Nicolle S. Tulve

Frequency of mouthing behavior in young children

Young children may be more likely than adults to be exposed to pesticides following a residential application as a result of hand- and object-to-mouth contacts in contaminated areas. However, relatively few studies have specifically evaluated mouthing behavior in children less than 5 years of age. Previously unpublished data collected by the Fred Hutchinson Cancer Research Center (FHCRC) were analyzed to assess the mouthing behavior of 72 children (37 males/35 females). Total mouthing behavior data included the daily frequency of both mouth and tongue contacts with hands, other body parts, surfaces, natural objects, and toys. Eating events were excluded. Children ranged in age from 11 to 60 months. Observations for more than 1 day were available for 78% of the children. The total data set was disaggregated by gender into five age groups (10–20, 20–30, 30–40, 40–50, 50–60 months). Statistical analyses of the data were then undertaken to determine if significant differences existed among the age/gender subgroups in the sample. A mixed effects linear model was used to test the associations among age, gender, and mouthing frequencies. Subjects were treated as random and independent, and intrasubject variability was accounted for with an autocorrelation function. Results indicated that there was no association between mouthing frequency and gender. However, a clear relationship was observed between mouthing frequency and age. Using a tree analysis, two distinct groups could be identified: children ≤24 and children >24 months of age. Children ≤24 months exhibited the highest frequency of mouthing behavior with 81±7 events/h (mean±SE) (n=28 subjects, 69 observations). Children >24 months exhibited the lowest frequency of mouthing behavior with 42±4 events/h (n=44 subjects, 117 observations). These results suggest that children are less likely to place objects into their mouths as they age. These changes in mouthing behavior as a child ages should be accounted for when assessing aggregate exposure to pesticides in the residential environment.

Release of Silver from Nanotechnology-Based Consumer Products for Children

We assessed the potential for childrens exposure to bioavailable silver during the realistic use of selected nanotechnology-based consumer products (plush toy, fabric products, breast milk storage bags, sippy cups, cleaning products, humidifiers, and humidifier accessory). We measured the release of ionic and particulate silver from products into water, orange juice, milk formula, synthetic saliva, sweat, and urine (1:50 product to liquid mass ratio); into air; and onto dermal wipes. Of the liquid media, sweat and urine yielded the highest amount of silver release, up to 38% of the silver mass in products; tap water yielded the lowest amount, ≤1.5%. Leaching from a blanket into sweat plateaued within 5 min, with less silver released after washing. Between 0.3 and 23 μg m(-2) of silver transferred from products to wipes. Aerosol concentrations were not significantly elevated during product use. Fabrics, a plush toy, and cleaning products were most likely to release silver. Silver leached mainly via dissolution and was facilitated in media with high salt concentrations. Levels of silver to which children may potentially be exposed during the normal use of these consumer products is predicted to be low, and bioavailable silver is expected to be in ionic rather than particulate form.

Organophosphorus and pyrethroid insecticide urinary metabolite concentrations in young children living in a southeastern United States city.

Pesticide metabolites are routinely measured in the urine of children in the United States. Although the sources of these metabolites are believed to include residues in food from agricultural applications and residues from applications in everyday environments (e.g., homes), few studies have been able to demonstrate an association between indoor residential pesticide applications and pesticide metabolite concentrations. To better quantify the effects of potential risk factors related to demographics, household characteristics, occupation, and pesticide use practices on urinary biomarker levels, we performed a study in a city (Jacksonville, Florida) previously determined to have elevated rates of pesticide use. We enrolled a convenience sample of 203 children ranging in age from 4 to 6 years; their caregivers completed a questionnaire and the children provided a urine sample, which was analyzed for a series of organophosphorus and pyrethroid insecticide metabolites. The questionnaire responses substantiated much higher pesticide use for the study participants as compared to other studies. Urinary metabolite concentrations were approximately an order of magnitude higher than concentrations reported for young children in other studies. Few statistically significant differences (at the p<0.05 level) were observed, however, several trends are worth noting. In general, mean urinary pesticide metabolite concentrations were higher for males, Caucasians, and those children living in homes with an indoor pesticide application occurring within the past four weeks. Comparing the urinary pesticide metabolite concentrations in this study to those reported in the NHANES and GerES studies showed that the children living in Jacksonville had substantially higher pyrethroid pesticide exposures than the general populations of the United States and Germany. Further research is needed in communities where routine pesticide use has been documented to obtain information on the most important routes and pathways of exposure and to develop the most effective strategies for reducing pesticide exposures for children.

