Grantee Research Project Results
Final Report: Study of Exposure and Body Burden of Children of Different Ages to Pesticides in the Environment
EPA Grant Number: R827444Title: Study of Exposure and Body Burden of Children of Different Ages to Pesticides in the Environment
Investigators: Raymer, James H. , Clayton, C. Andrew , Pellizzari, Edo D. , Akland, Gerald G. , Marrero, T.
Institution: Desert Research Institute
EPA Project Officer: Aja, Hayley
Project Period: September 1, 1999 through August 31, 2002
Project Amount: $819,063
RFA: Children's Vulnerability to Toxic Substances in the Environment (1999) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
It has become accepted that children are not simply small adults but are a unique population for health risk assessment. Their risks differ from adults for a variety of reasons, including differences in exposure, physiological factors, metabolism, pharmacokinetics, and diet (Guzelian, et al., 1992). During early development, measurements of children's internal dose of a chemical or its metabolites based on exposures to chemicals in air, water, soil, and food can be higher than adults based on body weight differences and surface to volume ratio, as well as other physiological and metabolic factors. Another factor that might increase exposure is the significant amount of time toddlers spend exploring their environment by crawling and orally exploring objects, including hand-to-mouth activity of soiled hands or objects. As a direct result, toddlers are more vulnerable than adults to emissions from new carpeting or rugs treated with pesticides and from dust and other particulates that settle on the floor or are carried indoors by house pets or adults (Mukerjee, 1998). The objective of this research project was to determine if these differences between adults and children result in measurable differences in dose and, therefore, risk.
Researchers and risk assessors have expressed the need for exposure-related data specific to children. Better data are needed on actual exposure pathways of young children, patterns of food consumption by age, and on actual pesticide/chemical residue levels and measured dose to improve the exposure component of risk assessments. The National Academy of Sciences, in its report on pesticides in the diet of children, recognized the need to improve methods of estimating exposure to pesticides and to obtain much needed exposure information specific to children (National Academy of Sciences, 1993).
Pesticides are especially important to study because the principal exposure of the general population of the United States to pesticides occurs in the home (Nigg, et al., 1990), where small children spend an average of 22 hours indoors at home per day (Klepeis, et al., 1996). Furthermore, unique pathways of exposure to pesticides potentially could result in significantly higher total exposures than those received by older children or adults living in the same household.
The main objective of the research project was to test the hypothesis that children have significantly higher environmental exposures and resulting doses than do adults living in the same home. The study design tested if the distribution of exposures for children living in urban environments is different from children living in rural environments.
Specific objectives of the research project were to:
- Compare exposure and dose levels between young children and adults in the same household;
- Compare exposure and dose levels among young children of different ages;
- Compare exposure and dose levels among young children in urban and rural households;
- Estimate the associations between exposure level and internal dose as well as age-specific differences in the associations;
- Identify age-specific childhood behavior patterns that increase or decrease a childs dose for a given ambient exposure level (using data from videos); and
- Quantify exposure and dose variability within age groups of young children and identify biological and physiological determinants of this variability.
Summary/Accomplishments (Outputs/Outcomes):
This study evaluated exposure and dose measurements for comparing the differences between exposures of children of different ages and adults sampled from both rural and urban homes. Sample collection was accomplished during the summers of 2000 and 2001 in two areas of Minnesota.
The following sections of this report describe how participants were recruited, how questionnaire data and samples were collected and analyzed, how data were prepared for statistical analysis, and the study results. Although videotapes showing children's behaviors were collected, there was not sufficient effort for detailed analysis. Similarly, limited work was done on the physiological aspects with regard to any physiologically based pharmacokinetic (PBPK) modeling.
Participant Selection and Recruitment
This research project sampled people from two areas of Minnesota: Minneapolis/St. Paul (urban) and Rice/Goodhue Counties (rural) in 2000 and Moorhead, Minnesota, in 2001. The sample of urban residents comprised residents living within the city limits of Minneapolis, Moorehead, and St. Paul, Minnesota. Rural residents were sampled from Goodhue and Rice Counties as well as rural areas outside of Moorhead.
Children between the ages of a few months and 12 years inclusive were sought. The upper age range reflects children who would be expected to exhibit different activity and dietary patterns, as well as different (more adult-like) metabolism rates.
Table 1 summarizes the characteristics of the study areas and the age characteristics for the children selected to participate in the research project. Table 2 summarizes the participants who were recruited into the research project.
