FEATURE
A Closer Look at Chemical Exposures in Children New research initiatives should help regulators more accurately assess risks and set exposure tolerances. CHARLES W. S C H M I D T
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he behavior of young children as they crawl on the ground, dragging themselves over carpets, floors, and lawns can be risky. They pick up random items, put them in their mouths, lick their fingers, and ingest house dust and soil. This behavior, compounded by mounting evidence (1) suggesting that childhood physiology, metabolism, diet, and chemical-specific response can increase their sensitivity to chemicals overall, has led public health officials to conclude that young children are uniquely prone to residential chemical exposures. Such concerns have sparked a series of legislative initiatives. The most tmporrant tnitiative, ,he 1997 Clinton administration mandate that federal agencies should explicitly take into account risks to children and infants in the assessment of environmental hazards, has stimulated efforts to fill data gaps in knowledge about childhood exposure to chemicals. Natalie Freeman, an adjunct assistant professor in the Department of Environmental and Community Medicine at the Robert Wood Johnson Medical School in Piscataway, N.J., and James Leckie, a professor in the Department of Civil and Environmental Engineering at Stanford University, Calif., are using video cameras to study hand-to-mouth and object-tomouth behavior in young children At the University of Washington's Department of Environmental Health in Seattle Richard Fenske is assessing the magnitude of childhood pesticide exposures by looking at metabolites in urine samples The results of these and other forthcoming research undertakings are eagerly awaited by government officials. An enriched understanding of childhood exposures patterns and behaviors should also improve estimates of chemical dose rates to children during site-specific risk assessments. Better exposure information, and improved knowledge of
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chemical toxicity, will allow regulators to more accurately conduct risk assessments needed for establishing pesticide tolerances, said Linda Sheldon, science lead for Human Exposure Measurement Studies at EPA's National Exposure Research Laboratory (NERL) in Research Triangle Park, N.C. According to Sheldon, childhood exposure research programs, ongoing at EPA for years, have become re-energized by the 1996 Food Quality Protection Act (FQPA), under which 9700 pesticide tolerances are to be evaluated and possibly revised if they are found to be insufficiently protective of children. The act has been hotly debated, however, particularly with respect to the controversial application of an additional 10-fold safety factor that could be used in the absence of sufficient data on toxicity or exposure. This issue is currentiy being addressed by the 10X Task Force, which is administered jointly by the EPA's Office of Prevention Pesticides and Toxic Substances the Office of Children's Health Protection and the Office of Research and Development (ORD) "In order to revise pesticide tolerances, EPA needs to perform risk assessments that take into account all routes of exposure. There's great uncertainty as well as very little data surrounding exposures in residential settings and day-care centers," commented Sheedon. Consequently, she noted, "The focus of most of our research is on dermal and nondietary ingestion routes because that's where most of the uncertainty lies." These FQPA-motivated exposure research programs have broad application across classes of chemicals—wider application than just pesticides, noted Chris Saint, an assistant director at ORD's Nattonal Center for Environmental Research and Quality Assurance (NCERQA). Children's activity patterns and exposure modeling are constructs that can be applied no matter what the chemical is; you just have to obtain additional chemical-specific information, he explained. © 1999 American Chemical Society
Hand contact activity of a child Hand contact activities of children can vary and are often of short duration, as indicated by the frequency of behavioral activities of a child who was observed for five hours. Each bar summarizes the frequency of the child's observed activities during a five-minute period: object-to-mouth behavior (OBJMTH), hand-to-mouth behavior (MOUTH), contact with a textured surface such as carpets or upholstered furniture (TXSURF), contact with a smooth surface such as a floor or a table (SMSURF); contact with single surfaces includes contact with objects (OBJECT), clothing (CLOTHING), and dirt (DIRT). (Courtesy Natalie Freeman, Rutgers University, Rutgers, N.J.)
