercury.

Methods

A cohort of 656 singleton births was formed in the Faroe Islands during 1999–2001. Duration of breast-feeding and history of asthma and atopic dermatitis were recorded at clinical examinations at 5 and 7 years of age. PCB and mercury concentrations were determined in blood samples obtained at parturition and at follow-up. Serum from 464 children (71%) at 7 years of age was analyzed for total immunoglobulin E (IgE) and grass-specific IgE.

Results

The total IgE concentration in serum at 7 years of age was positively associated both with the concomitant serum PCB concentration and with the duration of breast-feeding. However, the effect only of the latter was substantially attenuated in a multivariate analysis. A raised grass-specific IgE concentration compatible with sensitization was positively associated with the duration of breast-feeding and inversely associated with prenatal methylmercury exposure. However, a history of asthma or atopic dermatitis was not associated with the duration of breast-feeding, although children with atopic dermatitis had lower prenatal PCB exposures than did nonallergic children.

Conclusions

These findings suggest that developmental exposure to immunotoxicants may both increase and decrease the risk of allergic disease and that associations between breast-feeding and subsequent allergic disease in children may, at least in part, reflect lactational exposure to immunotoxic food contaminants.     

A Systematic Review and Meta-analysis of Childhood Leukemia and Parental Occupational Pesticide Exposure

Objectives

We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.

Data sources

Searches of MEDLINE (1950–2009) and other electronic databases yielded 31 included studies.

Data extraction

Two authors independently abstracted data and assessed the quality of each study.

Data synthesis

Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). There was no overall association between childhood leukemia and any paternal occupational pesticide exposure (OR = 1.09; 95% CI, 0.88–1.34); there were slightly elevated risks in subgroups of studies with low total-quality scores (OR = 1.39; 95% CI, 0.99–1.95), ill-defined exposure time windows (OR = 1.36; 95% CI, 1.00–1.85), and exposure information collected after offspring leukemia diagnosis (OR = 1.34; 95% CI, 1.05–1.70). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51–2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68–3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56–3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53–3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47–5.04) and herbicides (OR = 3.62; 95% CI, 1.28–10.3).

Conclusions

Childhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups. Associations with paternal occupational pesticide exposure were weaker and less consistent. Research needs include improved pesticide exposure indices, continued follow-up of existing cohorts, genetic susceptibility assessment, and basic research on childhood leukemia initiation and progression.     

Developmental Exposure to PCBs,MeHg, or Both: Long-Term Effects on Auditory Function

Background

Developmental exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg) can result in a variety of neurotoxic effects, including long-term auditory deficits. However, little is known about the effects of combined exposure to PCBs and MeHg on auditory function.

Objective

We developmentally exposed rats to PCBs and/or MeHg and assessed auditory function in adulthood to determine the effects of exposure to these contaminants individually and in combination.

Methods

We exposed female Long-Evans rats to 1 or 3 mg/kg PCB in corn oil, 1.5 or 4.5 ppm MeHg in drinking water, or combined exposure to 1 mg/kg PCB + 1.5 ppm MeHg or 3 mg/kg PCB + 4.5 ppm MeHg. Controls received corn oil vehicle and unadulterated water. Dosing began 28 days before breeding and continued until weaning at postnatal day (PND) 21. Auditory function of the offspring was assessed at approximately PND 200 by measuring distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs).

Results

Groups exposed to PCBs alone had attenuated DPOAE amplitudes, elevated DPOAE thresholds, and elevated ABR thresholds compared with controls. Groups exposed to MeHg alone did not differ from controls. Unexpectedly, the effects of PCB exposure appeared to be attenuated by coexposure to MeHg.

Conclusion

Developmental exposure to PCBs can result in permanent hearing deficits, and the changes in DPOAE amplitudes and thresholds suggest a cochlear site of action. Coexposure to MeHg appeared to attenuate the PCB-related deficits, but the mechanism for this unexpected interaction remains to be determined.     

