A lifestage approach to assessing children's exposure

Understanding and characterizing risks to children has been the focus of considerable research efforts at the U.S. Environmental Protection Agency (EPA). Potential health risks resulting from environmental exposures before conception and during pre‐ and postnatal development are often difficult to recognize and assess because of a potential time lag between the relevant periods of exposure during development and associated outcomes that may be expressed at later lifestages. Recognizing this challenge, a lifestage approach for assessing exposure and risk is presented in the recent EPA report titled A Framework for Assessing Health Risks of Environmental Exposures to Children (U.S. EPA, 2006 ). This EPA report emphasizes the need to account for the potential exposures to environmental agents during all stages of development, and consideration of the relevant adverse health outcomes that may occur as a result of such exposures. It identifies lifestage‐specific issues associated with exposure characterization for regulatory risk assessment, summarizes the lifestage‐specific approach to exposure characterization presented in the Framework, and discusses emerging research needs for exposure characterization in the larger public‐health context. This lifestage approach for characterizing children's exposures to environmental contaminants ensures a more complete evaluation of the potential for vulnerability and exposure of sensitive populations throughout the life cycle. Birth Defects Res (Part B) 2008. © 2008 Wiley‐Liss, Inc.     

Estimation of Multimedia Inorganic Arsenic Intake in the U.S. Population

Arsenic is widely distributed in the environment by natural and human means. The potential for adverse health effects from inorganic arsenic depends on the level and route of exposure. To estimate potential health risks of inorganic arsenic, the apportionment of exposure among sources of inorganic arsenic is critical. In this study, daily inorganic arsenic intake of U.S. adults from food, water, and soil ingestion and from airborne particle inhalation was estimated. To account for variations in exposure across the U.S., a Monte Carlo approach was taken using simulations for 100,000 individuals representing the age, gender, and county of residence of the U.S. population based on census data. Our analysis found that food is the greatest source of inorganic arsenic intake and that drinking water is the next highest contributor. Inhalation of airborne arsenic-containing particles and ingestion of arsenic-containing soils were negligible contributors. The exposure is best represented by the ranges of inorganic arsenic intake (at the 10^th and 90^th percentiles), which were 1.8 to 11.4 µg/day for males and 1.3 to 9.4 µg/day for females. Regional differences in inorganic arsenic exposure were due mostly to consumption of drinking water containing differing inorganic arsenic content rather than to food preferences.     

A Probabilistic Assessment of Household Exposures to MTBE from Drinking Water

The oxygenate methyl tertiary butyl ether (MTBE) has been added to reformulated gasoline in the U.S. to meet national ambient air quality standards. Although MTBE has provided significant health benefits in terms of reduced criteria and toxic air pollutants, detections of MTBE in some groundwater and drinking water sources have raised concerns about potential environmental contamination and human exposures. In this paper, we examine the frequency and concentration of MTBE detections in drinking water sources in California from 1995 to 1999, and provide a preliminary analysis of the distribution of household exposures to MTBE from water-related activities. Using published data on the toxicity and possible cancer hazard posed by MTBE, we estimate the likely cancer and non-cancer risks for the general population in California from past and potential future MTBE exposures. More highly exposed subgroups were also addressed. Our findings indicate that less than 2% of all sampled drinking water sources in California had detectable levels of MTBE in 1999, with average MTBE drinking water concentrations ranging from 0.09 to 4.9?ppb for this year. Both the detection rate for MTBE and average MTBE concentrations have remained relatively stable since 1995, despite increased sampling of drinking water sources in California. The probabilistic exposure analysis suggests that drinking water exposures to MTBE are unlikely to pose a significant health risk for the general population or more highly exposed individuals in California.     

Trends in childhood leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing.

