Urinary biomarkers of exposure to insecticides, herbicides, and one insect repellent among pregnant women in Puerto Rico

Abstract 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.http://deepblue.lib.umich.edu/bitstream/2027.42/109451/1/12940_2014_Article_800.pd

Urinary Perchlorate and Thyroid Hormone Levels in Adolescent and Adult Men and Women Living in the United States

BACKGROUND: Perchlorate is commonly found in the environment and known to inhibit thyroid function at high doses. Assessing the potential effect of low-level exposure to perchlorate on thyroid function is an area of ongoing research. OBJECTIVES: We evaluated the potential relationship between urinary levels of perchlorate and serum levels of thyroid stimulating hormone (TSH) and total thyroxine (T(4)) in 2,299 men and women, ≥ 12 years of age, participating in the National Health and Nutrition Examination Survey (NHANES) during 2001–2002. METHODS: We used multiple regression models of T(4) and TSH that included perchlorate and covariates known to be or likely to be associated with T(4) or TSH levels: age, race/ethnicity, body mass index, estrogen use, menopausal status, pregnancy status, premenarche status, serum C-reactive protein, serum albumin, serum cotinine, hours of fasting, urinary thiocyanate, urinary nitrate, and selected medication groups. RESULTS: Perchlorate was not a significant predictor of T(4) or TSH levels in men. For women overall, perchlorate was a significant predictor of both T(4) and TSH. For women with urinary iodine < 100 μg/L, perchlorate was a significant negative predictor of T(4) (p < 0.0001) and a positive predictor of TSH (p = 0.001). For women with urinary iodine ≥ 100 μg/L, perchlorate was a significant positive predictor of TSH (p = 0.025) but not T(4) (p = 0.550). CONCLUSIONS: These associations of perchlorate with T(4) and TSH are coherent in direction and independent of other variables known to affect thyroid function, but are present at perchlorate exposure levels that were unanticipated based on previous studies

Exposure to Perchlorate in Lactating Women and Its Associations With Newborn Thyroid Stimulating Hormone

Background: Perchlorate, thiocyanate, and nitrate can block iodide transport at the sodium iodide symporter (NIS) and this can subsequently lead to decreased thyroid hormone production and hypothyroidism. NIS inhibitor exposure has been shown to reduce iodide uptake and thyroid hormone levels; therefore we hypothesized that maternal NIS inhibitor exposure will influence both maternal and newborn thyroid function.Methods: Spot urine samples were collected from 185 lactating mothers and evaluated for perchlorate, thiocyanate, and nitrate concentrations. Blood and colostrum samples were collected from the same participants in the first 48 h after delivery. Thyroid hormones and thyroid-related antibodies (TSH, fT3, fT4, anti-TPO, anti-Tg) were analyzed in maternal blood and perchlorate was analyzed in colostrum. Also, spot blood samples were collected from newborns (n = 185) between 48 and 72 postpartum hours for TSH measurement. Correlation analysis was performed to assess the effect of NIS inhibitors on thyroid hormone levels of lactating mothers and their newborns in their first 48 postpartum hours.Results: The medians of maternal urinary perchlorate (4.00 μg/g creatinine), maternal urinary thiocyanate (403 μg/g creatinine), and maternal urinary nitrate (49,117 μg/g creatinine) were determined. Higher concentrations of all three urinary NIS inhibitors (μg/g creatinine) at their 75th percentile levels were significantly correlated with newborn TSH (r = 0.21, p &lt; 0.001). Median colostrum perchlorate level concentration of all 185 participants was 2.30 μg/L. Colostrum perchlorate was not significantly correlated with newborn TSH (p &gt; 0.05); however, there was a significant correlation between colostrum perchlorate level and maternal TSH (r = 0.21, p &lt; 0.01). Similarly, there was a significant positive association between colostrum perchlorate and maternal urinary creatinine adjusted perchlorate (r = 0.32, p &lt; 0.001).Conclusion: NIS inhibitors are ubiquitous in lactating women in Turkey and are associated with increased TSH levels in newborns, thus signifying for the first time that co-exposure to maternal NIS inhibitors can have a negative effect on the newborn thyroid function

Direct Measurement of Perchlorate Exposure Biomarkers in a Highly Exposed Population: A Pilot Study

