A longitudinal investigation of selected pesticide metabolites in urine.

As part of a longitudinal investigation of environmental exposures to selected chemical contaminants, concentrations of the pesticide metabolites 1-naphthol (INAP), 3,5,6-trichloro-2-pyridinol (TCPY), malathion dicarboxylic acid (MDA), and atrazine mercapturate (AM) were measured in repeated samples obtained from 80 individuals in Maryland during 1995-1996. Up to six urine samples were collected from each individual at intervals of approximately 8 weeks over a 1-year period (i.e., one sample per participant in each of six cycles). INAP (median=4.2 microg/l and 3.3 microg/g creatinine) and TCPY (median=5.3 microg/l and 4.6. microg/g creatinine) were present in over 80% of the samples, while MDA and AM were detected infrequently (6.6% and <1% of samples, respectively). Geometric mean (GM) concentrations of INAP in urine did not vary significantly among sampling cycles. In contrast, GM concentrations of TCPY were significantly greater in samples collected during the spring and summer of 1996 than in the preceding fall and winter. Repeated measurements of INAP and TCPY from the same individual over time were highly variable. The average range of INAP and TCPY concentrations from the same individual were approximately 200% and 50% greater than the respective population mean levels. Geometric mean (GM) TCPY concentrations differed significantly between Caucasian (n=42, GM=5.7 microg/g creatinine) and African-American (n=11, GM=4.0 microg/g) participants and among education levels, but were not significantly different among groups classified by gender, age, or household income. In future research, environmental measurements of the parent compounds and questionnaire data collected concurrently with the biomarker data will be used to characterize the determinants of variability in the urinary pesticide metabolite levels.     

Biological monitoring of pesticide exposures among applicators and their children in Nicaragua

Exposures were assessed for seven small-scale farmers using chlorpyrifos on corn and ten banana plantation employees applying diazinon, and for one child of each worker. Metabolites (TCPYand IMPY) were measured in urine before and after applications. TCPY concentrations peaked at 27 and 8.5 hours post-application for applicators and children, respectively (geometric means, 26 and 3.0 microg/L). Proximity to spraying and spray mixture preparation in homes were important exposure factors. IMPY concentrations differed substantially across workers at two plantations (geometric means, 1.3 and 168 mirog/L); however, their children had little or no diazinon exposure. These workers and children were also exposed to chlorpyrifos, most likely through contact with chlorpyrifos-impregnated bags used in banana production. Several recommendations are offered: (1) monitor children's activities during applications; (2) do not store or prepare pesticides in homes; (3) institute sound occupational hygiene practices at banana plantations; (4) dispose of plastic insecticide bags properly at the worksite.     

Pesticide urinary metabolite levels of children in eastern North Carolina farmworker households

BACKGROUND: In this investigation we documented the pesticide urinary metabolite levels of farmworker children in North Carolina, determined the number of different metabolites detected for each child, and delineated risk factors associated with the number of metabolites. METHODS: Urine samples were collected from 60 Latino farmworker children 1-6 years of age (34 female, 26 male). Interviews were completed by their mothers in Spanish. We analyzed urine samples for 14 pesticide metabolites, including the organophosphate pesticides chlorpyrifos, coumaphos, diazinon, isazaphos, malathion, pirimiphos, and parathion and its methyl counterpart; a common metabolite of at least 18 pyrethroid insecticides; the repellent DEET; and the herbicides 2,4,5-trichlorphenoxyacetic acid, 2,4-dichlorophenoxyacetic acid, acetochlor, atrazine, and metolachlor. Predictors included measures of paraoccupational, residential, and environmental exposure, child characteristics, and mother characteristics. RESULTS: Thirteen metabolites were present in the urine samples. Organophosphate pesticide metabolites were detected in a substantial proportion of children, particularly metabolites of parathion/methyl parathion (90.0%; geometric mean 1.00 microg/L), chlorpyrifos/chlorpyrifos methyl (83.3%; geometric mean 1.92 microg/L), and diazinon (55.0%; geometric mean 10.56 microg/L). The number of metabolites detected ranged from 0 to 7, with a mode of 4 detected (28.3%). Boys, children living in rented housing, and children with mothers working part-time had more metabolites detected. CONCLUSIONS: Children in farmworker homes experience multiple sources of pesticide exposure. Pesticides may remain in their environments for long periods. Environmental and occupational health changes are needed to address these exposures. Research is needed with more precise measures of exposure and on the health effects of concurrent exposure to multiple pesticides.     

Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the U.S. population

We report population-based concentrations, stratified by age, sex, and racial/ethnic groups, of dialkyl phosphate (DAP) metabolites of multiple organophosphorus pesticides. We measured dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP) concentrations in 1,949 urine samples collected in U.S. residents 6-59 years of age during 1999 and 2000 as a part of the ongoing National Health and Nutrition Examination Survey (NHANES). We detected each DAP metabolite in more than 50% of the samples, with DEP being detected most frequently (71%) at a limit of detection of 0.2 microg/L. The geometric means for the metabolites detected in more than 60% of the samples were 1.85 microg/L for DMTP and 1.04 microg/L for DEP. The 95th percentiles for each metabolite were DMP, 13 microg/L; DMTP, 46 microg/L; DMDTP, 19 micro g/L; DEP, 13 microg/L; DETP, 2.2 microg/L; and DEDTP, 0.87 microg/L. We determined the molar sums of the dimethyl-containing and diethyl-containing metabolites; their geometric mean concentrations were 49.4 and 10.5 nmol/L, respectively, and their 95th percentiles were 583 and 108 nmol/L, respectively. These data are also presented as creatinine-adjusted concentrations. Multivariate analyses showed concentrations of DAPs in children 6-11 years of age that were consistently significantly higher than in adults and often higher than in adolescents. Although the concentrations between sexes and among racial/ethnic groups varied, no significant differences were observed. These data will be important in evaluating the impact of organophosphorus pesticide exposure in the U.S. population and the effectiveness of regulatory actions.     

Measurement of children's exposure to pesticides: analysis of urinary metabolite levels in a probability-based sample.

The Minnesota Children's Pesticide Exposure Study is a probability-based sample of 102 children 3-13 years old who were monitored for commonly used pesticides. During the summer of 1997, first-morning-void urine samples (1-3 per child) were obtained for 88% of study children and analyzed for metabolites of insecticides and herbicides: carbamates and related compounds (1-NAP), atrazine (AM), malathion (MDA), and chlorpyrifos and related compounds (TCPy). TCPy was present in 93% of the samples, whereas 1-NAP, MDA, and AM were detected in 45%, 37%, and 2% of samples, respectively. Measured intrachild means ranged from 1.4 microg/L for MDA to 9.2 microg/L for TCPy, and there was considerable intrachild variability. For children providing three urine samples, geometric mean TCPy levels were greater than the detection limit in 98% of the samples, and nearly half the children had geometric mean 1-NAP and MDA levels greater than the detection limit. Interchild variability was significantly greater than intrachild variability for 1-NAP (p = 0.0037) and TCPy (p < 0.0001). The four metabolites measured were not correlated within urine samples, and children's metabolite levels did not vary systematically by sex, age, race, household income, or putative household pesticide use. On a log scale, mean TCPy levels were significantly higher in urban than in nonurban children (7.2 vs. 4.7 microg/L; p = 0.036). Weighted population mean concentrations were 3.9 [standard error (SE) = 0.7; 95% confidence interval (CI), 2.5, 5.3] microg/L for 1-NAP, 1.7 (SE = 0.3; 95% CI, 1.1, 2.3) microg/L for MDA, and 9.6 (SE = 0.9; 95% CI, 7.8, 11) microg/L for TCPy. The weighted population results estimate the overall mean and variability of metabolite levels for more than 84,000 children in the census tracts sampled. Levels of 1-NAP were lower than reported adult reference range concentrations, whereas TCPy concentrations were substantially higher. Concentrations of MDA were detected more frequently and found at higher levels in children than in a recent nonprobability-based sample of adults. Overall, Minnesota children's TCPy and MDA levels were higher than in recent population-based studies of adults in the United States, but the relative magnitude of intraindividual variability was similar for adults and children.     