Table 1. Definition Of The Target Population For The Childrens Vulnerability Study
1 |
Geographic Area : Minneapolis and St. Paul along with the City of Moorhead, Minnesota, for the urban portion; Rice and Goodhue Counties and farming areas near Moorhead for the rural portion. |
2 |
Type of residence: Housing units occupied as primary residences, excluding group quarters. Household units were selected from listed telephone numbers, which were identified as residential units and which were predicted to have children 10 years old or younger (Genesys Sampling Systems, Inc.). |
3 |
Type of residents: All permanent residents and those with no permanent residence elsewhere, except those who are absent for an extended period of time. |
4 |
Age range: Children between the ages of a few months and 12 years inclusive. The upper age range reflects children who would be expected to exhibit different activity and dietary patterns, as well as different (more adult-like) metabolism rates. |
5 |
Temporal dimension: All weeks in approximately 2-month data collection period in each of two years. � |
Table 2. Participant Distribution |
|||||
Study Year |
4 months to 3 years |
4 to 5 years |
6 to 12 years |
Adult |
Total |
2000 |
8 |
6 |
26 |
22 |
62 |
2001 |
7 |
6 |
16 |
19 |
48 |
Total: |
15 |
12 |
42 |
41 |
110 |
26 homes had two children; 9 of these had two children in a single age bracket. |
Media Sampled and Sample Collection Methods
The samples collected during this study are outlined in Table 3. Most of the children who wore body suits were also videotaped for approximately 1-hour that included a meal or eating event. Participants who agreed to wear volatile organic compound (VOC) badges were asked to provide breath samples.
Table 3. Samples Collected |
||
Sample Matrix |
Type* |
Sampling Method |
Air (pesticides, subset VOCs) |
I, P |
48-hour integrated, XAD with quartz fiber filter; 3M badge |
Dietary |
P |
Duplicate diet solids, two 1-day; two 1-day beverages without drinking water |
Surface Wipe |
I |
Isopropanol wipe in primary living area |
House Dust |
I |
Vacuum bag in primary living area |
Surface Press |
I |
Multiple locations with constant pressure |
Dermal Rinse (adhesion) |
P |
Hand wash with isopropanol |
Body Suits (adhesion) |
P |
1-day for infants and toddlers |
Urine |
P |
Two morning voids (days 2 and 3) |
Breath (subset) |
P |
Alveolar air into canister |
*I = Indoor, P = Personal |
Of the sample types shown in Table 3, the following matrices were analyzed: air (personal, indoor), house dust, dermal rinse, urine (selected samples to include creatinine analysis), dust wipes, surfaces press, body suits, and exhaled breath. In general, analyses were by gas chromatography (GC)/mass spectrometry (MS) in the selected ion monitoring mode. Creatinine was determined by a spectrophotometric method and the urine samples were analyzed using high performance liquid chromatography (HPLC)/MS/MS. The dietary samples were archived but not analyzed because of time and funding constraints. This study focused on four primary targets (malathion, chlorpyrifos, atrazine, and diazinon), but each sample was screened for evidence of the other analytes listed in Table 4. The four main targets were always quantified (primary and secondary ions) and the presence of a primary ion for the other pesticides triggered an evaluation of the secondary, confirmation ion. If it was found that the non-target pesticide was definitely present, the compound was quantified. Analysis approaches are summarized in Table 5. Analytical results were entered into a SAS database for statistical analysis.
