Examination of xylene exposure in the U.S. Population through biomonitoring: NHANES 2005-2006, 2011-2016.

Aim: Xylenes are aromatic hydrocarbons used for industrial applications such as the production of petrochemicals and plastics. Acute xylene exposures can negatively impact health through neurotoxicity and irritation of respiratory and dermal tissues. We quantified urinary biomarkers of xylene exposure [2-methylhippuric acid (2MHA) and a mixture of 3- and 4-methylhippuric acids (34MH)] in a representative sample of the U.S. population. Methods: Spot urine obtained during the National Health and Nutrition Examination Survey 2005-2006 and 2011-2016 was analysed using ultra-high-performance liquid chromatography/tandem mass spectrometry. Exclusive smokers were distinguished from non-users using a combination of self-report and serum cotinine data. Results: The median 2MHA and 34MH levels were higher for exclusive smokers (100 µg/g and 748 µg/g creatinine, respectively) than for non-users (27.4 µg/g and 168 µg/g creatinine, respectively). Participants who smoked cigarettes had significantly higher 2MHA and 34MH levels (p < 0.0001) than unexposed participants. Smoking 1-10, 11-20, and >20 cigarettes per day (CPD) was significantly associated with 181%, 339% and 393% higher 2MHA levels, respectively. For 34MH, smoking 1-10, 11-20, and >20 CPD was significantly associated with 201%, 398%, and 471% higher 34MH levels, respectively. Conclusion: We confirm that tobacco smoke is a significant source of xylene exposure as measured by urinary 2MHA and 34MH levels.

Urinary Acrylonitrile Metabolite Concentrations Before and after Smoked, Vaporized, and Oral Cannabis in Frequent and Occasional Cannabis Users.

Cannabis use through smoking, vaping, or ingestion is increasing, but only limited studies have investigated the resulting exposure to harmful chemicals. N-acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), a urinary metabolite of acrylonitrile, a possible carcinogen, is elevated in the urine of past-30-day cannabis users compared to non-cannabis users. Five frequent and five occasional cannabis users smoked and vaped cannabis on separate days; one also consumed cannabis orally. Urine samples were collected before and up to 72 h post dose and urinary 2CYEMA was quantified. We compared 2CYEMA pre-exposure levels, maximum concentration, time at maximum concentration for occasional versus frequent users following different exposure routes, and measured half-life of elimination. Smoking cannabis joints rapidly (within 10 min) increased 2CYEMA in the urine of occasional cannabis users, but not in frequent users. Urine 2CYEMA did not consistently increase following vaping or ingestion in either study group. Cigarette smokers had high pre-exposure concentrations of 2CYEMA. Following cannabis smoking, the half-lives of 2CYEMA ranged from 2.5 to 9.0 h. 2CYEMA is an effective biomarker of cannabis smoke exposure, including smoke from a single cannabis joint, however, not from vaping or when consumed orally. When using 2CYEMA to evaluate exposure in cannabis users, investigators should collect the details about tobacco smoking, route of consumption, and time since last use as possible covariates.

Correlation of creatinine- and specific gravity-normalized free and glucuronidated urine cannabinoid concentrations following smoked, vaporized, and oral cannabis in frequent and occasional cannabis users.

Variability in urine dilution complicates urine cannabinoid test interpretation. Normalizing urine cannabinoid concentrations to specific gravity (SG) or creatinine was proposed to account for donors' hydration states. In this study, all urine voids were individually collected from eight frequent and eight occasional cannabis users for up to 85 hours after each received on separate occasions 50.6 mg Δ9-tetrahydrocannabinol (THC) by smoking, vaporization, and oral ingestion in a randomized, within-subject, double-blind, double-dummy, placebo-controlled protocol. Each urine void was analyzed for 11 cannabinoids and phase I and II metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS), SG, and creatinine. Normalized urine concentrations were log10 transformed to create normal distributions, and Pearson correlation coefficients determined the degree of association between the two normalization methods. Repeated-measures linear regression determined if the degree of association differed by frequent or occasional cannabis use, or route of administration after adjusting for gender and time since dosing. Of 1880 urine samples examined, only 11-nor-9-carboxy-THC (THCCOOH), THCCOOH-glucuronide, THC-glucuronide, and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCVCOOH) were greater than the method's limits of quantification (LOQs). Associations between SG- and creatinine-normalized concentrations exceeded 0.90. Repeated-measures regression analysis found small but statistically significant differences in the degree of association between normalization methods for THCCOOH and THCCOOH-glucuronide in frequent vs occasional smokers, and in THCVCOOH and THC-glucuronide by route of administration. For the first time, SG- and creatinine-normalized urine cannabinoid concentrations were evaluated in frequent and occasional cannabis users and following oral, smoked, and inhaled cannabis. Both normalization methods reduced variability, improving the interpretation of urine cannabinoid concentrations and methods were strongly correlated.