Blood BTEX levels and neurologic symptoms in Gulf states residents.

BACKGROUND: The chemicals benzene, toluene, ethylbenzene, and xylenes (BTEX) are neuroactive. Exposures often co-occur because they share common sources. We examined neurologic effects of environmental BTEX exposure among U.S. Gulf coast residents taking into account concomitant exposures. METHODS: We measured blood concentrations of BTEX in 690 Gulf state residents. Neurologic symptoms were ascertained via telephone interview. We used log-binomial regression to estimate associations between blood BTEX levels and self-reported neurologic symptoms independently for the presence of any neurologic, central (CNS), or peripheral nervous system (PNS) symptoms. We estimated associations in single chemical models mutually adjusted for co-occurring BTEX and used weighted quantile sum regression to model associations between the combined BTEX mixture and neurologic symptoms. RESULTS: Half (49%) of participants reported at least one neurologic symptom. Each BTEX chemical was associated with increased CNS and PNS symptoms in single-chemical models comparing the highest to lowest quartile of exposure. After adjusting for coexposures, benzene was associated with CNS symptoms among all participants (PR = 2.13, 95% CI: 1.27, 3.57) and among nonsmokers (PR = 2.30, 95% CI: 1.35, 3.91). After adjusting for coexposures, associations with toluene were apparent only for reporting multiple PNS symptoms (PR = 2.00, 95% CI: 0.96, 4.16). In mixture analyses, a one-quartile increase in BTEX exposure was associated with neurologic symptoms (OR = 1.47, 95% CI: 1.11, 1.98). The weighted quantile sum index weighted benzene most heavily, which was consistent with single chemical analyses. CONCLUSIONS: Increasing blood benzene concentration was associated with increased prevalence of CNS symptoms. In this sample, BTEX-associated neurologic effects are likely driven by exposure to benzene and, to a lesser extent, toluene.

Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 2. Biomarkers of exposure.

A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) was conducted, and subjects' experience with the products was followed for 24 weeks. Differences in biomarkers of tobacco exposure between smokers and never smokers at baseline and among groups relative to each other and over time were assessed. Results indicated reduced exposure to many potentially harmful constituents found in cigarette smoke following product switching. Findings support differences in exposure from the use of various tobacco products and are relevant to the understanding of a risk continuum among tobacco products (ClinicalTrials.gov Identifier: NCT02061917).

[Characteristics of regulatory system in children exposed to the environmental chemical factors].

In children residing in areas with a high content of a number of aromatic hydrocarbons in ambient air and organochlorine compounds in drinking water there were studied the blood levels of these compounds, as well as the assessment of the indices of the immune and neuroendocrine systems was performed. The higher blood content of phenol and formaldehyde has been established and there was identified an array of organochlorine and aromatic compounds not detected in the control group children. In the blood of the children of a study group there was found an imbalance of indices of cellular components of innate and adaptive immunity, pro- and anti-inflammatory cytokines, as well as increased concentrations of free thyroxine and serotonin in the blood serum, which indicates to a change in the functions of regulatory systems in children exposed to organochlorine and aromatic compounds.

[Features of diurnal profile of blood pressure in workers having serum aromatic hydrocarbons level].

Features of diurnal profile of blood pressure in workers having serum level of benzol and ethylbenzene are high systolic and diastolic arterial blood pressure during the day, index of systolic arterial pressure time and index diastolic arterial pressure time was also high. These features should be considered in anti-hypertensives prescription.

[Immunologic and genetic markers of exposure to aromatic hydrocarbons in workers].

Workers exposed to aromatic hydrocarbons appeared to have prevalence of heterozygous variants of CYP1A1 gene (9893 A/G) and tumor necrosis factor gene reliably higher vs. the reference group 2.5 and 3.3 times respectively, and level of anti-benzene antibodies (IgG) increased vs. the reference group. The data presented demonstrate negative immunogenetic associations of aromatic hydrocarbons influence on oil extraction operators.

