ArticleLiterature Review

Trends in neurodevelopmental disability burden due to early life chemical exposure in the USA from 2001 to 2016: A population-based disease burden and cost analysis

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Abstract

Endocrine disrupting chemicals are known to cause neurodevelopmental toxicity through direct and indirect pathways. In this study we used data from the National Health and Nutrition Examination Surveys, along with known exposure-disease relationships, to quantify the intellectual disability burden attributable to in utero exposure to polybrominated diphenyl ethers (PBDEs), organophosphates, and methylmercury and early life exposure to lead. We also estimated the cost of the IQ points lost and cases of intellectual disability. PBDE exposure was the greatest contributor to intellectual disability burden, resulting in a total of 162 million IQ points lost and over 738,000 cases of intellectual disability. This was followed by lead, organophosphates, and methylmercury. From 2001 to 2016, IQ loss from PBDEs, methylmercury, and lead have decreased or remained stagnant. Organophosphate exposure measurements were only available up to 2008 but did show an increase in organophosphate-attributable IQ loss. Although most of these trends show benefit for children's neurodevelopmental health, they may also point towards the use of potentially harmful substitutions for chemicals that are being phased out.

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... The pentaBDE and other PBDEs used exacted a large toll on health. For example, between 2001 and 2016 in the U.S., those chemicals were responsible for 162 million lost IQ points and 738,00 cases of intellectual disability [60]. ...
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... Decisions have historically been made without a cost-benefit analysis that considers potential adverse health and ecological outcomes associated with flame retardants used to meet a proposed standard. The cost of flame retardant use to society has been extensive, with associated health impacts accounting for $3.6 to $7.0 trillion dollars of lost economic activity in the U.S. between 2001 and 2016 [60]. ...
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Methods: Topic-focused reviews that examine the effects of ocean pollution on human health, identify gaps in knowledge, project future trends, and offer evidence-based guidance for effective intervention. Environmental Findings: Pollution of the oceans is widespread, worsening, and in most countries poorly controlled. It is a complex mixture of toxic metals, plastics, manufactured chemicals, petroleum, urban and industrial wastes, pesticides, fertilizers, pharmaceutical chemicals, agricultural runoff, and sewage. More than 80% arises from land-based sources. It reaches the oceans through rivers, runoff, atmospheric deposition and direct discharges. It is often heaviest near the coasts and most highly concentrated along the coasts of low- and middle-income countries. Plastic is a rapidly increasing and highly visible component of ocean pollution, and an estimated 10 million metric tons of plastic waste enter the seas each year. Mercury is the metal pollutant of greatest concern in the oceans; it is released from two main sources – coal combustion and small-scale gold mining. Global spread of industrialized agriculture with increasing use of chemical fertilizer leads to extension of Harmful Algal Blooms (HABs) to previously unaffected regions. Chemical pollutants are ubiquitous and contaminate seas and marine organisms from the high Arctic to the abyssal depths. Ecosystem Findings: Ocean pollution has multiple negative impacts on marine ecosystems, and these impacts are exacerbated by global climate change. Petroleum-based pollutants reduce photosynthesis in marine microorganisms that generate oxygen. Increasing absorption of carbon dioxide into the seas causes ocean acidification, which destroys coral reefs, impairs shellfish development, dissolves calcium-containing microorganisms at the base of the marine food web, and increases the toxicity of some pollutants. Plastic pollution threatens marine mammals, fish, and seabirds and accumulates in large mid-ocean gyres. It breaks down into microplastic and nanoplastic particles containing multiple manufactured chemicals that can enter the tissues of marine organisms, including species consumed by humans. Industrial releases, runoff, and sewage increase frequency and severity of HABs, bacterial pollution, and anti-microbial resistance. Pollution and sea surface warming are triggering poleward migration of dangerous pathogens such as the Vibrio species. Industrial discharges, pharmaceutical wastes, pesticides, and sewage contribute to global declines in fish stocks. Human Health Findings: Methylmercury and PCBs are the ocean pollutants whose human health effects are best understood. Exposures of infants in utero to these pollutants through maternal consumption of contaminated seafood can damage developing brains, reduce IQ and increase children’s risks for autism, ADHD and learning disorders. Adult exposures to methylmercury increase risks for cardiovascular disease and dementia. Manufactured chemicals – phthalates, bisphenol A, flame retardants, and perfluorinated chemicals, many of them released into the seas from plastic waste – can disrupt endocrine signaling, reduce male fertility, damage the nervous system, and increase risk of cancer. HABs produce potent toxins that accumulate in fish and shellfish. When ingested, these toxins can cause severe neurological impairment and rapid death. HAB toxins can also become airborne and cause respiratory disease. Pathogenic marine bacteria cause gastrointestinal diseases and deep wound infections. With climate change and increasing pollution, risk is high that Vibrio infections, including cholera, will increase in frequency and extend to new areas. All of the health impacts of ocean pollution fall disproportionately on vulnerable populations in the Global South – environmental injustice on a planetary scale. 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Firemaster® 550 (FM 550) is a commercial flame retardant mixture of brominated and organophosphate compounds applied to polyurethane foam used in furniture and baby products. Due to widespread human exposure, and structural similarities with known endocrine disruptors, concerns have been raised regarding possible toxicity. We previously reported evidence of sex specific behavioral effects in rats resulting from developmental exposure. The present study expands upon this prior finding by testing for a greater range of behavioral effects, and measuring the accumulation of FM 550 compounds in placental tissue. Wistar rat dams were orally exposed to FM 550 during gestation (0, 300 or 1000 µg/day; GD 9 – 18) for placental measurements or perinatally (0, 100, 300 or 1000 µg/day; GD 9 – PND 21) to assess activity and anxiety-like behaviors. Placental accumulation was dose dependent, and in some cases sex specific, with the brominated components reaching the highest levels. Behavioral changes were predominantly associated with a loss or reversal of sex differences in activity and anxiety-like behaviors. These findings demonstrate that environmental chemicals may sex-dependently accumulate in the placenta. That sex-biased exposure might translate to sex-specific adverse outcomes such as behavioral deficits is a possibility that merits further investigation.
