BACKGROUND: Rabies expert on demand (REOD) telehealth service is provided by the U.S. Centers for Disease Control and Prevention (CDC) to assist public health practitioners, health providers, and the public to interpret national and international rabies prevention guidelines. REOD is staffed by subject matter experts of the CDC Poxvirus and Rabies Branch to assess each unique situation and provide evidence-based guidance to stakeholders. This study aims to describe the utilization of a rabies telehealth system and provide insight into common consultations. METHODS: A cross-sectional study of the nature of inquiries to REOD was done using the data collected from September 1, 2017 to September 30, 2021. An inquiry tracking form and Microsoft Access database were developed to document all inquiries received. Inquired ones were summarized to determine the frequency of inquiries by month, category, and location. RESULTS: Over a 49-month period, REOD received 5228 inquiries. Peak inquiries (n = 108) occurred during August 2019. The most frequent inquiries received pertained to risk assessment and management of rabies exposures (n = 1109), requests for testing assistance (n = 912), consultation for suspected human rabies (n = 746), rabies exposures and post-bite treatment occurring internationally (n = 310), and consultation for deviations in the recommended pre- and postexposure prophylaxis regimen (n = 300). CONCLUSION: REOD is a global resource for consultation related to managing rabies exposures, diagnostic issues, and rabies control strategies. REOD is a regularly utilized CDC service, as the demand for up-to-date rabies guidance remains high. REOD fulfills a critical role for the interpretation and consultation on rabies prevention guidelines to stakeholder.

We recently read the article of Song et al. on human biomonitoring of urinary metabolites of neonicotinoids with high interest.1 Our own experiments2 on the metabolism of imidacloprid after a single oral dose of 5 mg in a male volunteer do confirm the findings of Song and co-workers that 5-hydroxyimidacloprid (5-OH-IMI) and imidacloprid olefin are relevant metabolites of imidacloprid in humans. Unfortunately, the article, like several others, has a serious shortcoming from an analytical point of view. | | The metabolism of imidacloprid has previously been described in sufficient detail in mammals;3,4 whereas data in humans are scarce and mostly qualitative.5 Available studies indicate that 5-OH-IMI is a major specific metabolite of imidacloprid; however, not just any 5-OH-IMI but one that is hydroxylated at the 1H-imidazol moiety (1, CAS no. 155802–61–2). Therefore, using the correct 5-OH-IMI standard material for chemical analyses for human biomonitoring of imidacloprid is a critical first step. For example, in preparation for our controlled studies in humans, we had to synthesize 1 and a 13C2, 15N isotope labeled analogue because the substances were not commercially available at that time.

BACKGROUND: Neonicotinoids are used for insect control in agriculture, landscaping, and on household pets. Neonicotinoids have become popular replacements for organophosphate and carbamate insecticides, and use is on the rise. OBJECTIVES: To assess human exposure to neonicotinoid insecticides in a representative sample of the U.S. general population 3 years and older from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). METHODS: We used online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry after enzymatic hydrolysis of conjugates to quantify in 3038 samples the urinary concentrations of six neonicotinoid biomarkers: four parent compounds (acetamiprid, clothianidin, imidacloprid, thiacloprid) and two metabolites (N-desmethyl-acetamiprid, 5-hydroxy-imidacloprid). We calculated distribution percentiles, and used regression models to evaluate associations of various demographic parameters and fasting time with urinary concentrations above the 95th percentile (a value selected to represent higher than average concentrations) of neonicotinoid biomarkers. RESULTS: Weighted detection frequencies were 35% (N-desmethyl-acetamiprid), 19.7% (5-hydroxy imidacloprid), 7.7% (clothianidin), 4.3% (imidacloprid), and <0.5% (acetamiprid, thiacloprid). The weighted frequency of having detectable concentrations of at least one of the six biomarkers examined was 49.1%. The 95th percentile concentrations for N-desmethyl-acetamiprid, 5-hydroxy imidacloprid, and clothianidin were 1.29, 1.37, and 0.396mug/L, respectively. For people who fasted <8h, regardless of race/ethnicity and sex, 3-5 year old children were more likely to have N-desmethyl-acetamiprid concentrations above the 95th percentile than adolescents (adjusted odds ratio (OR)=3.12; 95% confidence interval [CI], (0.98-9.98)) and adults (adjusted OR=4.29; 95% CI, (2.04-9.0)); and children 6-11 years of age were more likely than adults to have N-desmethyl-acetamiprid concentrations above the 95th percentile (adjusted OR=2.65; 95% CI, (1.2-5.84)). Asians were more likely than non-Asians to have concentrations above the 95th percentile of N-desmethyl-acetamiprid (adjusted OR=1.94; 95% CI, (1.08-3.49)) and 5-hydroxy-imidacloprid (adjusted OR=2.25; 95% CI, (1.44-3.51)). Samples collected during the summer were more likely to have metabolite concentrations above the 95th percentile than those collected in the winter (adjusted OR 1.55 for N-desmethyl-acetamiprid, and 2.43 for 5-hydroxy-imidacloprid). CONCLUSIONS: The detection of neonicotinoid metabolites more frequently and at much higher concentrations than the corresponding parent compounds suggests that the metabolites may be suitable biomarkers to assess background exposures. About half of the U.S. general population 3 years of age and older was recently exposed to neonicotinoids. Compared to other age ranges and ethnicities, young children and Asians may experience higher exposures. At present, reasons for such differences remain unknown.

