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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
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.
... With a prevalence of 10-15% in US children, NDD includes autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and intellectual disability (ID) and is consistently reported with greater prevalence in males [2]. Research has suggested a loss of $22,268 for each reduction in IQ score and a lifetime loss of $1,272,470 for a person with ID [3]. Although the etiology is not fully understood, there is a consensus that many NDDs are driven by interactions between genes and environmental triggers [4,5]. ...
... Certain metals and metalloids like Pb, Hg, and As are wellknown neurotoxicants [39]. With recognized associations between IQ reduction and Pb and Hg exposures [3], heavy metal exposures are of public health concern. Although the placenta offers some protection against chemical exposures, many toxicants like heavy metals can easily cross the placenta and the blood-brain barrier, which is not fully developed until a few months after birth [42]. ...
... Exposure to endocrine-disrupting chemicals (EDCs), such as PAHs, can influence levels of hormones essential for brain development [44], significantly reduce IQ, and increase the associated economic burden in the USA [3,45]. Both studies of PAHs were cohort studies using data from African-American and Hispanic women enrolled in the Columbia Center for Children's Environmental Health (CCCEH) cohort study investigating prenatal exposures. ...
Purpose of review:
Neurotoxicant exposures are of particular concern in historically marginalized communities. Often a consequence of structural racism, low-income minoritized populations experience a disproportionate burden of hazardous exposures through proximity to industrial facilities, high traffic roads, and suboptimal housing. Here, we summarize reports on exposures and neurodevelopment focused on differences by education, income, race/ethnicity, or immigration status from 2015 to 2022, discuss the importance of such investigations in overburdened communities, and recommend areas for future research.
Recent findings:
We found 20 studies that investigated exposure disparities and neurodevelopment in children. Most were conducted in the USA, and many focused on air pollution, followed by metal exposures and water contamination. Although several studies showed differences in exposure-outcome associations by income and education, many examining differences by race/ethnicity did not report notable disparities between groups. However, measures of individual race and ethnicity are not reliable measures of discrimination experienced as a consequence of structural racism. Our review supports scientific evidence that the reduction of individual and widespread municipal exposures will improve child development and overall public health. Identified research gaps include the use of better indicators of economic status and structural racism, evaluations of effect modification and attributable fraction of outcomes by these factors, and considerations of multidimensional neighborhood factors that could be protective against environmental insults. Considering that vulnerable populations have disparities in access to and quality of care, greater burden of exposure, and fewer resources to incur associated expenses, such populations should be prioritized.
... Drinking water Chemicals in particulate phase (aerosols, suspended dust) Personal care products Despite these pathways, the specific chemical properties of each pollutant are determinants of its behaviour in the human body, establishing the risk level, symptoms, and diseases generated. Prenatal and early life exposure have negative impacts on the neurological development of babies, affecting their endocrine and non-endocrine systems [12]. Based on this factor, decision-makers can design different strategies in order to prioritise economic resources to manage polluted discharges and risky products [11]. ...
... Such chemicals are toxic substances present in the air, food, and water that are not easily controlled by the population itself. The work of Gaylord et al. [12] highlighted that methylmercury in the United States is not properly regulated since coal-fired electric power facilities are the main source of this pollutant, and corresponding environmental regulations stopped in 2011. Consequently, there are some plants still operating and maintaining population exposure along with the risk of neurodevelopment impairment and loss of intelligence quotient in young children. ...
... Data from 2001 reported $190 billion in treatments, but in 2016, this value decreased to $38 billion. Reducing exposure to polybrominated diphenyl ethers has generated $153 billion in economic benefits, which represents a significant improvement to quality of life in childhood [12]. The healthcare costs of other endocrine disruptors have also been assessed in the literature [93][94][95][96]. ...
Diffuse pollution is one type of pollution generated by agricultural, livestock, and urban runoff that is responsible for surface and groundwater pollution. As a result, the exposed population develops different diseases that affect their short, medium, and long-term quality of life. Researchers need to be able to assess the loss of quality of life in monetary terms to include this social impact in decision-making processes. Specifically, if no measure is implemented to correct the situation, these costs can be considered as the non-action costs of the social impact of water pollution. This study assesses the importance of measuring healthcare costs as a proxy for non-action costs for the economic assessment of water pollution consequences. Thanks to this analysis, it is possible to identify the health costs produced by the current environmental situation, making it possible to obtain an economic baseline scenario prior to the implementation of any project or measure. This approach is a novelty in the literature since, to date, healthcare costs have not been related to non-action costs. Including these costs in economic feasibility studies allow us to assess in detail both the social impact of pollution and the social benefits of develop water-quality improvement projects.
... 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]. ...
... The furniture industry and state regulators estimate that as of January 2020, the vast majority of residential and business furniture manufactured in the U.S. is made without flame retardants in the foam [71,72]. This result, as a consequence of regulatory changes, has been recognized as a major advance for public and environmental health and can provide a model for reforming flammability standards for other products [60]. ...
... 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]. ...
Flammability standards for furniture, building insulation and electronics were established in an attempt to mitigate fire risk. However, research suggests that some of these flammability standards should be reconsidered. High levels of flame retardant chemicals, primarily organohalogens, are added to these products in order to comply with fire safety standards. Organohalogen and organophosphate flame retardants are associated with adverse health effects such as diminished immune function, endocrine disruption, and cancer. Further, flame retardants may not provide a significant fire safety benefit as used in many products, and these chemicals can hinder material recycling. We reviewed evidence of how flammability standards drive the continued use of harmful flame retardants and investigated cases in which flame retardants are used to achieve standard compliance without providing a significant fire safety benefit. The widespread continuous use of toxic flame retardant chemicals demonstrates that toxicological evidence and chemical-by-chemical regulation alone are not sufficient to prevent their inclusion in consumer products. However, recent experiences show that updated flammability standards can reduce the use of flame retardants while maintaining, or even increasing, fire safety. Additional opportunities exist for improved standards that could further decrease flame retardant use and maintain fire safety.
... However, some studies revealed a larger role of non-dietary exposure to PBDE, since ingestion and dermal contact of dust were the major pathways of exposure to PBDE in an American study, accounting for 56-77% of the total exposure in toddlers, children, adolescents and adults, whereas diet only accounted for 20-40% (Johnson-Restepro and Kannan, 2009). In another recent American biomonitoring study, PBDEs exposure was the greatest contributor to IQ loss, followed by lead, organo-phosphates and methyl mercury (Gaylord et al., 2020), while our results show that the contribution of PBDEs to the combined exposure was only limited. This is likely explained by our inability to capture non-dietary exposures to PBDEs in our study; exposure from all routes is accounted for in human biomonitoring studies. ...
... We selected the loss of 1 IQ point as a measure of cognitive de"cits in the developing child, since this degree of cognitive decline at the population level can have an economic impact on societies (Gould, 2009;Grandjean et al., 2012;Bellanger et al., 2013;Trasande and Liu, 2011;Pichery et al., 2011;Gaylord et al., 2020). IQ tests usually consists of several subtests, each measuring a different aspect of cognitive development, such as memory, verbal and spatial reasoning, planning, learning and the comprehension and use of language. ...
We performed a mixture risk assessment (MRA) case study of dietary exposure to the food contaminants lead, methylmercury, inorganic arsenic (iAs), fluoride, non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and polybrominated diphenyl ethers (PBDEs), all substances associated with declines in cognitive abilities measured as IQ loss. Most of these chemicals are frequently measured in human biomonitoring studies. A componentbased, personalised modified reference point index (mRPI) approach, in which we expressed the exposures and potencies of our chosen substances as lead equivalent values, was applied to perform a MRA for dietary exposures. We conducted the assessment for four different age groups (toddlers, children, adolescents, and women aged 18–45 years) in nine European countries. Populations in all countries considered exceeded combined tolerable levels at median exposure levels. NDL-PCBs in fish, other seafood and dairy, lead in grains and fruits, methylmercury in fish and other seafoods, and fluoride in water contributed most to the combined exposure. We identified uncertainties for the likelihood of co-exposure, assessment group membership, endpointspecific
reference values (ESRVs) based on epidemiological (lead, methylmercury, iAs, fluoride and NDL-PCBs) and animal data (PBDE), and exposure data. Those uncertainties lead to a complex pattern of under- and overestimations, which would require probabilistic modelling based on expert knowledge elicitation for integration of the identified uncertainties into an overall uncertainty estimate. In addition, the identified uncertainties could be used to refine future MRA for cognitive decline.
... However, some studies revealed a larger role of non-dietary exposure to PBDE, since ingestion and dermal contact of dust were the major pathways of exposure to PBDE in an American study, accounting for 56-77% of the total exposure in toddlers, children, adolescents and adults, whereas diet only accounted for 20-40% (Johnson-Restepro and Kannan, 2009). In another recent American biomonitoring study, PBDEs exposure was the greatest contributor to IQ loss, followed by lead, organo-phosphates and methyl mercury (Gaylord et al., 2020), while our results show that the contribution of PBDEs to the combined exposure was only limited. This is likely explained by our inability to capture non-dietary exposures to PBDEs in our study; exposure from all routes is accounted for in human biomonitoring studies. ...
