Human Physiologic Factors in Respiratory Uptake of 1,3-Butadiene

Lin, Yu‐Sheng; Smith, Thomas J.; Kelsey, Karl T.; Wypij, David

doi:10.2307/3454993

Cited by 6 publications

(8 citation statements)

References 33 publications

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“…The observation that females had higher levels of BTEX in their blood at a given exposure is consistent with findings from toxicokinetic models and a controlled human inhalation study of 1,3-butadiene, where females retained more 1,3-butadiene than males (Kohn and Melnick, 1993;Lin et al, 2001). Since the BTEX compounds, as well as 1,3-butadiene, are lipophilic substances, this finding probably relates to the increased proportion of body fat in females compared to males.…”

Section: Discussionsupporting

confidence: 85%

“…Increased body fat may also explain the trends toward increasing levels of BTEX compounds in blood with increasing BMI, after adjusting for exposure, especially for obese subjects (BMI 430) ( Table 6). The marginal effect of decreasing blood BTEX levels with age is also comparable to results from controlled 1,3-butadiene exposures (Lin et al, 2001), and may reflect a decrease in the efficiency of pulmonary gas exchange with increasing age, especially after age 30 (Crapo and Morris, 1981;Sprung et al, 2006; American Society of Anesthesiologists). Neither smoking nor the other covariates significantly altered the relationships between levels in air and blood for chloroform, 1,4-DCB, MTBE, and tetrachloroethene.…”

Section: Discussionmentioning

confidence: 62%

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

Lin

Egeghy

Rappaport

2007

J Expo Sci Environ Epidemiol

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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.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 62%

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

Lin

Egeghy

Rappaport

2007

J Expo Sci Environ Epidemiol

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“…To determine the blood/air partition coefficient of BD, we used a modification of the closedvial, headspace equilibration approach (11,12) and the National Institute for Occupational Safety and Health analytical method for the measurement of BD (13). Briefly, for the headspace method, we used a gas-tight syringe (Hamilton Company, Reno, NV) to spike 50 µL pure BD vapor (> 99.99%) (Aldrich Chemical Co., Milwaukee, WI) into a closed 20 mL vial containing a 6 mL blood sample.…”

Section: Methodsmentioning

confidence: 99%

Association of the blood/air partition coefficient of 1,3-butadiene with blood lipids and albumin.

Lin¹,

Smith²,

Wypij³

et al. 2002

Environ Health Perspect

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Pulmonary gas uptake is a function of the blood solubility of a vapor, indicated by the blood/air partition coefficient. We hypothesized that blood lipid compositions are associated with the blood/air partition coefficients of lipophilic toxic vapors such as 1,3-butadiene. Our goal was to investigate cross-sectional and longitudinal relationships of blood triglycerides, total cholesterol, and albumin to the blood/air partition coefficient of butadiene. We collected blood samples from 24 subjects at three time points: a fasting baseline and 2 and 4 hr after drinking a standardized high-fat milk shake (107 g fat, 80 g sugar, and 27 g protein). The blood/air partition coefficient was determined using the closed vial-equilibrium technique. Triglycerides and total cholesterol were analyzed by an enzymatic method, and albumin was analyzed with an immunoassay technique. We used multiple linear regression and general linear models to examine the cross-sectional and longitudinal relationship, respectively. The results showed that the blood/air partition coefficient of butadiene was cross-sectionally associated only with triglycerides at baseline, and longitudinally related to baseline triglycerides, total cholesterol, and the change in triglycerides over time. The blood/air partition coefficient of butadiene increased, on average, by approximately 20% and up to 40% for subjects with borderline higher triglyceride levels after ingestion of a standardized milk shake. In addition, a time factor beyond lipids was also significant in predicting the blood/air partition coefficient of butadiene. This may represent the effects of other unmeasured parameters related to time or time of day on the blood/air partition coefficient of butadiene. Because the blood/air partition coefficient is a major determinant of gas uptake, ingestion of a high fat meal before this type of exposure may significantly increase an individual's absorbed dose, possibly increasing the risk of adverse effects.

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“…As described in more detail previously (Lin et al 2001(Lin et al , 2002, our study involved a group of 144 volunteers. Human subjects committee of the Harvard school of public health approved the study.…”

Section: Data Descriptionmentioning

confidence: 99%

“…4 ("Appendix"), where f ds was the percentage of dead space computed for each individual, PC ab was the blood-air partition coefficient, computed as the steady-state ratio of BD concentration in venous blood to the BD concentration in headspace air (Lin et al 2001). C inhaled was the amount of BD given to each subject (continuous exposure of 2 ppm of BD for 20 min).…”

Section: The Pbpk Modelmentioning

confidence: 99%

Estimating metabolic rate for butadiene at steady state using a Bayesian physiologically-based pharmacokinetic model

et al. 2009

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In a study of 133 volunteer subjects, demographic, physiologic and pharmacokinetic data through exposure to 1,3-Butadiene (BD) were collected in order to estimate the percentage of BD concentration metabolized at steady state, and to determine whether this percentage varies across gender, racial, and age groups. During the 20 min of continuous exposure to 2 parts per million (ppm) of BD, five measurements of exhaled concentration were made on each subject. In the following 40 min washout period, another five measurements were collected. A Bayesian hierarchical compartmental physiologically-based pharmacokinetic model (PKPB) was used. Using prior information on the model parameters, Markov Chain Monte Carlo (MCMC) simulation was conducted to obtain posterior distributions. The overall estimate of the mean percent of BD metabolized at steady state was 12.7% (95% credible interval: 7.7-17.8%). There was no significant difference in gender with males having a mean of 13.5%, and females 12.3%. Among the racial groups, Hispanic (13.9%), White (13.0%), Asian (12.1%), and Black (10.9%), the significant difference came from the difference between Black and Hispanic with a 95% credible interval from −5.63 to −0.30%. Those older than 30 years had a mean of 12.2% versus 12.9% for the Stat (2011) 18:131-146 younger group; although this was not a statistically significant difference. Given a constant inhalation input of 2 ppm, at steady state, the overall mean exhaled concentration was estimated to be 1.75 ppm (95% credible interval: 1.64-1.84). An equivalent parameter, first-order metabolic rate constant, was also estimated and found to be consistent with the percent of BD metabolized at steady state across gender, race, and age strata.123 132 Environ Ecol

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Human Physiologic Factors in Respiratory Uptake of 1,3-Butadiene

Cited by 6 publications

References 33 publications

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

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

Association of the blood/air partition coefficient of 1,3-butadiene with blood lipids and albumin.

Estimating metabolic rate for butadiene at steady state using a Bayesian physiologically-based pharmacokinetic model

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