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BackgroundUrine is an abundant and useful medium for measuring biomarkers related to chemical exposures in infants and children. Identification of novel biomarkers is greatly enhanced with non-targeted analysis (NTA), a powerful methodology for broad chemical analysis of environmental and biological specimens. However, collecting urine in non-toilet trained children presents many challenges, and contamination from specimen collection can impact NTA results.ObjectivesWe optimized a caregiver-driven method for collecting urine from infants and children using cotton pads and commercially available disposable diapers for NTA and demonstrate its applicability to various children biomonitoring studies.MethodsExperiments were first performed to evaluate the effects of processing method (i.e., centrifuge vs. syringe), storage temperature, and diaper brand on recovery of urine absorbed to cotton pads. Caregivers of 11 children (<2 years) used and retained diapers (with cotton pads) to collect their child’s urine for 24 h. Specimens were analyzed via a NTA method implementing an exclusion list of ions related to contamination from collection materials.ResultsCentrifuging cotton pads through a small-pore membrane, compared to a manual syringe method, and storing diapers at 4 °C, compared to room temperature, resulted in larger volumes of recovered sample. This method was successfully implemented to recover urine from cotton pads collected in the field; between 5–9 diapers were collected per child in 24 h, and the total mean volume of urine recovered was 44.7 (range 26.7–71.1) mL. NTA yielded a list of compounds present in urine and/or stool that may hold promise as biomarkers of chemical exposures from a variety of sources.Impact StatementInfant and children urine is a valuable matrix for studies of the early life exposome, in that numerous biological markers of exposure and outcome can be derived from a single analysis. Depending on the nature of the exposure study, it may be the case that a simple collection method that can be facilitated by caregivers of young children is desirable, especially when time-integrated samples or large volumes of urine are needed. We describe the process for development and results of an optimized method for urine collection and analysis using commercially available diapers and non-target analysis.

There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ -tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ -tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513.

BackgroundThere are over 700,000 hairdressers in the United States, and it is estimated that >90% are female and 31% are Black or Hispanic/Latina. Racial and ethnic minorities in this workforce may be exposed to a unique mixture of potentially hazardous chemicals from products used and services provided. However, previous biomonitoring studies of hairdressers target a narrow list of compounds and few studies have investigated exposures among minority hairdressers.ObjectiveTo assess occupational chemical exposures in a sample of US-based Black and Latina hairdressers serving an ethnically diverse clientele by analyzing urine specimens with a suspect screening method.MethodsPost-shift urine samples were collected from a sample of US female hairdressers (n = 23) and office workers (n = 17) and analyzed via reverse-phase liquid chromatography coupled to high-resolution mass spectrometry. Detected compounds were filtered based on peak area differences between groups and matching with a suspect screening list. When possible, compound identities were confirmed with reference standards. Possible exposure sources were evaluated for detected compounds.ResultsThe developed workflow allowed for the detection of 24 compounds with median peak areas ≥2x greater among hairdressers compared to office workers. Product use categories (PUCs) and harmonized functional uses were searched for these compounds, including confirmed compounds methylparaben, ethylparaben, propylparaben, and 2-naphthol. Most product use categories were associated with “personal use” and included 11 different “hair styling and care” product types (e.g., hair conditioner, hair relaxer). Functional uses for compounds without associated PUCs included fragrance, hair and skin conditioning, hair dyeing, and UV stabilizer.SignificanceOur suspect screening approach detected several compounds not previously reported in biomonitoring studies of hairdressers. These results will help guide future studies to improve characterization of occupational chemical exposures in this workforce and inform exposure and risk mitigation strategies to reduce potential associated work-related health disparities.

As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 ± 0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect ( p  = 0.001), as well as a significant drug × time-point interaction effect ( p  = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect ( p  = 0.001), as well as a trend-level drug × time-point interaction effect ( p  = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect ( p  = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.