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Background: Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison. Methods: We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure-response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure-response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (€1=$1·33). Findings: The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2·33% of GDP] vs $217 billion [1·28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12·6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion). Interpretation: EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention. Funding: Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation.
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The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community abouthow environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, andepigeneticchanges, therebyproducingeffects inexposedindividuals as well as theirdescendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in arange that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings canbemuchbetter translated tohumanhealth. Armedwith this information, researchers, physicians, andother healthcare providers can guide regulators and policymakers as they make responsible decisions.
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Organophosphorus flame retardants (flame retardants, FRs) have been used for several decades in many industries, including the production of dyes, varnishes, adhesives, synthetic resins, polyvinyl chloride, hydraulic fluids, plastics and textiles. Their importance in recent times has increased due to i.a., significantly reduced use of polybrominated diphenyl ethers (PBDEs) - persistent organic pollutants, dangerous for the environment. The aim of this study was to review the available literature data concerning phosphorous FRs primarily for neurotoxic, fertility, reproductive and carcinogenic effects. The analysis concerned the following most commonly used substances: tris(2-ethylhexyl)phosphate (TEHP), tris(2-butoxyethyl)phosphate (TBEP), triphenyl phosphate (TPP), tris(2-chloroethyl)phosphate (TCEP), tetrakis(hydroxymethyl)-phosphonium chloride (THPC), tributyl phosphate (TBP), tricresyl phosphate (TCP), tris(2-chloroisopropyl)phosphate (TCPP), tris(1,3-dichloroisopropyl)phosphate (TDCP) and tetrakis(hydroxymethyl)phosphonium sulphate (THPS). In animal studies neurotoxic effects were found after exposure to TBEP, THPC, TBP and TCP, while in humans they were observed only after exposure to TCP. TCEP, THPS, TBP, TCP and TDCP caused disorders in fertility and/or fetal development of animals. Adverse effects on reproduction in humans may be caused by TPP, TCP, and TDCP. In laboratory animals the development of tumors was observed after high doses of TEHP, TCEP, TBP and TDCP. None of these compounds is classified as a human carcinogen. The environmental toxicity of phosphate FRs is low (except for TPP, TCEP and TBEP). They are not stable compounds, in living organisms they are metabolised and quickly excreted. Therefore, they can be used as an alternative to PBDEs.
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A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of €163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs.
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Context: Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. Objective: The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. Design: An expert panel applied a weight-of-evidence characterization adapted from the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder, and annual costs for attention-deficit hyperactivity disorder. Setting, Patients and Participants, and Intervention: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. Results: The panel identified a 70-100% probability that polybrominated diphenyl ether and organophosphate exposures contribute to IQ loss in the European population. Polybrominated diphenyl ether exposures were associated with 873,000 (sensitivity analysis, 148,000 to 2.02 million) lost IQ points and 3290 (sensitivity analysis, 3290 to 8080) cases of intellectual disability, at costs of €9.59 billion (sensitivity analysis, €1.58 billion to €22.4 billion). Organophosphate exposures were associated with 13.0 million (sensitivity analysis, 4.24 million to 17.1 million) lost IQ points and 59 300 (sensitivity analysis, 16,500 to 84,400) cases of intellectual disability, at costs of €146 billion (sensitivity analysis, €46.8 billion to €194 billion). Autism spectrum disorder causation by multiple EDCs was assigned a 20-39% probability, with 316 (sensitivity analysis, 126-631) attributable cases at a cost of €199 million (sensitivity analysis, €79.7 million to €399 million). Attention-deficit hyperactivity disorder causation by multiple EDCs was assigned a 20-69% probability, with 19 300 to 31 200 attributable cases at a cost of €1.21 billion to €2.86 billion. Conclusions: EDC exposures in Europe contribute substantially to neurobehavioral deficits and disease, with a high probability of >€150 billion costs/year. These results emphasize the advantages of controlling EDC exposure.
