Exposure to Triclosan and Bisphenol Analogues B, F, P, S and Z in Repeated Duplicate-Diet Solid Food Samples of Adults.

Triclosan (TCS) and bisphenol analogues are used in a variety of consumer goods. Few data exist on the temporal exposures of adults to these phenolic compounds in their everyday diets. The objectives were to determine the levels of TCS and five bisphenol analogues (BPB, BPF, BPP, BPS, and BPZ) in duplicate-diet solid food (DDSF) samples of adults and to estimate maximum dietary exposures and intake doses per phenol. Fifty adults collected 776 DDSF samples over a six-week monitoring period in North Carolina in 2009-2011. The levels of the target phenols were concurrently quantified in the DDSF samples using gas chromatography/mass spectrometry. TCS (59%), BPS (32%), and BPZ (28%) were most often detected in the samples. BPB, BPF, and BPP were all detected in <16% of the samples. In addition, 82% of the total samples contained at least one target phenol. The highest measured concentration of 394 ng/g occurred for TCS in the food samples. The adults' maximum 24-h dietary intake doses per phenol ranged from 17.5 ng/kg/day (BPB) to 1600 ng/kg/day (TCS). An oral reference dose (300,000 ng/kg/day) is currently available for only TCS, and the adult's maximum dietary intake dose was well below a level of concern.

Dietary Exposures and Intake Doses to Bisphenol A and Triclosan in 188 Duplicate-Single Solid Food Items Consumed by US Adults.

Few data exist on bisphenol A (BPA) or triclosan (TCS) residue levels in foods consumed by adults in everyday settings. In a further analysis of study data, the objectives were to determine BPA and TCS residue concentrations in duplicate-single solid food items consumed by adults and to estimate dietary exposure and intake doses per food item. A convenience sample of 50 adults was recruited in North Carolina (2009-2011). Participants completed 24 h food diaries and collected 24 h duplicate-diet solid food samples consumed on days 1 and 2 during sampling weeks 1, 2, and 6. A total of 188 of the collected 776 duplicate-diet solid food samples contained a single, solid food item. BPA and TCS residue levels were quantified in the 188 food items using GC-MS. BPA and TCS were detected in 37% and 58% of these food items, respectively. BPA concentrations were highest in a cheese and tomato sandwich (104 ng/g), whereas the highest TCS concentrations were in a burrito (22.1 ng/g). These chemicals co-occurred in 20% of the samples (maximum = 54.7 ng/g). Maximum dietary intake doses were 429 ng/kg/day for BPA in a vegetable soup with tortilla sample and 72.0 ng/kg/day for TCS in a burrito sample.

Dietary Pyrethroid Exposures and Intake Doses for 188 Duplicate-Single Solid Food Items Consumed by North Carolina Adults.

Few studies have measured pyrethroid residue concentrations in food items consumed by adults in their daily environments. In a further analysis of study data, the objectives were to determine pyrethroid residue levels in single, solid food items consumed by adults and to estimate dietary pyrethroid exposures and intake doses per food item. A total of 50 adults collected 782 duplicate-diet solid food samples over a six-week monitoring period in North Carolina between 2009 and 2011. Of these samples, 188 contained a single, solid food item (i.e., lasagna). Levels of eight pyrethroids were quantified in the 188 food items using LC-MS/MS. At least one pyrethroid was detected in 39% of these food items. Cis-permethrin (17%), bifenthrin (15%), trans-permethrin (14%), and deltamethrin (14%) were detected the most often. Cyfluthrin, cyhalothrin, cypermethrin, and esfenvalerate were all detected in <6% of the samples. The highest residue level was found in a pizza sample containing both cis-permethrin (96.4 ng/g) and trans-permethrin (73.7 ng/g). For cis-permethrin, median residue levels (>LOQ) were significantly higher (p = 0.001) in foods that contained a fruit/vegetable compared to foods that did not. For individual pyrethroids, the participants' maximum dietary intake doses in the single food items ranged from 38.1 (deltamethrin) to 939 ng/kg/day (cis/trans-permethrin).

Pyrethroid insecticides and their environmental degradates in repeated duplicate-diet solid food samples of 50 adults.