•Controlled administration of uncooked poppy seeds with known opiate content.•Each urine void collected for 32h.•26.6% specimens with morphine >2000μg/L.•Median (range) peak morphine 5239μg/L (2413–7522).•Last morphine >2000μg/L 2.6–18h after last dose. Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45g oral poppy seed doses 8h apart, each containing 15.7mg morphine and 3mg codeine. Urine was collected ad libitum up to 32h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2000 and 300μg/L cutoffs, and the ThermoFisher CEDIA® heroin metabolite (6-acetylmorphine, 6-AM) and Lin-Zhi 6-AM immunoassays with 10μg/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32h following dosing; 26.6% and 83.4% were positive for morphine at 2000 and 300μg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7522μg/L with a median peak concentration of 5239μg/L. The median first morphine-positive urine sample at 2000μg/L cutoff concentration occurred at 6.6h (1.2–12.1), with the last positive from 2.6 to 18h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2000μg/L, but 20.2% exceeded 300μg/L, with peak concentrations of 658μg/L (284–1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300μg/L cutoffs. The CEDIA 6-AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results.

Opiates are included in drug testing programs because of their psychoactive properties and abuse potential, but excluding poppy seed ingestion is necessary to correctly interpret positive opiate results. There are few available data for plasma and oral fluid (OF) following poppy seed ingestion, and most do not report opiate content in the ingested poppy seeds. We quantified plasma and OF morphine and codeine concentrations via a fully validated liquid chromatography–tandem mass spectrometry method after controlled administration of two doses (8 h apart) of raw, uncooked poppy seeds (45-g) each containing 15.7 mg of morphine and 3.1 mg of codeine. Simultaneous specimens were collected before and up to 32 h after the first dose. Maximum OF morphine and codeine concentrations (3.6–110 and 2.1–22.4 µg/l, respectively) were significantly greater than simultaneously collected maximum plasma concentrations (2.8–9.3 and 1.1–2.0 µg/l, respectively). OF and plasma morphine and codeine concentrations were significantly correlated, but large variabilities preclude plasma concentration estimations from OF results. The median OF morphine time of first detection ( t first ) and time of last detection ( t last ) were both 0.5 h with cutoffs from 20 to 40 µg/l, with 0.9–6.7 % positive specimens. Codeine was detected only at low 15–20 µg/l OF cutoffs; median t first and t last were 0.5–1.3 h and 0.5–2.3 h, respectively, with only 0.4–1.8 % specimens positive. After two large, raw, uncooked poppy seed doses, significant differences between plasma and OF opiate pharmacokinetics were observed. Less than 6.7 % positive OF tests and a median morphine OF detection time of only 0.5 h with cutoffs from 20 to 40 µg/l suggest that few OF positive morphine tests can be explained by poppy seed ingestion.

Roadside oral fluid (OF) Δ -tetrahydrocannabinol (THC) detection indicates recent cannabis intake. OF and blood THC pharmacokinetic data are limited and there are no on-site OF screening performance evaluations after controlled edible cannabis. We reviewed OF and blood cannabinoid pharmacokinetics and performance evaluations of the Draeger DrugTest 5000 (DT5000) and Alere™ DDS 2 (DDS2) on-site OF screening devices. We also present data from a controlled oral cannabis administration session. OF THC maximum concentrations (C ) were similar in frequent as compared to occasional smokers, while blood THC C were higher in frequent [mean (range) 17.7 (8.0-36.1) μg/L] smokers compared to occasional [8.2 (3.2-14.3) μg/L] smokers. Minor cannabinoids Δ -tetrahydrocannabivarin and cannabigerol were never detected in blood, and not in OF by 5 or 8 h, respectively, with 0.3 μg/L cutoffs. Recommended performance (analytical sensitivity, specificity, and efficiency) criteria for screening devices of ≥80% are difficult to meet when maximizing true positive (TP) results with confirmation cutoffs below the screening cutoff. TPs were greatest with OF confirmation cutoffs of THC ≥1 and ≥2 μg/L, but analytical sensitivities were <80% due to false negative tests arising from confirmation cutoffs below the DT5000 and DDS2 screening cutoffs; all criteria were >80% with an OF THC ≥5 μg/L cutoff. Performance criteria also were >80% with a blood THC ≥5 μg/L confirmation cutoff; however, positive OF screening results might not confirm due to the time required to collect blood after a crash or police stop. OF confirmation is recommended for roadside OF screening.ClinicalTrials.gov identification number: NCT02177513.