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Background: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that have been widely used as flame retardants in furniture, carpet padding, car seats, and other consumer products during the past three decades. Objective: We examined whether in utero exposure to PBDEs is associated with child cognitive function and behavior in a U.S. study sample. Methods: In a prospective birth cohort, we measured maternal serum concentrations of BDE-47 and other PBDE congeners in 309 women at 16 weeks of gestation during 2003–2006 and followed their children in Cincinnati, Ohio. We measured cognitive and motor abilities using the Bayley Scales of Infant Development-II at ages 1, 2, and 3 years; intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III at age 5 years; and children’s behaviors using the Behavioral Assessment System for Children-2 annually at ages 2–5 years. We used linear mixed models or generalized estimating equations with adjustment for potential confounders to estimate associations between these outcomes and log10-transformed PBDE concentrations. Results: The geometric mean of BDE-47 in maternal serum (20.1 ng/g lipid) was comparable with U.S. adult national reference values. Prenatal BDE-47 was not significantly associated with Bayley Mental or Psychomotor Development Indices at 1–3 years, but a 10-fold increase in prenatal BDE-47 was associated with a 4.5-point decrease (95% CI: –8.8, –0.1) in Full-Scale IQ and a 3.3-point increase (95% CI: 0.3, 6.3) in the hyperactivity score at age 5 years. Conclusions: Prenatal exposure to PBDEs was associated with lower IQ and higher hyperactivity scores in children. Citation: Chen A, Yolton K, Rauch SA, Webster GM, Hornung R, Sjödin A, Dietrich KN, Lanphear BP. 2014. Prenatal polybrominated diphenyl ether exposures and neurodevelopment in U.S. children through 5 years of age: the HOME study. Environ Health Perspect 122:856–862; http://dx.doi.org/10.1289/ehp.1307562
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background: California children’s exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals. Objective: Here we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort. Methods: We measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children’s attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323). Results: Maternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination—particularly in the nondominant—at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels. Conclusions: Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.
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In the US the dominant sources of lead through much of the 20th Century (eg, vehicular emissions, plumbing, household paint) have been significantly diminished. The reductions in adult and pediatric average blood lead levels in the US have been extraordinary. Progress continues: the US Environmental Protection Agency recently developed a new air standard for lead. In the 21st Century, the average blood lead level in a society may be seen as a marker of the status of their public's health. However, the threat of lead exposure remains a significant public health problem among subpopulation groups in the US and in many less developed countries. This paper examines some of the specific issues involved in the reduction of blood lead in a post-industrial era. These involve the control of the remaining exogenous primary sources, both general (eg, industrial emissions) and specific (eg, at-risk occupations), exogenous secondary sources (eg, contaminated urban soils, legacy lead-based paints), an endogenous source (ie, cumulative body lead burden) and emergent sources.
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The impact of environmental chemicals on children's neurodevelopment is sometimes dismissed as unimportant because the magnitude of the impairments are considered to be clinically insignificant. Such a judgment reflects a failure to distinguish between individual and population risk. The population impact of a risk factor depends on both its effect size and its distribution (or incidence/prevalence). The objective was to develop a strategy for taking into account the distribution (or incidence/prevalence) of a risk factor, as well as its effect size, in order to estimate its population impact on neurodevelopment of children. The total numbers of Full-Scale IQ points lost among U.S. children 0-5 years of age were estimated for chemicals (methylmercury, organophosphate pesticides, lead) and a variety of medical conditions and events (e.g., preterm birth, traumatic brain injury, brain tumors, congenital heart disease). Although the data required for the analysis were available for only three environmental chemicals (methylmercury, organophosphate pesticides, lead), the results suggest that their contributions to neurodevelopmental morbidity are substantial, exceeding those of many nonchemical risk factors. A method for comparing the relative contributions of different risk factors provides a rational basis for establishing priorities for reducing neurodevelopmental morbidity in children.
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Environmental chemicals that act as endocrine disruptors do not appear to pose a risk to human reproduction; however, their effects on the central nervous systems are less well understood. Animal studies suggested that maternal exposure to endocrine-disrupting chemicals (EDC) produced changes in rearing behavior, locomotion, anxiety, and learning/memory in offspring, as well as neuronal abnormalities. Some investigations suggested that EDC exert effects on central monoaminergic neurons, especially dopaminergic neurons. Our data demonstrated that EDC attenuate the development of dopaminergic neurons, which might be involved in developmental disorders. Perinatal exposure to EDC might affect neuronal plasticity in the hippocampus, thereby potentially modulating neuronal development, leading to impaired cognitive and memory functions. Endocrine disruptors also attenuate gender differences in brain development. For example, the locus ceruleus is larger in female rats than in males, but treatments with bisphenol-A (BPA) enlarge this region in males. Some reports indicated that EDC induce hypothyroidism, which might be evidenced as abnormal brain development. Endocrine disruptors might also affect mature neurons, resulting in neurodegenerative disorders such as Parkinson's disease. The current review focused on alterations in the brain induced by EDC, specifically on the possible involvement of EDC in brain development and neurodegeneration.
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A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.