Coordination and focus Currently, much of the federal-level research effort is being coordinated by ORD, and, in particular, NCERQA. A major undertaking currently administered by the NCERQA is the Science to Achieve Results (STAR) program, which hosted a March 1998 workshop in Washington, D.C. on children's exposure to pesticides. Saint said that the STAR program is looking to improve databases associated with all exposure routes. "The STAR program is multimedia and multipathway," he said. "We're looking at inhalation, dermal contact, ingestion, and to some extent, nondietary ingestion pathways associated with air, water, food, and soil," he remarked. Intermittent exposure is also a dominant theme in NCERQA's current Request for Application, "Children's Vulnerability to Toxic Substances in the Environment," which was released under the STAR program this June. "We are trying to stimulate more research on microactivity patterns among children," explained Saint. The intermittent, high-level, short-term exposures are targeted under the premise
that in residential settings, children will receive more and larger intermittent exposures than those of exposed adults. According to Saint, the focus on intermittent rather than chronic exposures is driven by the perception that most childhood exposures to chemicals occur during specific, discrete events, such as during application of lawn chemicals or indoor pest treatments. These exposure scenarios are often dominated by dermal pathways, as well as hand- and object-tomouth activities, which are poorly characterized in exposure research literature, said Dennis Klonne, a consultant to the Outdoor Residential Exposure Task Force based in Raleigh, N.C. The organization is among the largest and most organized of industry research efforts. It is evaluating dermal exposures in children, working to obtain better estimates of handto-mouth activity, cind. cv3luating dislod.263.ble residues of pesticides adhere to skin surfaces from turf. Sheldon agreed with Klonne's assessment and said that information about the frequency and duration FEB. 1, 1999 / ENVIRONMENTAL SCIENCE & TECHNOLOGY / NEWS • 7 3 A
of mouthing (hand-to-mouth and object-tomouth) behavior is particularly lacking. NERL is working with a number of researchers to gather data that will support improved quantitative estimates of these exposure parameters. Freeman's NERL-supported research suggests the richness of these early childhood activities (seefigureon previous page). "We are trying to estimate when [mouthing behavior] is most likely to happen," she explained. "We think it is more likely that it occurs indoors during quiet time, like watching TV or resting. For two- to threeyear-old children, this is "The focus of most a comfort activity and of our research is not one that they do when they are active," on dermal and she said. Leckie's exposure renondietary search group has also been working to deingestion routes velop improved estimates of hand- and obbecause that's ject-to-mouth activity in young children. He and where most of the a former graduate stuuncertainty lies." dent, Valerie Zartarian, now at EPA's National —Linda Sheldon, National Exposure Research Laboratory, recently develExposure Research oped a software packLaboratory, Research age known as VideoTraq, Triangle Park, N.C. which is designed to translate videotaped movements of children into quantitative estimates of exposure via dermal and nondietary ingestion routes (2) "This approach gives you detailed information on the freauency and duration of these behaviors " said Leckie There is significant uncertainty associated with the duration of time that a chemical is likely to remain on a child's skin he noted To quantify this uncertaintv he and Zartarian have developed the Dermal Exposuii Reduction Model (DERlvn which is a physical stochastic model that uses videotaped activity data to give a profile of the tem1
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poral and spatial concentration of chemicals at the skin surface (3). Leckie explained that in the next phase of his research, he will combine output from DERM, which gives a mass loading at the skin surface, and pharmacokinetic models that describe dermal penetration, in order to calculate absorbed dose rates. "DERM, therefore, could be a step toward improving inputs to dose models that typically assume a fixed loading at the skin surface," said Zartarian. The goal of this research is to convert chemical exposures from each pathway into absorbed dose rates expressed in the same units, noted Leckie. "This will give US 3. normative measure, so that we can compare the [magnitude of doses associated] with different exposure pathways," he said. According to Leckie, chemical-specific information is crucial to understanding the significance of the dermal pathway as a component of overall exposure. "There's still a lot of work to be done, particularly in the 7 4 A • FEB. 1, 1999 / ENVIRONMENTAL SCIENCE & TECHNOLOGY / NEWS