Exposure to perchlorate is ubiquitous in the United States and has been found to be widespread in food and drinking water. People living in the lower Colorado River region may have perchlorate exposure because of perchlorate in ground water and locally-grown produce. Relatively high doses of perchlorate can inhibit iodine uptake and impair thyroid function, and thus could impair neurological development in utero. We examined human exposures to perchlorate in the Imperial Valley among individuals consuming locally grown produce and compared perchlorate exposure doses to state and federal reference doses. We collected 24-hour urine specimen from a convenience sample of 31 individuals and measured urinary excretion rates of perchlorate, thiocyanate, nitrate, and iodide. In addition, drinking water and local produce were also sampled for perchlorate. All but two of the water samples tested negative for perchlorate. Perchlorate levels in 79 produce samples ranged from non-detect to 1816 ppb. Estimated perchlorate doses ranged from 0.02 to 0.51 µg/kg of body weight/day. Perchlorate dose increased with the number of servings of dairy products consumed and with estimated perchlorate levels in produce consumed. The geometric mean perchlorate dose was 70% higher than for the NHANES reference population. Our sample of 31 Imperial Valley residents had higher perchlorate dose levels compared with national reference ranges. Although none of our exposure estimates exceeded the U. S. EPA reference dose, three participants exceeded the acceptable daily dose as defined by bench mark dose methods used by the California Office of Environmental Health Hazard Assessment

LC-MS/MS Analysis of Sugars, Alditols, and Humectants in Smokeless Tobacco Products

Globally, smokeless tobacco (ST) includes a wide array of chemically diverse products generally used in the oral cavity. Although ST has been widely investigated, this study was undertaken to determine the levels of sugars (mono- and di-saccharides), alditols, and humectants present in major ST categories/subcategories by using high performance liquid chromatography coupled with a triple quadrupole mass spectrometer (HPLC-MS/MS). The products studied included chewing tobacco (loose leaf, plug, twist), US moist snuff, Swedish snus, creamy snuff, dry snuff, dissolvable tobacco products, and tobacco-coated toothpicks. The highest mean sugar level was detected in chewing tobacco (9.3–27.5%, w/w), followed by dissolvable tobacco (2.1%); all other products were lower than 1%. Creamy snuff had the highest mean alditol levels (22.6%), followed by dissolvable tobacco (15.4%); all others had levels lower than 1%. The detected mean humectant levels ranged from non-detectable to 5.9%. This study demonstrates the broad chemical diversity among ST. This research may aid researchers and public health advocates investigating the exposures and risks of ST. [Beitr. Tabakforsch. Int. 28 (2019) 203–213

Analysis of Toxic Metals in Liquid from Electronic Cigarettes

As the technology of electronic nicotine delivery systems (ENDS), including e-cigarettes, evolves, assessing metal concentrations in liquids among brands over time becomes challenging. A method for quantification of chromium, nickel, copper, zinc, cadmium, tin, and lead in ENDS liquids using triple quadrupole inductively coupled plasma mass spectrometry was developed. The method&rsquo;s limits of detection (LODs) were 0.031, 0.032, 3.15, 1.27, 0.108, 0.099, 0.066 &micro;g/g for Cr, Ni, Cu, Zn, Cd, Sn, and Pb respectively. Liquids analyzed were from different brands and flavors of refill bottles or single-use, rechargeable, and pod devices from different years. Scanning electron microscopy with energy dispersive spectroscopy further evaluated the device components&rsquo; compositions. Refill liquids before contacting a device were below lowest reportable levels (LRL) for all metals. Copper and zinc were elevated in liquids from devices containing brass. Cadmium was &lt;LRL in all liquids and was not observed in device components. Cr, Ni, Cu, Zn, Sn, and Pb, reported in &micro;g/g, ranged from &lt;LRL to 0.396, 4.04, 903, 454, 0.898, and 13.5 respectively. Elevated metal concentrations in the liquid were also elevated in aerosol from the corresponding device. The data demonstrates the impact of device design and materials on toxic metals in ENDS liquid

A Low-Cost, High-Throughput Digital Image Analysis of Stain Patterns on Smoked Cigarette Filter Butts to Estimate Mainstream Smoke Exposure