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Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates. We examined the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months and 6-9 years. The Mount Sinai Children's Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urine samples were collected and analyzed for organophosphate metabolites (n = 360). Prenatal maternal blood was analyzed for PON1 activity and genotype. Children returned for neurodevelopment assessments ages 12 months (n = 200), 24 months (n = 276), and 6-9 (n = 169) years of age. Prenatal total dialkylphosphate metabolite level was associated with a decrement in mental development at 12 months among blacks and Hispanics. These associations appeared to be enhanced among children of mothers who carried the PON1 Q192R QR/RR genotype. In later childhood, increasing prenatal total dialkyl- and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon, with a monotonic trend consistent with greater decrements with increasing prenatal exposure. Our findings suggest that prenatal exposure to organophosphates is negatively associated with cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood. PON1 may be an important susceptibility factor for these deleterious effects.
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Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children's cognitive development. We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children. We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment. Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children's urinary DAP concentrations were not consistently associated with cognitive scores. Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population.
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Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds that are persistent and bioaccumulative and therefore have become ubiquitous environment contaminants. Animal studies suggest that prenatal PBDE exposure may result in adverse neurodevelopmental effects. In a longitudinal cohort initiated after 11 September 2001, including 329 mothers who delivered in one of three hospitals in lower Manhattan, New York, we examined prenatal PBDE exposure and neurodevelopment when their children were 12-48 and 72 months of age. We analyzed 210 cord blood specimens for selected PBDE congeners and assessed neurodevelopmental effects in the children at 12-48 and 72 months of age; 118, 117, 114, 104, and 96 children with available cord PBDE measurements were assessed at 12, 24, 36, 48, and 72 months, respectively. We used multivariate regression analyses to evaluate the associations between concentrations of individual PBDE congeners and neurodevelopmental indices. Median cord blood concentrations of PBDE congeners 47, 99, and 100 were 11.2, 3.2, and 1.4 ng/g lipid, respectively. After adjustment for potential confounders, children with higher concentrations of BDEs 47, 99, or 100 scored lower on tests of mental and physical development at 12-48 and 72 months. Associations were significant for 12-month Psychomotor Development Index (BDE-47), 24-month Mental Development Index (MDI) (BDE-47, 99, and 100), 36-month MDI (BDE-100), 48-month full-scale and verbal IQ (BDE-47, 99, and 100) and performance IQ (BDE-100), and 72-month performance IQ (BDE-100). This epidemiologic study demonstrates neurodevelopmental effects in relation to cord blood PBDE concentrations. Confirmation is needed in other longitudinal studies.
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In this study we quantify economic benefits from projected improvements in worker productivity resulting from the reduction in children's exposure to lead in the United States since 1976. We calculated the decline in blood lead levels (BLLs) from 1976 to 1999 on the basis of nationally representative National Health and Nutrition Examination Survey (NHANES) data collected during 1976 through 1980, 1991 through 1994, and 1999. The decline in mean BLL in 1- to 5-year-old U.S. children from 1976-1980 to 1991-1994 was 12.3 microg/dL, and the estimated decline from 1976 to 1999 was 15.1 microg/dL. We assumed the change in cognitive ability resulting from declines in BLLs, on the basis of published meta-analyses, to be between 0.185 and 0.323 IQ points for each 1 g/dL blood lead concentration. These calculations imply that, because of falling BLLs, U.S. preschool-aged children in the late 1990s had IQs that were, on average, 2.2-4.7 points higher than they would have been if they had the blood lead distribution observed among U.S. preschool-aged children in the late 1970s. We estimated that each IQ point raises worker productivity 1.76-2.38%. With discounted lifetime earnings of $723,300 for each 2-year-old in 2000 dollars, the estimated economic benefit for each year's cohort of 3.8 million 2-year-old children ranges from $110 billion to $319 billion.
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Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.
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Lead (Pb2+), a heavy metal, has been used by humans for many technological purposes, which is the main reason for its present widespread distribution. Although various actions have been taken to decrease the use and distribution of lead in the environment, it remains a significant health hazard. The toxic mechanism of lead is caused by its ability to substitute for other polyvalent cations (particularly divalent cations, such as calcium [Ca2+] and zinc [Zn2+]) in the molecular machinery of living organisms. These interactions allow lead to affect different biologically significant processes, including metal transport, energy metabolism, apoptosis, ionic conduction, cell adhesion, inter- and intracellular signaling, diverse enzymatic processes, protein maturation, and genetic regulation. Membrane ionic channels and signaling molecules seem to be one of the most relevant molecular targets contributing to lead's neurotoxicity; the developing central nervous system is particularly susceptible. At critical times in development, lead may have a disorganizing influence with long-lasting effects that may continue into teenage years and beyond. Pediatric lead poisoning is more common than adult lead poisoning, and its effects may occur at reduced blood levels with subclinical symptoms, thus a high index of suspicion is necessary for physicians when dealing with pediatric patients. Long-term effects of lead poisoning may produce cognitive and motor impairment, with behavioral alterations. This review is centered on the description of the molecular mechanisms of lead toxicity and its repercussions on cellular functions.