Influence of Glutathione S-Transferase Polymorphisms on Cognitive Functioning Effects Induced by p,p′-DDT among Preschoolers

Background

Early-life exposure to p,p′-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] is associated with a decrease in cognitive skills among preschoolers at 4 years of age. We hypothesized that genetic variability in glutathione S-transferase (GST) genes (GSTP1, GSTM1, and GSTT1) could influence the effects of prenatal exposure to p,p′-DDT.

Methods

We used data from 326 children assessed in a prospective population-based birth cohort at the age of 4 years. In that study, the McCarthy Scales of Children’s Abilities were administrated by psychologists, organochlorine compounds were measured in cord serum, and genotyping was conducted for the coding variant Ile105Val from GSTP1 and for null alleles from GSTM1 and GSTT1. We used linear regression models to measure the association between organochlorines and neurodevelopmental scores by GST polymorphisms.

Results

p,p′-DDT cord serum concentration was inversely associated with general cognitive, memory, quantitative, and verbal skills, as well as executive function and working memory, in children who had any GSTP1 Val-105 allele. GSTP1 polymorphisms and prenatal p,p′-DDT exposure showed a statistically significant interaction for general cognitive skills (p = 0.05), quantitative skills (p = 0.02), executive function (p = 0.01), and working memory (p = 0.02). There were no significant associations between p,p′-DDT and cognitive functioning at 4 years of age according to GSTM1 and GSTT1 polymorphisms.

Conclusions

Results indicate that children with GSTP1 Val-105 allele were at higher risk of the adverse cognitive functioning effects of prenatal p,p′-DDT exposure.     

Sensory and cognitive effects of acute exposure to hydrogen sulfide

Background

Some epidemiologic studies have reported compromised cognitive and sensory performance among individuals exposed to low concentrations of hydrogen sulfide (H₂S).

Objectives

We hypothesized a dose–response increase in symptom severity and reduction in sensory and cognitive performance in response to controlled H₂S exposures.

Methods

In separate exposure sessions administered in random order over three consecutive weeks, 74 healthy subjects [35 females, 39 males; mean age (± SD) = 24.7 ± 4.2; mean years of education = 16.5 ± 2.4], were exposed to 0.05, 0.5, and 5 ppm H₂S. During each exposure session, subjects completed ratings and tests before H₂S exposure (baseline) and during the final hour of the 2-hr exposure period.

Results

Dose–response reduction in air quality and increases in ratings of odor intensity, irritation, and unpleasantness were observed. Total symptom severity was not significantly elevated across any exposure condition, but anxiety symptoms were significantly greater in the 5-ppm than in the 0.05-ppm condition. No dose–response effect was observed for sensory or cognitive measures. Verbal learning was compromised during each exposure condition.

Conclusions

Although some symptoms increased with exposure, the magnitude of these changes was relatively minor. Increased anxiety was significantly related to ratings of irritation due to odor. Whether the effect on verbal learning represents a threshold effect of H₂S or an effect due to fatigue across exposure requires further investigation. These acute effects in a healthy sample cannot be directly generalized to communities where individuals have other health conditions and concomitant exposures.     

Prenatal Exposure to Airborne Polycyclic Aromatic Hydrocarbons and Children’s Intelligence at 5 Years of Age in a Prospective Cohort Study in Poland

Background

In this prospective cohort study of Caucasian mothers and children in Krakow, Poland, we evaluated the role of prenatal exposure to urban air pollutants in the pathogenesis of neurobehavioral disorders.

Objectives

The objective of this study was to investigate the relationship between prenatal polycyclic aromatic hydrocarbon (PAH) exposure and child intelligence at 5 years of age, controlling for potential confounders suspected to play a role in neurodevelopment.