[Biomonitoring serum aromatic hydrocarbons in workers engaged in oil extraction industry].

Federal Research Center of Medical and preventive technologies of risk management to public health: in this paper, we present the results of aromatic hydrocarbons biomonitoring in blood of oil-producing industry workers.

Determinants of polychlorinated aromatic hydrocarbons in serum in three age classes--Methodological implications for human biomonitoring.

Human biomonitoring provides an integrated measure for individual exposure to environmental pollutants. Better insight in inter-individual variability of biomarkers of exposure may help in the interpretation of biomonitoring studies. The aim was to study the impact of outliers, determine the optimal unit for fat-soluble biomarkers in serum and quantify the major determinants for biomarkers of exposure to polychlorinated aromatic hydrocarbons (PCAHs) in three age groups. Data were obtained from the Flemish Environment and Health Study (2002-2006). Marker PCBs (sum of 138, 153, 180), hexachlorobenzene (HCB) and p,p'-DDE were measured in cord blood samples of 1196 newborns, in serum samples of 1679 adolescents (14-15 years) and 1583 adults (50-65 years). Exclusion of influential outliers in multiple linear regression models lead to models that are better applicable to the general population. In terms of adjusted R2, the regression model with the pollutant expressed in volume-based units and blood fat as a separate independent variable was superior compared to models with other units. We found highly consistent relationships between the serum concentration of PCAHs and blood fat, age, changes in body weight, animal fat in the diet, local vegetable consumption (HCB and p,p'-DDE only) and being breastfed as a baby (in adolescents only). The impact of sex and BMI differed by age. For biomarkers of persistent pollutants that reflect long-term exposure, the relation between the covariates and the biomarkers can be well quantified.

Dynamic headspace analysis using online measurements: Modeling of average and initial concentration.

Dynamic headspace sampling is an important technique for the analysis of consumer products, the study of biological samples and environmental water analyses. This paper shows the influence of experimental conditions, such as the sampling time, sampling flow rate, headspace volume, liquid volume and Henry coefficient on the measured average concentration values. A corresponding closed expression as function of these variables is introduced in order to quantify the deviation of the initial headspace concentration. The proposed bi-exponential function embeds different current existing models for recovery calculation in dynamic sampling analyses in one single expression. A fully automated and user-friendly Excel® file to investigate or to model the dynamic headspace sampling results is added to everyone's easy use.

The Utility of Sonogashira Coupling Reaction for the Derivatization of Aryl Halides with Fluorescent Alkyne.

Aryl halides are a very important category of compounds that include many vital drugs and key industrial additives, such as clofibrate and bromobenzene, respectively. Due to their importance, our research group previously developed a novel fluorescence labeling approach for their analysis using a fluorescent aryl boronic acid as a reagent, based on the Suzuki coupling reaction. This coupling reaction was successfully applied for the determination of aryl halides in biological fluids; however, there was a limitation of low reactivity towards ortho-substituted aryl halides. In the present study, a novel fluorescence derivatization approach for aryl halides was developed using, 2-(4-ethynylphenyl)-4,5-diphenyl-1H-imidazole (DIB-ET) as a fluorescent alkyne reagent, based on the Sonogashira coupling reaction. DIB-ET reacted with aryl bromides in the presence of palladium and copper as catalysts, yielding fluorescent derivatives that could be subsequently determined by an HPLC system with fluorescence detection. The detection limits (S/N = 3) for aryl bromides were in the range of 14 - 23 nM, which is 3.5 - 18-times more sensitive than our previously developed approach, Suzuki coupling derivatization. Moreover, in contrast to the previous technique, the reactivity of DIB-ET to ortho-substituted aryl bromides was almost equivalent to that of the para-substituted aryl bromides. Hence, by using this newly developed approach we could label the aryl halides with more sensitivity and reactivity. Finally, the proposed method was successfully applied for the selective determination of aryl bromides in human serum with good recovery (84.6 - 107%), which proves the ability of the developed method to determine occupational exposure to aryl halides.