Standard machine smoking protocols provide useful information for examining the impact of design parameters, such as filter ventilation, on mainstream smoke delivery. Unfortunately, their results do not accurately reflect human smoke exposure. Clinical research and topography devices in human studies yield insights into how products are used, but a clinical setting or smoking a cigarette attached to such a device may alter smoking behavior. To better understand smokers’ use of filtered cigarette products in a more natural environment, we developed a low-cost, high-throughput approach to estimate mainstream cigarette smoke exposure on a per-cigarette basis. This approach uses an inexpensive flatbed scanner to scan smoked cigarette filter butts and custom software to analyze tar-staining patterns. Total luminosity, or optical staining density, of the scanned images provides quantitative information proportional to mainstream smoke-constituent deliveries on a cigarette-by-cigarette basis. Duplicate sample analysis using this new approach and our laboratory’s gold-standard liquid chromatography/tandem mass spectrometry (LC/MS/MS) solanesol method yielded comparable results (+7% bias) from the analysis of 20 commercial cigarettes brands (menthol and nonmentholated). The brands varied in design parameters such as length, filter ventilation, and diameter. Plots correlating the luminosity to mainstream smoked-nicotine deliveries on a per-cigarette basis for these cigarette brands were linear (average R2 &gt; 0.91 for nicotine and R2 &gt; 0.83 for the tobacco-specific nitrosamine NNK), on a per-brand basis, with linearity ranging from 0.15 to 3.00 mg nicotine/cigarette. Analysis of spent cigarette filters allows exposures to be characterized on a per-cigarette basis or a “daily dose” via summing across results from all filter butts collected over a 24 h period. This scanner method has a 100-fold lower initial capital cost for equipment than the LC/MS/MS solanesol method and provides high-throughput results (~200 samples per day). Thus, this new method is useful for characterizing exposure related to filtered tobacco-product use

Radioactive Iodide (131I−) Excretion Profiles in Response to Potassium Iodide (KI) and Ammonium Perchlorate (NH4ClO4) Prophylaxis

Radioactive iodide (131I−) protection studies have focused primarily on the thyroid gland and disturbances in the hypothalamic-pituitary-thyroid axis. The objective of the current study was to establish 131I− urinary excretion profiles for saline, and the thyroid protectants, potassium iodide (KI) and ammonium perchlorate over a 75 hour time-course. Rats were administered 131I− and 3 hours later dosed with either saline, 30 mg/kg of NH4ClO4 or 30 mg/kg of KI. Urinalysis of the first 36 hours of the time-course revealed that NH4ClO4 treated animals excreted significantly more 131I− compared with KI and saline treatments. A second study followed the same protocol, but thyroxine (T4) was administered daily over a 3 day period. During the first 6–12 hour after 131I− dosing, rats administered NH4ClO4 excreted significantly more 131I− than the other treatment groups. T4 treatment resulted in increased retention of radioiodide in the thyroid gland 75 hour after 131I− administration. We speculate that the T4 treatment related reduction in serum TSH caused a decrease synthesis and secretion of thyroid hormones resulting in greater residual radioiodide in the thyroid gland. Our findings suggest that ammonium perchlorate treatment accelerates the elimination rate of radioiodide within the first 24 to 36 hours and thus may be more effective at reducing harmful exposure to 131I− compared to KI treatment for repeated dosing situations. Repeated dosing studies are needed to compare the effectiveness of these treatments to reduce the radioactive iodide burden of the thyroid gland

Urinary concentrations of PAH and VOC metabolites in marijuana users

Background: Marijuana is seeing increased therapeutic use, and is the world\u27s third most-popular recreational drug following alcohol and tobacco. This widening use poses increased exposure to potentially toxic combustion by-products from marijuana smoke and the potential for public health concerns. Objectives: To compare urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) among self-reported recent marijuana users and nonusers, while accounting for tobacco smoke exposure. Methods: Measurements of PAH and VOC metabolites in urine samples were combined with questionnaire data collected from participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2012 in order to categorize participants (≥18 years) into exclusive recent marijuana users and nonusers. Adjusted geometric means (GMs) of urinary concentrations were computed for these groups using multiple regression analyses to adjust for potential confounders. Results: Adjusted GMs of many individual monohydroxy PAHs (OH-PAHs) were significantly higher in recent marijuana users than in nonusers (p\u3c0.05). Urinary thiocyanate (p\u3c0.001) and urinary concentrations of many VOC metabolites, including metabolites of acrylonitrile (p\u3c0.001) and acrylamide (p\u3c0.001), were significantly higher in recent marijuana users than in nonusers. Conclusions: We found elevated levels of biomarkers for potentially harmful chemicals among self-identified, recent marijuana users compared with nonusers. These findings suggest that further studies are needed to evaluate the potential health risks to humans from the exposure to these agents when smoking marijuana