... We selected the loss of 1 IQ point as a measure of cognitive deficits in the developing child, since this degree of cognitive decline at the population level can have an economic impact on societies (Gould, 2009;Grandjean et al., 2012;Bellanger et al., 2013;Trasande and Liu, 2011;Pichery et al., 2011;Gaylord et al., 2020). IQ tests usually consists of several subtests, each measuring a different aspect of cognitive development, such as memory, verbal and spatial reasoning, planning, learning and the comprehension and use of language. ...
... Even if the impact of exposure to such environmental contaminants has been decreasing thanks to increasing awareness and control of both industrial emissions and main sources of exposure [104], the estimated impact on healthcare expenditure remains considerable. MeHg is generated by anaerobic bacteria in water sediments and undergoes bioaccumulation and bioamplification in the food chain. ...
... The neurodevelopmental impact of these environmental contaminants has been evaluated based on estimated intellectual disability and IQ points loss due to prenatal exposure. For MeHg, the annual cost has been estimated to be 2.84 billion USD [104]. For PFOS and PFOA, the annual increase in health expenditure attributable to loss of IQ points associated with low birth weight was estimated to be 1.11 billion and 10.7 billion USD for PFOA and PFOS, respectively [105]. ...
Exposure to chemicals may pose a greater risk to vulnerable groups, including pregnant women, fetuses, and children, that may lead to diseases linked to the toxicants’ target organs. Among chemical contaminants, methylmercury (MeHg), present in aquatic food, is one of the most harmful to the developing nervous system depending on time and level of exposure. Moreover, certain man-made PFAS, such as PFOS and PFOA, used in commercial and industrial products including liquid repellants for paper, packaging, textile, leather, and carpets, are developmental neurotoxicants. There is vast knowledge about the detrimental neurotoxic effects induced by high levels of exposure to these chemicals. Less is known about the consequences that low-level exposures may have on neurodevelopment, although an increasing number of studies link neurotoxic chemical exposures to neurodevelopmental disorders. Still, the mechanisms of toxicity are not identified. Here we review in vitro mechanistic studies using neural stem cells (NSCs) from rodents and humans to dissect the cellular and molecular processes changed by exposure to environmentally relevant levels of MeHg or PFOS/PFOA. All studies show that even low concentrations dysregulate critical neurodevelopmental steps supporting the idea that neurotoxic chemicals may play a role in the onset of neurodevelopmental disorders.
... Current studies on the disease burden associated with PBDEs have mainly focused on neurotoxicity. Gaylord et al. reported that the economic costs of IQ loss and intellectual disability attributable to PBDEs were USD 4551.65 billion from 2001 to 2016 [25]. Another study conducted by the EU found that the economic costs of intellectual disability caused by PBDEs in 2010 were EUR 9.59 billion [8]. ...
... However, organophosphate esters (OPEs), bisphenol A (BPA), dichlorodiphenyltrichloroethane (DDT), and heavy metals have also been reported to account for a proportion of the disease burden, such as intellectual disability, childhood obesity, adult diabetes, and female uterine fibroids. For example, a study in the US found that OPE exposure caused economic losses of USD 593.67 billion between 2001 and 2016 [25]. In 2010, the economic costs of childhood obesity caused by BPA were USD 2.4 billion in the US [9] and EUR 1.54 billion in the EU [8]. ...
Increasing evidence indicates that endocrine-disrupting chemicals (EDCs) cause a variety of adverse health outcomes and contribute to substantial disease burden. This study summarized the exposure status of polybrominated diphenyl ethers (PBDEs) and phthalates (PAEs) in China and evaluated the disease burden attributable to PBDEs and PAEs in 2015. The results showed that PBDE and PAE concentrations were higher in coastal areas. The disease burden attributable to PBDEs was 0.77 million cases, and the economic costs were CNY 18.92 billion. Meanwhile, 3.02 million individuals suffered from diseases attributable to PAEs, and the economic costs were CNY 49.20 billion. The economic burden caused by PBDEs and PAEs accounted for 0.28% and 0.72% of China’s Gross Domestic Product (GDP) in 2015, respectively. When comparing China’s results from 2010, it was determined that the GDP ratio of economic costs caused by PAEs in 2015 (0.72%) was lower than in 2010 (1.42%). Finally, compared with the results of the European Union and North America, the GDP ratios of economic costs caused by PAEs in 2015 were 0.19% in Canada (lower than China), 0.29% in the United States (lower than China), and 1.44% in the European Union (higher than China). This study provides important reference values for China’s health governance, and further research should be conducted in the future.
... PBDE body burden in infants and toddlers is estimated to be three-to nine-fold higher than in adults due to exposure from maternal milk and household dust. In light of this, the most significant known impact of PBDE exposure is the effect on neuropsychological development of children (Drobná et al., 2019;Gaylord et al., 2020). Continuing widespread contamination of PBDEs was estimated have EU human health costs of around €10 billion 159 (primarily due to IQ loss/intellectual disability and cryptorchidism with the evidence for testicular cancer being relatively limited) (Trasande et al., 2016). ...
... PBDEs are one of the most significant chemical contributors to IQ loss and intellectual disability in children (Drobná et al., 2019;Gaylord et al., 2020;Herbstman et al., 2010). There is a growing body of evidence of PBDE associations with testicular cancer, cryptorchidism, maternal depression and thyroid homeostasis disruption (Chevrier et al., 2010;Vuong et al., 2018;Allen et al., 2016;Liu et al., 2017). ...
Persistent Organic Pollutants (POPs) are chemicals that are persistent, bio-accumulative, and toxic to humans and/or the environment. Consequently, their releases to the environment must be minimised and, where feasible eliminated as soon as possible. The main goal of this study is to support DG Environment in preparing an impact assessment accompanying a legislative proposal to amend Annexes IV and V of the POPs Regulation (Regulation (EU) No 2019/1021) which set concentration limits for POP substances in waste. The study provides an impact assessment of Annex IV Low POP Content Limit (LPCL) options for the following substances: polybrominated diphenyl ethers (PBDEs); short-chain chlorinated paraffins) (SCCPs); perfluorooctanoic acid (PFOA), its salts and PFOA-related compounds; perfluorohexane sulfonic acid (PFHxS), its salts and PFHxS-related compounds; polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs); polychlorinated biphenyls (PCBs) (differentiating between dioxin-like (dl) PCBs and non-dioxin like (ndl) PCBs); pentachlorophenol (PCP), its salts and esters; and hexabromocyclododecane (HBCDD).
... Compared to the general population, individuals with intellectual disabilities are more likely to face challenges in accessing equitable healthcare and experience premature mortality (16). A study conducted in the United States by Gaylord et al. (17) reported that the difference in cost attributed to intellectual disabilities (from 2001 to 2016) would continue to yield ongoing benefits of $38 billion. Therefore, it is essential for us to comprehend the epidemiological characteristics of this disease. ...
Objective
The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019.
Methods
Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software.
Results
In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030.
Conclusion
This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.
... We also know little about the effects of exposure to multiple pollutants. Most investigations have focused on only one type of toxicant class or medium of exposure (e.g., ozone from ambient air pollution); in actuality, however, individuals, especially those living in disadvantaged communities, are exposed to multiple contaminants from multiple sources simultaneously (28)(29)(30). Despite the fact that different pollutants (e.g., ozone, particulate matter, copper, manganese) have distinct physicochemical characteristics, epidemiologic and toxicologic studies indicate that they have common effects on brain structure and function [see (31,32) for reviews], underscoring the importance of examining the cumulative impact of pollutants on brain development. ...
Background
Exposure to environmental pollutants early in life has been associated with increased prevalence and severity of depression in adolescents; however, the neurobiological mechanisms underlying this association are not well understood. In the current longitudinal study, we investigated whether pollution burden in early adolescence (9–13 years) was associated with altered brain activation and connectivity during implicit emotion regulation and changes in depressive symptoms across adolescence.
Methods
One hundred forty-five participants (n = 87 female; 9–13 years) provided residential addresses, from which we determined their relative pollution burden at the census tract level, and performed an implicit affective regulation task in the scanner. Participants also completed questionnaires assessing depressive symptoms at 3 time points, each approximately 2 years apart, from which we calculated within-person slopes of depressive symptoms. We conducted whole-brain activation and connectivity analyses to examine whether pollution burden was associated with alterations in brain function during implicit emotion regulation of positively and negatively valenced stimuli and how these effects were related to slopes of depressive symptoms across adolescence.
Results
Greater pollution burden was associated with greater bilateral medial prefrontal cortex activation and stronger bilateral medial prefrontal cortex connectivity with regions within the default mode network (e.g., temporoparietal junction, posterior cingulate cortex, precuneus) during implicit regulation of negative emotions, which was associated with greater increases in depressive symptoms across adolescence in those exposed to higher pollution burden.
Conclusions
Adolescents living in communities characterized by greater pollution burden showed altered default mode network functioning during implicit regulation of negative emotions that was associated with increases in depressive symptoms across adolescence.