Metabolites of organophosphorous insecticides in urine specimens from inhabitants of a residential area

The most frequently used pesticide in U.S. homes, as well as in schools and day care centers, is chlorpyrifos. In 1998, this insecticide was detected in household dust from the former U.S. Forces housing estates in Frankfurt am Main, Germany, resulting from its earlier use up to 1993, i.e., at least 4 years ago. This led to great concern in the new inhabitants. To investigate their internal exposure to the substance, they were offered the opportunity of taking part in biomonitoring examinations. Children playing on the floor were assumed to be especially at risk due to increased exposure to chlorpyrifos via oral or dermal intake. A total of 1146 inhabitants took part in this voluntary investigation. All of them stated that they had never used chlorpyrifos in their homes. Spot urine samples of the study participants were analyzed for six metabolites of organophosphorous insecticides [dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), diethylthiophosphate (DETP), dimethyldithiophosphate (DMDTP), and diethyldithiophosphate (DEDTP)] using a very sensitive gas chromatographic method with mass-selective detection and a limit of detection of 1 microg/L. No evidence was found of increased internal exposure due to former chlorpyrifos application in these homes (>4 years ago), either in children or in adults. The median values and 95th percentiles of the urinary metabolite concentrations in 484 adults were (microg/g creatinine): DMP, 15.5 and 102.5; DMTP, 13.5 and 125.8; DMDTP, <1 and 13.1; DEP, 2.1 and 11.6; DETP, <1 and 6.4; DEDTP, both <1. The urinary metabolite concentrations in children <6 years of age were higher; this was caused mainly by lower creatinine concentrations. To conclude, no increase in internal exposure due to former indoor application of chlorpyrifos could be found, and the reference values published for internal organophosphate exposure in adults in Germany were confirmed. However, as shown in other environmental studies, the urinary excretion of organophosphorous metabolites exceeds dietary intake several fold; this has been estimated from the data in various duplicate dietary studies. This observation calls for further investigation.     

Children's exposure to chlorpyrifos and parathion in an agricultural community in central Washington State

We measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and parathion--in residences, and their metabolic by-products, in the urine of children 6 years old or younger in a central Washington State agricultural community. Exposures to two dimethyl OP pesticides (azinphos-methyl and phosmet) in this same population have been reported previously. We categorized children by parental occupation and by household proximity to pesticide-treated farmland. Median chlorpyrifos house dust concentrations were highest for the 49 applicator homes (0.4 microg/g), followed by the 12 farm-worker homes (0.3 microg/g) and the 14 nonagricultural reference homes (0.1 microg/g), and were statistically different (p < 0.001); we observed a similar pattern for parathion in house dust. Chlorpyrifos was measurable in the house dust of all homes, whereas we found parathion in only 41% of the homes. Twenty-four percent of the urine samples from study children had measurable 3,5,6-trichloro-2-pyridinol (TCPy) concentrations [limits of quantitation (LOQ) = 8 microg/L], and 7% had measurable 4-nitrophenol concentrations (LOQ = 9 microg/L). Child urinary metabolite concentrations did not differ across parental occupational classifications. Homes in close proximity (200 ft/60 m) to pesticide-treated farmland had higher chlorpyrifos (p = 0.01) and parathion (p = 0.014) house dust concentrations than did homes farther away, but this effect was not reflected in the urinary metabolite data. Use of OP pesticides in the garden was associated with an increase in TCPy concentrations in children's urine. Parathion concentrations in house dust decreased 10-fold from 1992 to 1995, consistent with the discontinued use of this product in the region in the early 1990s.     

Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population

Bisphenol A (BPA) is used to manufacture polycarbonate plastic and epoxy resins, which are used in baby bottles, as protective coatings on food containers, and for composites and sealants in dentistry. 4-Nonylphenol (NP) is used to make nonylphenol ethoxylates, nonionic surfactants applied as emulsifying, wetting, dispersing, or stabilizing agents in industrial, agricultural, and domestic consumer products. The potential for human exposure to BPA and NP is high because of their widespread use. We measured BPA and NP in archived urine samples from a reference population of 394 adults in the United States using isotope-dilution gas chromatography/mass spectrometry. The concentration ranges of BPA and NP were similar to those observed in other human populations. BPA was detected in 95% of the samples examined at concentrations > or = 0.1 microg/L urine; the geometric mean and median concentrations were 1.33 microg/L (1.36 microg/g creatinine) and 1.28 microg/L (1.32 microg/g creatinine), respectively; the 95th percentile concentration was 5.18 microg/L (7.95 microg/g creatinine). NP was detected in 51% of the samples examined > or = 0.1 microg/L. The median and 95th percentile concentrations were < 0.1 microg/L and 1.57 microg/L (1.39 microg/g creatinine), respectively. The frequent detection of BPA suggests widespread exposure to this compound in residents of the United States. The lower frequency of detection of NP than of BPA could be explained by a lower exposure of humans to NP, by different pharmacokinetic factors (i.e., absorption, distribution, metabolism, elimination), by the fact that 4-n-nonylphenol--the measured NP isomer--represents a small percentage of the NP used in commercial mixtures, or a combination of all of the above. Additional research is needed to determine the best urinary biomarker(s) to assess exposure to NP. Despite the sample population's nonrepresentativeness of the U.S. population (although sample weights were used to improve the extent to which the results represent the U.S. population) and relatively small size, this study provides the first reference range of human internal dose levels of BPA and NP in a demographically diverse human population.     