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Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose-response information for this relationship is useful for estimating benefits of reduced mercury exposure. We estimated a dose-response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Inputs to the model consist of dose-response coefficients from studies conducted in the Faroe Islands, New Zealand, and the Seychelles Islands. IQ coefficients were available from previous work for the latter two studies, and a coefficient for the Faroe Islands study was estimated from three IQ subtests. Other tests of cognition/achievement were included in the hierarchical model to obtain more accurate estimates of study-to-study and end point-to-end point variability. We find a central estimate of -0.18 IQ points (95% confidence interval, -0.378 to -0.009) for each parts per million increase of maternal hair mercury, similar to the estimates for both the Faroe Islands and Seychelles studies, and lower in magnitude than the estimate for the New Zealand study. Sensitivity analyses produce similar results, with the IQ coefficient central estimate ranging from -0.13 to -0.25. IQ is a useful end point for estimating neurodevelopmental effects, but may not fully represent cognitive deficits associated with mercury exposure, and does not represent deficits related to attention and motor skills. Nevertheless, the integrated IQ coefficient provides a more robust description of the dose-response relationship for prenatal mercury exposure and cognitive functioning than results of any single study.
Article
Numerous recent studies have shown that endocrine disrupting chemicals (EDCs) in the body of pregnant women can pass through the placenta and be exposed to the fetus, leading to fetal development and cognitive impairment. Placentation through invasion of trophoblast cells and vascular remodeling is essential to maintaining maternal and fetal health throughout the pregnancy. Abnormal placentation can lead to pregnancy disorders such as preeclampsia (PE) and intrauterine growth retardation (IUGR). However, many studies have not been conducted on whether EDCs can inhibit the development and function of the placenta. Isolating placental tissues to analyze the effect of EDCs on placentation has several limitations. In this review, we discussed the types of EDCs that can pass through the placental barrier and accumulate in the placenta with relative outcome. EDCs can be released from a variety of products including plasticizers, pesticides, and retardant. We also discussed the development and dysfunction of the placenta when EDCs were treated on trophoblast cells or pregnant rodent models. The effects of EDCs on the placenta of livestock are also discussed, together with the molecular mechanism of EDCs acting in trophoblast cells. We describe how EDCs cross the membrane of trophoblasts to regulate signaling pathways, causing genetic and epigenetic changes that lead to changes in cell viability and invasiveness. Further studies on the effects of EDCs on placenta may draw attention to the correct use of products containing EDCs during pregnancy.
Article
The term organophosphate (OP) refers to a diverse group of chemicals that are found in hundreds of products worldwide. As pesticides, their most common use, OPs are clearly beneficial for agricultural productivity and the control of deadly vector-borne illnesses. However, as a consequence of their widespread use, OPs are now among the most common synthetic chemicals detected in the environment as well as in animal and human tissues. This is an increasing environmental concern because many OPs are highly toxic and both accidental and intentional exposures to OPs resulting in deleterious health effects have been documented for decades. Some of these deleterious health effects include a variety of long-term neurological and psychiatric disturbances including impairments in attention, memory, and other domains of cognition. Moreover, some chronic illnesses that manifest these symptoms such as Gulf War Illness and Aerotoxic Syndrome have (at least in part) been attributed to OP exposure. In addition to acute acetylcholinesterase inhibition, OPs may affect a number of additional targets that lead to oxidative stress, axonal transport deficits, neuroinflammation, and autoimmunity. Some of these targets could be exploited for therapeutic purposes. The purpose of this review is thus to: 1) describe the important uses of organophosphate (OP)-based compounds worldwide, 2) provide an overview of the various risks and toxicology associated with OP exposure, particularly long-term neurologic and psychiatric symptoms, 3) discuss mechanisms of OP toxicity beyond cholinesterase inhibition, 4) review potential therapeutic strategies to reverse the acute toxicity and long term deleterious effects of OPs.
Article
Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants. Technical mixtures PentaBDE and OctaBDE were phased out in 2004 through voluntary and regulatory actions with DecaBDE remaining in limited use until 2013. Biomonitoring studies have shown widespread presence of PBDEs in the US and worldwide population. While some studies suggest that human serum concentrations are declining over time, it is unclear whether this trend will continue. Our objective was to examine temporal trends of PentaBDEs and their hydroxylated metabolites (OH-PBDEs) between 2008 and 2014 in populations of ethnically diverse, pregnant women residing in Northern California (n = 111). Serum samples were collected and analyzed by high resolution mass spectrometry for five PentaBDE congeners and two OH-PBDEs. We found widespread exposures in participants from all three time points (2008/09, 2011/12, 2014). Temporal patterns varied substantially by congener. BDE -47, −99 and the OH-PBDEs decreased between 2008/09-2011/12 but plateaued between 2011/12-2014. In contrast, BDE-100 decreased across all years, BDE-153 decreased in the latter years, and BDE-28 decreased initially and then increased. These findings indicate that while policies to remove PBDEs from the marketplace have successfully lead to declines in exposures to some PBDE congeners, human exposures to these legacy pollutants could plateau and remain ubiquitous in human populations.