OBJECTIVE--To obtain further information about the risks of childhood leukaemia after exposure to ionising radiation at low doses and low dose rates before or after birth or to the father''s testes shortly before conception. DESIGN--Observational study of trends in incidence of childhood leukaemia in relation to estimated radiation exposures due to fallout from atmospheric nuclear weapons testing during the 1950s and 1960s. SETTING--Nordic countries. SUBJECTS--Children aged under 15 years. MAIN OUTCOME MEASURES--Incidence rates of leukaemia by age at diagnosis, sex, country, and calendar year of diagnosis or year of birth; exposure category; relation between leukaemia and exposure for children aged 0-14 and 0-4 separately. RESULTS--During the high fallout period the average estimated dose equivalent to the fetal red bone marrow was around 140 mu Sv and the average annual testicular dose 140 mu Sv. There was little evidence of increased incidence of leukaemia among children born in these years. Doses to the red bone marrow of a child after birth were higher, and during the high exposure period children would have been subjected to an additional dose equivalent of around 1500 mu Sv, similar to doses received by children in several parts of central and eastern Europe owing to the Chernobyl accident and about 50% greater than the annual dose equivalent to the red bone marrow of a child from natural radiation. leukaemia incidence and red marrow dose was not related overall, but rates of leukaemia in the high exposure period were slightly higher than in the surrounding medium exposure period (relative risk for ages 0-14: 1.07, 95% confidence interval 1.00 to 1.14; for ages 0-4: 1.11, 1.00 to 1.24). CONCLUSIONS--Current predicted risks of childhood leukaemia after exposure to radiation are not greatly underestimated for low dose rate exposures.     

Comparing Occupational and Environmental Risk Assessment Methodologies Using Pharmacokinetic Modeling

Human health risks from occupational exposures are managed by limiting exposures to acceptable levels established by the American Conference of Governmental Industrial Hygienists or another similar body. Acceptable environmental exposures are benchmarked by values such as U.S. Environmental Protection Agency's Reference Doses and Reference Concentrations. The approaches to establishing these values are different, as are the groups they are intended to protect, complicating direct comparisons. Occupational limits are based on a healthy workforce in a narrow age range and do not generally consider sensitive populations. Limits for environmental exposures consider sensitive populations. In this evaluation, physiologically based pharmacokinetic modeling was used to predict tissue doses from acceptable/safe exposures as established by different organizations and agencies. Internal doses calculated for an agency's acceptable/safe exposures via oral and inhalation routes may differ substantially, but are sometimes in excellent agreement. The finding that internal doses resulting from occupational exposures are almost uniformly greater than those from environmental exposures suggests different mindsets among these groups regarding how safe is “safe.”     

Distinguishing potential sources of genotoxic exposure via HPRT mutations

We utilize T-cell HPRT mutations to monitor exposure to environmental mutagens in siblings of children who have developed cancer at a persistently high rate in Toms River, New Jersey, U.S.A. A preliminary epidemiological study has found a statistically-significant association between drinking public water (by pregnant mother or infant) and subsequent risk for childhood cancer. Three potential sources of mutagenic exposures in Toms River may have increased the rate of carcinogenic initiation significantly in children: 1. Benzidine-based, other azo dye and anthraquinone dye wastes released by Ciba-Geigy, 2. Styrene-acrylonitrile (SAN) trimer and other plastic wastes of Union Carbide, and 3. Radium-224, present in unusually high concentrations in the Cohansey aquifer. Specific patterns of HPRT mutations are utilized to distinguish these various potential sources of carcinogenic exposures in the drinking water of families with childhood cancer and to differentiate chemically or radiologically induced cancers from those which occur spontaneously.     

Are There Health Risks from the Migration of Chemical Substances from Plastic Pipes into Drinking Water? A Review

Plastic pipes used to convey hot and cold drinking water are synthetic polymers containing numerous additives that enhance durability, impact strength, and toughness, and resist material degradation. Although some research studies have been conducted to evaluate the type and levels of chemical substances migrating from polymeric materials into drinking water, the potential adverse health effects associated with these compounds in potable water have not been described. This review evaluates the literature on the occurrence of regulated and unregulated substances in drinking water related to the use of plastic pipes, characterizes potential health hazards, and describes uncertainties associated with human health and exposure in need of further research. Of particular public health concern is the potential for sensitive populations to be exposed to short-term elevations in leachates during critical periods, and for co-occurring leachates targeting the same organ(s) and/or sharing a common mode of toxic action to have additive or synergistic effects. Contaminants are measured in the distribution system, not at the tap where human exposure actually occurs. For increased health protection, it is important to identify compounds that migrate from plastic pipes into drinking water and to better quantify human exposures and health hazards to these substances and their degradates.     