Contributions of children's activities to pesticide hand loadings following residential pesticide application

The role of childrens activities in leading to pesticide exposure was evaluated by comparing pesticide loadings on the hands of children with the activities of the same children observed over a 4-h period. In all, 10 children ranging in age from 24 to 55 months were videotaped on the second day following a routine professional crack and crevice chlorpyrifos application in their homes. Before and following the video session, the childrens hands were rinsed in isopropyl alcohol. Thus, only the chlorpyrifos that accumulated on and remained on the childs hands during the videotaping were removed for analysis after the videotaping session. The rinsate was analyzed for chlorpyrifos. The childrens behaviors were quantified using virtual tracking device and the frequency and duration of behaviors, the hourly rate of behaviors, and the locations in which behaviors occurred were compared to hand loadings of pesticides. Pesticide hand loadings obtained following the videotaping sessions were associated with pesticide levels on surfaces and toys, but not with air levels. Pesticide loadings obtained following the videotaping sessions were also associated with frequencies, durations, and hourly rates of contact with bottles, and object-to-mouth behaviors, as well as contact duration with upholstered/textured surfaces. The hand loadings were also associated with the number of locations where the children exhibited object-to-mouth behavior and with childrens use of house space during the videotaping sessions.

Characterization of silver nanoparticles in selected consumer products and its relevance for predicting children’s potential exposures

Due to their antifungal, antibacterial, antiviral, and antimicrobial properties, silver nanoparticles (AgNPs) are used in consumer products intended for use by children or in the home. Children may be especially affected by the normal use of consumer products because of their physiological functions, developmental stage, and activities and behaviors. Despite much research to date, childrens potential exposures to AgNPs are not well characterized. Our objectives were to characterize selected consumer products containing AgNPs and to use the data to estimate a childs potential non-dietary ingestion exposure. We identified and cataloged 165 consumer products claiming to contain AgNPs that may be used by or near children or found in the home. Nineteen products (textile, liquid, plastic) were selected for further analysis. We developed a tiered analytical approach to determine silver content, form (particulate or ionic), size, morphology, agglomeration state, and composition. Silver was detected in all products except one sippy cup body. Among products in a given category, silver mass contributions were highly variable and not always uniformly distributed within products, highlighting the need to sample multiple areas of a product. Electron microscopy confirmed the presence of AgNPs. Using this data, a childs potential non-dietary ingestion exposure to AgNPs when drinking milk formula from a sippy cup is 1.53 μg Ag/kg. Additional research is needed to understand the number and types of consumer products containing silver and the concentrations of silver in these products in order to more accurately predict childrens potential aggregate and cumulative exposures to AgNPs.

Chlorpyrifos Accumulation Patterns for Child-Accessible Surfaces and Objects and Urinary Metabolite Excretion by Children for 2 Weeks after Crack-and-Crevice Application

The Children’s Post-Pesticide Application Exposure Study (CPPAES) was conducted to look at the distribution of chlorpyrifos within a home environment for 2 weeks after a routine professional crack-and-crevice application and to determine the amount of the chlorpyrifos that is absorbed by a child living within the home. Ten residential homes with a 2- to 5-year-old child in each were selected for study, and the homes were treated with chlorpyrifos. Pesticide measurements were made from the indoor air, indoor surfaces, and plush toys. In addition, periodic morning urine samples were collected from each of the children throughout the 2-week period. We analyzed the urine samples for 3,5,6-trichloropyridinol, the primary urinary metabolite of chlorpyrifos, and used the results to estimate the children’s absorbed dose. Average chlorpyrifos levels in the indoor air and surfaces were 26 (pretreatment)/120 (posttreatment) ng/m3 and 0.48 (pretreatment)/2.8 (posttreatment) ng/cm2, respectively, reaching peak levels between days 0 and 2; subsequently, concentrations decreased throughout the 2-week period. Chlorpyrifos in/on the plush toys ranged from 7.3 to 1,949 ng/toy postapplication, with concentrations increasing throughout the 2-week period, demonstrating a cumulative adsorption/absorption process indoors. The daily amount of chlorpyrifos estimated to be absorbed by the CPPAES children postapplication ranged from 0.04 to 4.8 μg/kg/day. During the 2 weeks after the crack-and-crevice application, there was no significant increase in the amount of chlorpyrifos absorbed by the CPPAES children.

Review of Pesticide Urinary Biomarker Measurements from Selected US EPA Children’s Observational Exposure Studies

Children are exposed to a wide variety of pesticides originating from both outdoor and indoor sources. Several studies were conducted or funded by the EPA over the past decade to investigate children’s exposure to organophosphate and pyrethroid pesticides and the factors that impact their exposures. Urinary metabolite concentration measurements from these studies are consolidated here to identify trends, spatial and temporal patterns, and areas where further research is required. Namely, concentrations of the metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol or TCPy), diazinon (2-isopropyl-6-methyl-4-pyrimidinol or IMP), and permethrin (3-phenoxybenzoic acid or 3-PBA) are presented. Information on the kinetic parameters describing absorption and elimination in humans is also presented to aid in interpretation. Metabolite concentrations varied more dramatically across studies for 3-PBA and IMP than for TCPy, with TCPy concentrations about an order of magnitude higher than the 3-PBA concentrations. Temporal variability was high for all metabolites with urinary 3-PBA concentrations slightly more consistent over time than the TCPy concentrations. Urinary biomarker levels provided only limited evidence of applications. The observed relationships between urinary metabolite levels and estimates of pesticide intake may be affected by differences in the contribution of each exposure route to total intake, which may vary with exposure intensity and across individuals.