Article
Polybrominated diphenyl ethers (PBDEs) and heavy metals are two key groups of electric and electronic equipment contaminants. Despite their co-occurrence in aquatic environments, their combined effects remain largely unknown, particularly under a chronic exposure regime. In the present study, adult zebrafish (Danio rerio) were exposed to environmentally relevant concentrations of BDE-209 and lead (Pb), or their binary mixtures, for 3 months. After chronic parental exposure, increased transfer of BDE-209 and Pb to the offspring eggs was activated in the coexposure groups, with BDE-197 being the predominant PBDE congener, indicating the dynamic metabolism of BDE-209 in parental zebrafish. In the presence of Pb, culturing the eggs in clean water until 5 days post-fertilization (dpf) further accelerated the debromination of BDE-209 towards BDE-197 in the offspring, caused by the preferential removal of bromine atoms at meta positions. BDE-209 and Pb combinations induced reproductive and thyroid endocrine disruption in adults, which resulted in an imbalanced deposition of hormones in the eggs. However, compared with single chemical exposure, the larval offspring at 5 dpf from the coexposure groups had reversed the adverse influences from maternal origin. In addition, the interaction between BDE-209 and Pb led to transgenerational developmental neurotoxicity in the larval offspring, where inhibited neuronal growth and neurotransmitter signaling, disorganized muscular assembly, and impaired visual function contributed to the observed neurobehavioral deficits. Overall, depending on specific biological events, the complex interaction between BDE-209 and Pb under chronic exposure resulted in significant alterations in their environmental fate and toxicological actions, thus complicating the accurate evaluation of ecological risks and constituting an unquantified threat to environmental safety.
Article
Objectives: We analyzed differences in pediatric elevated blood lead level incidence before and after Flint, Michigan, introduced a more corrosive water source into an aging water system without adequate corrosion control. Methods: We reviewed blood lead levels for children younger than 5 years before (2013) and after (2015) water source change in Greater Flint, Michigan. We assessed the percentage of elevated blood lead levels in both time periods, and identified geographical locations through spatial analysis. Results: Incidence of elevated blood lead levels increased from 2.4% to 4.9% (P < .05) after water source change, and neighborhoods with the highest water lead levels experienced a 6.6% increase. No significant change was seen outside the city. Geospatial analysis identified disadvantaged neighborhoods as having the greatest elevated blood lead level increases and informed response prioritization during the now-declared public health emergency. Conclusions: The percentage of children with elevated blood lead levels increased after water source change, particularly in socioeconomically disadvantaged neighborhoods. Water is a growing source of childhood lead exposure because of aging infrastructure. (Am J Public Health. Published online ahead of print December 21, 2015: e1-e8. doi:10.2105/AJPH.2015.303003).
Article
Coal-fired power plants in the United States are required to reduce their emissions of mercury (Hg) into the atmosphere to lower the exposure of Hg to humans. The effectiveness of power-plant emission controls on the atmospheric concentrations of Hg in the United States is largely unknown because there are few long-term high-quality atmospheric Hg data sets. Here, we present the atmospheric concentrations of Hg and sulfur dioxide (SO2) measured from 2006 to 2015 at a relatively pristine location in western Maryland that is several (>50 km) kilometers downwind of power plants in Ohio, Pennsylvania, and West Virginia. Annual average atmospheric concentrations of gaseous oxidized mercury (GOM), SO2, fine particulate mercury (PBM2.5), and gaseous elemental mercury (GEM) declined by 75%, 75%, 43%, and 13%, respectively, and were strongly correlated with power-plant Hg emissions from the upwind states. These results provide compelling evidence that reductions in Hg emissions from power plants in the United States had their intended impact to reduce regional Hg pollution.
Article
Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental neurotoxicants-manganese, fluoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these efforts and to accelerate translation of science into prevention, we propose the urgent formation of a new international clearinghouse.
Article
Background: There is increasing evidence of the role that exposure to industrial chemicals plays in the development of childhood disease. The USA and the European Union (EU) have taken divergent policy approaches to managing this issue, and economic estimates of disease costs attributable to environmental exposures in children are available in the USA but not the EU. We undertook the first economic evaluation of the impacts of childhood environmental chemical exposures in the EU. Methods: We used a cost-of-illness approach to estimate health care system costs, and used environmentally attributable fraction modelling to estimate the proportion of childhood disease due to environmental exposures. We analysed data on exposures, disease prevalence and costs at a country level, and then aggregated costs across EU member states to estimate overall economic impacts within the EU. Results: We found the combined environmentally attributable costs of lead exposure, methylmercury exposure, developmental disabilities, asthma and cancer to be $70.9 billion in 2008 (range: $58.9-$90.6 billion). These costs amounted to ~0.480% of the gross domestic product of the EU in 2008. Conclusions: Childhood chemical exposures present a significant economic burden to the EU. Our study offers an important baseline of disease costs before the implementation of Registration, Evaluation and Authorization of Chemicals, which is important for studying the impacts of this policy regime.
