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.).

Caffeine Concentrations in Coffee, Tea, Chocolate, and Energy Drink Flavored E-liquids.

INTRODUCTION: Most electronic cigarettes (e-cigarettes) contain a solution of propylene glycol/glycerin and nicotine, as well as flavors. E-cigarettes and their associated e-liquids are available in numerous flavor varieties. A subset of the flavor varieties include coffee, tea, chocolate, and energy drink, which, in beverage form, are commonly recognized sources of caffeine. Recently, some manufacturers have begun marketing e-liquid products as energy enhancers that contain caffeine as an additive. METHODS: A Gas Chromatography-Mass Spectrometry (GC-MS) method for the quantitation of caffeine in e-liquids was developed, optimized and validated. The method was then applied to assess caffeine concentrations in 44 flavored e-liquids from cartridges, disposables, and refill solutions. Products chosen were flavors traditionally associated with caffeine (ie, coffee, tea, chocolate, and energy drink), marketed as energy boosters, or labeled as caffeine-containing by the manufacturer. RESULTS: Caffeine was detected in 42% of coffee-flavored products, 66% of tea-flavored products, and 50% of chocolate-flavored e-liquids (limit of detection [LOD] - 0.04 µg/g). Detectable caffeine concentrations ranged from 3.3 µg/g to 703 µg/g. Energy drink-flavored products did not contain detectable concentrations of caffeine. Eleven of 12 products marketed as energy enhancers contained caffeine, though in widely varying concentrations (31.7 µg/g to 9290 µg/g). CONCLUSIONS: E-liquid flavors commonly associated with caffeine content like coffee, tea, chocolate, and energy drink often contained caffeine, but at concentrations significantly lower than their dietary counterparts. Estimated daily exposures from all e-cigarette products containing caffeine were much less than ingestion of traditional caffeinated beverages like coffee. IMPLICATIONS: This study presents an optimized and validated method for the measurement of caffeine in e-liquids. The method is applicable to all e-liquid matrices and could potentially be used to ensure regulatory compliance for those geographic regions that forbid caffeine in e-cigarette products. The application of the method shows that caffeine concentrations and estimated total caffeine exposure from e-cigarette products is significantly lower than oral intake from beverages. However, because very little is known about the effects of caffeine inhalation, e-cigarette users should proceed with caution when using caffeine containing e-cigarette products. Further research is necessary to determine associated effects from inhaling caffeine.

Breast milk iodine and perchlorate concentrations in lactating Boston-area women.

CONTEXT: Breastfed infants rely on adequate maternal dietary iodine intake. OBJECTIVE: Our objective was to measure breast milk iodine and perchlorate, an inhibitor of iodide transport into the thyroid and potentially into breast milk, in Boston-area women. PARTICIPANTS: The study included 57 lactating healthy volunteers in the Boston area. MEASUREMENTS: Breast milk iodine and perchlorate concentrations and urine iodine, perchlorate, and cotinine concentrations were measured. For comparison, iodine and perchlorate levels in infant formulae were also measured. RESULTS: Median breast milk iodine content in 57 samples was 155 microg/liter (range, 2.7-1968 microg/liter). Median urine iodine was 114 microg/liter (range, 25-920 microg/liter). Perchlorate was detectable in all 49 breast milk samples (range, 1.3-411 microg/liter), all 56 urine samples (range, 0.37-127 microg/liter), and all 17 infant formula samples (range, 0.22-4.1 microg/liter) measured. Breast milk iodine content was significantly correlated with urinary iodine per gram creatinine and urinary cotinine but was not significantly correlated with breast milk or urinary perchlorate. CONCLUSIONS: Perchlorate exposure was not significantly correlated with breast milk iodine concentrations. Perchlorate was detectable in infant formula but at lower levels than in breast milk. Forty-seven percent of women sampled may have been providing breast milk with insufficient iodine to meet infants' requirements.

Urinary phytoestrogen concentrations in the U.S. population (1999-2000).