Concentrations of the sunscreen agent benzophenone-3 in residents of the United States: National Health and Nutrition Examination Survey 2003--2004

BACKGROUND: The capability of benzophenone-3 (BP-3) to absorb and dissipate ultraviolet radiation facilitates its use as a sunscreen agent. BP-3 has other uses in many consumer products (e.g., as fragrance and flavor enhancer, photoinitiator, ultraviolet curing agent, polymerization inhibitor). OBJECTIVES: Our goal was to assess exposure to BP-3 in a representative sample of the U.S. general population > or = 6 years of age. METHODS: Using automated solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry, we analyzed 2,517 urine samples collected as part of the 2003--2004 National Health and Nutrition Examination Survey. RESULTS: We detected BP-3 in 96.8% of the samples. The geometric mean and 95th percentile concentrations were 22.9 microg/L (22.2 microg/g creatinine) and 1,040 microg/L (1,070 microg/g creatinine), respectively. Least-square geometric mean (LSGM) concentrations were significantly higher (p < or = 0.04) for females than for males, regardless of age. LSGM concentrations were significantly higher for non-Hispanic whites than for non-Hispanic blacks (p < or = 0.01), regardless of age. Females were more likely than males [adjusted odds ratio (OR) = 3.5; 95% confidence interval (95% CI), 1.9-6.5], and non-Hispanic whites were more likely than non-Hispanic blacks (adjusted OR = 6.8; 95% CI, 2.9-16.2) to have concentrations above the 95th percentile. CONCLUSIONS: Exposure to BP-3 was prevalent in the general U.S. population during 2003--2004. Differences by sex and race/ethnicity probably reflect differences in use of personal care products containing BP-3.     

Exposure to nonpersistent insecticides and male reproductive hormones

BACKGROUND: Urinary metabolites of several nonpersistent insecticides have been measured in a high percentage of men in the general population, suggesting widespread environmental exposures to these compounds. The present study explored the association of urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, and 1-naphthol (1N), a metabolite of carbaryl and naphthalene, with serum reproductive hormone levels in adult men. METHODS: Subjects (n = 268) were the male partners in couples presenting to a Massachusetts infertility clinic in years 2000 through 2003. TCPY and 1N were measured in a spot urine sample from each subject and adjusted for dilution using specific gravity. Reproductive hormones (follicle-stimulating hormone, leuteinizing hormone, inhibin B, testosterone, and sex hormone-binding globulin) were measured in serum collected from subjects during the same clinic visit. RESULTS: Multiple linear regression models showed an inverse association between TCPY and testosterone concentration. An interquartile range (IQR) increase in TCPY was associated with a decline of 25 ng/dL (95% confidence interval = -40 to -10) in testosterone concentration. The association appeared to be dose-dependent when exposure was divided into quintiles. The highest TCPY quintile was associated with a testosterone decline of 83 ng/dL (-128 to -39) compared with the lowest TCPY quintile. We also found inverse associations between TCPY and free androgen index and between 1N and testosterone, and suggestive inverse associations between TCPY and leuteinizing hormone and between 1N and free androgen index. CONCLUSION: In adult men, TCPY and 1N were associated with reduced testosterone levels. On a population level, these reductions are of potential public health importance because of widespread exposure to these nonpersistent insecticides.     