Article
Thyroid hormones (TH) are critical for growth and development and particularly brain development. There are numerous environmental agents that lead to marginal reductions of circulating TH. Although it is clear that severe developmental hypothyroidism is profoundly detrimental to neurodevelopment, there is less information regarding the consequences of modest degrees of thyroid. The impact of low level TH disruptions induced by environmental contaminants has not been defined. This paper is a synopsis from four invited speakers who presented at the 13th International Neurotoxicology Association meeting held in Xi'an, China during the summer of 2011. An overview of the role of TH in brain development and a review of human and animal data on the neurological sequelae of disruption of the thyroid axis in the pre- and early post-natal periods were presented by Mary Gilbert and Joanne Rovet. Iodine deficiency, a common cause of TH insufficiency and mental retardation in many countries, including China, was addressed by Zupei Chen. In this presentation the current incidence of iodine deficiency and neurological outcome in China and the efficacy of recently implemented iodinization programs to eliminate this cause of mental retardation were reviewed. Joanne Rovet described the impact of TH disruption during pregnancy and under conditions of congenital hypothyroidism. Children born with normal thyroid function, but who experienced TH insufficiency in the womb, display subtle cognitive impairments and abnormalities in brain imaging. Despite early detection and treatment, deficiencies also exist in children born with thyroid disorders. Different patterns of cognitive effects result from prenatal versus postnatal TH insufficiency. Mary Gilbert reported on the effects of environmental contaminants with thyroid disrupting action on brain development in animals. Results of neurophysiological, behavioral, structural and molecular alterations that accompany modest perturbations of the thyroid axis were reviewed. Noriyuki Koibuchi described molecular targets of TH-mediated signalling accompanying exposure to persistent organic pollutants. Both polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are prevalent environmental contaminants that disrupt TH signalling at the receptor level. This action by these chemical classes could contribute to the negative impact of these chemicals on brain function. In summary, epidemiological, preclinical and animal research has clearly identified the critical role of TH in brain development. Additional work is required to understand the impact of low level perturbations of the thyroid axis to evaluate the risk associated with environmental contaminants with thyroid action.
Article
Methylmercury is a widely distributed environmental toxicant with detrimental effects on the developing and adult nervous system. Due to its accumulation in the food chain, chronic exposure to methylmercury via consumption of fish and sea mammals is still a major concern for human health, especially developmental exposure that may lead to neurological alterations, including cognitive and motor dysfunctions. Mercury-induced neurotoxicity and the identification of the underlying mechanisms has been a main focus of research in the neurotoxicology field. Three major mechanisms have been identified as critical in methylmercury-induced cell damage including (i) disruption of calcium homeostasis, (ii) induction of oxidative stress via overproduction of reactive oxygen species or reduction of antioxidative defenses and (iii) interactions with sulfhydryl groups. In vivo and in vitro studies have provided solid evidence for the occurrence of neural cell death, as well as cytoarchitectural alterations in the nervous system after exposure to methylmercury. Signaling cascades leading to cell death induced by methylmercury involve the release of mitochondrial factors, such as cytochrome c and AIF with subsequent caspase-dependent or -independent apoptosis, respectively; induction of calcium-dependent proteases calpains; interaction with lysosomes leading to release of cathepsins. Interestingly, several pathways can be activated in parallel, depending on the cell type. In this paper, we provide an overview of recent findings on methylmercury-induced neurotoxicity and cell death pathways that have been described in neural and endocrine cell systems.
Article
This review reports current knowledge regarding the roles that cadmium (Cd), mercury (Hg), arsenic (As), lead (PB), manganese (Mn), and zinc (Zn) play as endocrine-disrupting chemicals (EDCs). The influence of these metals on the endocrine system, possible mechanisms of action, and consequent health effects were correlated between experimental animals and humans. Analysis of the studies prompted us to identify some critical issues related to this area and showed the need for more rigorous and innovative studies. Consequently, it was recommended that future studies need to: (1) identify the mechanisms of action, because at the present time only a few have been elucidated-in this context, the possible presence of hormesis need to be determined, as currently this was reported only for exposure Cd and As; (2) study the possible additive, synergistic, or antagonistic effects on the endocrine system following exposure to a mixture of metals since there is a lack of these studies available, and in general or occupational environments, humans are simultaneously exposed to different classes of xenobiotics, including metals, but also to organic compounds that might also be EDCs; (3) assess the potential adverse effects on the endocrine system of low-level exposures to metals, as most of the information currently available on EDCs originates from studies in which exposure levels were particularly high; and (4) assess the effects on the endocrine and reproductive systems of other metals that are present in the general and occupational environment that have not yet been evaluated.
Article
During the past several years, there has been a renewed interest in the mechanisms by which lead poisoning disrupts brain function. In part, this is related to clinical observations that imply an absence of threshold for toxicity in the immature brain. Many of the neurotoxic effects of lead appear related to the ability of lead to mimic or in some cases inhibit the action of calcium as a regulator of cell function. At a neuronal level, exposure to lead alters the release of neurotransmitter from presynaptic nerve endings. Spontaneous release is enhanced and evoked release is inhibited. The former may be due to activation of protein kinases in the nerve endings and the latter to blockade of voltage-dependent calcium channels. This disruption of neuronal activity may, in turn, alter the developmental processes of synapse formation and result in a less efficient brain with cognitive deficits. Brain homeostatic mechanisms are disrupted by exposure to higher levels of lead. The final pathway appears to be a breakdown in the blood-brain barrier. Again, the ability of lead to mimic or mobilize calcium and activate protein kinases may alter the behavior of endothelial cells in immature brain and disrupt the barrier. In addition to a direct toxic effect upon the endothelial cells, lead may alter indirectly the microvasculature by damaging the astrocytes that provide signals for the maintenance of blood-brain barrier integrity.