Table 4. Target Analytes |
|||
� Pesticides |
� Volatile Organic Compounds |
||
Dichlorovos |
Dichloran |
1,1-Dichloroethane |
|
Simazine |
Atrazine | Chloroform |
|
Lindane |
Terbufos |
Benzene |
|
Fonofos |
Diazinon | Carbon tetrachloride |
|
Disulfoton |
Acetochlor |
Toluene |
|
Malathion | Metolachlor |
Tetrachloroethylene |
|
Chlorpyrifos | Parathion |
m,p-Xylene |
|
Dacthal |
Isofenphos |
Styrene |
|
trans-Chlordane |
Endosulfan I |
o-Xylene |
|
cis-Chlordane |
Dieldrin |
p-Dichlorobenzene |
|
DDE |
Endrin |
o-Dichlorobenzene |
|
DDD |
DDT |
||
Permethrin |
Asana (2001) |
||
Pesticides in bold represent primary target analytes. |
Table 5. Analytical Methods |
||
Sample Matrix |
Type* |
Sampling Method |
Air (pesticides, subset VOCs) |
I, P |
Solvent extraction (dichloromethane) with sonication, volume reduction, GC/MS; solvent extraction of each stage separately with CS2, GC/MS |
Dietary |
P |
Homogenization, solvent extraction (hexane:acetone, 1:1), volume reduction |
Surface Wipe |
I |
Extraction using n-hexane/ethyl ether (95/5, v/v) with sonication, volume reduction, GC/MS |
House Dust |
I |
Extraction using n-hexane/ethyl ether (95/5, v/v), filtration, volume reduction, GC/MS |
Surface Press |
I |
Extraction using n-hexane/ethyl ether (95/5, v/v) with sonication, volume reduction, GC/MS |
Dermal Rinse (adhesion) |
P |
Volume reduction, GC/MS |
Body Suits (adhesion) |
P |
Extraction with n-hexane/acetone (95/5, v/v), volume reduction, GC/MS |
Urine |
P |
With and without hydrolysis, extraction via acidification using 1:4 methylene chloride/ethyl ether and solvent transfer to acetonitrile, volume reduction, HPLC/MS/MS |
Breath (subset) |
P |
Cryo-focusing, GC/MS |
*I = Indoor, P = Personal |
The video analysis approach focused on specific activities of the children during an eating event. The number of hand movements to hard surfaces, soft surfaces, body suit, mouth, and body were tabulated along with the duration for each activity.
Questionnaire data were entered into a spreadsheet by field staff and read into SAS as part of the overall study database. Data were double-keyed and compared to ensure accurate entry.
Results
Pesticides and Pesticide Metabolites . There were eight different types of media sampled and analyzed for pesticides and their metabolites as defined above. Using the criteria that n was greater than or equal to 15 with a percent measurable greater than or equal to 20 percent, none of the analytes were detected in vacuum dust, surface press, dermal rinse, body suits, and dust wipes. Three compounds were found only in the personal air and/or indoor air media of the environmental samples: heptachlor, alachlor, and trans-chlordane. These three compounds were measured in 44 percent of the samples (53% for heptachlor-personal and indoor air, 33% for alachlor, and 21% for trans-chlordane-indoor air only). The median concentrations of all three pesticides were greater than the median concentration of the matrix blanks. Five compounds were detected only in the urine of adults and children: atrazine, 3,5,6-trichloro-2-pyridinol, 2-isopropyl-6-methyl-4-pyrimidinol, chlorpyrifos oxon, and fonofos. It was not expected that the oxon of chlorpyrifos would be detected but both the primary and daughter ions were measured in the HPLC/MS/MS analysis. As with the environmental samples, the median concentrations of each of the three pesticides were greater than the median concentration of the matrix blanks. Dichlorvos is reported in Table 6 because it has a mean concentration greater than the mean matrix blank concentration. The 3,5,6-trichloro-2-pyridinol and chlorpyrifos oxon are chlorpyrifos metabolites, and the 2-isopropyl-6-methyl-4-pyrimidinol is a diazinon metabolite. Two compounds, simazine and dichlorvos, were found above background levels in environmental samples and urine. The remaining analytes had median concentrations less than the median concentration of the matrix blank or were not detected.
Table 6 reports the magnitude of difference between the mean values of the pesticides or pesticide metabolites in urine for adults versus children and younger children (0-3 years) versus older children (4-12 years) when the P value was less than 0.05.
VOCs. Personal air and breath were sampled for VOCs. Seven different VOCs were found in the air or breath samples with a median concentration greater than the median concentration of the matrix blank: benzene, carbon tetrachloride, chloroform, tetrachloroethylene, toluene, m,p-xylene, and o-xylene. Only toluene was found in both the personal air and exhaled breath. Four compounds were not detected or the detected values were less than the median concentration of the matrix blank.