Methyl Ethyl Ketone Safety Characterization for Infants and Children: Assessment in the USEPA Voluntary Children's Chemical Evaluation Program

A safety characterization specific to children was performed for methyl ethyl ketone (MEK) according to the guidelines of the Voluntary Children's Chemical Evaluation Program (VCCEP). The characterization indicates that MEK exposures are not expected to pose an acute or chronic risk to children. Hazard information, summarized as per the VCCEP Tier structure, indicated no need for additional studies. All exposure pathways potentially relevant to children were considered, including child contact with environmental media, food, drinking water, parental transfer to child (human milk or dermal contact), direct consumer product use, and presence during product use. The assessment found that exposures from anthropogenic sources that children may encounter on a daily basis are very low, and in particular well below the chronic inhalation and oral health benchmarks (RfC and RfD) derived by the U.S. Environmental Protection Agency (USEPA). Indoor uses of consumer products can result in higher acute exposures, but these are short-lived and also fall below chronic benchmarks adjusted to an acute timeframe. In addition, MEK is rapidly metabolized and excreted, thus acute exposures do not lead to an increase in body burden over time. The USEPA concluded the VCCEP submission sufficiently characterized potential risks to children, and that no additional toxicity tests were needed for MEK.     

Radiation effects on breast cancer risk: a pooled analysis of eight cohorts

Breast cancer incidence rates after radiation exposure in eight large cohorts are described and compared. The nature of the exposures varies appreciably, ranging from a single or a small number of high-dose-rate exposures (Japanese atomic bomb survivors, U.S. acute post-partum mastitis patients, Swedish benign breast disease patients, and U.S. infants with thymic enlargement) to highly fractionated high-dose-rate exposures (two U.S. tuberculosis cohorts) and protracted low-dose-rate exposure (two Swedish skin hemangioma cohorts). There were 1,502 breast cancers among 77,527 women (about 35,000 of whom were exposed) with 1.8 million woman-years of follow-up. The excess risk depends linearly on dose with a downturn at high doses. No simple unified summary model adequately describes the excess risks in all groups. Excess risks for the thymus, tuberculosis, and atomic bomb survivor cohorts have similar temporal patterns, depending on attained age for relative risk models and on both attained age and age at exposure for excess rate models. Excess rates were similar in these cohorts, whereas, related in part to the low breast cancer background rates for Japanese women, the excess relative risk per unit dose in the bomb survivors was four times that in the tuberculosis or thymus cohorts. Excess rates were higher for the mastitis and benign breast disease cohorts. The hemangioma cohorts showed lower excess risks suggesting ameliorating dose-rate effects for protracted low-dose-rate exposures. For comparable ages at exposure (approximately 0.5 years), the excess risk in the hemangioma cohorts was about one-seventh that in the thymus cohort, whose members received acute high-dose-rate exposures. The results support the linearity of the radiation dose response for breast cancer, highlight the importance of age and age at exposure on the risks, and suggest a similarity in risks for acute and fractionated high-dose-rate exposures with much smaller effects from low-dose-rate protracted exposures. There is also a suggestion that women with some benign breast conditions may be at elevated risk of radiation-associated breast cancer.     