Urinary phytoestrogen concentrations in the U.S. population (1999-2000)

We report population-based urinary concentrations of phytoestrogens stratified by age, sex, and composite racial/ethnic variables. We measured the isoflavones - genistein, daidzein, equol, and O-desmethylangolensin (O-DMA) - and the lignans - enterolactone and enterodiol - in approximately 2500 urine samples from individuals aged 6 years and older who participated in the National Health and Nutrition Examination Survey (NHANES) in 1999 and 2000. We detected all phytoestrogens in over 70% of the samples analyzed; enterolactone was detected in the highest concentrations, and daidzein was detected with the highest frequency. The geometric means for each phytoestrogen were as follows: genistein, 22.3 microg/g; daidzein, 68.6 microg/g; equol, 7.65 microg/g; O-DMA, 3.95 microg/g; enterolactone, 217 microg/g; and enterodiol, 24.3 microg/g creatinine. The 95th percentiles for each phytoestrogen were as follows: genistein, 380 microg/g; daidzein, 944 microg/g; equol, 50.3 microg/g; O-DMA, 217 microg/g; enterolactone, 2240 microg/g; and enterodiol, 240 microg/g creatinine. Multivariate analyses showed statistically significant differences among many of the demographic subgroups. Adolescents had higher concentrations of genistein and equol than adults. Non-Hispanic whites had higher concentrations of enterodiol and equol than Mexican Americans or non-Hispanic blacks. Non-Hispanic whites also had higher concentrations of enterolactone and O-DMA than Mexican Americans. Mexican Americans had higher concentrations of genistein than non-Hispanic blacks; however, the opposite was found for O-DMA. Determination of phytoestrogen exposure in the US population will help us to better understand phytoestrogen consumption in the US and will assist us in elucidating the potential role of phytoestrogens in protecting against cancer and heart disease.     

Levels of seven urinary phthalate metabolites in a human reference population

Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 microg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 microg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 microg/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate. Women of reproductive age (20-40 years) were found to have significantly higher levels of monobutyl phthalate, a reproductive and developmental toxicant in rodents, than other age/gender groups (p < 0.005). Current scientific and regulatory attention on phthalates has focused almost exclusively on health risks from exposure to only two phthalates, di-(2-ethylhexyl) phthalate and di-isononyl phthalate. Our findings strongly suggest that health-risk assessments for phthalate exposure in humans should include diethyl, dibutyl, and benzyl butyl phthalates.     

The relationship of urinary metabolites of carbaryl/naphthalene and chlorpyrifos with human semen quality

Most of the general population is exposed to carbaryl and other contemporary-use insecticides at low levels. Studies of laboratory animals, in addition to limited human data, show an association between carbaryl exposure and decreased semen quality. In the present study we explored whether environmental exposures to 1-naphthol (1N), a metabolite of carbaryl and naphthalene, and 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, are associated with decreased semen quality in humans. Subjects (n=272) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary concentrations of 1N and TCPY adjusted using specific gravity. Semen quality was assessed as sperm concentration, percent motile sperm, and percent sperm with normal morphology, along with sperm motion parameters (straight-line velocity, curvilinear velocity, and linearity). Median TCPY and 1N concentrations were 3.22 and 3.19microg/L, respectively. For increasing 1N tertiles, adjusted odds ratios (ORs) were significantly elevated for below-reference sperm concentration (OR for low, medium, and high tertiles = 1.0, 4.2, 4.2, respectively; p-value for trend =0.01) and percent motile sperm (1.0, 2.5, 2.4; p-value for trend = 0.01). The sperm motion parameter most strongly associated with 1N was straight-line velocity. There were suggestive, borderline-significant associations for TCPY with sperm concentration and motility, whereas sperm morphology was weakly and nonsignificantly associated with both TCPY and 1N. The observed associations between altered semen quality and 1N are consistent with previous studies of carbaryl exposure, although suggestive associations with TCPY are difficult to interpret because human and animal data are currently limited.     

Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population

Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures. However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [beta(adjusted) = -0.41 weeks per log10 unit increase; 95% confidence interval (CI), -0.75 -- -0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (beta(adjusted) = 0.34 weeks per unit increase; 95% CI, 0.13-0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population.     

Reference range concentrations of N-acetyl-S-(2-hydroxyethyl)-L-cysteine, a common metabolite of several volatile organic compounds, in the urine of adults in the United States.