Previous research has reported concurrent levels of pyrethroid insecticides and their environmental degradates in foods. These data raise concerns about using these same pyrethroid degradates found in the diet as urinary biomarkers of exposures in humans. The primary objective was to quantify levels of selected pyrethroids and their environmental degradates in duplicate-diet solid food samples of 50 adults over a six-week monitoring period. The study was conducted at the US EPA's Human Studies Facility in North Carolina and at participants' residences in 2009-2011. Participants collected duplicate-diet solid food samples on days 1 and 2 during weeks 1, 2, and 6 of the monitoring period. These samples were collected over three consecutive time periods each sampling day. A total of 782 food samples were homogenized and analyzed by LC/MS/MS for seven pyrethroids (bifenthrin, λ-cyhalothrin, cyfluthrin, cypermethrin, cis-deltamethrin, esfenvalerate, and cis/trans-permethrin) and six pyrethroid degradates. Results showed that 49% and 2% of all the samples contained at least one target pyrethroid or pyrethroid degradate, respectively. Cis/trans-permethrin (20%) and bifenthrin (20%) were the most frequently detected pyrethroids. The results suggest that the pyrethroid degradates were likely not present in sufficient levels in the diet to substantially impact the adults' urinary biomarker concentrations.

Distribution, variability, and predictors of urinary bisphenol A levels in 50 North Carolina adults over a six-week monitoring period.

Bisphenol A (BPA) is commonly manufactured to make polycarbonate plastics and epoxy resins for use in consumer products and packaged goods. BPA has been found in several different types of environmental media (e.g., food, dust, and air). Many cross-sectional studies have frequently detected BPA concentrations in adult urine samples. However, limited data are available on the temporal variability and important predictors of urinary BPA concentrations in adults. In this work, the major objectives were to: 1) quantify BPA levels in duplicate-diet solid food, drinking water, hard floor surface wipe, and urine samples (first-morning void [FMV], bedtime, and 24-h) collected from adults over a six-week monitoring period; 2) determine the temporal variability of urinary BPA levels using concentration, specific gravity (SG) adjusted, creatinine (CR) adjusted, and excretion rate values, and; 3) examine associations between available study factors and urinary BPA concentrations. In 2009-2011, a convenience sample of 50 adults was recruited from residential settings in North Carolina. The participants completed diaries and collected samples during weeks 1, 2, and/or 6 of a six-week monitoring period. BPA was detected in 38%, 4%, and 99% of the solid food (n=775), drinking water (n=50), and surface wipe samples (n=138), respectively. Total BPA (free plus conjugated) was detected in 98% of the 2477 urine samples. Median urinary BPA levels were 2.07ng/mL, 2.20ng/mL-SG, 2.29ng/mg, and 2.31ng/min for concentration, SG-adjusted, CR-adjusted, and excretion rate values, respectively. The intraclass correlation coefficient (ICC) estimates for BPA showed poor reproducibility (≤0.35) for all urine sample types and methods over a day, week, and six weeks. CR-adjusted bedtime voids collected over six-weeks required the fewest, realistic number of samples (n=11) to obtain a reliable biomarker estimate (ICC=0.80). Results of linear mixed-effects models showed that sex, race, season, and CR-level were all significant predictors (p<0.05) of the adults' urinary BPA concentrations. BPA levels in the solid food and surface wipe samples did not contribute significantly to the participants' urinary BPA concentrations. However, a significant positive relationship was observed between solid food intake and urine-based estimates of BPA dose, when aggregated over 24-h periods. Ingestion of BPA via solid food explained only about 20% of the total dose (at the median of the dose distribution), suggesting that these adults were likely exposed to other major unknown (non-dietary) sources of BPA in their everyday environments.

Measurement of pyrethroids and their environmental degradation products in fresh fruits and vegetables using a modification of the quick easy cheap effective rugged safe (QuEChERS) method.