Article
Endocrine disrupting chemicals are a newly defined category of environmental contaminants that may affect animal and human populations by interfering with normal hormone action. There is substantial concern that these agents could have a range of subtle and long-lasting effects. Because of the sensitivity of the developing central nervous system to low levels of endogenous gonadal hormones during development, the central nervous system may be a target for the action of endocrine disrupting chemicals.
Article
Mercury concentrations were measured in paired hair and blood samples from a cohort of about 1000 children examined at birth and at 7 and 14 years of age. The ratio between concentrations in maternal hair (in microg/g) and in cord blood (microg/L) was approximately 200, but samples from the children at age 14 years showed a ratio of about 250. These findings are in accordance with previous data from smaller studies. However, an even higher ratio of about 360 was seen at 7 years of age, suggesting that hair strands at this age retain more mercury. The 95th percentile of the hair-to-blood ratio was between five-fold and nine-fold greater than the 5th percentile. The results were examined in structural equation models to estimate the total imprecision of the individual biomarker results and the possibility that the ratio may not be constant. The hair-to-blood ratio was found to increase at lower mercury concentrations, a tendency that could not be explained by potential confounders, such as alcohol intake or number of amalgam fillings. The total imprecision (coefficient of variation) for the blood determinations averaged about 30%, thereby substantially exceeding normal laboratory imprecision. Yet hair-mercury results had an even greater imprecision, which suggested that preanalytical factors, such as variable sample characteristics, impacted the results. These findings are in accordance with other evidence that the cord blood concentration is a better predictor of neurobehavioral toxicity than is the maternal hair concentration. Although practical for field studies and monitoring purposes, hair-mercury concentration results, therefore, need to be calibrated and interpreted in regard to each specific study setting.
Article
Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper quantifies the impact of prenatal MeHg exposure on cognitive development. Other papers quantify the beneficial impact of prenatal intake of n-3 PUFAs on cognitive function and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This analysis aggregates results from three major prospective epidemiology studies to quantify the association between prenatal MeHg exposure and cognitive development as measured by intelligence quotient (IQ). It finds that prenatal MeHg exposure sufficient to increase the concentration of mercury in maternal hair at parturition by 1 microg/g decreases IQ by 0.7 points. This paper identifies important sources of uncertainty influencing this estimate, concluding that the plausible range of values for this loss is 0 to 1.5 IQ points.
Article
Pyrethroids are pesticides with high selectivity for insects. In order to identify strengths and gaps in the database for pyrethroid neurobehavioral toxicology, we have critically analyzed the data from peer-reviewed literature. This review includes dose-response data that have been recently generated demonstrating consistent findings for low-dose, acute, oral exposure to pyrethroids in small rodents. All pyrethroids tested (i.e., about twenty compounds), regardless of structure, produce a decrease in motor activity in a variety of test protocols. The range of relative potencies varies more than two orders of magnitude, and thresholds for motor activity were found well below doses that produce overt signs of poisoning. Six compounds (allethrin, permethrin, cis-permethrin, deltamethrin, cypermethrin, and fenvalerate) impair schedule-controlled operant responding, seven compounds (pyrethrum, bifenthrin, S-bioallethrin, permethrin, beta-cyfluthrin, cypermethrin, and deltamethrin) decrease grip strength, and two compounds (deltamethrin and alpha-cypermethrin) produce incoordination using the rotarod. In addition, while compounds lacking an alpha-cyano group (e.g., cismethrin, permethrin, bifenthrin) induce an increase in acoustic-evoked startle response amplitude, cyano compounds (e.g., deltamethrin, cypermethrin, cyfluthrin) produce the opposite outcome. Other endpoints (e.g., tremor intensity, sensory response) have been only occasionally explored. A synthesis of the neurobehavioral evidence relating to the action of pyrethroids indicates that some differences in the experimental findings across compounds are also present in the low-effective dose range. For risk assessment purposes, a strategy that takes into account data from an array of neurobehavioral endpoints is needed to capture the heterogeneity of pyrethroid-induced adverse effects and accurately inform policy decisions.
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IOM, 1981. Costs of Environment-Related Health Effects: a Plan for Continuing Study. National Academy Press, Washington, D.C.
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NHANES, 2017. Laboratory Procedures Manual. Retrieved from. https://www.cdc.gov/ nchs/nhanes/.
EPA Administrator Pruitt Denies Petition To Ban Widely Used Pesticide [Speeches, Testimony And Transcripts
  • Us Epa
US EPA, 2017a. EPA Administrator Pruitt Denies Petition To Ban Widely Used Pesticide [Speeches, Testimony And Transcripts]. [updated 2017-05-30]. https://www.epa. gov/newsreleases/epa-administrator-pruitt-denies-petition-ban-widely-usedpesticide-0.