Table 6. Summary-Magnitude of Mean Values |
||
Adult versus Child |
Child 0-3 years versus 4-12 years |
|
3,5,6-trichloro-2-pyridinol (Chlorpyrifos metabolite) |
Child 2 times greater (hydrolyzed urine, Days 2 and 3) |
Older Child 7 times greater (non-hydrolyzed urine, Day 3) |
Dichlorvos |
Results not significant |
Older Child 7.5 times greater (hydrolyzed urine, Day 2) |
Atrazine |
Child 2 times greater (non-hydrolyzed urine, Day 3) |
Older Child 14 times greater (non-hydrolyzed urine, Day 2) |
2-isoprpyl-6-methyl-4-pyrimidinol (Diazinon metabolite) |
Child 7 times greater (non-hydrolyzed urine, Day 3) |
Younger Child 16 times greater (non-hydrolyzed urine, Day 2) |
Chlorpyrifos oxon (Chlorpyrifos metabolite) |
Results not significant |
Younger Child 2 times greater (non-hydrolyzed urine, Day 2) |
Conclusions:
Several overall conclusions can be made from the data:
- Simazine and dichlorovos were present at sufficient levels in air and urine samples to be detected as the parent compound. There were no significant differences between concentrations measured in adults versus children.
- In urine, three of the original targets (atrazine, chlorpyrifos, and diazinon) were detected in some samples as the parent compound or the metabolite. Malathion was not detected in any of the samples.
- Adults and all children are differentially exposed to atrazine, 3,5,6-trichloro-2-pyridinol (chlorpyrifos metabolite), and 2-isopropyl-6-methyl-4-pyrimidinol (diazinone metaboolite) or their precursors. The evidence suggests that children of all ages studied do receive higher doses relative to adults
- Children from 0-3 and 4-12 years of age are differentially exposed to atrazine, chlorpyrifos oxon, 3,5,6-trichloro-2-pyridinol, and 2-isopropyl-6-methyl-4-pyrimidinol (or their precursors). The largest difference was measured for the diazinon metabolite.
- There were no significant differences in any of the VOC concentrations in the personal samples of adults compared to children. P values ranged from 0.126 to 0.842.
- Adults exhaled toluene at higher absolute concentrations than children (mean: adults 14 ng/L, children 6.2 ng/L, P value = 0.074).
- Because atrazine, chlorpyrifos, and diazinon were not detected in the environmental sampling but were present in urine as the parent or metabolite, they were most likely introduced through dietary or other activities not captured, such as outdoor play.
The number of participants in this study was small, especially for the comparisons among different age groups for the same target analyte. In many cases, a compound was detected in one or more participants in a home but not all of the participants in a home. Comparisons, therefore, are based on averages over a given age category and could overestimate or underestimate the actual differences based on the real concentrations in the home. Because many of the children spent time outdoors during the study, some fraction of the analytes measured in urine are likely to have been derived form outdoor sources and are probably influenced by the specific activities of the children. Activity diary data did not contain specific activities outdoors. Other differences, especially for the chemicals with agricultural use (e.g., atrazine and the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol), also could have arisen from dietary exposures. This could have been supported or refuted by the food concentrations of the same analytes, although those data are not available.
Adults and children are exposed to VOCs through normal activities. This is not surprising because many of our target compounds, including toluene, are found in gasoline evaporative emissions and are ubiquitous in the environment. Some of the other targets are found as disinfection byproducts in tap water (e.g. chloroform) or are used in industrial processes like dry cleaning (e.g., tetrachloroethylene or perchloroethylene).
It is also important to note that heptachlor and chlordane still persist in the indoor environment and that, although exposures would be expected to decrease over time, they are still relevant to the potential body burden of both adults and children.
The data generated during this study can be used to make informed decisions about acceptable residues permitted in the home if it appears that children become more highly exposed as a result of interacting with that microenvironment.
Journal Articles:
No journal articles submitted with this report: View all 5 publications for this projectSupplemental Keywords:
multi-media exposure analysis, toxic substances, metabolism, toxics, children's health, epidemiology, health risk assessment, pesticides, age dependent response, age-related differences, air pollution, exposure, health effects, metabolites, indoor air, pesticide exposure,, RFA, Health, Scientific Discipline, Geographic Area, Health Risk Assessment, State, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Biochemistry, Children's Health, Molecular Biology/Genetics, genetic susceptability, health effects, pesticide exposure, urban air, MN, Minnesota, sensitive populations, metabolites, multi-pathway study, age-related differences, dermal contact, exposure, Human Health Risk Assessment, air pollution, children, assessment of exposure, children's vulnerablity, human exposure, pesticide residues, exposure pathways, indoor air, age dependent response, biomedical research, body burden, environmental hazard exposuresRelevant Websites:
http://www.rti.org Exit Synthesis Report of Research from EPA’s Science to Achieve Results (STAR) Grant Program: Feasibility of Estimating Pesticide Exposure and Dose in Children Using Biological Measurements (PDF) (42 pp, 3.87 MB)
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.