Pyrethroid insecticides are used extensively in agriculture, and they, as well as their environmental degradates, may remain as residues on foods such as fruits and vegetables. Since pyrethroid degradates can be identical to the urinary markers used in human biomonitoring, it is important to understand the contribution of these degradates when studying sources of human pyrethroid exposure. We modified the widely used Quick Easy Cheap Effective Rugged Safe (QuEChERS) method to measure several current-use pyrethroids (cis/trans-permethrin, cypermethrin, deltamethrin, esfenvalerate, bifenthrin, cyfluthrin, and cyhalothrin) and their environmental degradation products (3-PBA, cis/trans-DCCA, 4-F-3-PBA, DBCA, and MPA) in selected fresh fruits and vegetables. Using fortified samples, we determined extraction efficiencies from: tomatoes, oranges (whole, peeled, and rind), grapes, apples, bananas (peeled and rind only), onions, lettuce, green peppers, carrots and broccoli. For a subset of these food items (apples, grapes, tomatoes, lettuce and banana peel), we also established limits of detection (MDLs) and quantitation (MQLs). Each sample was homogenized (1kg) then spiked with the target pyrethroids and their degradation products. Sub-samples (15g) were extracted with acetonitrile, then salted out and partitioned with NaCl and MgSO4. The extract was divided and further cleaned using solid phase extraction (SPE) cartridges containing either graphitized non-porous carbon (pyrethroids) or C18 (degradation products). Sample analysis was via liquid chromatography/tandem mass spectrometry (LC-MS/MS). Considering the mean recoveries each of the 14 analytes in all 13 matrices: 42% of the recoveries were ≥90%, 70% were ≥80%, and 90% were ≥70%. All MDL's were less than 100ng/kg, except 3-PBA (132ng/kg, tomato), MPA (129ng/kg, tomato), and trans-permethrin (141ng/kg, banana peel). We then applied the method to non-spiked samples (subset of 5 for which the MDLs/MQLs had been determined) collected weekly for four weeks from local supermarkets. At least one pyrethroid was present in measureable concentrations in all matrices except banana peels. In contrast, the only degradation products detected were cis/trans-DCCA, in one lettuce sample.

Temporal variability of pyrethroid metabolite levels in bedtime, morning, and 24-h urine samples for 50 adults in North Carolina.

Pyrethroid insecticides are widely used to control insects in both agricultural and residential settings worldwide. Few data are available on the temporal variability of pyrethroid metabolites in the urine of non-occupationally exposed adults. In this work, we describe the study design and sampling methodology for the Pilot Study to Estimate Human Exposures to Pyrethroids using an Exposure Reconstruction Approach (Ex-R study). Two major objectives were to quantify the concentrations of several pyrethroid metabolites in bedtime, first morning void (FMV), and 24-h urine samples as concentration (wet weight), specific-gravity (SG) corrected, creatinine (CR) corrected, and excretion rate values for 50 Ex-R adults over a six-week monitoring period and to determine if these correction approaches for urine dilution reduced the variability of the biomarker levels. The Ex-R study was conducted at the United States Environmental Protection Agency's Human Studies Facility in Chapel Hill, North Carolina USA and at participants' homes within a 40-mile radius of this facility. Recruitment of participants and field activities occurred between October 2009 and May 2011. Participants, ages 19-50 years old, provided daily food, activity, and pesticide-use diaries and collected their own urine samples (bedtime, FMV, and 24-h) during weeks 1, 2, and 6 of a six-week monitoring period. A total of 2503 urine samples were collected from the study participants. These samples were analyzed for the pyrethroid metabolites 3-phenoxybenzoic acid (3-PBA), cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis/trans-DCCA), and 2-methyl-3-phenylbenzoic acid (MPA) using high performance liquid chromatography/tandem mass spectrometry. Only 3-PBA was frequently detected (>50%) in the adult urine samples. Median urinary 3-PBA levels were 0.88 ng/mL, 0.96 ng/mL-SG, 1.04 ng/mg, and 1.04 ng/min for concentration, SG-corrected, CR-corrected, and excretion rate values, respectively, across all urine samples. The results showed that median urinary 3-PBA concentrations were consistently the lowest in FMV samples (0.77 ng/mL, 0.68 ng/mL-SG, 0.68 ng/mg, and 0.58 ng/min) and the highest in 24-h samples (0.92 ng/mL, 1.06 ng/mL-SG, 1.18 ng/mg, and 1.19 ng/min) across all four methods. Intraclass correlation coefficient (ICC) estimates for 3-PBA indicated poor reproducibility (<0.22) for all urine sample types and methods over a day, week, and six weeks. Correcting for urine sample dilution, based on either SG, CR or urine output, introduced additional measurement variability both between- and within-individuals. These results indicate that a single measure of urinary 3-PBA was not sufficient to characterize average exposure regardless of sample type, correction method, and time frame of collection. In addition, the study results can be used to inform the design of exposure characterization strategies in relevant environmental epidemiology studies in the future.