... These disorders have significant societal and economic impacts, including lost productivity and the need for lifelong care, which can amount to millions of dollars per case. Gaylord et al. (2020) analyzed National Health and Nutrition Examination Survey (NHANES) data from 2001-2016 to assess the neurodevelopmental disability burden and associated costs due to early life exposure to PBDEs, organophosphates, methylmercury, and lead in the USA. PBDE exposure in utero contributed the most to intellectual disability (ID) burden, resulting in 162 million IQ points lost and 738,000 ID cases, followed by lead, organophosphates, and methylmercury. ...
Developmental neurotoxicity (DNT) testing has seen enormous progress over the last two decades. Preceding even the publication of the animal-based OECD test guideline for DNT testing in 2007, a series of non-animal technology workshops and conferences (starting in 2005) shaped a community that has delivered a comprehensive battery of in vitro test methods (IVB). Its data interpretation is covered by a very recent OECD test guidance (No. 377). Here, we aim to overview the progress in the field, focusing on the evolution of testing strategies, the role of emerging technologies, and the impact of OECD test guidelines on DNT testing. In particular, this is an example of a targeted development of an animal-free testing approach for one of the most complex hazards of chemicals to human health. These developments started literally from a blank slate, with no proposed alternative methods available. Over two decades, cutting-edge science enabled the design of a testing approach that spares animals and enables throughput for this challenging hazard. While it is evident that the field needs guidance and regulation, the massive economic impact of decreased human cognitive capacity caused by chemical exposure should be prioritized more highly. Beyond this, the claim to fame of DNT in vitro testing is the enormous scientific progress it has brought for understanding the human brain, its development, and how it can be perturbed.
... Upstream disparities in exposures that are causally associated with ID may also contribute to disparities in rates of co-occurring ID in children with autism. Exposures that have been found to disproportionately affect underserved populations include lead poisoning and other environmental toxins (Carrington et al., 2019;Emerson et al., 2019;Gaylord et al., 2020;Grineski et al., 2022;Thompson et al., 2022) and pre-and perinatal complications (Bilder et al., 2013;Huang et al., 2016;Yeargin-Allsopp et al., 1995). These factors may also contribute to the higher prevalence of ID in NH Black children without autism Van Naarden Braun et al., 2015). ...
Intellectual disability (ID) commonly co‐occurs in children with autism. Although diagnostic criteria for ID require impairments in both cognitive and adaptive functioning, most population‐based estimates of the frequency of co‐occurring ID in children with autism—including studies of racial and ethnic disparities in co‐occurring autism and ID—base the definition of ID solely on cognitive scores. The goal of this analysis was to examine the effect of including both cognitive and adaptive behavior criteria on estimates of co‐occurring ID in a well‐characterized sample of 2‐ to 5‐year‐old children with autism. Participants included 3264 children with research or community diagnoses of autism enrolled in the population‐based Study to Explore Early Development (SEED) phases 1–3. Based only on Mullen Scales of Early Learning (MSEL) composite cognitive scores, 62.9% (95% confidence interval [CI]: 61.1, 64.7%) of children with autism were estimated to have co‐occurring ID. After incorporating Vineland Adaptive Behavior Scales, Second Edition (VABS‐II) composite or domains criteria, co‐occurring ID estimates were reduced to 38.0% (95% CI: 36.2, 39.8%) and 45.0% (95% CI: 43.1, 46.9%), respectively. The increased odds of meeting ID criteria observed for non‐Hispanic (NH) Black and Hispanic children relative to NH White children when only MSEL criteria were used were substantially reduced, though not eliminated, after incorporating VABS‐II criteria and adjusting for selected socioeconomic variables. This study provides evidence for the importance of considering adaptive behavior as well as socioeconomic disadvantage when describing racial and ethnic disparities in co‐occurring ID in epidemiologic studies of autism.
... The long-term application of PBDEs has resulted in their common presence throughout the environment which may constitute a potential threat to human health based on their toxicological properties. They interfere with the homeostasis of thyroid gland hormones, i.e. triiodothyronine (T 3 ) and thyroxine (T 4 ) [11][12][13], are neurotoxic [14][15][16][17][18] and cause negative reproductive health outcomes, among others [19,20]. Addition of PDBEs to fodder fed to laboratory animals, revealed oxidative stress-related damage to multiple organs [21][22][23], with the liver found to be the most affected [1]. ...
... In addition to the individual impacts, the economic impact is enormous. In fact, from 2001 to 2016, exposure to lead, mercury, PBDEs, and OPPs cost over $6 trillion in the US alone due to IQ point loss [153]. The results of this meta-analysis provide much needed insight into one of the influential factors in the sex bias of intellectual disabilities and highlight the possibility for early identification and prevention. ...
Background
Early life exposure to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with lowered IQ in children. In some studies, these neurotoxicants impact males and females differently. We aimed to examine the sex-specific effects of exposure to developmental neurotoxicants on intelligence (IQ) in a systematic review and meta-analysis.
Method
We screened abstracts published in PsychINFO and PubMed before December 31st, 2021, for empirical studies of six neurotoxicants (lead, mercury, PCBs, PBDEs, OPPs, and phthalates) that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or before age six; and (3) provided effect estimates on general, nonverbal, and/or verbal IQ by sex. We assessed each study for risk of bias and evaluated the certainty of the evidence using Navigation Guide. We performed separate random effect meta-analyses by sex and timing of exposure with subgroup analyses by neurotoxicant.
Results
Fifty-one studies were included in the systematic review and 20 in the meta-analysis. Prenatal exposure to developmental neurotoxicants was associated with decreased general and nonverbal IQ in males, especially for lead. No significant effects were found for verbal IQ, or postnatal lead exposure and general IQ. Due to the limited number of studies, we were unable to analyze postnatal effects of any of the other neurotoxicants.
Conclusion
During fetal development, males may be more vulnerable than females to general and nonverbal intellectual deficits from neurotoxic exposures, especially from lead. More research is needed to examine the nuanced sex-specific effects found for postnatal exposure to toxic chemicals.
... Nonetheless, PBDEs are also not chemically bound to polymers and can be easily released into the environment, which made them ubiquitous pollutants (De Wit, 2002). In addition, PBDEs have been related to several impacts on human health, such as immunotoxicity, alterations in neurological development, and endocrine disruption (Pietron et al., 2021;Zhang et al., 2014, Gaylord et al., 2020. The identification of these compounds within infant formulas serves as a notable risk factor, representing a potential source of exposure for infants and children. ...
Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI – 3.57 and 0.36 μg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84% detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53%. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.
... During the 1970s, the commercial Hg production was at its highest, and it has decreased ever since, along with their release in air (20%), water (30%), soil (30%), and landfills (20%) [5,49]. Toxic Release Inventory and U.S Environmental Protection Agency has reported two third of all mercury released in atmosphere in USA is generated from coal-based power plants [50]. ...
Owing to various industrial applications of mercury (Hg), its release into the environment at high concentration is becoming a great threat to living organisms on a global scale. Human exposure to Hg is greatly correlated with contamination in the food chain through cereal crops and sea foods. Since Hg is a non-essential component and does not possess a biological role and exhibits carcinogenic and genotoxic behaviour, biomonitoring with a focus on biomagnification of higher living animals and plants is the need of the hour. This review traces the plausible relationship between Hg concentration, chemical form, exposure, bioavailability, bioaccumulation, distribution, and ecotoxicology. The toxicity with molecular mechanisms, oxidative stress (OS), protein alteration, genomic change, and enzymatic disruptions are discussed. In addition, this review also elaborates advanced strategies for reducing Hg contamination such as algal and phytoremediation, biochar application, catalytical oxidation, and immobilization. Furthermore, there are challenges to overcome and future perspectives considering Hg concentrations, biomarkers, and identification through the nature of exposures are recommended.
... According to Dunnick et al. (2018) PBDE can induce transcriptomic changes and reduction of fertility in humans. Human health disorders like neurodevelopmental disability burden in the USA also strongly coincide with the introduction and use of PBDEs (Gaylord et al. 2020). PBDE residues have been detected in serum, breast milk, and adipose tissue from individuals (Meerts et al. 2002). ...
... Similarly, early childhood exposure to PCBs and pesticides in utero and infancy is associated with neurodevelopmental deficits [8]. In the U.S., OPFRs and PBDEs account for an estimated 200 million IQ points lost [9]. Long-term exposure to organic pollutants also carries a high societal cost and economic impacts. ...
... Concerningly, many of the damaging effects of chemical exposure are seen in children. Exposure to heavy metals has significant impacts with lead being linked to Attention Deficit Hyperactivity Disorder (ADHD) (Froehlich et al., 2009) and lead and methylmercury to loss of IQ points (Boyle et al., 2021;Gaylord et al., 2020). Other chemical exposures include those associated with the use of plastics including flame retardants (e.g. ...
This chapter presents a conceptual asset, Brain Capital, to inform novel policies. The concept builds on previous work, the Brain Capital Grand Strategy, that considers Brain Capital in all policies and offers a comprehensive investment plan and the development of an index or a dashboard. The premise, enablers, and barriers towards a Brain Capital Building Policy Agenda are outlined. Engagement with communities is proposed, and approaches for educating policymakers are described. Brain Capital building policies should be considered in sectors such as human development, migration, gender issues, social justice, multi-cultural affairs, economics, protections, and international relations. Novel approaches for public investment including brain bonds and social impact investing are considered.