N-acetyl-S-(2-hydroxyethyl)-L-cysteine (2-hydroxyethyl mercapturic acid, HEMA) is a urinary metabolite of several hazardous chemicals, including vinyl chloride (VC), ethylene oxide (EO), and ethylene dibromide (EDB). Information about the levels of HEMA in the general population is useful for assessing human exposures to HEMA parent compounds, including VC, EO, and EDB. To establish reference range concentrations for HEMA, we analyzed urine samples from 412 adult participants in the Third National Health and Nutrition Examination Survey (NHANES II) by using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). HEMA was detected in 71% of the samples examined. Creatinine-corrected concentrations ranged from less than 0.68 microg/g creatinine to 58.7 microg/g creatinine; the 95th percentile concentration was 11.2 microg/g creatinine; and the geometric mean and median creatinine-corrected concentrations were both 1.6 microg/g creatinine. We observed a statistically significant difference (P=0.0001) in the creatinine-corrected geometric mean concentration values of HEMA between smokers (2.8 microg/g creatinine) and nonsmokers (1.1 microg/g creatinine). The high levels of HEMA seen among smokers likely originated from HEMA-producing chemicals known to be present in tobacco smoke.     

GerES IV pilot study: assessment of the exposure of German children to organophosphorus and pyrethroid pesticides

Organophosphorus pesticides and pyrethroids are widely used in German agriculture and residential settings. Their occurrence in human biological samples can be used as an indicator for the exposure of children to these compounds. Using multivariate evaluation the routes of exposure can be identified. In the pilot study of GerES IV, metabolites of pyrethroids and organophosporus pesticides were analysed in urine of children aged 2-17 years (n = 396 and 363). The 95th percentiles for the metabolites of the pyrethroids in urine were: cis-DCCA 0.74 microg/l, trans-DCCA 1.7 microg/l, DBCA 0.52 microg/l, F-PBA < 0.1 microg/l, and 3-PBA 2.4 microg/l. 3-PBA was detected in 90% of the samples. The 95th percentiles for the organophosphorus metabolites in urine were: DMP 118 microg/l, DEP 20 microg/l, DMTP 124 microg/l, DETP 11 microg/l, DMDTP 11 microg/l, DEDTP < 1.0microg/l. DMTP was the metabolite most frequently detected in the samples (90%). Based on the metabolites analysed in urine the exposure to organophosphorus pesticides is mainly influenced by age, consumption of fresh fruits and fruit juice, living in an urban area, and season. A rough estimation revealed that the ADI values for organophosphorus pesticides might be exceeded. However, these results require further exploration. The exposure to pyrethroids is influenced by age, sampling location, consumption of boiled vegetables, and the use of biocides indoors at home. In addition, a significant correlation between permethrin in house dust and the metabolite concentrations in urine could be observed. Thus it seems likely that ingestion of house dust contributes to children's exposure.     

Urinary 3,5,6-trichloro-2-pyridinol (TCPY) in pregnant women from Mexico City: Distribution,temporal variability,and relationship with child attention and hyperactivity

Attention Deficit Hyperactivity Disorder (ADHD) is the most commonly diagnosed and studied cognitive and behavioral disorder in school-age children. The etiology of ADHD and ADHD-related behavior is unclear, but genetic and environmental factors, such as pesticides, have been hypothesized. The objective of this study was to investigate the relationship between in utero exposure to chlorpyrifos, chlorpyrifos-methyl, and/or 3,5,6-trichloro-2-pyridinol (TCPY) and ADHD in school-age Mexican children using TCPY as a biomarker of exposure. The temporal reliability of repeated maternal urinary TCPY concentrations across trimesters was also explored (N = 21). To explore associations with ADHD-related outcomes in children, third trimester urinary TCPY concentrations in were measured in 187 mother-child pairs from a prospective birth cohort. Child neurodevelopment in children 6–11 years of age was assessed using Conners’ Parental Rating Scales-Revised (CRS-R), Conners’ Continuous Performance Test (CPT), and Behavior Assessment System for Children-2 (BASC-2). Multivariable linear regression models were used to test relationships for all children combined and also stratified by sex. Intraclass correlation coefficients (ICC) calculations were based on a random effects model. The ICC was 0.41 for uncorrected TCPY, and ranged from 0.29 to 0.32 for specific gravity-corrected TCPY. We did not observe any statistically significant associations between tertiles of maternal TCPY concentrations and ADHD-related outcomes in children. However, compared to the lowest tertile we found suggestive evidence for increased ADHD index in the highest TCPY tertile in boys (β = 5.55 points; 95% CI (−0.19, 11.3); p = 0.06) and increased attention problems for the middle tertile in girls (β = 5.81 points; 95% CI (−0.75, 12.4); p = 0.08). Considering the continued widespread agricultural and possible residential use of chlorpyrifos and chlorpyrifos-methyl in Mexico and the educational implications of cognitive and behavior deficits, these relationships deserve further study.     