Predictors of urinary levels of 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridinol, 3-phenoxybenzoic acid, and pentachlorophenol in 121 adults in Ohio.

Limited data exist on the driving factors that influence the non-occupational exposures of adults to pesticides using urinary biomonitoring. In this work, the objectives were to quantify the urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol (TCP), 3-phenoxybenzoic acid (3-PBA), and pentachlorophenol (PCP) in 121 adults over a 48-h monitoring period and to examine the associations between selected sociodemographic and lifestyle factors and urinary levels of each pesticide biomarker. Adults, ages 20-49 years old, were recruited from six counties in Ohio (OH) in 2001. The participants collected 4-6 spot urine samples and completed questionnaires and diaries at home over a 48-h monitoring period. Urine samples were analyzed for 2,4-D, TCP, 3-PBA, and PCP by gas chromatography/mass spectrometry. Multiple regression modeling was used to determine the impact of selected sociodemographic and lifestyle factors on the log-transformed (ln) levels of each pesticide biomarker in adults. The pesticide biomarkers were detected in ≥ 89% of the urine samples, except for 3-PBA (66%). Median urinary levels of 2,4-D, TCP, 3-PBA, and PCP were 0.7, 3.4, 0.3, and 0.5 ng/mL, respectively. Results showed that 48-h sweet/salty snack consumption, 48-h time spend outside at home, and ln(creatinine) levels were significant predictors (p < 0.05), and race was a marginally significant predictor (p = 0.093) of the adults' ln(urinary 2,4-D) concentrations. Strong predictors (p < 0.05) of the adults' ln(urinary TCP) concentrations were urbanicity, employment status, sampling season, and ln(creatinine) levels. For 3-PBA, sampling season, pet ownership and removal of shoes before entering the home were significant predictors (p < 0.05) of the adults' ln(urinary 3-PBA) levels. Finally for PCP, removal of shoes before entering the home and ln(creatinine) levels were significant predictors (p < 0.05), and pet ownership was a marginally significant predictor (p = 0.056) of the adults' ln(urinary PCP) concentrations. In conclusion, specific sociodemographic and lifestyle factors were identified that increased the exposures of these adults to several different pesticides in their daily environments.

Using urinary biomarkers to evaluate polycyclic aromatic hydrocarbon exposure in 126 preschool children in Ohio.

Limited data exist on exposures of young children to polycyclic aromatic hydrocarbons (PAHs) in the United States (US). The urinary metabolite of pyrene, 1-hydroxypyrene (1-OHPyr), is widely used as a biomarker of total PAH exposure. Our objectives were to quantify urinary 1-OHPyr levels in 126 preschool children over a 48-h period and to examine associations between selected sociodemographic/lifestyle factors and urinary 1-OHPyr levels. Monitoring was performed at 126 homes and 16 daycares in Ohio in 2001, and questionnaires and urine samples were collected. The median urinary 1-OHPyr level was 0.33 ng/mL. In a multiple regression model, sampling season (p = 0.0001) and natural log (ln)-transformed creatinine concentration (p = 0.0006) were highly significant predictors of ln-transformed 1-OH-Pyr concentration; cooking appliance type (p = 0.096) was a marginally significant predictor of ln(1-OHPyr). These children had higher median urinary 1-OHPyr levels compared to other US children (≤ 0.15 ng/mL) in previously published studies, which suggests possible geographical differences in PAH exposure.

Analysis of inflammatory cytokines in human blood, breath condensate, and urine using a multiplex immunoassay platform.