... States approximately $50 billion in 2016 [1,2]. Despite calls from the Institute of Medicine to increase training for clinicians regarding environmental health since the 1990s, environmental health content is only being introduced slowly into the medical school curriculum [3]. ...
Context
Environmental exposures are associated with approximately 19% of disease globally, and exposure to neurotoxic chemicals is estimated to cost the United States $50 billion per year. Despite calls from the Institute of Medicine to increase training for clinicians regarding environmental health since the 1990s, there is still little instruction in environmental health for clinicians. This leaves gaps in knowledge that need to be bridged through outreach and education to practicing clinicians. Academic detailing (AD) is an educational intervention associated with improved prescribing practices in healthcare professionals but has not been applied to preventive or environmental health. Childhood lead exposure is a common condition associated with lifetime increased risk of cognitive and behavioral problems. Ohio has more than 2 million homes built before 1978, making exposure to lead-based paint a significant public health problem; however, only 50% of high-risk children are tested for lead. Few receive health promotion information regarding lead poisoning prevention, in part because this is not a part of training for healthcare providers (HCPs).
Objectives
The objectives of this study were twofold: (1) implement a pilot of AD sessions on the topic of childhood lead poisoning prevention with frontline HCPs and their staff in different practice settings; and (2) evaluate the acceptability of these training sessions utilizing quantitative and qualitative methods.
Methods
Physicians, nurses, social workers, community health workers, and clinical office staff were recruited from clinics who care for children at high risk for lead exposure. Trainings consisting of small group AD style sessions were presented at these sites. Learning objectives included increasing knowledge regarding lead testing requirements, enabling identification of lead’s impact on child development and equipping participants to provide anticipatory guidance for parents regarding lead poisoning prevention. Participants provided feedback through an anonymous questionnaire and qualitative feedback.
Results
There were 46 participants (12 physicians in practice/in training, 21 nursing or office staff, and 13 community health or social workers); more than 90% of the participants reported that the training achieved its learning objectives. Small-group presentations were preferred (91%); approximately 39% of participants requested an online format. Participants preferred that the presenters be either a public health or lead clinical expert, and they suggested that future activities include clinical vignettes.
Conclusions
Academic-detailing style training shows promise in promoting childhood lead poisoning prevention for frontline HCPs.
... Concerningly, many of the damaging effects of chemical exposure are seen in children. Exposure to heavy metals has significant impacts with lead being linked to Attention Deficit Hyperactivity Disorder (ADHD) (Froehlich et al., 2009) and lead and methylmercury to loss of IQ points (Boyle et al., 2021;Gaylord et al., 2020). Other chemical exposures include those associated with the use of plastics including flame retardants (e.g. ...
... Societal costs of toxic-element exposures are substantial (37)(38)(39). Table 1 briefly describes 2 types of studies: those that link diets or foods with biomarkers of toxic-element exposure in young children and those that investigate the associations between toxic elements in the postnatal period and their relations to children's health. It is important to clarify that studies on health effects are mostly based on biomarkers of exposure, which integrate across all sources, not only diet. ...
Concerns have been raised regarding toxic-element (arsenic, cadmium, lead, and mercury) contamination of commercially available infant foods around the world. Young children are vulnerable to the effects of toxic elements, based on higher absorption levels and potentially poorer detoxification capacities. Toxic-element exposures in early life exact high societal costs, but it is unclear how much dietary exposure to these elements contributes to adverse health outcomes. Well-designed epidemiological studies conducted in different geographical and socioeconomic contexts need to estimate dietary toxicant exposure in young children and to determine whether causal links exist between toxicants in children's diets and health outcomes. This commentary outlines the methodological considerations and data needs to advance such research.
... Due to continued widespread use, FRs are prevalent pollutants in the natural and human environment including house dust and food sources [1][2][3]. This is concerning because multiple FRs are thought to be neurotoxic and endocrine disrupting [4][5][6]. In response to these toxicological concerns, over the last 2 decades, the FR landscape has changed considerably with some phasing out and others phasing in. ...
Introduction:
Flame retardants (FRs) are common bodily and environmental pollutants, creating concern about their potential toxicity. We and others have found that the commercial mixture, FireMaster® 550 (FM 550) or its individual brominated (BFR) and organophosphate ester (OPFR) components are potential developmental neurotoxicants. Using Wistar rats, we previously reported developmental exposure to FM 550 or its component classes produced sex- and compound-specific effects on adult socioemotional behaviors. The underlying mechanisms driving the behavioral phenotypes are unknown.
Methods:
To further mechanistic understanding, here we conducted transcriptomics in parallel with a novel lipidomics approach using cortical tissues from newborn siblings of the rats in the published behavioral study. Inclusion of lipid composition is significant because it is rarely examined in developmental neurotoxicity studies. Pups were gestationally exposed via oral dosing to the dam to FM 550 or the BFR or OPFR components at environmentally relevant doses.
Results:
The neonatal cortex was highly sexually dimorphic in lipid and transcriptome composition, and males were more significantly impacted by FR exposure. Multiple adverse modes of action for the BFRs and OPFRs on neurodevelopment were identified, with the OPFRs more disruptive than the BFRs via multiple mechanisms including dysregulation of mitochondrial function and disruption of cholinergic and glutamatergic systems. Disrupted mitochondrial function by environmental factors has been linked to higher risk of autism spectrum disorders. Impacted lipid classes included the ceramides, sphingomyelins, and triacylglycerides. Robust ceramide upregulation in the OPFR females could suggest heightened risk of brain metabolic disease.
Conclusions:
This study reveals multiple mechanisms by which the components of a common FR mixture are developmentally neurotoxic and that the OPFRs may be the compounds of greatest concern.
... According to Dunnick et al. (2018) PBDE can induce transcriptomic changes and reduction of fertility in humans. Human health disorders like neurodevelopmental disability burden in the USA also strongly coincide with the introduction and use of PBDEs (Gaylord et al. 2020). PBDE residues have been detected in serum, breast milk, and adipose tissue from individuals (Meerts et al. 2002). ...
... The brain is probably the most sensitive of all organs during development. For instance, exposure to polybrominated diphenyl ethers is estimated to be responsible for a cumulative loss of 162 million intelligent quotient points in American children from 2001 to 2016 (Gaylord et al. 2020). This loss is higher than that of well-known neurotoxins such as lead, mercury and pesticides. ...
... Although it was recently shown that the degradation of spalt-like transcription factor 4 (SALL4) may be an essential component of TMD-induced teratogenicity that causes severe birth defects in the fetus [19,20], this mechanism is not enough to explain developmental neurotoxicity of TMD observed in in vitro and in vivo experiments. In addition, 2,2 ,4,4 -tetrabromodiphenyl ether (BDE-47), bisphenol A (BPA), and 4-hydroxy-2,2 ,3,4 ,5,5 ,6-heptachlorobiphenyl (4OH-PCB187) were also included in this study in comparison to TMD, since they show a high association with neuronal developmental disorders in epidemiologic studies and in animal and cellular experiments [21][22][23][24]. Grandjean and Landrigan suggested polybrominated diphenyl ethers (PBDEs) as one group of newly recognized developmental neurotoxicants including organophosphate pesticides, herbicides, fungicides and manganese. ...
20(S)-Protopanaxadiol (PPD) and 20(S)-Protopanaxatriol (PPT) are major metabolites of ginseng in humans and are considered to have estrogenic activity in cellular bioassays. In this study, we conducted in silico analyses to determine whether PPD and PPT interact with estrogen receptor alpha (ERα) and compared them with ERα agonists, partial agonists, and antagonists to identify their ERα activity. The transcriptome profile of 17β-estradiol (E2), PPD, and PPT in MCF-7 cells expressing ERα was further compared to understand the ERα activity of ginsenoside metabolites. The results showed that PPD and PPT interacted with the 1ERE, 1GWR, and 3UUD ERα proteins in the E2 interaction model, the 3ERD protein in the diethylstilbestrol (DES) interaction model, and the 1X7R protein in the genistein (GEN) interaction model. Conversely, neither the 4PP6 protein of the interaction model with the antagonist resveratrol (RES) nor the 1ERR protein of the interaction model with the antagonist raloxifene (RAL) showed the conformation of amino acid residues. When E2, PPD, and PPT were exposed to MCF-7 cells, cell proliferation and gene expression were observed. The transcriptomic profiles of E2, PPD, and PPT were compared using a knowledge-based pathway. PPD-induced transcription profiling was similar to that of E2, and the neural transmission pathway was detected in both compounds. In contrast, PPT-induced transcription profiling displayed characteristics of gene expression associated with systemic lupus erythematosus. These results suggest that ginsenoside metabolites have ERα agonist activity and exhibit neuroprotective effects and anti-inflammatory actions. However, a meta-analysis using public microarray data showed that the mother compounds GRb1 and GRg1 of PPD and PPT showed metabolic functions in insulin signaling pathways, condensed DNA repair and cell cycle pathways, and immune response and synaptogenesis. These results suggest that the ginsenoside metabolites have potent ERα agonist activity; however, their gene expression profiles may differ from those of E2.