area of diffusion through skin," he said. "Phenol, for example, is almost completely absorbed through the skin, but other larger compounds pass slowly. There's quite a range," he explained. Based in Palo Alto, Calif., the Electric Power Research Institute (EPRI), a nonprofit research group that focuses on the needs of the power industry, is also working to develop innovative methods for assessing dermal penetration by chemicals. According to Lawrence Goldstein, manager of toxicology in EPRI's Environmental Division, EPRI-funded research is examining dermal penetration of aged coal tars from soil, using radio-labeled benzo(a)pyrene as a surrogate compound (4). These studies are being conducted using an in vitro model, with abdominal cadaver skin which tends to have a higher porosity relative to skin taken from other areas of the body. In this respect it is comparable to the skin of young children. Lawrence explained that in addition to providing an experimental model that can be used to assess dermal absorption of other chemicals the approach also enables researchers to determine the extent to which dermal absorption is inhibited by soil matrix interferences The goal is to characterize soil parameters that influence the rate and transfer of chemicals from soil he said and noted that "these include humic content soil rvne poros itv and particle size " Research provides clues Most researchers tend to agree that toddlers up to the age of three likely represent the most highly exposed age group. Because exposures are measured in terms of dose per unit of body weight, exposure magnitude as a function of age can be determined using dermal surface area and inhalation to bodyweight ratios for specific age groups. These ratios generally tend to increase for younger children, which suggests that the younger the child is, the greater the overall exposure. However, as the age of the child decreases, a point is reached where exposures are driven more by activity patterns than by physiology. Compared to older individuals, the way kids between oneand-a-half and three move around puts them at the greatest risk of exposure from contaminated surfaces and objects. Infants, on the other hand, do not have an opportunity to move around unsupervised; they are not as independent, explained Sheldon. According to Klonne, the transfer process is chemical-specific and depends on each chemical's physical properties. He emphasized that there can be significant differences in how children are exposed in indoor and outdoor environments. These differences relate both to behavior—for example, hand-tomouth activity appears to be less frequent in children playing outdoors—as does the consistency of exposure. "Most data we are aware of indicate that most pesticides disappear rapidly from grass surfaces. Typically, within 24 hours, the bulk of a pesticide is gone," he said. According to Klonne, die mechanism and extent of pesticide degradation used in an outdoor environment can differ from that which characterizes its degradation behavior in an indoor environment Supporting this observation a reduced chemical degra-
dation rate in an indoor environment compared to that which occurs outdoors was observed by Fenske and coworkers (5) in a study of pesticide exposures in agricultural versus nonagricultural families. This finding implies that some pesticide residues can persist in indoor environments and increase the duration of residential exposure. The finding is not unusual, given that a primary fate process for many pesticides is hydrolysis, which is affected by moisture content. Compared to outdoor environments, indoor environments are relatively dry. Fenske's research, supported by the STAR program, also identified a strong positive association between proximity to farming operations and concentrations of organophosphate pesticides in house dust. This finding suggests that children from agricultural families may be at elevated risk from pesticide exposures. Results of his studies on urinary biomarkers indicate that children from agricultural families with higher concentrations of pesticides in house dust evidenced elevated urinary metabolites (5, 6). He noted, however, mat the observed association is weak. "If you expect that house dust concentrations are a strong predictor of urinary metabolites, we didn't see that. In fact our regression analyses indicated that house dust concentrations only predicted about a quarter of the [observed] urinary concentrations " he said The relative contribution of other potential sources to the overall observed exposure remains a mystery he commented According to Leckie the amount of pesticides that children get from food is also low "The literature suggests that children get verv little pesticide exposures from food if they've been prepared the normal wav" he said "Exposure is a complicated process" addpd Fenske "There's a lot r»f vari abilitv in behavior timp dpnpndenrv and ahsornrion Thprp's akn a lot of variahilitv in our PYnprimpntal mpth j