A change in the expression of cytokines in human biological media indicates an inflammatory response to external stressors and reflects an early step along the adverse outcome pathway (AOP) for various health endpoints. To characterize and interpret this inflammatory response, methodology was developed for measuring a suite of 10 different cytokines in human blood, exhaled breath condensate (EBC), and urine using an electrochemiluminescent multiplex Th1/Th2 cytokine immunoassay platform. Measurement distributions and correlations for eight interleukins (IL) (1ß, 2, 4, 5, 8, 10, 12p70 and 13), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were evaluated using 90 blood plasma, 77 EBC, and 400 urine samples collected from nominally healthy adults subjects in North Carolina in 2008-2012. The in vivo results show that there is sufficient sensitivity for characterizing all 10 cytokines at levels of 0.05-0.10 ρg/ml with a dynamic range up to 100 ng/ml across all three of these biological media. The measured in vivo results also show that the duplicate analysis of blood, EBC and urine samples have average estimated fold ranges of 2.21, 3.49, and 2.50, respectively, which are similar to the mean estimated fold range (2.88) for the lowest concentration (0.610 ρg/ml) from a series of spiked control samples; the cytokine method can be used for all three biological media. Nine out of the 10 cytokines measured in EBC were highly correlated within one another with Spearman ρ coefficients ranging from 0.679 to 0.852, while the cytokines measured in blood had a mix of negative and positive correlations, ranging from -0.620 to 0.836. Almost all correlations between EBC and blood were positive. This work also represents the first successful within- and between-person evaluation of ultra trace-level inflammatory markers in blood, EBC, and urine.

Exposures of 129 preschool children to organochlorines, organophosphates, pyrethroids, and acid herbicides at their homes and daycares in North Carolina.

Few data exist on the concurrent exposures of young children to past-use and current-use pesticides in their everyday environments. In this further analysis of study data, we quantified the potential exposures and intake doses of 129 preschool children, ages 20 to 66 months, to 16 pesticides (eight organochlorines, two organophosphates, three pyrethroids, and three acid herbicides). Environmental samples (soil, dust, outdoor air, and indoor air) and personal samples (hand wipes, solid food, and liquid food) were collected at 129 homes and 13 daycare centers in six counties in North Carolina between 2000 and 2001. α-Chlordane, γ-chlordane, heptachlor, chlorpyrifos, diazinon, cis-permethrin, trans-permethrin, and 2,4-dichlorophenoxyacetic acid (2,4-D) were detected ≥50% in two or more media in both settings. Of these pesticides, the children's estimated median potential intake doses through dietary ingestion, nondietary ingestion, and inhalation routes were the highest for 2,4-D and cis/trans-permethrin (both 4.84 ng/kg/day), cis/trans-permethrin (2.39 ng/kg/day), and heptachlor (1.71 ng/kg/day), respectively. The children's estimated median potential aggregate intake doses by all three routes were quantifiable for chlorpyrifos (4.6 ng/kg/day), cis/trans-permethrin (12.5 ng/kg/day), and 2,4-D (4.9 ng/kg/day). In conclusion, these children were likely exposed daily to several pesticides from several sources and routes at their homes and daycares.

Dietary predictors of young children's exposure to current-use pesticides using urinary biomonitoring.

Few data exist on the association between dietary habits and urinary biomarker concentrations of pesticides in children. The objective was to examined the association between the weekly intake frequency of 65 food items and urinary biomarkers of exposure to chlorpyrifos (3,5,6-trichloro-2-pyridinol [TCP]), permethrin (3-phenoxybenzoic acid [3-PBA]), and 2,4-dichlorophenoxyacetic acid [2,4-D] in 135 preschool-aged children. TCP and 3-PBA are nonspecific biomarkers as they are also urinary metabolites of other pesticides. TCP, 3-PBA, and 2,4-D were detected in 99%, 64%, and 92% of the urine samples, respectively. Mean urinary TCP concentrations were statistically significantly higher in children consuming fresh apples (9.40±15.5 ng/mL versus 5.76±3.57 ng/mL, p=0.040) and fruit juices (8.41±11.5 ng/mL versus 4.11±2.77 ng/mL, p=0.020) ≥3 times a week compared to <3 times a week. For 3-PBA, mean urinary metabolite concentrations were statistically significantly greater in children consuming chicken/turkey meats (0.79±0.81 versus 0.41±0.39, p=0.013) ≥3 times a week compared to <3 times a week. No association occurred between the consumption of any food item and children's mean urinary 2,4-D concentrations by intake group. In conclusion, frequent consumption of fresh apples and fruit juices or chicken/turkey meats were significant dietary predictors of urinary levels of TCP or 3-PBA, respectively.

