Samuel E. Baker

Urinary Concentrations of Metabolites of Pyrethroid Insecticides in the General U.S. Population: National Health and Nutrition Examination Survey 1999–2002

Background Pyrethroid insecticides are the most commonly used residential insecticides in the United States. Objectives Our objective was to assess human exposure via biomonitoring to pyrethroid insecticides in a representative sample of the general U.S. population ≥ 6 years of age. Methods By using isotope-dilution high-performance liquid chromatography/electrospray chemical ionization/tandem mass spectrometry, we measured five urinary metabolites of pyrethroid insecticides in 5,046 samples collected as a part of the 1999–2002 National Health and Nutrition Examination Survey (NHANES). Univariate, multivariate, and Pearson correlation analyses were performed using SUDAAN and SAS software, incorporating the appropriate sample weights into the analyses. Multivariate analyses included age, sex, race/ethnicity, creatinine, fasting status, and urine collection time as covariates. Results We detected 3-phenoxybenzoic acid (3PBA), a metabolite common to many pyrethroid insecticides, in more than 70% of the samples. The least-squares geometric mean (LSGM) concentration (corrected for covariates) of 3PBA and the frequency of detection increased from 1999–2000 (0.292 ng/mL) to 2001–2002 (0.318 ng/mL) but not significantly. Non-Hispanic blacks had significantly higher LSGM 3PBA concentrations than did non-Hispanic whites and Mexican Americans in the 2001–2002 survey period and in the combined 4-year survey periods but not in the 1999–2000 survey period. Children had significantly higher LSGM concentrations of 3PBA than did adolescents in both NHANES periods and than adults in NHANES 1999–2000. Cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid were highly correlated with each other and with 3PBA, suggesting that urinary 3PBA was derived primarily from exposure to permethrin, cypermethrin, or their degradates. Conclusions Pyrethroid insecticide exposure in the U.S. population is widespread, and the presence of its metabolites in the urine of U.S. residents indicates that children may have higher exposures than adolescents and adults.

Quantification of selected pesticide metabolites in human urine using isotope dilution high-performance liquid chromatography/tandem mass spectrometry

The annual domestic use of pesticides is continually increasing, virtually ensuring that everyone is exposed to some level of pesticides on a regular basis through diet or environment. The potential developmental and physical adverse effects these chronic pesticide exposures have on children are of increasing concern. To adequately evaluate the potential adverse effects resulting from these exposures, accurate methods to measure the amount of the pesticide absorbed by the body must be developed. We have developed a sensitive method to measure the urinary metabolites of atrazine, diazinon, malathion, 2,4-dichlorophenoxyacetic acid (2,4-D), and certain synthetic pyrethroids in human urine. In our method, stable isotopically labeled analogues of the metabolites were spiked into the urine, which was subsequently extracted at both a neutral and acidic pH using organic solvents. The extracts were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) using atmospheric pressure chemical ionization. Our method has limits of detection ranging from 20 to 500 ng/l (parts per trillion) and relative standard deviations of less than 11%. This method has been used to measure the internal doses of these pesticides in both adults and children (n=130) with no documented exposure to the pesticides. We detected atrazine and synthetic pyrethroid metabolites in less than 12% of the samples analyzed. The metabolites of 2,4-D, malathion, and diazinon were detected in 22%, 32%, and 57% of the samples, respectively.

Urinary biomarkers of exposure to insecticides, herbicides, and one insect repellent among pregnant women in Puerto Rico

BackgroundThere are potential adverse health risks to the mother and fetus from exposure to pesticides. Thus, studies of exposure to pesticides among pregnant women are of interest as they will assist with understanding the potential burden of exposure globally, identifying sources of exposure, and designing epidemiology studies.MethodsWe measured urinary concentrations of the insect repellent N-N-diethyl-meta-toluamide (DEET) and two of its metabolites [3-diethyl-carbamoyl benzoic acid (DCBA) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB)], four pyrethroid insecticide metabolites [4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA); 3-phenoxybenzoic acid (3-PBA); trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA); and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA)], and two chlorophenoxy herbicides [2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)] in 54 pregnant women from Puerto Rico at three separate time points (20 ± 2 weeks, 24 ± 2 weeks, and 28 ± 2 weeks of gestation). We calculated the distributions of the biomarker concentrations and compared them to those of women of reproductive age from the general U.S. population where available, and estimated the within-subject temporal variability of these repeated measurements. We also collected questionnaire data on demographics, consumption of select fruits, vegetables, and legumes in the past 48-hr, and pest-related issues, and associations between these variables and biomarker concentrations were examined.ResultsWe found that 95th percentile urinary concentrations of DEET, 3-PBA, trans-DCCA, and 2,4-D were lower than women of reproductive age on the U.S. mainland, whereas 95th percentile urinary concentrations of 4-F-3-PBA, cis-DBCA, and 2,4,5-T were similar. DCBA, the only urinary biomarker detected in >50% of the samples, showed fair to good reproducibility across pregnancy (intraclass correlation coefficient: 0.60). Women were more likely (p <0.05) to have greater urinary concentrations of pesticide biomarkers if they were less educated (DCBA and trans-DCCA), unemployed (DHMB), or married (2,4-D), had consumed collards or spinach in past 48-hr (2,4-D) or had been using insect repellent since becoming pregnant (DCBA), or were involved with residential applications of pesticides (trans-DCCA).ConclusionsWe identified concentrations and predictors of several pesticides among pregnant women in Puerto Rico. Further research is needed to understand what aspects of the predictors identified lead to greater exposure, and whether exposure during pregnancy is associated with adverse health.