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something associated with spraying over a 24- to 48hour period? It's not really clear." According to Saint, another important issue concerns how the newly generated childhood exposure data, in conjunction with currently available information, will be managed and used. Presently recommended values for childhood residential exposure assessments can be found in the Office of Pesticide Programs (OPP) guidance document, Standard Operating Procedures for Residential Exposure Assessments, released July 1997 (7). The report provides de"Sometimes the tailed descriptions of residential exposure scenarios, a num[exposure] models ber of w h i c h are focused specifically on children. Tim overpredict Leighton an environmental health scientist with the exposure, and Health Effects Division at OPP described the guidance as sometimes they flexible dynamic and continually updated as new inforunderpredict it." mation becomes available According to T^ighton risk as—Richard Fenske, sessors working on hazardDepartment of ous waste site proiects can h n n p to ii«p t h e r o n t i n u Environmental Health, onslv unrlatpH prnrpdnrps in University of rnninnrtinn with nthpr pctah Washington, Seattle. lishpH fpHpral and statp cniiH Hnmments «nch an thp Risk Assessment Guidance for Superfund (8), and the Exposure Factors Handbook (9). He commented that as new information is developed, when justified, it can be substituted for what is presently contained 1
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Interestingly, Fenske's measured concentrations of urinary metabolites were often found to be higher than those predicted by exposure modeling, particularly if the predictive models were based on distributional Monte Carlo analyses. On the other hand, point-estimate models based on consecutive upperbound parameters often overestimated urinary levels, said Fenske. "The important message is that biological samples provide a real-world check. They provide a perspective on how big an [exposure] problem we actually have and how good the models actually are: Sometimes the [exposure] models overpredict exposure and sometimes they underpredict it" he said. Fenske cautioned however that whereas metabolites provide 3Ji indication of the total chemical dose they do not reveal much cibout hovv expo~ actually Fenske's research group has recently been selected as one of eight Children's Environmental Health Centers, which will be funded jointly by EPA and the National Institute of Environmental Health Sciences. His research under this grant will explore pesticide drift from agricultural operations and its relationship to childhood exposure. "We have questions about all the pathways," he said. "If we just consider diet, air, and soil, we're missing something. Is [exposure] transient? Is it
References (1) National Academy of Sciences. Pesticides sinhe Diets of Infants and Children; National Academy of Sciences Press: Washington, DC, 1993. (2) Zartarian, V; Ferguson, A; Ong, C; Leckie, J. /. Exp. Anal. Environ. Epidemiol. 1997, 7(7), 536-542. (3) Zartarian, V; Leckie, Environ. Sci. Technol. 1998,32(5), 134A137A. (4) Roy, T; Kruger, A; Taylor, B; Mauro, D; Goldstein, L. Environ. Scii Technol. 1998, 32(20), 3113-3-17. (5) Simcox, N.; Fenske, R.; Wolz, S.; Lee, I-C; Kalman, D. Environ. Heallh Perspect. 1995, i03(12) 2)26-1134. (6) Loewenherz, C; Fenske, R.; Simcox, N.; Bellamy, G; Kalman, D. Environ. Heallh Perspect. 1997, i 0i(12), 1,441353. (7) U.S. Environmental Protection Agency. Standard Operating Procedures for Residential Exposure Assessments. hrtp:/h www.epa.gov/opp00001/SAP/September/sopindex.htm; (accessed October 1998). (8) Risk Assessment Guidance for Superfund, Volume 1: Human Health Evaluatton Manual (Part A, Baseline Risk Assessment, Interim Final); ;PA/540/0-89/002; U.S. Environmental Protection Agency, Office of Emergency and Remedial Response, U.S. Government Printing Office: Washington, DC, 1989 (9) Exposure Factors Handbook; EPA/600/P-95/002Ba; Office of Research and Development, U.S. Environmental Protection Agency, Office of Emergency and Remedial Response, U.S. Government Printing Office: Washington, DC, 1996. Charles W. Schmidt is a freeeance writer based in Portland, Maine. FEB. 1, 1999/ENVIRONMENTAL SCIENCE & TECHNOLOGY/NEWS " 75 A