Children's exposures to pyrethroid insecticides at home: a review of data collected in published exposure measurement studies conducted in the United States.

Pyrethroid insecticides are frequently used to control insects in residential and agriculture settings in the United States and worldwide. As a result, children can be potentially exposed to pyrethroid residues in food and at home. This review summarizes data reported in 15 published articles from observational exposure measurement studies conducted from 1999 to present that examined children's (5 months to 17 years of age) exposures to pyrethroids in media including floor wipes, floor dust, food, air, and/or urine collected at homes in the United States. At least seven different pyrethroids were detected in wipe, dust, solid food, and indoor air samples. Permethrin was the most frequently detected (>50%) pyrethroid in these media, followed by cypermethrin (wipes, dust, and food). 3-phenoxybenzoic acid (3-PBA), a urinary metabolite of several pyrethroids, was the most frequently (≥67%) detected pyrethroid biomarker. Results across studies indicate that these children were likely exposed to several pyrethroids, but primarily to permethrin and cypermethrin, from several sources including food, dust, and/or on surfaces at residences. Dietary ingestion followed by nondietary ingestion were the dominate exposure routes for these children, except in homes with frequent pesticide applications (dermal followed by dietary ingestion). Urinary 3-PBA concentration data confirm that the majority of the children sampled were exposed to one or more pyrethroids.

Population variability of phthalate metabolites and bisphenol A concentrations in spot urine samples versus 24- or 48-h collections.

Human exposure to phthalates and bisphenol A (BPA) can be assessed through urinary biomonitoring, but methods to infer daily intakes assume that spot sample concentrations are comparable to daily average concentrations. We evaluate this assumption using human biomonitoring data from Germany and the United States (US). The German data comprised three regional studies with spot samples and one with full-day samples analyzed for phthalate metabolites. The US data included: a study on DEHP metabolites and BPA involving eight persons supplying all urine voids (from which 24-h samples were constructed) for seven consecutive days; NHANES spot sample data on DEHP metabolites and BPA; and a regional study of children with 48-h samples analyzed for BPA. In the German data, measures of central tendency differed, but spot and 24-h samples showed generally comparable variance including 95th percentiles and maxima equidistant from central tendency measures. In contrast, the US adult data from the eight-person study showed similar central tendencies for phthalate metabolites and BPA, but generally greater variability for the spot samples, including higher 95th percentiles and maxima. When comparing children's BPA concentrations in NHANES spot and 48-h samples, distributions showed similar central tendency and variability. Overall, spot urinary concentrations of DEHP metabolites and BPA have variability roughly comparable with corresponding 24-h average concentrations obtained from a comparable population, suggesting that spot samples can be used to characterize population distributions of intakes. However, the analysis also suggests that caution should be exercised when interpreting the high end of spot sample data sets.

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.

Assessing the quantitative relationships between preschool children's exposures to bisphenol A by route and urinary biomonitoring.

Limited published information exists on young children's exposures to bisphenol A (BPA) in the United States using urinary biomonitoring. In a previous project, we quantified the aggregate exposures of 257 preschool children to BPA in environmental and personal media over 48-h periods in 2000-2001 at homes and daycares in North Carolina and Ohio. In the present study for 81 Ohio preschool children ages 23-64 months, we quantified the children's urinary total BPA (free and conjugated) concentrations over these same 48-h periods in 2001. Then, we examined the quantitative relationships between the children's intakes doses of BPA through the dietary ingestion, nondietary ingestion, and inhalation routes and their excreted amounts of urinary BPA. BPA was detected in 100% of the urine samples. The estimated median intake doses of BPA for these 81 children were 109 ng/kg/day (dietary ingestion), 0.06 ng/kg/day (nondietary ingestion), and 0.27 ng/kg/day (inhalation); their estimated median excreted amount of urinary BPA was 114 ng/kg/day. Our multivariable regression model showed that dietary intake of BPA (p = 0.04) and creatinine concentration (p = 0.004) were significant predictors of urinary BPA excretion, collectively explaining 17% of the variability in excretion. Dietary ingestion of BPA accounted for >95% of the children's excreted amounts of urinary BPA.