... A 2-point drop, on an individual level, may not be noticed by the affected individual but is worrying since a 2-point shift in IQ level of a population will lead to less individuals with very high IQ and increase the number of individuals with very low IQ (Bellinger, 2007). A shift in population IQ can lead to increased intellectual disability and productivity loss, which brings high costs for the society (Bellanger et al., 2015;Gaylord et al., 2020). Considering the fact that almost all (91%) of the SELMA mothers that were included in this study had BPF levels above the LOD, and that this exposure is likely to increase due to BPA substitution, we consider our findings as alarming from a public health perspective. ...
Background
Experimental evidence demonstrates that exposure to bisphenol A (BPA), and the recently introduced alternatives bisphenol S (BPS) and bisphenol F (BPF) alter normal neurodevelopment. More research is needed to evaluate the associations between exposure to individual BPA alternatives and neurodevelopmental outcomes in humans.
Objective
The present study aimed at examining the individual associations between prenatal BPA, BPS and BPF exposure and cognitive outcomes in children at age 7 years.
Method
Women were enrolled in the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study, at gestational median week 10.0, and their children were examined for cognitive function at 7 years of age (N = 803). Maternal urinary BPA, BPS, and BPF concentrations were measured at enrollment and childreńs cognitive function at the age of 7 years was measured using the Wechsler Intelligence Scale for Children IV (WISC-IV).
Results
All three bisphenols were detected in over 90% of the women, where BPA had the highest geometric mean concentrations (1.55 ng/mL), followed by BPF (0.16 ng/mL) and BPS (0.07 ng/mL). Prenatal BPF exposure was associated with decreased full scale IQ (β = −1.96, 95%CI; −3.12; −0.80), as well as with a decrease in all four sub scales covering verbal comprehension, perceptual reasoning, working memory and processing speed. This association corresponded to a 1.6-point lower IQ score for an inter-quartile-range (IQR) change in prenatal BPF exposure (IQR = 0.054–0.350 ng/mL). In sex-stratified analyses, significant associations with full scale IQ were found for boys (β = −2.86, 95%CI; −4.54; −1.18), while the associations for girls did not reach significance (β = −1.38, 95%CI; −2.97; 0.22). No significant associations between BPA nor BPS and cognition were found.
Discussion
Prenatal exposure to BPF was significantly associated with childreńs cognitive function at 7 years. Since BPF is replacing BPA in numerous consumer products globally, this finding urgently call for further studies.
... Although it was recently shown that the degradation of spalt-like transcription factor 4 (SALL4) may be an essential component of TMD-induced teratogenicity that causes severe birth defects in the fetus [19,20], this mechanism is not enough to explain developmental neurotoxicity of TMD observed in in vitro and in vivo experiments. In addition, 2,2 ,4,4 -tetrabromodiphenyl ether (BDE-47), bisphenol A (BPA), and 4-hydroxy-2,2 ,3,4 ,5,5 ,6-heptachlorobiphenyl (4OH-PCB187) were also included in this study in comparison to TMD, since they show a high association with neuronal developmental disorders in epidemiologic studies and in animal and cellular experiments [21][22][23][24]. Grandjean and Landrigan suggested polybrominated diphenyl ethers (PBDEs) as one group of newly recognized developmental neurotoxicants including organophosphate pesticides, herbicides, fungicides and manganese. ...
Stress in early life has been linked with the development of late-life neurological disorders. Early developmental age is potentially sensitive to several environmental chemicals such as alcohol, drugs, food contaminants, or air pollutants. The recent advances using three-dimensional neural sphere cultures derived from pluripotent stem cells have provided insights into the etiology of neurological diseases and new therapeutic strategies for assessing chemical safety. In this study, we investigated the neurodevelopmental effects of exposure to thalidomide (TMD); 2,2′,4,4′-tetrabromodiphenyl ether; bisphenol A; and 4-hydroxy-2,2′,3,4′,5,5′,6-heptachlorobiphenyl using a human embryonic stem cell (hESC)-derived sphere model. We exposed each chemical to the spheres and conducted a combinational analysis of global gene expression profiling using microarray at the early stage and morphological examination of neural differentiation at the later stage to understand the molecular events underlying the development of hESC-derived spheres. Among the four chemicals, TMD exposure especially influenced the differentiation of spheres into neuronal cells. Transcriptomic analysis and functional annotation identified specific genes that are TMD-induced and associated with ERK and synaptic signaling pathways. Computational network analysis predicted that TMD induced the expression of DNA-binding protein inhibitor ID2, which plays an important role in neuronal development. These findings provide direct evidence that early transcriptomic changes during differentiation of hESCs upon exposure to TMD influence neuronal development in the later stages.
... It is not surprising that household levels of PBDEs have gone to the extent of reducing fertility in humans . Human health disorders like neurodevelopmental disability burden in the USA also strongly coincide with the introduction and use of PBDEs (Gaylord et al., 2020). The question, therefore, is whether the available insights on PBDEs are enough to protect human health from the residential emissions of PBDEs. ...
Polybrominated diphenyl ethers (PBDEs) serve as flame retardants in many household materials such as electrical and electronic devices, furniture, textiles, plastics, and baby products. Though the use of PBDEs like penta-, octa- and deca-BDE greatly reduces the fire damage, indoor pollution by these toxic emissions is ever-growing. In fact, a boom in the global market projections of PBDEs threatens human health security. Therefore, efforts are made to minimize PBDEs pollution in USA and Europe by encouraging voluntary phasing out of the production or imposing compelled regulations through Stockholm Convention, but >500 kilotons of PBDEs still exist globally. Both ‘environmental persistence’ and ‘bioaccumulation tendencies’ are the hallmarks of PBDE toxicities; however, both these issues concerning household emissions of PBDEs have been least addressed theoretically or practically. Critical physiological functions, lipophilicity and toxicity, trophic transfer and tissue specificities are of utmost importance in the benefit/risk assessments of PBDEs. Since indoor debromination of deca-BDE often yields many products, a better understanding on their sorption propensity, environmental fate and human toxicities is critical in taking rigorous measures on the ever-growing global deca-BDE market. The data available in the literature on human toxicities of PBDEs have been validated following meta-analysis. In this direction, the intent of the present review was to provide a critical evaluation of the key aspects like compositional patterns/isomer ratios of PBDEs implicated in bioaccumulation, indoor PBDE emissions versus human exposure, secured technologies to deal with the toxic emissions, and human toxicity of PBDEs in relation to the number of bromine atoms. Finally, an emphasis has been made on the knowledge gaps and future research directions related to endurable flame retardants which could fit well into the benefit/risk strategy.
Neurotoxicity is important to consider as a component of occupational and environmental safety and health programs. The failure to do so has contributed to a number of tragic cases in which people were irreparably harmed by exposure to compounds that proved toxic to the nervous system. The field of neurotoxicology originated in response to several episodes of mass poisoning and developed through advances in clinical practice, scientific research, and regulatory actions. This chapter reviews broadly the development of the field of neurotoxicity and discusses some of the predominant current issues. The chapter includes consideration of the features of the nervous system that make it susceptible to toxicity, the response to injury, the evaluation of sensory, cognitive, and motor functions, and effects on emotionality, mood, and social conduct. An emphasis is placed on functional outcomes that may be especially important in occupational and industrial hygiene settings. There is increasingly an emphasis on potential toxic effects on neurodevelopment and contributions to neurodegenerative diseases. Also, there is a large and growing effort to develop more rapid and cost‐efficient screening tests for potential neurotoxicity. A brief overview of some of the major classes of neurotoxic substances is provided including metals, solvents, pesticides, persistent organic compounds, and air pollution. Finally, the need for programs to prevent neurotoxic illness is discussed.
This study analysed settled dust samples in Sweden to assess children's combined exposure to 39 organohalogenated flame retardants (HFRs) and 11 organophosphate esters (OPEs) from homes and preschools. >94 % of the targeted compounds were present in dust, indicating widespread use of HFRs and OPEs in Swedish homes and preschools. Dust ingestion was the primary exposure pathway for most analytes, except BDE-209 and DBDPE, where dermal contact was predominant. Children's estimated intakes of ∑emerging HFRs and ∑legacy HFRs from homes were 1-4 times higher than from preschools, highlighting higher exposure risk for HFRs in homes compared to preschools. In a worst-case scenario, intakes of tris(2-butoxyethyl) phosphate (TBOEP) were 6 and 94 times lower than the reference dose for children in Sweden, indicating a potential concern if exposure from other routes like inhalation and diet is as high. The study also found significant positive correlations between dust concentrations of some PBDEs and emerging HFRs and the total number of foam mattresses and beds/m2, the number of foam-containing sofas/m2, and the number of TVs/m2 in the microenvironment, indicating these products as the main source of those compounds. Additionally, younger preschool building ages were found to be linked to higher ΣOPE concentrations in preschool dust, suggesting higher ΣOPE exposure. The comparison with earlier Swedish studies indicates decreasing dust concentrations for some banned and restricted legacy HFRs and OPEs but increasing trends for several emerging HFRs and several unrestricted OPEs. Therefore, the study concludes that emerging HFRs and OPEs are replacing legacy HFRs in products and building materials in homes and preschools, possibly leading to increased exposure of children.