Predictors of blood volatile organic compound levels in Gulf coast residents.

To address concerns among Gulf Coast residents about ongoing exposures to volatile organic compounds, including benzene, toluene, ethylbenzene, o-xylene, and m-xylene/p-xylene (BTEX), we characterized current blood levels and identified predictors of BTEX among Gulf state residents. We collected questionnaire data on recent exposures and measured blood BTEX levels in a convenience sample of 718 Gulf residents. Because BTEX is rapidly cleared from the body, blood levels represent recent exposures in the past 24 h. We compared participants' levels of blood BTEX to a nationally representative sample. Among nonsmokers we assessed predictors of blood BTEX levels using linear regression, and predicted the risk of elevated BTEX levels using modified Poisson regression. Blood BTEX levels in Gulf residents were similar to national levels. Among nonsmokers, sex and reporting recent smoky/chemical odors predicted blood BTEX. The change in log benzene was -0.26 (95% CI: -0.47, -0.04) and 0.72 (0.02, 1.42) for women and those who reported odors, respectively. Season, time spent away from home, and self-reported residential proximity to Superfund sites (within a half mile) were statistically associated with benzene only, however mean concentration was nearly an order of magnitude below that of cigarette smokers. Among these Gulf residents, smoking was the primary contributor to blood BTEX levels, but other factors were also relevant.

QSAR modeling of adipose/blood partition coefficients of Alcohols, PCBs, PBDEs, PCDDs and PAHs: A data gap filling approach.

Physiologically-based toxicokinetic (PBTK) model has immense role to play in the risk assessment process due to specified mathematical representation of the absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) of chemicals in diverse environmental compartment. Determination of adipose/blood partition coefficient [logP(adipose/blood)] is regarded as one of the crucial constraints of PBTK models. In respect to the challenge for identifying the chemical-definite parameters for these models, especially within short time frame and with limited resources, quantitative structure-activity relationship (QSAR) models are beneficial for providing the chemical-specific parameters of PBTK models. In the present study, we have developed robust, statistically highly significant (R2 = 0.92, QLOO2 = 0.90, RPred2 = 0.92) and mechanistically interpretable three descriptors QSAR models for 67 environmental chemicals [Alcohols, polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzodioxins (PCDDs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs)] employing the experimental values of adipose/blood partition coefficient for human. The partitioning of chemicals into adipose tissue and blood offers information related to distribution and toxicological effects of these molecules in to the mammal system. The developed models are helpful to understand the mechanistic basis of toxicokinetic processes into the mammal system followed by risk assessment and risk management process. The applicability domain (AD) of the developed model was checked and followed by its employment to predict adipose/blood partition coefficient of 513 environmental contaminants consist of PCBs, PBDEs, PCDDs and PAHs from USA Environmental protection agency (US EPA) site.

Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons.

A quasi-experimental field study was carried out in 24 volunteers with the aim of: (i) assessing personal exposure to aromatic hydrocarbons polluting urban areas; and (ii) exploring the role of polymorphic enzymes relevant to the biotransformation of benzene in the inter-individual variability of biomarkers. Each subject covered by bicycle: (i) inner city routes with often jammed traffic; and (ii) open rural routes. Time-weighted average airborne concentrations of benzene, toluene, ethylbenzene and xylenes (BTEX) were determined during 2-h runs. BTEX were determined by solid-phase micro-extraction (SPME) followed by gas chromatography coupled with mass spectrometry (GC-MS) in blood and spot urine samples collected just before and immediately after the runs. Urinary t,t-muconic acid was measured by high performance liquid chromatography (HPLC)-UV. Genotypes of epoxide hydrolase (EH) and glutathione-S-transferase class mu-1 (GSTM1) were also characterised. As compared to pre-run values, benzene and toluene in blood, and toluene and xylenes in urine significantly increased after urban runs. Urinary t,t-muconic acid was significantly higher in post-run samples after both urban (P < 0.001) and rural runs (P < 0.05). Despite a narrow range of exposure levels, a significant relationship was observed between airborne benzene and post-run t,t-muconic acid (r2 = 0.349, P < 0.00). When subgroups were distinguished according to EH and GSTM, subjects bearing both the EH wild type and GSTM 'null' genotype showed significant exposure-related changes in t,t-muconic acid excretion. Even at very low exposure levels, a 2-h bike run in a polluted urban environment may give rise to measurable changes in biomarkers of internal dose of selected aromatic hydrocarbons. Genetically-based metabolic differences may account for part of the inter-individual variability of biomarkers of exposure.