The reliability of using urinary biomarkers to estimate children's exposures to chlorpyrifos and diazinon.

A few studies have reported concurrent levels of chlorpyrifos (CPF) and diazinon (DZN) and their environmentally occurring metabolites, 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-6-methyl-4-pyrimidinol (IMP), in food and in environmental media. This information raises questions regarding the reliability of using these same metabolites, TCP and IMP, as urinary biomarkers to quantitatively assess the everyday exposures of children to CPF and DZN, respectively. In this study, we quantified the distributions of CPF, DZN, TCP, and IMP in several environmental and personal media at the homes and day-care centers of 127 Ohio preschool children and identified the important sources and routes of their exposures. The children were exposed to concurrent levels of these four chemicals from several sources and routes at these locations. DZN and IMP were both detected above 50% in the air and dust samples. CPF and TCP were both detected in greater than 50% of the air, dust (solid), food, and hand wipe samples. TCP was detected in 100% of the urine samples. Results from our regression models showed that creatinine levels (<0.001), and dietary (P<0.001) and inhalation (P<0.10) doses of TCP were each significant predictors of urinary TCP, collectively explaining 27% of the urinary TCP variability. This information suggests that measurement of urinary TCP did not reliably allow quantitative estimation of the children's everyday environmental exposures to CPF.

Biomonitoring data for 2,4-dichlorophenoxyacetic acid in the United States and Canada: interpretation in a public health risk assessment context using Biomonitoring Equivalents.

BACKGROUND: Several extensive studies of exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) using urinary concentrations in samples from the general population, farm applicators, and farm family members are now available. Reference doses (RfDs) exist for 2,4-D, and Biomonitoring Equivalents (BEs; concentrations in urine or plasma that are consistent with those RfDs) for 2,4-D have recently been derived and published. OBJECTIVE: We reviewed the available biomonitoring data for 2,4-D from the United States and Canada and compared them with BE values to draw conclusions regarding the margin of safety for 2,4-D exposures within each population group. DATA SOURCES: Data on urinary 2,4-D excretion in general and target populations from recent published studies are tabulated and the derivation of BE values for 2,4-D summarized. DATA SYNTHESIS: The biomonitoring data indicate margins of safety (ratio of BE value to biomarker concentration) of approximately 200 at the central tendency and 50 at the extremes in the general population. Median exposures for applicators and their family members during periods of use appear to be well within acute exposure guidance values. CONCLUSIONS: Biomonitoring data from these studies indicate that current exposures to 2,4-D are below applicable exposure guidance values. This review demonstrates the value of biomonitoring data in assessing population exposures in the context of existing risk assessments using the BE approach. Risk managers can use this approach to integrate the available biomonitoring data into an overall assessment of current risk management practices for 2,4-D.

An observational study of the potential for human exposures to pet-borne diazinon residues following lawn applications.