Neonicotinoid insecticides are widely used replacements for organophosphate and carbamate insecticides, but the extent of human exposure is largely unknown. On the other hand, based on urinary concentrations of DEET metabolites, human exposure to N,N-diethyl-m-toluamide (DEET) appears to be widespread. We developed a fast online solid-phase extraction high-performance liquid chromatography-isotope dilution tandem mass spectrometry (HPLC-MS/MS) method to measure in 200 muL of human urine the concentrations of six neonicotinoid biomarkers (acetamiprid, N-desmethyl-acetamiprid, clothianidin, imidacloprid, 5-hydroxy-imidacloprid, thiacloprid), and two DEET biomarkers (3-diethyl-carbamoyl benzoic acid, 3-ethyl-carbamoyl benzoic acid). Limits of detection ranged from 0.01 to 0.1 mug/L, depending on the biomarker. Accuracy ranged from 91 to 116% and precision ranged from 3.7 to 10 %RSD. The presented method can be used to increase our understanding of exposure to neonicotinoid insecticides and DEET, and to evaluate the potential health effects from such exposures.

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 (>0.08mug/L-45.1mug/L) much lower than those of 3-(diethylcarbamoyl)benzoic acid (DCBA) (>0.48mug/L-30,400mug/L) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB) (>0.09mug/L-332mug/L). DCBA was the most frequently detected metabolite (~84%). Regardless of survey cycle and the person's 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.

BACKGROUND: There 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. METHODS: We 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. RESULTS: We 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). CONCLUSIONS: We 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.

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 0.1mL 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 0.1ngmL(-1) to 1.0ngmL(-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.

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 11ng/mL, and the linear range was 4.4-20,000ng/mL. The relative standard deviation at 100, 1000, and 5000ng/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.

Diethylene glycol (DEG), a chemical that has been implicated in multiple medication-associated mass poisonings, can result in renal and neurological toxicity if ingested. Three previous such mass poisonings implicated Chinese manufacturers as the origin of contaminated ingredients. No literature exists on potential DEG or triethylene glycol (TEG), a related compound, contamination of health products imported from Asian countries to the USA. Our primary objective was to quantitatively assess the amount of DEG present in a convenience sampling of these health products. The study's secondary objectives were to: (1) evaluate for, and quantify TEG levels in these samples; (2) compare DEG and TEG levels in these products directly to levels in medications implicated in previous similar mass poisonings; and (3) to estimate DEG dose (in mg/kg) based on the manufacturer's instructions and compare these values to toxic doses from past mass poisonings and the literature. A quantitative assessment of DEG and TEG was performed in a convenience sampling of over-the-counter health products imported from Asian countries. Results were converted to volume to volume (v/v) % and compared with DEG levels in medications implicated in previous mass poisonings. Estimated doses (based on the manufacturer's instructions) of each product with detectable levels of DEG for a 70 kg adult were compared to toxic doses of DEG reported in the literature. Seventeen of 85 (20%) samples were not able to be analyzed for DEG or TEG due to technical reasons. Fifteen of 68 (22%) samples successfully tested had detectable levels of DEG (mean, 18.8 mug/ml; range, 0.791-110.1 mug/ml; and volume to volume (v/v) range, 0.00007-0.01%). Two of 68 (3%) samples had TEG levels of 12.8 and 20.2 mug/ml or 0.0012% and 0.0018% TEG v/v. The product with the highest DEG% by v/v was 810 times less than the product involved in the Panama DEG mass poisoning (8.1%). The lowest reported toxic dose from a past DEG mass poisoning (14 mg/kg) was more than 150 times higher than the highest daily dose estimated in our study (0.09 mg/kg). Sixty-eight of 85 (80%) samples were able to be successfully analyzed for DEG and TEG. DEG and TEG were detectable in 15/68 (22%) and 2/68 (3%) samples, respectively. Based on current standards, these levels probably do not represent an acute public health threat. Additional research focusing on why DEG is found in these products and on the minimum amount of DEG needed to result in toxicity is needed.

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. EDITOR'S SUMMARY: Synthetic pyrethroid insecticides are being used with greater frequency in the United States to replace residential and some agricultural organophosphorus (OP) and carbamate insecticides. The pyrethroids are considered to be less toxic to humans than the OPs and carbamates, but like many other classes of insecticides, they are acute neurotoxicants. Barr et al. (p. 742) assessed human exposure to pyrethroid insecticides in a representative sample of the general U.S. population ≥ 6 years of age. 3-Phenoxybenzoic acid (3PBA), a metabolite common to many pyrethroid insecticides, was detected in > 70% of urine samples tested. Non-Hispanic blacks had significantly higher 3BPA concentrations than non-Hispanic whites and Mexican Americans, and children had significantly higher concentrations of 3PBA than adolescents and adults. 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 primarily derived from exposure to permethrin, cypermethrin, or their degradates. The authors conclude that pyrethroid insecticide exposure in the U.S. population is widespread and that children may have higher exposures than adolescents and adults.