We report population-based urinary concentrations of phytoestrogens stratified by age, sex, and composite racial/ethnic variables. We measured the isoflavones - genistein, daidzein, equol, and O-desmethylangolensin (O-DMA) - and the lignans - enterolactone and enterodiol - in approximately 2500 urine samples from individuals aged 6 years and older who participated in the National Health and Nutrition Examination Survey (NHANES) in 1999 and 2000. We detected all phytoestrogens in over 70% of the samples analyzed; enterolactone was detected in the highest concentrations, and daidzein was detected with the highest frequency. The geometric means for each phytoestrogen were as follows: genistein, 22.3 microg/g; daidzein, 68.6 microg/g; equol, 7.65 microg/g; O-DMA, 3.95 microg/g; enterolactone, 217 microg/g; and enterodiol, 24.3 microg/g creatinine. The 95th percentiles for each phytoestrogen were as follows: genistein, 380 microg/g; daidzein, 944 microg/g; equol, 50.3 microg/g; O-DMA, 217 microg/g; enterolactone, 2240 microg/g; and enterodiol, 240 microg/g creatinine. Multivariate analyses showed statistically significant differences among many of the demographic subgroups. Adolescents had higher concentrations of genistein and equol than adults. Non-Hispanic whites had higher concentrations of enterodiol and equol than Mexican Americans or non-Hispanic blacks. Non-Hispanic whites also had higher concentrations of enterolactone and O-DMA than Mexican Americans. Mexican Americans had higher concentrations of genistein than non-Hispanic blacks; however, the opposite was found for O-DMA. Determination of phytoestrogen exposure in the US population will help us to better understand phytoestrogen consumption in the US and will assist us in elucidating the potential role of phytoestrogens in protecting against cancer and heart disease.

Urinary and serum concentrations of seven phytoestrogens in a human reference population subset.

Diets rich in naturally occurring plant estrogens (phytoestrogens) are strongly associated with a decreased risk for cancer and heart disease in humans. Phytoestrogens have estrogenic and, in some cases, antiestrogenic and antiandrogenic properties, and may contribute to the protective effect of some diets. However, little information is available about the levels of these phytoestrogens in the general US population. Therefore, levels of phytoestrogens were determined in urine (N=199) and serum (N=208) samples taken from a nonrepresentative subset of adults who participated in NHANES III, 1988-1994. The phytoestrogens quantified were the lignans (enterolactone, enterodiol, matairesinol); the isoflavones (genistein, daidzein, equol, O-desmethylangolensin); and coumestrol (urine only). Phytoestrogens with the highest mean urinary levels were enterolactone (512 ng/ml), daidzein (317 ng/ml), and genistein (129 ng/ml). In serum, the concentrations were much less and the relative order was reversed, with genistein having the highest mean level (4.7 ng/ml), followed by daidzein (3.9 ng/ml) and enterolactone (3.6 ng/ml). Highly significant correlations of phytoestrogen levels in urine and serum samples from the same persons were observed for enterolactone, enterodiol, genistein, and daidzein. Determination of phytoestrogen concentrations in large study populations will give a better insight into the actual dietary exposure to these biologically active compounds in the US population.

Enterolactone inhibits the growth of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in the rat.

The inverse association between a high enterolactone (ENL) concentration in both urine and serum, and the risk of breast cancer found in epidemiological studies suggests a chemopreventive action for ENL. However, no causal relationship has been established in clinical studies or in experimental models for breast cancer. In the present study, the potential chemopreventive action of p.o. administered ENL (1 or 10 mg/kg of body weight) was tested in 7,12-dimethylbenz(a)anthracene-induced mammary cancers of the rat. Rats were maintained on a standard open-formula chow diet. Daily p.o. administration of ENL at a dose of 10 mg/kg of body weight for 7 weeks significantly inhibited tumor growth. The growth-inhibitory effect of ENL was more pronounced on the new tumors, which developed during the treatment period, but ENL also inhibited the growth of those tumors established before the start of the lignan administration. The rat serum concentration of ENL, which illustrated a permanent positive effect on breast cancer growth, was 0.4 microM, which is >10-fold as compared with the serum concentrations found in the general human population. The effect of ENL was not restricted to any specific histological tumor type. ENL was demonstrated to act as a weak aromatase inhibitor in vitro and to reduce the relative uterine weight of the 7,12-dimethylbenz(a)anthracene-treated nonovariectomized rats. However, in a short-term assay ENL had no effect on the uterine growth of the intact or androstenedione-treated immature rats. Thus, the mechanism of the ENL action and its minimum or optimal daily dose remains to be clarified.