Quantitative evaluation of volatile hydrocarbons in post-mortem blood in forensic autopsy cases of fire-related deaths.

Volatile hydrocarbons in post-mortem blood from victims of fires were analyzed quantitatively by headspace gas chromatography mass spectrometry. The benzene and styrene concentrations in the blood were positively correlated with the carboxyhemoglobin (CO-Hb) concentration, which is evidence that the deceased inhaled the hydrocarbons and carbon monoxide simultaneously. By contrast, the concentrations of toluene and CO-Hb in the blood were not significantly correlated. This lack of correlation could be explained by two different sources of toluene, with low blood concentrations of toluene arising when the deceased inhaled smoke and high blood concentrations of toluene arising when the deceased inhaled petroleum vapor or other unknown vapors. The quantity of soot deposited in the respiratory tract was classified into four grades (-, 1+, 2+, 3+). The mean CO-Hb concentration in the 1+ soot group was significantly lower than those in the 2+ (p<0.05) and 3+ (p<0.01) soot groups. The blood CO-Hb concentrations in the 1+ soot group were all below 30%. Those indicated that the deceased aspirated smoke that contained both soot and carbon monoxide. The wide variation in CO-Hb concentrations for each soot classification could be caused by the different types of smoke produced by different materials. For example, petroleum combustion with a limited supply of oxygen, like in a compartment fire, may produce a large volume of dense black smoke that contains a large quantity of soot. Soot deposits in the airways and the blood CO-Hb concentration are basic and essential autopsy findings that are used to investigate fire-related deaths. The quantitative GC-MS analysis of blood volatile hydrocarbons can provide additional useful information on the cause of the fire and the circumstances surrounding the death. In combination, these three findings are useful for the reconstruction of cases.

Relationships between levels of volatile organic compounds in air and blood from the general population.

The relationships between levels of volatile organic compounds (VOCs) in blood and air have not been well characterized in the general population where exposure concentrations are generally at parts per billion levels. This study investigates relationships between the levels of nine VOCs, namely, benzene, chloroform, 1,4-dichlorobenzene, ethylbenzene, methyl tert-butyl ether (MTBE), tetrachloroethene, toluene, and m-/p- and o-xylene, in blood and air from a stratified random sample of the general US population. We used data collected from 354 participants, including 89 smokers and 265 nonsmokers, aged 20-59 years, who provided samples of blood and air in the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Demographic and physiological characteristics were obtained from self-reported information; smoking status was determined from levels of serum cotinine. Multiple linear regression models were used to investigate the relationships between VOC levels in air and blood, while adjusting for effects of smoking and demographic factors. Although levels of VOCs in blood were positively correlated with the corresponding air levels, the strength of association (R(2)) varied from 0.02 (ethylbenzene) to 0.68 (1,4-DCB). Also the blood-air relationships of benzene, toluene, ethylbenzene, and the xylenes (BTEX) were influenced by smoking, exposure-smoking interactions, and by gender, age, and BMI, whereas those of the other VOCs were not. Interestingly, the particular exposure-smoking interaction for benzene was different from those for toluene, ethylbenzene, and the xylenes. Whereas smokers retained more benzene in their blood at increasing exposure levels, they retained less toluene, ethylbenzene, and xylenes at increasing exposure levels. Investigators should consider interaction effects of exposure levels and smoking when exploring the blood-air relationships of the BTEX compounds in the general population.