The National Health and Nutrition Examination Survey (NHANES) has been continuously biomonitoring Americans’ exposure to two families of harmful environmental chemicals: polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). However, biomonitoring these chemicals is expensive. To save cost, in 2005, NHANES resorted to pooled biomonitoring; i.e., amalgamating individual specimens to form a pool and measuring chemical levels from pools. Despite being publicly available, these pooled data gain limited applications in health studies. Among the few studies using these data, racial/age disparities were detected, but there is no control for confounding effects. These disadvantages are due to the complexity of pooled measurements and a dearth of statistical tools. Herein, we developed a regression-based method to unzip pooled measurements, which facilitated a comprehensive assessment of disparities in exposure to these chemicals. We found increasing dependence of PCBs on age and income, whereas PBDEs were the highest among adolescents and seniors and were elevated among the low-income population. In addition, Hispanics had the lowest PCBs and PBDEs among all demographic groups after controlling for potential confounders. These findings can guide the development of population-specific interventions to promote environmental justice. Moreover, both chemical levels declined throughout the period, indicating the effectiveness of existing regulatory policies.
Methylmercury (MeHg) is a neurodevelopmental toxicant that is widespread in the environment and food. Considering the presence of multiple sources of MeHg exposure in the environment, the burden attributable to different exposure sources needs to be determined. This study aimed to estimate the burden of mild intellectual disability (MID) caused by in-utero exposure to MeHg and identify the attributable burden related to MeHg exposure from different sources in China. We applied the hair mercury concentrations from studies to evaluate the burden of MID associated with maternal MeHg exposure and quantify it by disability-adjusted life years (DALYs). The DALYs attributable to MeHg exposure sources were calculated by combining the total DALYs and the contribution rates of various sources of MeHg exposure. The maternal MeHg exposure resulted in 6504 MID cases and a loss of 63,354 DALYs in China in 2017. The contribution rates of aquatic products and rice were 52.2% and 27.1%, respectively, leading to health losses of 28,115 and 18,011 DALYs. The burden of MeHg-induced MID associated with aquatic products was high in coastal areas. Several sites such as Zhejiang, Hunan, and Guangxi had high DALYs caused by rice MeHg exposure. Regions with high DALYs of MID related to MeHg exposure require more attention. Local governments should establish targeted measures to reduce MeHg exposure, thus preventing health loss.
Polybrominated diphenyl ethers (PBDEs) are considered emerging organic contaminants that attract more attention in the environment. Herein, online coupling of solid-phase microextraction and ultrahigh-resolution mass spectrometry was developed for rapid screening of eight PBDEs in water samples. This procedure was completed in 22 min, about 6 times faster than the routine workflow such as solid-phase extraction coupled with gas chromatography-mass spectrometry. Thermal desorption and solvent-assisted atmospheric pressure chemical ionization were developed for the effective coupling of solid-phase microextraction (SPME) with ultrahigh-resolution mass spectrometry (UHRMS), which contributed to the signal enhancement and made the methodology feasible for environmental screening. The limits of detection and quantification were 0.01-0.50 ng/mL and 0.05-4.00 ng/mL, respectively. The recoveries were 57.2-75.2% for quality control samples at spiking levels of 0.8-10 ng/mL (4-50 ng/mL for BDE209), with relative standard deviation less than 19.0%. Twelve water samples from different river sites near industrial areas were screened using the developed method. The results showed that BDE-209 was the dominant PBDE (1.02-1.28 ng/mL in positive samples), but its amount was lower than the human health ambient water quality criteria. Consequently, the developed method provides a rapid and reliable way of evaluating contamination status and risks of PBDEs in aqueous environment.
Polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants with developmental neurotoxicity, the mechanism of which remains obscure. The present study aimed to evaluate cognitive deficits and microglia-originated neuroinflammation in the hippocampus of offspring rats exposed to BDE-209 (30 and 100 mg/kg) during perinatal period. Compared to the control, BDE-209-treated rats showed significant longer escape latency and less platform crossings in tests of Morris water maze. Besides obvious hippocampal neuron damage, increased microglial activation and pro-inflammatory markers (CD86, TNFα, and IL-1β), meanwhile, decreased anti-inflammatory molecules (CD206, IL-10, and Arg1) were induced by BDE-209. Furthermore, we investigated the neuroprotection of melatonin against BDE-209 and whether through sirtuin 1 (SIRT1). Consistent with restored SIRT1 activity, enhanced deacetylation of HMGB1 and inhibited cytoplasmic translocation of HMGB1, reduced expression of proteins involved in TLR4-NF-κB pathway and nuclear transfer of phosphorylated-NF-κB p65, and ultimately suppressed microglial activation and improved spatial memory were observed in 10 mg/kg melatonin-pretreated rats, compared with BDE-209-exposed alone. These results demonstrated that melatonin ameliorated BDE-209-caused cognitive impairment partially through shifting microglia polarization towards anti-inflammatory phenotype in a SIRT1-dependent manner, suggesting a potential mechanism for prevention.
Youth worldwide are regularly exposed to pollutants and chemicals (i.e., toxicants) that may interfere with healthy brain development, and a surge in MRI research has begun to characterize the neurobiological consequences of these exposures. Here, a systematic review following PRISMA guidelines was conducted on developmental MRI studies of toxicants with known or suspected neurobiological impact. Associations were reviewed for 9 toxicant classes, including metals, air pollution, and flame retardants. Of 1,264 identified studies, 46 met inclusion criteria. Qualitative synthesis revealed that most studies: (1) investigated air pollutants or metals, (2) assessed exposures prenatally, (3) assessed the brain in late middle childhood, (4) took place in North America or Western Europe, (5) drew samples from existing cohort studies, and (6) have been published since 2017. Given substantial heterogeneity in MRI measures, toxicant measures, and age groups assessed, more research is needed on all toxicants reviewed here. Future studies should also include larger samples, employ personal exposure monitoring, study independent samples in diverse world regions, and assess toxicant mixtures.
The food we eat becomes the basic building blocks of our biology. A poor diet creates poor-functioning cells, tissues, organs, and biological systems and leads to disease. A nutrient-rich whole foods diet does the opposite. Inflammation is a common denominator in most chronic diseases, and our modern-day lifestyle is primarily to blame. An overload of processed foods, sugar, starch, and exposure to toxic chemicals damages our mitochondria, overwhelms our detox organs, creates oxidative stress, hormonal and mood imbalances, cognitive decline, and so much more. Functional Medicine treats disease by removing what is causing damage and providing the body with what it needs to repair itself to regain proper functionality.
Fetal brain development depends on maternofetal thyroid function. In rodents and sheep, perinatal BPA exposure is associated with maternal and/or fetal thyroid disruption and alterations in central nervous system development as demonstrated by metabolic modulations in the encephala of mice. We hypothesized that a gestational exposure to a low dose of BPA affects maternofetal thyroid function and fetal brain development in a region-specific manner. Pregnant ewes, a relevant model for human thyroid and brain development, were exposed to BPA (5µg/kg bw/d, sc). The thyroid status of ewes during gestation and term fetuses at delivery was monitored. Fetal brain development was assessed by metabolic fingerprints at birth in 10 areas followed by metabolic network-based analysis. BPA treatment was associated with a significant time-dependent decrease in maternal TT4 serum concentrations. For 8 fetal brain regions, statistical models allowed discriminating BPA-treated from control lambs. Metabolic network computational analysis revealed that prenatal exposure to BPA modulated several metabolic pathways, in particular excitatory and inhibitory amino-acid, cholinergic, energy and lipid homeostasis pathways. These pathways might contribute to BPA-related neurobehavioral and cognitive disorders. Discrimination was particularly clear for the dorsal hippocampus, the cerebellar vermis, the dorsal hypothalamus, the caudate nucleus and the lateral part of the frontal cortex. Compared with previous results in rodents, the use of a larger animal model allowed to examine specific brain areas, and generate evidence of the distinct region-specific effects of fetal BPA exposure on the brain metabolome. These modifications occur concomitantly to subtle maternal thyroid function alteration. The functional link between such moderate thyroid changes and fetal brain metabolomic fingerprints remains to be determined as well as the potential implication of other modes of action triggered by BPA such as estrogenic ones. Our results pave the ways for new scientific strategies aiming at linking environmental endocrine disruption and altered neurodevelopment.
While heavy metals exposure is associated with intellectual disability (ID), little is known about associations between industrial pollution and ID. The objective of this analysis is to assess associations between estimated perinatal industrial pollution exposures from the US Environmental Protection Agency's Risk Screening Environmental Indicators Microdata and children's ID risk. We conducted a case-control study of children born in Utah from 2000 to 2008 (n = 1679). Cases were identified through the Center for Disease Control's Autism and Developmental Disabilities Monitoring Network's Utah site and matched with controls based on birth year, sex, and birth county. We used multivariable generalized estimating equations to examine associations between estimated perinatal industrial pollution exposures and ID risk. The fourth quartile of industrial pollution exposure was associated with increased odds of ID relative to the first (Odds Ratio [OR]: 1.73, 95% Confidence Interval [CI]: 1.23–2.44) and second (OR: 1.67, CI: 1.19–2.35) quartiles. Similarly, the third quartile was associated with increased odds of ID relative to the first (OR: 1.47, CI: 1.06–2.03) and second (OR: 1.41, CI: 1.02–1.96) quartiles. Findings were robust to varied model specifications. Maternal residential exposures to industrial pollution were associated with increased ID prevalence in Utah. Since environmental correlates of ID are understudied, additional research is needed.