Methods

A cohort of pregnant, healthy, nonsmoking women was enrolled in Krakow, Poland, between 2001 and 2006. During pregnancy, participants were invited to complete a questionnaire and undergo 48-hr personal air monitoring to estimate their babies’ exposure, and to provide a blood sample and/or a cord blood sample at the time of delivery. Two hundred fourteen children were followed through 5 years of age, when their nonverbal reasoning ability was assessed using the Raven Coloured Progressive Matrices (RCPM).

Results

We found that higher (above the median of 17.96 ng/m³) prenatal exposure to airborne PAHs (range, 1.8–272.2 ng/m³) was associated with decreased RCPM scores at 5 years of age, after adjusting for potential confounding variables (n = 214). Further adjusting for maternal intelligence, lead, or dietary PAHs did not alter this association. The reduction in RCPM score associated with high airborne PAH exposure corresponded to an estimated average decrease of 3.8 IQ points.

Conclusions

These results suggest that prenatal exposure to airborne PAHs adversely affects children’s cognitive development by 5 years of age, with potential implications for school performance. They are consistent with a recent finding in a parallel cohort in New York City.     

Measured Prenatal and Estimated Postnatal Levels of Polychlorinated Biphenyls (PCBs) and ADHD-Related Behaviors in 8-Year-Old Children

Background

Epidemiologic studies of postnatal PCB exposure and behavior have not reported consistent evidence of adverse associations, possibly because of challenges in exposure estimation. We previously developed a pharmacokinetic model to improve estimation of children’s PCB exposure.

Objectives

We aimed to assess whether estimated serum PCB levels in infancy are associated with attention deficit/hyperactivity disorder (ADHD)–related behaviors at 8 years of age among children whose cord serum PCB levels were previously shown to be associated with ADHD-related behaviors.

Methods

We used a pharmacokinetic model to estimate monthly serum polychlorinated biphenyl (PCB)–153 levels in 441 infants (ages 1–12 months) based on parameters such as breastfeeding and cord serum PCB-153 levels. Behavior was evaluated at age 8 using the Conners’ Rating Scale for Teachers (CRS-T). Associations between PCB-153 levels and ADHD-related CRS-T indices were assessed using multivariable quantile regression at the 50th and 75th percentiles of CRS-T scores, where higher percentiles reflect more adverse behaviors.

Results

Cord serum PCB-153 levels (median, 38 ng/g lipids) were associated with ADHD-related behaviors, although statistical significance was observed with quantile regression models only at the 75th percentile. Associations with postnatal exposure estimates were attenuated. For example, hyperactive-impulsive behavior scores at age 8 years were 0.9 points (95% CI: 0.2, 2.5), 0.5 points (95% CI: 0.3, 2.3), and 0.3 points (95% CI: –0.2, 1.5) higher in association with interquartile range increases in serum PCB-153 at birth, 2 months, and 12 months of age, respectively.

Conclusions

Associations between estimated postnatal PCB-153 exposures and ADHD-related behaviors at 8 years of age were weaker than associations with PCB-153 concentrations measured in cord serum at birth.

Citation

Verner MA, Hart JE, Sagiv SK, Bellinger DC, Altshul LM, Korrick SA. 2015. Measured prenatal and estimated postnatal levels of polychlorinated biphenyls (PCBs) and ADHD-related behaviors in 8-year-old children. Environ Health Perspect 123:888–894; http://dx.doi.org/10.1289/ehp.1408084     

Oxidative Damage to DNA and Lipids as Biomarkers of Exposure to Air Pollution

Background

Air pollution is thought to exert health effects through oxidative stress, which causes damage to DNA and lipids.

Objective

We determined whether levels of oxidatively damaged DNA and lipid peroxidation products in cells or bodily fluids from humans are useful biomarkers of biologically effective dose in studies of the health effects of exposure to particulate matter (PM) from combustion processes.

Data sources

We identified publications that reported estimated associations between environmental exposure to PM and oxidative damage to DNA and lipids in PubMed and EMBASE. We also identified publications from reference lists and articles cited in the Web of Science.

