Novel methods for the analysis of toxicants in bronchoalveolar lavage fluid samples from e-cigarette, or vaping, product use-associated lung injury cases: Selected petroleum distillates.

RATIONALE: Over 2700 e-cigarette, or vaping, product use-associated lung injury (EVALI) cases were reported to the Centers for Disease Control and Prevention (CDC) during August 2019-February 2020. Bronchoalveolar lavage (BAL) fluid samples from 51 EVALI and 99 non-EVALI cases were analyzed for toxicants including petroleum distillates. We describe a novel method to measure petroleum distillates in BAL fluid using gas chromatography-mass spectrometry (GC/MS). METHODS: n-Hexane, n-heptane, n-octane, methylcyclopentane, and cyclohexane were measured in BAL fluid specimens by headspace solid-phase microextraction/GC/MS. We created and characterized BAL fluid pools from non-EVALI individuals to determine assay accuracy, precision, linearity, limits of detection (LODs), and analytical specificity. All measurements were conducted in accordance with the rigorous method validation procedures of CDC's Division of Laboratory Sciences. RESULTS: Matrix validation experiments showed that calibration curves in BAL fluid and saline had similar slopes, with differences less than 5%. Assay precision ranged from 1.98% to 18%. In addition, the LODs for the five analytes ranged from 0.05 to 0.10 µg/L, and their linearity was confirmed with R2 values >0.99. The analysis of selected petroleum distillates in BAL fluid analysis was shown to be comparable with their analysis in blood in which the 95th percentiles are below detection. CONCLUSIONS: We developed and validated a method to quantify petroleum distillates in BAL fluid specimens using GC/MS. The assay provided precise and accurate analyses of EVALI and non-EVALI BAL fluid specimens in support of CDC's EVALI response. This method is applicable to the determination of a broad range of volatile organic compounds in BAL fluid specimens.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

Synthesis of less toxic gold nanorods by using dodecylethyldimethylammonium bromide as an alternative growth-directing surfactant.

Gold nanoparticles having a rod-like morphology are regularly investigated as potential nano-therapeutic materials owing to their interesting optical properties, facile surface modification, tunable aspect ratios, and low cytotoxicity. Gold nanorods are historically prepared starting from HAuCl4 in the presence of ascorbic acid, silver nitrate, and the growth directing surfactant, cetyltrimethylammonium bromide (CTAB). While CTAB drives a rod-like morphology, it is known to be cytotoxic. This inherent toxicity is often addressed by removing or masking the native CTAB surfactant present on the nanorod surface. In the current study we have investigated a less toxic alternative surfactant, dodecylethyldimethylammonium bromide (C12EDMAB), as a possible growth-directing agent. Monodisperse gold nanorods having various lengths have been grown in the presence of C12EDMAB. SEM data suggests that the quantity of C12EDMAB on the rod's surface is much higher than that of CTAB. Toxicity assays were performed on HEp-2 and A549 cells showing lower toxicity at select concentrations for C12EDMAB coated rods.