As an important environmental pollutant, lead exposure can result in idiopathic developmental intellectual disability (IDII). However, the latest spatiotemporal patterns across the world are unclear. Therefore, in this study, the global burden of lead exposure-related IDII was assessed using the Global Burden of Disease (GBD) study (2019). The data were downloaded from the Institute for Health Metrics and Evaluation (IHME), and the estimated annual percentage change (EAPC) was calculated to assess the changing trend of the age-standardized disability-adjusted life-years (DALYs) rates (ASDR) of global IDII attributed to lead exposure. In 2019, the number of global DALYs of IDII attributed to lead exposure was 2.72 million, the corresponding ASDR was 35.70 per 100,000. The ASDR was highest in children and adolescents, and low- and middle-income countries. From 1990 to 2019, the global number of DALYs of IDII attributable to lead exposure increased by 7.89%, while the ASDR of IDII decreased by 19.19% [EAPC = −0.78, 95% confidence interval (CI): (−0.90, −0.66)]. The downward trends were seen in most GBD regions and countries, especially in high-income countries, but 11 countries presented an upward trend. Therefore, it is important to continue to improve primary mental healthcare globally, especially in low- and middle-income countries. Meanwhile, the implementation of effective strategies to reduce lead exposure should be continually strengthened.
This opinion focuses on basic considerations of environmental monitoring with surface plasmon resonance imaging (SPRi) and nanomaterials. Theoretical aspects of non-covalent interactions of nanomaterials as receptor surfaces are discussed to develop cross-reactivity sensors. It is pointed out that continuous, online, and long-term water monitoring will be best suited by a combination of different nanomaterial functionalized receptor spots that are capable of interacting with non-covalent interactions such as electrostatic interactions, π-stacking, or hydrophobic effects. Only a smart combination of those nanomaterials will be able to reach the desired selectivity for a comprehensive overview of water quality. Additionally, improvements in the sensor's sensitivity by nanomaterials are discussed, which can be achieved by using a nanostructured gold surface or plasmonic materials.
While theories of ‘American Empire’ are discussed across disciplines, little attention has been paid to how subjects of this empire are socially produced through the highly intimate process of raising children. There has been little examination of parenting as a performance of in/security. This chapter contends that examining the securitization of parenting practices is essential if we wish to better understand childhood and parenting in an age of American Empire. The chapter argues that a particular kind of subject—the children of empire—is produced through an assemblage of neoliberalism, biopolitics, militarism and play and is visible in parenting practices oriented around expert knowledge of risk and protection, the normalization of regimes of surveillance and sorting, and the cultivation of playful militarism that blurs the lines between violence and fun.
Background: Pollution – unwanted waste released to air, water, and land by human activity – is the largest environmental cause of disease in the world today. It is responsible for an estimated nine million premature deaths per year, enormous economic losses, erosion of human capital, and degradation of ecosystems. Ocean pollution is an important, but insufficiently recognized and inadequately controlled component of global pollution. It poses serious threats to human health and well-being. The nature and magnitude of these impacts are only beginning to be understood. Goals: (1) Broadly examine the known and potential impacts of ocean pollution on human health. (2) Inform policy makers, government leaders, international organizations, civil society, and the global public of these threats. (3) Propose priorities for interventions to control and prevent pollution of the seas and safeguard human health.
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.
Conclusions: Ocean pollution is a global problem. It arises from multiple sources and crosses national boundaries. It is the consequence of reckless, shortsighted, and unsustainable exploitation of the earth’s resources. It endangers marine ecosystems. It impedes the production of atmospheric oxygen. Its threats to human health are great and growing, but still incompletely understood. Its economic costs are only beginning to be counted. Ocean pollution can be prevented. Like all forms of pollution, ocean pollution can be controlled by deploying data-driven strategies based on law, policy, technology, and enforcement that target priority pollution sources. Many countries have used these tools to control air and water pollution and are now applying them to ocean pollution. Successes achieved to date demonstrate that broader control is feasible. Heavily polluted harbors have been cleaned, estuaries rejuvenated, and coral reefs restored. Prevention of ocean pollution creates many benefits. It boosts economies, increases tourism, helps restore fisheries, and improves human health and well-being. It advances the Sustainable Development Goals (SDG). These benefits will last for centuries.
Recommendations: World leaders who recognize the gravity of ocean pollution, acknowledge its growing dangers, engage civil society and the global public, and take bold, evidence-based action to stop pollution at source will be critical to preventing ocean pollution and safeguarding human health. Prevention of pollution from land-based sources is key. Eliminating coal combustion and banning all uses of mercury will reduce mercury pollution. Bans on single-use plastic and better management of plastic waste reduce plastic pollution. Bans on persistent organic pollutants (POPs) have reduced pollution by PCBs and DDT. Control of industrial discharges, treatment of sewage, and reduced applications of fertilizers have mitigated coastal pollution and are reducing frequency of HABs. National, regional and international marine pollution control programs that are adequately funded and backed by strong enforcement have been shown to be effective. Robust monitoring is essential to track progress. Further interventions that hold great promise include wide-scale transition to renewable fuels; transition to a circular economy that creates little waste and focuses on equity rather than on endless growth; embracing the principles of green chemistry; and building scientific capacity in all countries. Designation of Marine Protected Areas (MPAs) will safeguard critical ecosystems, protect vulnerable fish stocks, and enhance human health and well-being. Creation of MPAs is an important manifestation of national and international commitment to protecting the health of the seas.
Firemaster 550 (FM550) is a flame retardant (FR) mixture that has become one of the most commonly used FRs in household items such as foam-based furniture and baby products. Because this mixture readily leaches from products, contamination of the environment and human tissues is widespread. Prior work by us and others has reported sex-specific behavioral deficits in rodents and zebrafish following early life exposure. In an effort to understand the mechanisms by which these behavioral effects occur, here we explored the effects of its constituents on behavioral outcomes previously shown to be altered by developmental FM550 exposure. The FM550 commercial mixture is composed of two brominated compounds (BFR) and two organophosphate compounds (OPFRs) at almost equivalent proportions. Both the BFR and the OPFR components are differentially metabolized and structurally distinct, but similar to known neurotoxicants. Here we examined adult Wistar rat offspring socioemotional behaviors following perinatal exposure (oral, to the Dam) to vehicle, 2000 μg/day FM550, 1000 μg/day BFR or 1000 μg/day OPFR from gestation day 0 to weaning. Beginning on postnatal day 65 offspring from all groups were subjected to a series of behavioral tasks including open field, elevated plus maze, marble burying, social interaction tests, and running wheel. Effects were exposure-, sex- and task-specific, with BFR exposure resulting in the most consistent behavioral deficits. Overall, exposed females showed more deficits compared to males across all dose groups and tasks. These findings help elucidate how different classes of flame retardants, independently and as a mixture, contribute to sex-specific behavioral effects of exposure.
For over three-quarters of a century, organophosphorus (OP) insecticides have been ubiquitously used in agricultural, residential, and commercial settings and in public health programs to mitigate insect borne diseases. Their broad-spectrum insecticidal effectiveness is accounted for by the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that catalyzes acetylcholine (ACh) hydrolysis, in the nervous system of insects. However, because AChE is evolutionarily conserved, OP insecticides are also toxic to mammals, including humans, and acute OP intoxication remains a major public health concern in countries where OP insecticide usage is poorly regulated. Environmental exposures to OP levels that are generally too low to cause marked inhibition of AChE and to trigger acute signs of intoxication, on the other hand, represent an insidious public health issue worldwide. Gestational exposures to OP insecticides are particularly concerning because of the exquisite sensitivity of the developing brain to these insecticides. The present article overviews and discusses: (i) the health effects and therapeutic management of acute OP poisoning during pregnancy, (ii) epidemiological studies examining associations between environmental OP exposures during gestation and health outcomes of offspring, (iii) preclinical evidence that OP insecticides are developmental neurotoxicants, and (iv) potential mechanisms underlying the developmental neurotoxicity of OP insecticides. Understanding how gestational exposures to different levels of OP insecticides affect pregnancy and childhood development is critical to guiding implementation of preventive measures and direct research aimed at identifying effective therapeutic interventions that can limit the negative impact of these exposures on public health.
The relative toxicity of three legacy and six emerging brominated flame retardants* was studied in the male Harlan Sprague Dawley rat. The hepatocellular and thyroid toxicity of each flame retardant was evaluated following five-day exposure to each of the nine flame retardants (oral gavage in corn oil) at 0.1 – 1000 μmol/kg body weight per day. Histopathology and transcriptomic analysis were performed on the left liver lobe. Centrilobular hypertrophy of hepatocytes and increases in liver weight were seen following exposure to two legacy (PBDE-47, HBCD) and to one emerging flame retardant (HCDBCO). Total thyroxine (TT4) concentrations were reduced to the greatest extent after PBDE-47 exposure. The PBDE-47, decaBDE, or HBCD liver transcriptome was characterized by upregulation of liver disease-related and/or metabolic transcripts. Fewer liver disease or metabolic transcript changes were detected for the other flame retardants studied (TBB, TBPH, TBBPA-DBPE, BTBPE, DBDPE, or HCDBCO). PBDE-47 exhibited the most disruption of hepatocellular toxic endpoints, with the Nrf2 antioxidant pathway transcripts upregulated to the greatest extent, although some activation of this pathway also occurred after decaBDE, HBCD, TBB, and HCBCO exposure. These studies provide information that can be used for prioritizing the need for more in-depth brominated flame retardant toxicity studies.