Estimating Childhood Multi-Media Lead Exposure: Expanded Exposure/Uptake/Biokinetic Model

Abstract

Despite significant reductions over the past decade, lead exposure continues to be a problem for millions of children in the US. Minimizing further exposure to lead from its numerous and diverse sources is a priority of various regulatory components of the Environmental Protection Agency (EPA), as well as other Federal and State agencies. A critical step in assessing lead risks is the estimation of childhood lead exposure in the future under alternative regulatory scenarios. Using a wide variety of year- and age-specific data on lead concentrations in multiple media, exposure and activity patterns, absorption rates and biokinetics, an integrated uptake/biokinetic model was developed by EPA in its review of the lead National Ambient Air Quality Standard. The model can estimate blood lead distributions among childhood populations over time. It was validated using measured environmental and blood lead data around a primary lead smelter, and has been successfully applied to other point sources. An enhanced version of the model has been developed to deal with a wider variety of exposure situations, especially those at high levels. A personal computer (PC) compatible version is available for assessments of Superfund sites, paint lead abatement strategies, drinking water contamination and other problems.     

Human Exposure Pathways of Heavy Metals in a Lead-Zinc Mining Area,Jiangsu Province,China

Heavy metal pollution is becoming a serious issue in developing countries such as China, and the public is increasingly aware of its adverse health impacts in recent years. We assessed the potential health risks in a lead-zinc mining area and attempted to identify the key exposure pathways. We evaluated the spatial distributions of personal exposure using indigenous exposure factors and field monitoring results of water, soil, food, and indoor and outdoor air samples. The risks posed by 10 metals and the contribution of inhalation, ingestion and dermal contact pathways to these risks were estimated. Human hair samples were also analyzed to indicate the exposure level in the human body. Our results show that heavy metal pollution may pose high potential health risks to local residents, especially in the village closest to the mine (V1), mainly due to Pb, Cd and Hg. Correspondingly, the residents in V1 had higher Pb (8.14 mg/kg) levels in hair than those in the other two villages. Most of the estimated risks came from soil, the intake of self-produced vegetables and indoor air inhalation. This study highlights the importance of site-specific multipathway health risk assessments in studying heavy-metal exposures in China.     

Human Health Risk Assessment of Non-Regulated Xenobiotics in Recycled Water: A Review

Water suppliers face increased pressure to explain the relative health risks from non-regulated xenobiotics that may be present in recycled water, including pharmaceuticals and personal care products (PPCPs) and endocrine disrupting compounds. This report reviews their occurrence, fate, and recent human health risk assessments for potable and non-potable water reuse. The most effective advanced treatment for PPCPs is reverse osmosis (RO) followed by advanced oxidation. During soil aquifer treatment, the majority of PPCPs are attenuated relatively quickly (within 100 days), yet some are persistent and can migrate to the underlying groundwater at low concentrations. Recently, several investigations have assessed the potential human health risks associated with xenobiotics in recycled water, focusing on exposure from drinking water (e.g., planned and unplanned indirect potable reuse) and non-potable reuse (e.g., exposure via recreational, occupational, and irrigation-related activities at sites utilizing recycled water). Risk assessments conducted over the last 10 years have found no adverse human health effects or significant risks. Though advanced treatment of wastewater that is discharged or recycled may not be required to protect public health, it may be necessary to prevent potential effects on exposed biota and to address, to some degree, the public's perception of water reuse.     

Risk Analysis,Uncertainty Factors,and the Susceptibilities of Children

This article examines the use of uncertainty factors (UFs) by the Agency for Toxic Substances and Disease Registry (ATSDR) when developing health guidance values known as minimal risk levels (MRLs) in environmental risk analysis as it applies to children. Improvements in the chemical-specific databases often reveal new information and thereby reduce uncertainty or alternatively raise new concerns. As a result, MRLs can and will change. Children, in particular, are not “small adults” and in some instances demonstrate greater risks of exposure to environmental toxicants and greater susceptibility for adverse health effects once exposed. Recent experience with risk analysis for three toxicants (organic mercury, dioxin, and manganese) is recounted to demonstrate how ATSDR has revised MRLs as the emerging science generates greater knowledge and awareness of children's special vulnerabilities to toxic substances in the environment.     