On-line solid phase extraction-high performance liquid chromatography–isotope dilution–tandem mass spectrometry approach to quantify N,N-diethyl-m-toluamide and oxidative metabolites in urine

Human exposure to N,N-diethyl-m-toluamide (DEET) occurs because of the widespread use of DEET as an active ingredient in insect repellents. However, information on the extent of such exposure is rather limited. Therefore, we developed a fast on-line solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry (HPLC-MS/MS) method to measure in urine the concentrations of DEET and two of its oxidative metabolites: N,N-diethyl-3-(hydroxymethyl)benzamide and 3-(diethylcarbamoyl)benzoic acid (DCBA). To the best of our knowledge, this is the first HPLC-MS/MS method for the simultaneous quantification of DEET and its select metabolites in human urine. After enzymatic hydrolysis of the conjugated species in 0.1 mL of urine, the target analytes were retained and pre-concentrated on a monolithic column, separated from each other and from other urinary biomolecules on a reversed-phase analytical column, and detected by atmospheric pressure chemical ionization in positive ion mode. The limits of detection ranged from 0.1 ng mL(-1) to 1.0 ng mL(-1), depending on the analyte. Accuracy ranged between 90.4 and 104.9%, and precision ranged between 5.5 and 13.1% RSD, depending on the analyte and the concentration. We tested the usefulness of this method by analyzing 75 urine samples collected anonymously in the Southeastern United States in June 2012 from adults with no known exposure to DEET. Thirty eight samples (51%) tested positive for at least one of the analytes. We detected DCBA most frequently and at the highest concentrations. Our results suggest that this method can be used for the analysis of a large number of samples for epidemiological studies to assess human exposure to DEET.

Quantification of riboflavin in human urine using high performance liquid chromatography-tandem mass spectrometry.

We developed a selective method to measure riboflavin in human urine. Sample preparation involved solid phase extraction and concentration of the target analyte in urine. The urine concentrate was analyzed using high performance liquid chromatography-tandem mass spectrometry. Riboflavin concentrations were quantified using an isotopically labeled internal standard. The limit of detection was 11 ng/mL, and the linear range was 4.4-20,000 ng/mL. The relative standard deviation at 100, 1000, and 5000 ng/mL was 17%, 17%, and 12%, respectively. The accuracy was 90%. On average, 100 samples, including calibration standards and quality control samples, were prepared per day. Using our method, we measured concentrations of riboflavin in human urine samples that were collected from participants in a study where riboflavin was used as a surrogate chemical to simulate exposure to an environmental toxicant.

Novel exposure biomarkers of N,N-diethyl-m-toluamide (DEET): Data from the 2007-2010 National Health and Nutrition Examination Survey.

BACKGROUND N,N-diethyl-m-toluamide (DEET) is a widely used insect repellent in the United States. OBJECTIVES To assess exposure to DEET in a representative sample of persons 6years and older in the U.S. general population from the 2007-2010 National Health and Nutrition Examination Survey. METHODS We analyzed 5348 urine samples by using online solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. We used regression models to examine associations of various demographic parameters with urinary concentrations of DEET biomarkers. RESULTS We detected DEET in ~3% of samples and at concentration ranges (>0.08μg/L-45.1μg/L) much lower than those of 3-(diethylcarbamoyl)benzoic acid (DCBA) (>0.48μg/L-30,400μg/L) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB) (>0.09μg/L-332μg/L). DCBA was the most frequently detected metabolite (~84%). Regardless of survey cycle and the persons race/ethnicity or income, adjusted geometric mean concentrations of DCBA were higher in May-Sep than in Oct-Apr. Furthermore, non-Hispanic whites in the warm season were more likely than in the colder months [adjusted odds ratio (OR)=10.83; 95% confidence interval (CI), 3.28-35.79] and more likely than non-Hispanic blacks (OR=3.45; 95% CI, 1.51-7.87) to have DCBA concentrations above the 95th percentile. CONCLUSIONS The general U.S. population, including school-age children, is exposed to DEET. However, reliance on DEET as the sole urinary biomarker would likely underestimate the prevalence of exposure. Instead, oxidative metabolites of DEET are the most adequate exposure biomarkers. Differences by season of the year based on demographic variables including race/ethnicity likely reflect different lifestyle uses of DEET-containing products.

Erratum to: Diethylene Glycol in Health Products Sold Over-the-Counter and Imported from Asian Countries

Erratum to: J. Med. Toxicol. DOI 10.1007/s13181-010-0111-9 Dietary supplements are regulated by the Food and Drug Administration. Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), dietary supplements can be marketed without pre-approval by the FDA. The dietary supplement manufacturer is responsible for ensuring that a dietary supplement is safe before it is marketed. FDA is authorized to take enforcement action against any unsafe dietary supplement product.