Roadside oral fluid (OF) Δ9-tetrahydrocannabinol (THC) detection indicates recent cannabis intake. OF and blood THC pharmacokinetic data are limited and there are no on-site OF screening performance evaluations after controlled edible cannabis. We reviewed OF and blood cannabinoid pharmacokinetics and performance evaluations of the Draeger DrugTest®5000 (DT5000) and Alere™ DDS®2 (DDS2) on-site OF screening devices. We also present data from a controlled oral cannabis administration session. OF THC maximum concentrations (Cmax) were similar in frequent as compared to occasional smokers, while blood THC Cmax were higher in frequent [mean (range) 17.7 (8.0-36.1) µg/L] smokers compared to occasional [8.2 (3.2-14.3) xg/L] smokers. Minor cannabinoids Δ9sup -tetrahydrocannabivarin and cannabigerol were never detected in blood, and not in OF by 5 or 8 h, respectively, with 0.3 µg/L cutoffs. Recommended performance (analytical sensitivity, specificity, and efficiency) criteria for screening devices of ≥80% are difficult to meet when maximizing true positive (TP) results with confirmation cutoffs below the screening cutoff. TPs were greatest with OF confirmation cutoffs of THC ≥1 and ≥2 µg/L, but analytical sensitivities were <80% due to false negative tests arising from confirmation cutoffs below the DT5000 and DDS2 screening cutoffs; all criteria were >80% with an OF THC ≥5 µg/L cutoff. Performance criteria also were >80% with a blood THC ≥5 µg/L confirmation cutoff; however, positive OF screening results might not confirm due to the time required to collect blood after a crash or police stop. OF confirmation is recommended for roadside OF screening.

Roadside oral fluid (OF) Δ9-tetrahydrocannabinol (THC) detection indicates recent cannabis intake. OF and blood THC pharmacokinetic data are limited and there are no on-site OF screening performance evaluations after controlled edible cannabis.BACKGROUNDRoadside oral fluid (OF) Δ9-tetrahydrocannabinol (THC) detection indicates recent cannabis intake. OF and blood THC pharmacokinetic data are limited and there are no on-site OF screening performance evaluations after controlled edible cannabis.We reviewed OF and blood cannabinoid pharmacokinetics and performance evaluations of the Draeger DrugTest®5000 (DT5000) and Alere™ DDS®2 (DDS2) on-site OF screening devices. We also present data from a controlled oral cannabis administration session.CONTENTWe reviewed OF and blood cannabinoid pharmacokinetics and performance evaluations of the Draeger DrugTest®5000 (DT5000) and Alere™ DDS®2 (DDS2) on-site OF screening devices. We also present data from a controlled oral cannabis administration session.OF THC maximum concentrations (Cmax) were similar in frequent as compared to occasional smokers, while blood THC Cmax were higher in frequent [mean (range) 17.7 (8.0-36.1) μg/L] smokers compared to occasional [8.2 (3.2-14.3) μg/L] smokers. Minor cannabinoids Δ9-tetrahydrocannabivarin and cannabigerol were never detected in blood, and not in OF by 5 or 8 h, respectively, with 0.3 μg/L cutoffs. Recommended performance (analytical sensitivity, specificity, and efficiency) criteria for screening devices of ≥80% are difficult to meet when maximizing true positive (TP) results with confirmation cutoffs below the screening cutoff. TPs were greatest with OF confirmation cutoffs of THC ≥1 and ≥2 μg/L, but analytical sensitivities were <80% due to false negative tests arising from confirmation cutoffs below the DT5000 and DDS2 screening cutoffs; all criteria were >80% with an OF THC ≥5 μg/L cutoff. Performance criteria also were >80% with a blood THC ≥5 μg/L confirmation cutoff; however, positive OF screening results might not confirm due to the time required to collect blood after a crash or police stop. OF confirmation is recommended for roadside OF screening.ClinicalTrials.gov identification number: NCT02177513.SUMMARYOF THC maximum concentrations (Cmax) were similar in frequent as compared to occasional smokers, while blood THC Cmax were higher in frequent [mean (range) 17.7 (8.0-36.1) μg/L] smokers compared to occasional [8.2 (3.2-14.3) μg/L] smokers. Minor cannabinoids Δ9-tetrahydrocannabivarin and cannabigerol were never detected in blood, and not in OF by 5 or 8 h, respectively, with 0.3 μg/L cutoffs. Recommended performance (analytical sensitivity, specificity, and efficiency) criteria for screening devices of ≥80% are difficult to meet when maximizing true positive (TP) results with confirmation cutoffs below the screening cutoff. TPs were greatest with OF confirmation cutoffs of THC ≥1 and ≥2 μg/L, but analytical sensitivities were <80% due to false negative tests arising from confirmation cutoffs below the DT5000 and DDS2 screening cutoffs; all criteria were >80% with an OF THC ≥5 μg/L cutoff. Performance criteria also were >80% with a blood THC ≥5 μg/L confirmation cutoff; however, positive OF screening results might not confirm due to the time required to collect blood after a crash or police stop. OF confirmation is recommended for roadside OF screening.ClinicalTrials.gov identification number: NCT02177513.