Exposure and Health Risk from Swimming in Outdoor Pools Contaminated by Trichloroethylene

A method was developed that evaluated the exposure and health risk to children from swimming in outdoor pools filled with contaminated water. It was found that dermal absorption of trichloroethylene (TCE) was significantly larger than the inhalation component of the exposures. It was estimated that the inhalation route accounted for only 1% of the total exposure, whereas accidental ingestion was 7% of the child's total intake and the dermal absorbed dose was 92% of the total exposure. The relative percentage of the total exposure estimated for each exposure route indicated that the dermal exposure route and accidental ingestion of pool water should not be ignored for volatile compounds when evaluating exposure.

The method utilized was simple enough to use computer spreadsheets for the calculations and can be easily adapted to various swimming scenarios and age groups. This method also included an assessment of the uncertainty in the exposure and risk estimates. The range of estimated exposures was 40 μ g to 442 μ g of TCE per swimming season. All values in this range were below the health benchmark for both non-carcinogenic and carcinogenic endpoints.     

Trace elements as paradigms of developmental neurotoxicants: Lead,methylmercury and arsenic

Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available several decades ago so that past and cumulated exposures could be easily characterized through analysis of biological samples, e.g. blood and urine. The first compelling evidence resulted from unfortunate poisoning events that allowed scrutiny of long-term outcomes of acute exposures that occurred during early development. Pursuant to this documentation, prospective studies of children's cohorts that applied sensitive neurobehavioral methods supported the notion that the brain is uniquely vulnerable to toxic damage during early development. Lead, methylmercury, and arsenic thereby serve as paradigm neurotoxicants that provide a reference for other substances that may have similar adverse effects. Less evidence is available on manganese, fluoride, and cadmium, but experience from the former trace elements suggest that, with time, adverse effects are likely to be documented at exposures previously thought to be low and safe.     

Is Parental Control over Children's Eating Associated with Childhood Obesity? Results from a Population‐Based Sample of Third Graders

Objective: Identifying parental behaviors that influence childhood obesity is critical for the development of effective prevention and treatment programs. Findings from a prior laboratory study suggest that parents who impose control over their children's eating may interfere with their children's ability to regulate intake, potentially resulting in overweight. These findings have been widely endorsed; however, the direct relationship between parental control of children's intake and their children's degree of overweight has not been shown in a generalized sample. Research Methods and Procedures: This study surveyed 792 third‐grade children with diverse ethnic and socioeconomic backgrounds from 13 public elementary schools. Parental control over children's intake was assessed through telephone interviews using a state‐of‐the‐art instrument, and children were measured for height, weight, and triceps skinfold thickness. Results: Counter to the hypothesis, parental control over children's intake was inversely associated with overweight in girls, as measured by body mass index, r = ?0.12, p < 0.05, and triceps skinfolds, r = ?0.11, p < 0.05. This weak relationship became only marginally significant when controlling for parents’ perceptions of their own weight, level of household education, and children's age. No relationship between parental control of children's intake and their children's degree of overweight was found in boys. Discussion: Previous observations of the influence of parental control over children's intake in middle‐class white families did not generalize to 8‐ to 9‐year‐olds in families with diverse socioeconomic and ethnic backgrounds. The present findings reveal a more complex relationship between parental behaviors and children's weight status.     

Exposure reconstruction for reducing uncertainty in risk assessment: example using MTBE biomarkers and a simple pharmacokinetic model

Adverse health risks from environmental agents are generally related to average (long-term) exposures. Because a given individual's contact with a pollutant is highly variable and dependent on activity patterns, local sources and exposure pathways, simple ‘snapshot’ measurements of surrounding environmental media may not accurately assign the exposure level. Furthermore, susceptibility to adverse effects from contaminants is considered highly variable in the population so that even similar environmental exposure levels may result in differential health outcomes in different individuals. The use of biomarker measurements coupled to knowledge of rates of uptake, metabolism and elimination has been suggested as a remedy for reducing this type of uncertainty. To demonstrate the utility of such an approach, we invoke results from a series of controlled human exposure tests and classical first-order rate kinetic calculations to estimate how well spot measurements of methyl tertiary butyl ether and the primary metabolite, tertiary butyl alcohol, can be expected to predict different hypothetical scenarios of previous exposures. We found that blood and breath biomarker measurements give similar results and that the biological damping effect of the metabolite production gives more stable estimates of previous exposure. We also explore the value of a potential urinary biomarker, 2-hydroxyisobutyrate suggested in the literature. We find that individual biomarker measurements are a valuable tool in reconstruction of previous exposures and that a simple pharmacokinetic model can identify the time frames over which an exogenous chemical and the related chemical biomarker are useful. These techniques could be applied to broader ranges of environmental contaminants to assess cumulative exposure risks if ADME (Absorption, Distribution, Metabolization and Excretion) is understood and systemic biomarkers can be measured.     