*three legacy brominated flame retardants: polybrominated diphenyl ether 47 (PBDE 47), decabromodiphenyl ether (decaBDE), and hexabromocyclododecane (HBCD); **six “emerging” brominated flame retardants: 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), tetrabromobisphenol A-bis(2,3-dibromopropyl ether (TBBPA-DBPE), 1,2-bis(tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO).
Pyrethroids are potent neurotoxicants that may elicit multiple pathways of toxicity in non-target organisms. Comparative studies on the mechanistic and developmental effects of types I and II pyrethroids against non-target aquatic species are limited. This study assessed the effects of the two pyrethroid types against embryo-larval zebrafish (Danio rerio) at environmentally relevant and laboratory concentrations. Zebrafish embryos were exposed to type-I (permethrin, bifenthrin) and type-II (deltamethrin, λ-cyhalothrin, fenvalerate, esfenvalerate) pyrethroids at 1000, 10, 0.1, 0.01, 0.0 μg/L, starting at 5-h post-fertilization (hpf) through 5-d post-fertilization (dpf) under static exposure conditions. Swimming behavior (distance traveled and velocity) was assessed at 5-dpf. The relative expression of Nrf2a, GST, Casp-9 and p53 mRNA transcripts, carboxyl esterase (CES) activity and total reactive oxygen species (ROS) were measured. The stability of the pyrethroids across 5 days was analyzed. Bifenthrin-(10 μg/L) and esfenvalerate-(1000 μg/L) significantly (p < 0.05) reduced total distance traveled by larvae while 1000 μg/L deltamethrin and λ-cyhalothrin were lethal causing body axis curvature and pericardial edema. At environmentally relevant concentrations-(μg/L) compared to control, permethrin-(0.122) upregulated Nrf2a and Casp-9 expressions while λ-cyhalothrin-(0.053) downregulated Nrf2a and fenvalerate-0.037 downregulated GST. At laboratory concentrations-(μg/L), permethrin-(1000) upregulated Nrf2a, Casp-9 and p53 expressions, bifenthrin-(10) upregulated Casp-9 while fenvalerate-(0.1) and esfenvalerate-(1000) downregulated GST. There was concentration dependent increase in CES activity which correlated positively with total ROS. Pyrethroid concentrations decreased significantly by day 5. This study showed disparity in the mechanistic effects across the pyrethroids types and their instability in aqueous media may underestimate toxicity against non-target aquatic species when exposed in their natural environment.
Thyroid hormones are crucial in normal brain development. Transient and mild thyroid hormone insufficiency in pregnancy is also associated with impaired neurodevelopment in the offspring (e.g., 3–4 IQ score loss in association with maternal free thyroxine in the lowest fifth percentile). While inadequate iodine intake remains the most common underlying cause of mild thyroid hormone insufficiency in vulnerable populations including pregnant women, other factors such as exposure to environmental contaminants have recently attracted increasing attention, in particular in interaction with iodine deficiency. Endocrine-disrupting chemicals (EDCs) are natural and synthetic substances with ubiquitous exposure in children and adults including pregnant women. EDCs interfere, temporarily or permanently, with hormonal signaling pathways in the endocrine system by binding to hormone receptors and modifying gene expression. Other mechanisms involve alterations in production, metabolism, and transfer of hormones. Experimental studies have shown that exposures to EDCs affect various brain processes such as neurogenesis, neural differentiation and migration, as well as neural connectivity. Neuroimaging studies confirm brain morphological abnormalities (e.g., cortical thinning) consistent with neurodevelopmental impairments as a result of EDC exposures at standard use levels. In this review, we provide an overview of present findings from toxicological and human studies on the anti-thyroid effect of EDCs with a specific attention to fetal and early childhood exposure. This brief overview highlights the need for additional multidisciplinary studies with a focus on thyroid disruption as an underlying mechanism for developmental neurotoxicity of EDC, which can provide insight into modifiable risk factors of developmental delays in children.
Polybrominated diphenyl ethers (PBDEs) were used extensively as flame retardants in furniture containing polyurethane foam until they were phased out of use, beginning in 2004. We examined temporal changes in plasma PBDE concentrations from 1998 to 2013 and characterized patterns of exposure over the early lifecourse among 334 children (903 samples) between birth and 9 years. We examined time trends by regressing PBDE concentration on year of sample collection in age-adjusted models and characterized developmental trajectories using latent class growth analysis (LCGA). Controlling for age, BDE-47 concentrations decreased 5% (95% confidence interval (CI): −9, −2) per year between 1998 and 2013. When considering only postnatal samples, this reduction strengthened to 13% (95% CI: −19, −9). Findings for BDE-99, 100 and 153 were similar, except that BDE-153 decreased to a lesser extent when both prenatal and postnatal samples were considered (−2%, 95% CI: −7, 0). These findings suggest that, on average, pentaBDE body burdens have decreased since the 2004 phase-out of these chemicals. When examining developmental period, PBDE concentrations peaked during toddler years for the majority of children, however, our observation of several unique trajectories suggests that a single measure may not accurately reflect exposure to PBDEs throughout early life.
Firemaster 550 (FM 550) is a flame retardant (FR) mixture that has become one of the most commonly used FRs in foam-based furniture and baby products. Human exposure to this commercial mixture, comprised of brominated and organophosphate components, is widespread. We have repeatedly shown that developmental exposure can lead to sex-specific behavioral effects in rats. Accruing evidence of endocrine disruption and potential neurotoxicity have raised concerns regarding the neurodevelopmental effects of FM 550 exposure, but the specific mechanisms of action remains unclear. Additionally, we observed significant, and in some cases sex-specific, accumulation of FM 550 in placental tissue following gestational exposure. Because the placenta is an important source of hormones and neurotransmitters for the developing brain, it may be a critical target of toxicity to consider in the context of developmental neurotoxicity. Using a mixture of targeted and exploratory approaches, the goal of the present study was to identify possible mechanisms of action in the developing forebrain and placenta. Wistar rat dams were orally exposed to FM 550 (0, 300, or 1,000 µg/day;) for 10 days during gestation and placenta and fetal forebrain tissue collected for analysis. In placenta, evidence of endocrine, inflammatory, and neurotransmitter signaling pathway disruption was identified. Notably, 5-HT turnover was reduced in placental tissue and fetal forebrains indicating that 5-HT signaling between the placenta and the embryonic brain may be disrupted. These findings demonstrate that environmental contaminants, like FM 550, have the potential to impact the developing brain by disrupting normal placental functions.
Strong evidence now supports the notion that organophosphate pesticides damage the fetal brain and produce cognitive and behavioral dysfunction through multiple mechanisms, including thyroid disruption. A regulatory ban was proposed, but actions to end the use of one such pesticide, chlorpyrifos, in agriculture were recently stopped by the Environmental Protection Agency under false scientific pretenses. This manuscript describes the costs and consequences of this policy failure and notes how this case study is emblematic of a broader dismissal of scientific evidence and attacks on scientific norms. Scientists have a responsibility to rebut and decry these serious challenges to human health and scientific integrity.
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.
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 (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 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 (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.
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.
Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.
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 tat-gets 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.
Significance
Anthropogenic mercury poses risks to humans and ecosystems when converted to methylmercury. A longstanding conundrum has been the apparent disconnect between increasing global emissions trends and measured declines in atmospheric mercury in North America and Europe. This work shows that locally deposited mercury close to coal-fired utilities has declined more rapidly than previously anticipated because of shifts in speciation from air pollution control technology targeted at SO 2 and NO x . Reduced emissions from utilities over the past two decades and the phase-out of mercury in many commercial products has led to lower global anthropogenic emissions and associated deposition to ecosystems. This implies that prior policy assessments underestimated the regional benefits of declines in mercury emissions from coal-fired utilities.
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.
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.
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.
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
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.
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.
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.
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.
A 2002 analysis documented 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.
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.
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.
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.
This study is a cost-benefit analysis that quantifies the social and economic benefits to household lead paint hazard control compared with the investments needed to minimize exposure to these hazards.
This research updates estimates of elevated blood lead levels among a cohort of children < or = 6 years of age and compiles recent research to determine a range of the costs of lead paint hazard control (11 billion) and the benefits of reduction attributed to each cohort for health care (53 billion), lifetime earnings (233 billion), tax revenue (35 billion), special education (146 million), attention deficit-hyperactivity disorder (1.7 billion).
Each dollar invested in lead paint hazard control results in a return of 221 or a net savings of $181-269 billion.
There are substantial returns to investing in lead hazard control, particularly targeted at early intervention in communities most likely at risk. Given the high societal costs of inaction, lead hazard control appears to be well worth the price.
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 110 billion to $319 billion.
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.
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.
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.
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.
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.