This study examined the potential for pet dogs to be an important pathway for transporting diazinon residues into homes and onto its occupants following residential lawn applications. The primary objectives were to investigate the potential exposures of occupants and their pet dogs to diazinon after an application to turf at their residences and to determine if personal contacts between occupants and their pet dogs resulted in measurable exposures. It was conducted from April to August 2001 before the Agency phased out all residential uses of diazinon in December 2004. Six families and their pet dogs were recruited into the study. Monitoring was conducted at pre-, 1, 2, 4, and 8 days post-application of a commercial, granular formulation of diazinon to the lawn by the homeowner. Environmental samples collected included soil, indoor air, carpet dust, and transferable residues from lawns and floors. Samples collected from the pet dogs consisted of paw wipes, fur clippings, and transferable residues from the fur by a technician or child wearing a cotton glove(s). First morning void (FMV) urine samples were collected from each child and his/her parent on each sampling day. Diazinon was analyzed in all samples, except urine, by GC-MS. The metabolite 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy) was analyzed in the urine samples by HPLC-MS/MS. Mean airborne residues of diazinon on day 1 post-application were at least six times higher in both the living rooms (235+/-267 ng/m(3)) and children's bedrooms (179+/-246 ng/m(3)) than at pre-application. Mean loadings of diazinon in carpet dust samples were at least 20 times greater on days 2, 4, and 8 post-application than mean loadings (0.03+/-0.04 ng/cm(2)) at pre-application. The pet dogs had over 900 times higher mean loadings of diazinon residues on their paws on day 1 post-application (88.1+/-100.1 ng/cm(2)) compared to mean loadings (<0.09 ng/cm(2)) at pre-application. The mean diazinon loadings on the fur clippings were at least 14 times higher on days 1, 2, 4, and 8 post-application than mean loadings (0.8+/-0.4 ng/cm(2)) at pre-application. For transferable residues from dog fur, the mean loadings of diazinon on the technician's cotton glove samples were the lowest before application (0.04+/-0.08 ng/cm(2)) and the highest on day 1 post-application (10.4+/-23.9 ng/cm(2)) of diazinon to turf. Urinary IMPy concentrations for the participants ranged from <0.3 to 5.5 ng/mL before application and <0.3-12.5 ng/mL after application of diazinon. The mean urinary IMPy concentrations for children or adults were not statistically different (p>0.05) at pre-application compared to post-application of diazinon to turf. The results showed that the participants and their pet dogs were likely exposed to low levels of diazinon residues from several sources (i.e., air, dust, and soil), through several pathways and routes, after lawn applications at these residences. Lastly, the pet dog appears to be an important pathway for the transfer and translocation of diazinon residues inside the homes and likely exposed occupants through personal contacts (i.e., petting).

Adult and children's exposure to 2,4-D from multiple sources and pathways.

In this study, we investigated the 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide exposures of 135 preschool-aged children and their adult caregivers at 135 homes in North Carolina (NC) and Ohio (OH). Participants were randomly recruited from six NC and six OH counties. Monitoring was performed over a 48-h period at the participants' homes. Environmental samples included soil, outdoor air, indoor air, and carpet dust. Personal samples collected by the adult caregivers concerning themselves and their children consisted of solid food, liquid food, hand wipe, and spot urine samples. All samples were analyzed for 2,4-D (free acid form) by gas chromatography/mass spectrometry. 2,4-D was detected in all types of environmental samples but most often in carpet dust samples, with detection frequencies of 83% and 98% in NC and OH, respectively. The median level of 2,4-D in the carpet dust samples was about three times higher in OH homes compared to NC homes (156 vs. 47.5 ng/g, P<0.0002). For personal samples, 2,4-D was more frequently detected in the hand wipe samples from OH participants (>48%) than from NC participants (<9%). Hand wipe levels at the 95th percentile were about five times higher for OH children (0.1 ng/cm(2)) and adults (0.03 ng/cm(2)) than for the NC children (0.02 ng/cm(2)) and adults (<0.005 ng/cm(2)). 2,4-D was detected in more than 85% of the child and adult urine samples in both states. The median urinary 2,4-D concentration was more than twice as high for OH children compared to NC children (1.2 vs. 0.5 ng/ml, P<0.0001); however, the median concentration was identical at 0.7 ng/ml for both NC and OH adults. The intraclass correlation coefficient of reliability for an individual's urinary 2,4-D measurements, estimated from the unadjusted (0.31-0.62) and specific gravity-adjusted (0.37-0.73) values, were somewhat low for each group in this study. The variability in urinary 2,4-D measurements over the 48-h period for both children and adults in NC and OH suggests that several spot samples were needed to adequately assess these participants' exposures to 2,4-D in residential settings. Results from this study showed that children and their adult caregivers in NC and OH were likely exposed to 2,4-D through several pathways at their homes. In addition, our findings suggest that the OH children might have been exposed to higher levels of 2,4-D through the dermal and nondietary routes of exposure than the NC children and the NC and OH adults.