The extended relationship between child cardiovascular risks and academic performance measures

Objective: To examine the relationship between children's overweight status and other cardiovascular risk fitness factors and academic performance among fifth‐grade students. Research Methods and Procedures: Using a sample of 968 fifth‐grade students (50.7% boys; mean age = 10.6 years), children's cardiovascular risks (BMI, blood pressure, acanthosis nigricans) and fitness measures were compared with their mean group performance scores across four subscales (mathematics, reading/language arts, science, and social studies) of a statewide standardized academic performance test. Results: Of this sample, 39% were either at risk for being overweight or were already overweight; slightly over one half were of normal weight. Initial findings revealed a significant relationship between children's weight category and their reading/language arts, mathematics, and science test scores even after controlling for a proxy of socioeconomic status. When additional cardiovascular risk and fitness measures were included in the model, however, children's BMI status had no association. Instead, a composite fitness index, children's blood pressure, sex, and proxy of socioeconomic status were significantly associated with children's academic test scores. Discussion: This study expanded our understanding of the connection between children's overweight risks and academic performance by examining the impact of other cardiovascular risk factors such as high blood pressure and measures of fitness. These findings support the development and implementation of childhood cardiovascular risk surveillance programs that evaluate not only children's overweight risks but also their fitness, risk for type 2 diabetes, and/or high blood pressure by showing a relationship between some of these risks and children's academic test performance.     

Children's health and their mothers’ risk of divorce or separation

Abstract

The purpose of this study is to determine how children's health conditions are related to their mothers’ risk of divorce or separation. The study is based on data from over 7,000 children born to once‐married mothers identified in the 1988 Child Health Supplement to the National Health Interview Survey. The effects of 15 childhood health conditions on the mothers’ risk of divorce are estimated with Cox's proportional hazard models. Controlling for demographic, marital, and reproductive measures, we find that mothers’ prospects for divorce are affected both positively or negatively by their children's health status, depending on the type of childhood condition and, in the case of low birth weight children, timing within the marriage. Women whose children have congenital heart disease, cerebral palsy, are blind, or had low birth weight appear to have higher risks of marital disruption than mothers of healthy children. In contrast, mothers whose children have migraines, learning disabilities, respiratory allergies, missing/deformed digits or limbs, or asthma have somewhat lower rates of divorce.     

Distributions Selected for Use in Probabilistic Human Health Risk Assessments in Oregon

In 1995, Oregon enacted amendments to its state Cleanup Law that emphasize risk-based remedial action decisions and allow a responsible party to conduct probabilistic human health risk assessments. This change required selection and/or development of probability density functions for exposure factors frequently used in human health risk assessments. Methods used to obtain distributions for body weight, soil, water, vegetable/fruit, fish, and animal product ingestion, soil adherence, daily inhalation rate, various event and exposure frequencies, and exposure duration are described. Primary data sources were U.S. Environmental Protection Agency guidance and peer-reviewed scientific literature. These distributions of exposure factors may be used, in conjunction with a probabilistic age- and gender-based model, to calculate prospective exposures and risks. A brief overview of this model, which handles temporal parameters (age, exposure frequency, exposure duration) in a manner substantially different from that typically used in deterministic assessments, is also provided. Oregon's development of an age/ gender-based exposure model, and its selection of exposure factor value distributions for that model, represents one of the first attempts to develop practical approaches to using probabilistic techniques in a hazardous waste regulatory program.