Serum concentrations of perfluorinated compounds (PFC) among selected populations of children and Adults in California

Perfluorinated compounds (PFCs) have been widely used in industrial applications and consumer products. Their persistent nature and potential health impacts are of concern. Given the high cost of collecting serum samples, this study is to understand whether we can quantify PFC serum concentrations using factors extracted from questionnaire responses and indirect measurements, and whether a single serum measurement can be used to classify an individuals exposure over a one-year period. The study population included three demographic groups: young children (2-8 years old) (N=67), parents of young children (<55 years old) (N=90), and older adults (>55 years old) (N=59). PFC serum concentrations, house dust concentrations, and questionnaires were collected. The geometric mean of perfluorooctane sulfonic acid (PFOS) was highest for the older adults. In contrast, the geometric mean of perfluorooctanoic acid (PFOA) was highest for children. Serum concentrations of the parent and the child from the same family were moderately correlated (Spearman correlation (r)=0.26-0.79, p<0.05), indicating common sources within a family. For adults, age, having occupational exposure or having used fire extinguisher, frequencies of consuming butter/margarine, pork, canned meat entrées, tuna and white fish, freshwater fish, and whether they ate microwave popcorn were significantly positively associated with serum concentrations of individual PFCs. For children, residential dust concentrations, frequency of wearing waterproof clothes, frequency of having canned fish, hotdogs, chicken nuggets, French fries, and chips, and whether they ate microwave popcorn were significant positive predictors of individual PFC serum concentrations. In addition, the serum concentrations collected in a subset of young children (N=20) and the parents (N=42) one year later were strongly correlated (r=0.68-0.98, p<0.001) with the levels measured at the first visits, but showed a decreasing trend. Children had moderate correlation (r=0.43) between serum and dust concentrations of PFOS, indicating indoor sources contribute to exposure. In conclusion, besides food intake, occupational exposure, consumer product use, and exposure to residential dust contribute to PFC exposure. The downward temporal trend of serum concentrations reflects the reduction of PFCs use in recent years while the year-to-year correlation indicates that a single serum measurement could be an estimate of exposure relative to the population for a one-year period in epidemiology studies.

Urinary pyrethroid and chlorpyrifos metabolite concentrations in Northern California families and their relationship to indoor residential insecticide levels, part of the Study of Use of Products and Exposure Related Behavior (SUPERB).

Since the 2001 U.S. federally mandated phase-out of residential uses of organophosphates (OPs), use of and potential for human exposure to pyrethroids in the indoor residential environment has increased. We report concentrations of common pyrethroids, pyrethroid metabolites, and chlorpyrifos in floor wipes, and urinary concentrations of pyrethroid metabolites and 3,5,6-trichloro-2-pyridinol (TCPy) in samples collected in 2007-2009 from 90 northern California families as part of the Study of Use of Products and Exposure Related Behavior (SUPERB). Correlation and regression analyses examined associations between floor wipe and urine sample concentrations. The most frequently detected urinary metabolites were TCPy (64.7%, median concentration of 1.47 ng/mL) and 3-phenoxybenzoic acid (3PBA) (62.4%, 0.79 ng/mL). Compared to the National Health and Nutrition Examination Survey (NHANES) 2001-2002 general U.S. population, this population had substantially higher pyrethroid metabolite and lower TCPy urinary concentrations. This may be related to the increased residential use of pyrethroids after the phase-out of OPs. Chlorpyrifos (98.7%), cis- and trans-permethrin (97.5%), bifenthrin (59.3%), and 3PBA (98.7%) were frequently detected in the floor wipes. Floor wipe concentrations for pyrethroid insecticides were found to be significant predictors of child creatinine-adjusted urinary metabolite concentrations (log-log regression coefficients ranging from 0.26 to 0.29; p < 0.05) suggesting that indoor residential exposure to pyrethroid insecticides is an important exposure route for children.

Quantifying children's aggregate (dietary and residential) exposure and dose to permethrin: application and evaluation of EPA's probabilistic SHEDS-Multimedia model

Reliable, evaluated human exposure and dose models are important for understanding the health risks from chemicals. A case study focusing on permethrin was conducted because of this insecticides widespread use and potential health effects. SHEDS-Multimedia was applied to estimate US population permethrin exposures for 3- to 5-year-old children from residential, dietary, and combined exposure routes, using available dietary consumption data, food residue data, residential concentrations, and exposure factors. Sensitivity and uncertainty analyses were conducted to identify key factors, pathways, and research needs. Model evaluation was conducted using duplicate diet data and biomonitoring data from multiple field studies, and comparison to other models. Key exposure variables were consumption of spinach, lettuce, and cabbage; surface-to-skin transfer efficiency; hand mouthing frequency; fraction of hand mouthed; saliva removal efficiency; fraction of house treated; and usage frequency. For children in households using residential permethrin, the non-dietary exposure route was most important, and when all households were included, dietary exposure dominated. SHEDS-Multimedia model estimates compared well to real-world measurements data; this exposure assessment tool can enhance human health risk assessments and inform childrens health research. The case study provides insights into childrens aggregate exposures to permethrin and lays the foundation for a future cumulative pyrethroid pesticides risk assessment.