A positive drug test may result in suspension of one’s driving license, loss of employment, or removal of children from the home, making it imperative that multiple factors be considered when interpreting results. Controlled research is critical for providing the data to improve result interpretation. Two drug administration studies were conducted to address drug test interpretation of opiates, amphetamines and cannabis results. In the first, participants consumed two raw, uncooked poppy seed doses (15.7 mg morphine, 3.1 mg codeine per dose), and administered seven doses of intranasal l-methamphetamine (Vicks® VapoInhaler™) per manufacturer’s recommendations. Positive OF morphine tests >2.5 h or positive OF codeine tests with a 15 μg/L confirmation cutoff suggest an alternate route of opiate exposure other than from poppy seeds. Prevalence of positive OF l-methamphetamine tests was ≤7.5% and last detection times were >32 h after the first dose with a 25 μg/L screening cutoff. Screening OF with a selective d-methamphetamine assay prevented positive test results. In the second, frequent and occasional cannabis smokers were administered placebo, smoked, vaporized, and oral (6.9% Δ9-tetrahydrocannabinol [THC], ~50.6 mg) cannabis. Cannabinol (CBN) and cannabigerol (CBG) were the best blood markers for identifying recent cannabis intake, but not after oral dosing. OF Δ9-tetrahydrocannabivarin (THCV) identified use within 10 h after all administrations, useful for driving under the influence of drugs (DUID), while OF CBG may identify use within 26 h, useful for daily drug treatment compliance programs monitoring relapse. Blood 11-nor-9-carboxy-THCV (THCVCOOH) or OF THCV or CBG also discriminated medicinal synthetic THC from intake of cannabis plant products. OF THC on-site screening devices demonstrated best performance with a 5 μg/L cutoff, but there were more true positive results with a 2 μg/L cutoff; an OF THC ≥2 μg/L confirmation cutoff is suitable for drug treatment programs to detect intake within 26-32 h. Oral cannabis intake significantly increased performance impairment in occasional smokers only. Partial tolerance to cannabis’ subjective effects were observed in frequent smokers after all doses. Additionally, vaporization exposed users to significantly less carbon monoxide than smoking. These data improve result interpretation and guide development of evidence-based drug policies and legislation.