Data extraction

For each study, we obtained information on the estimated effect size to calculate the standardized mean difference (unitless) and determined the potential for errors in exposure assessment and analysis of each of the biomarkers, for total and stratified formal meta-analyses.

Data synthesis

In the meta-analysis, the standardized mean differences (95% confidence interval) between exposed and unexposed subjects for oxidized DNA and lipids were 0.53 (0.29–0.76) and 0.73 (0.18–1.28) in blood and 0.52 (0.22–0.82) and 0.49 (0.01–0.97) in urine, respectively. The standardized mean difference for oxidized lipids was 0.64 (0.07–1.21) in the airways. Restricting analyses to studies unlikely to have substantial biomarker or exposure measurement error, studies likely to have biomarker and/or exposure error, or studies likely to have both sources of error resulted in standardized mean differences of 0.55 (0.19–0.90), 0.66 (0.37–0.95), and 0.65 (0.34–0.96), respectively.

Conclusions

Exposure to combustion particles is consistenly associated with oxidatively damaged DNA and lipids in humans, suggesting that it is possible to use these measurements as biomarkers of biologically effective dose.     

Urinary,Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Background

Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. Importantly, results from a large number of biomonitoring studies are at odds with the results from two toxicokinetic studies.

Objective

We examined several possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions.

Data sources

We examined > 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism.

Data extraction and synthesis

The > 80 biomonitoring studies examined included measurements in thousands of individuals from several different countries, and these studies overwhelmingly detected BPA in individual adults, adolescents, and children. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Some regulatory agencies have relied solely on these toxicokinetic models in their risk assessments.

Conclusions

Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.     

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.     

In Utero Exposure to Bisphenol A Shifts the Window of Susceptibility for Mammary Carcinogenesis in the Rat

Background

Bisphenol A (BPA) is a ubiquitous environmental chemical with reported endocrine-disrupting properties.

Objective

Our goal in this study was to determine whether prenatal exposure to BPA predisposes the adult rat mammary gland to carcinogenesis.

Methods

Pregnant rats were treated orally with 0, 25, or 250 μg BPA/kg body weight (BW) from gestation day (GD) 10 to GD21. For tumorigenesis experiments, prenatally exposed female offspring received a single gavage of 7,12-dimethylbenz(a)anthracene (DMBA; 30 mg/kg BW) on postnatal day (PND) 50, or PND100.

Results

Prenatal exposure of the dam to 250 μg BPA/kg BW combined with a single exposure of female offspring to DMBA on PND100, but not on PND50, significantly increased tumor incidence while decreasing tumor latency compared with the control group. Prenatal exposure of the dam to 250 μg BPA/kg BW, in the absence of DMBA to the female offspring, increased cell proliferation and elicited differential effects at the protein level at PND100 compared with PND50. Differentially regulated proteins in the mammary gland included estrogen receptor-α, progesterone receptor-A, Bcl-2, steroid receptor coactivators, epidermal growth factor receptor, phospho-insulin-like growth factor 1 receptor, and phospho-Raf.

Conclusions

Our study demonstrates that oral prenatal exposure to BPA increases mammary cancer susceptibility in offspring and shifts the window of susceptibility for DMBA-induced tumorigenesis in the rat mammary gland from PND50 to PND100. These changes are accompanied by differential effects of prenatal BPA exposure on the expression of key proteins involved in cell proliferation.     

Manganese and Parkinson’s Disease: A Critical Review and New Findings

Background

Excess accumulation of manganese (Mn) in the brain results in a neurological syndrome with cognitive, psychiatric, and movement abnormalities. The highest concentrations of Mn in the brain are achieved in the basal ganglia, which may precipitate a form of parkinsonism with some clinical features that are similar and some that are different to those in Parkinson’s disease (PD). Recently, scientists have debated the possibility that Mn may have an etiological role in PD or that it may accelerate the expression of PD.

Objective

The goal of this review was to examine whether chronic Mn exposure produces dopamine neuron degeneration and PD or whether it has a distinct neuropathology and clinical presentation.