House dust levels of selected insecticides and a herbicide measured by the EL and LWW samplers and comparisons to hand rinses and urine metabolites

During the Minnesota Children's Pesticide Exposure Study (MNCPES), comparisons were made between the insecticide/herbicide loadings obtained with two household dust/insecticide or herbicide samplers: the Edwards and Lioy (EL) press sampler (used for dust collection from carpets or other surfaces) and the Lioy, Waimnan and Weisel (LWW) surface wipe sampler. The results were compared with hand rinse levels, and urine metabolite levels obtained from 102 children (ages 3-13). All measurements were made during a 1-week sampling period, and information was obtained on household pesticide use and each child's activities. Of the homes, <5% had recent spot uses of a pesticide but none had recent general applications. The analyses focused primarily on atrazine (a herbicide), and malathion, diazinon, and chlorpyrifos (insecticides). Metabolites were measured for atrazine, malathion and chlorpyrifos. The atrazine levels obtained using the EL indicate that this compound was transported into the home by an unquantified transport mechanism (e.g. tracking of soil). Two malathion hand rinse values exceeded >170 ng/cm2, suggesting that since indoor surface levels were low, these children had other sources of exposure. Atrazine, chlorpyrifos and malathion were detectable in >30% of the homes by the EL, LWW or hand rinse. Only chlorpyrifos had detectable levels in > or = 50% of the samples for all types, i.e. compound or metabolite, which is consistent with it being a common household pesticide. The median (and maximum) chlorpyrifos levels for the EL surface, EL carpet, LWW surface (two rooms), hand rinse, and urine metabolites were: 0.07 (32.6) ng/cm2; 0.07 (44.5) ng/cm2; 0.34 (3.64) ng/cm2; 0.42 (14.4) ng/cm2; 0.03 (2.14) ng/hand and 6.9 (59.0) microg/g, respectively. A strong correlation was found for chlorpyrifos between the EL surface and carpet samples. Chlorpyrifos levels detected by LWW had a different distribution and concentration range than the EL, indicating that it collected more than the surface dislodgeable insecticide. EL was directly comparable to the hand rinse or urine levels, but only the LWW had a weak correlation with hand rinse levels, suggesting that the children had other sources of chlorpyrifos exposure. Thus, mechanistic exposure studies are needed to more accurately establish exposure dose relationships in residential settings.     

Susceptibility of black fly larvae (Diptera: Simuliidae) to lawn-care insecticides individually and as mixtures

Urban and suburban watersheds have the potential to be highly impacted by chemicals, especially insecticides to control insect pests on lawns, ornamental plants, and home gardens. Three of the most common lawn-care insecticides detected in urban watersheds, carbaryl, chlorpyrifos, and malathion, have been evaluated using an acute orbital shaker toxicity test to determine their respective concentrations that produce 50% mortality (LC50) in Simulium vittatum Zetterstedt cytospecies IS-7 larvae. Results of the 48-h LC50 tests show chlorpyrifos to be the most toxic to black fly larvae (LC50 = 0.28 microg/L) followed by carbaryl (LC50 = 23.72 microg/L) and malathion (LC50 = 54.20 microg/L). These insecticides were also tested as binary and ternary mixtures using the toxic unit (TU) approach. Toxicity was shown to be greater than additive for the ternary mixture of chlorpyrifos-carbaryl-malathion (LC50 = 0.56 TU) and the binary mixtures of chlorpyrifos-malathion (LC50 = 0.72 TU) and carbaryl-malathion (LC50 = 0.78 TU). The binary combination of chlorpyrifos and carbaryl was shown to be additive (LC50 = 0.98 TU). These results indicate that aquatic invertebrate populations in urban and suburban streams may experience a higher-than-expected increase in toxicity-related effects when all three chemicals are present in the waterway.