Data source

I reviewed available clinical, neuroimaging, and neuropathological studies in humans and nonhuman primates exposed to Mn or other human conditions that result in elevated brain Mn concentrations.

Data extraction

Human and nonhuman primate literature was examined to compare clinical, neuroimaging, and neuropathological changes associated with Mn-induced parkinsonism.

Data synthesis

Clinical, neuroimaging, and neuropathological evidence was used to examine whether Mn-induced parkinsonism involves degeneration of the nigrostriatal dopaminergic system as is the case in PD.

Conclusions

The overwhelming evidence shows that Mn-induced parkinsonism does not involve degeneration of midbrain dopamine neurons and that l-dopa is not an effective therapy. New evidence is presented on a putative mechanism by which Mn may produce movement abnormalities. Confirmation of this hypothesis in humans is essential to make rational decisions about treatment, devise effective therapeutic strategies, and set regulatory guidelines.     

Evaluation of the cardiovascular effects of methylmercury exposures: current evidence supports development of a dose-response function for regulatory benefits analysis

Background

The U.S. Environmental Protection Agency (U.S. EPA) has estimated the neurological benefits of reductions in prenatal methylmercury (MeHg) exposure in past assessments of rules controlling mercury (Hg) emissions. A growing body of evidence suggests that MeHg exposure can also lead to increased risks of adverse cardiovascular impacts in exposed populations.

Data extraction

The U.S. EPA assembled the authors of this article to participate in a workshop, where we reviewed the current science concerning cardiovascular health effects of MeHg exposure via fish and seafood consumption and provided recommendations concerning whether cardiovascular health effects should be included in future Hg regulatory impact analyses.

Data synthesis

We found the body of evidence exploring the link between MeHg and acute myocardial infarction (MI) to be sufficiently strong to support its inclusion in future benefits analyses, based both on direct epidemiological evidence of an MeHg–MI link and on MeHg’s association with intermediary impacts that contribute to MI risk. Although additional research in this area would be beneficial to further clarify key characteristics of this relationship and the biological mechanisms that underlie it, we consider the current epidemiological literature sufficiently robust to support the development of a dose–response function.

Conclusions

We recommend the development of a dose–response function relating MeHg exposures with MIs for use in regulatory benefits analyses of future rules targeting Hg air emissions.     

Maternal Serum Preconception Polychlorinated Biphenyl Concentrations and Infant Birth Weight

Background

Prenatal and postnatal polychlorinated biphenyl (PCBs) exposure has been associated with decrements in fetal and infant growth and development, although exposures during the preconception window have not been examined despite recent evidence suggesting that this window may correspond with the highest serum concentrations.

Objectives

We assessed maternal serum PCB concentrations at two sensitive developmental windows in relation to birth weight.

Methods

Serum samples were collected from 99 women as they began trying to become pregnant (preconception) and after a positive pregnancy test (prenatal); 52 (53%) women gave birth and represent the study cohort. Using daily diaries, women recorded sexual intercourse, menstruation, and home pregnancy test results until pregnant or up to 12 menstrual cycles with intercourse during the estimated fertile window. With gas chromatography with electron capture, 76 PCB congeners were quantified (nanograms per gram serum) and subsequently categorized by purported biologic activity. Serum PCBs were log-transformed and entered both as continuous and categorized exposures along with birth weight (grams) and covariates [smoking (yes/no), height (inches), and infant sex (male/female)] into linear regression.

Results

A substantial reduction in birth weight (grams) was observed for women in the highest versus the lowest tertile of preconception antiestrogenic PCB concentration (β = −429.3 g, p = 0.038) even after adjusting for covariates (β = −470.8, p = 0.04).

Conclusions

These data reflect the potential developmental toxicity of antiestrogenic PCBs, particularly during the sensitive preconception critical window among women with environmentally relevant chemical exposures, and underscore the importance of PCB congener–specific investigation.