Pharmacokinetics of benzene

Travis, Curtis C.; Quillen, Jeffery L.; Arms, Angela D.

doi:10.1016/0041-008x(90)90037-u

Cited by 103 publications

(50 citation statements)

References 38 publications

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“…This behavior was unexpected, given current toxicokinetic models that indicate that saturable benzene metabolism should not be observed below about 3 to 10 ppm in humans (49,50). Thus, our results suggest that current toxicokinetic models for benzene are not accurate for air concentrations below 3 ppm.…”

Section: Discussioncontrasting

confidence: 46%

Modeling Human Metabolism of Benzene Following Occupational and Environmental Exposures

Kim

Vermeulen

Waidyanatha

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

103

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We used natural spline (NS) models to investigate nonlinear relationships between levels of benzene metabolites (E,Emuconic acid, S-phenylmercapturic acid, phenol, hydroquinone, and catechol) and benzene exposure among 386 exposed and control workers in Tianjin, China. After adjusting for background levels (estimated from the 60 control subjects with the lowest benzene exposures), expected mean trends of all metabolite levels increased with benzene air concentrations from 0.03 to 88.9 ppm. Molar fractions for phenol, hydroquinone, and E,E-muconic acid changed continuously with increasing air concentrations, suggesting that competing CYP-mediated metabolic pathways favored E,Emuconic acid and hydroquinone below 20 ppm and favored phenol above 20 ppm. Mean trends of dose-specific levels (Mmol/L/ppm benzene) of E,E-muconic acid, phenol, hydroquinone, and catechol all decreased with increasing benzene exposure, with an overall 9-fold reduction of total metabolites. Surprisingly, about 90% of the reductions in dosespecific levels occurred below about 3 ppm for each major metabolite. Using generalized linear models with NSsmoothing functions (GLM + NS models), we detected significant effects upon metabolite levels of gender, age, and smoking status. Metabolite levels were about 20% higher in females and decreased between 1% and 2% per year of life. In addition, levels of hydroquinone and catechol were greater in smoking subjects. Overall, our results indicate that benzene metabolism is highly nonlinear with increasing benzene exposure above 0.03 ppm, and that current human toxicokinetic models do not accurately predict benzene metabolism below 3 ppm. Our results also suggest that GLM + NS models are ideal for evaluating nonlinear relationships between environmental exposures and levels of human biomarkers. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2246 -52)

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Section: Discussioncontrasting

confidence: 46%

Modeling Human Metabolism of Benzene Following Occupational and Environmental Exposures

Kim

Vermeulen

Waidyanatha

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

103

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“…Following inhalation, benzene vapor is rapidly absorbed into the blood and distributed throughout the body (22,23). The kinetics of benzene uptake and distribution have been investigated among human volunteers under experimental conditions (24)(25)(26)(27)(28)(29)(30) and among occupationally exposed workers (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41).…”

mentioning

confidence: 99%

Environmental and biological monitoring of benzene during self-service automobile refueling.

Egeghy

Tornero‐Velez

Rappaport

2000

Environ Health Perspect

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Although automobile refueling represents the major source of benzene exposure among the nonsmoking public, few data are available regarding such exposures and the associated uptake of benzene. We repeatedly measured benzene exposure and uptake (via benzene in exhaled breath) among 39 self-service customers using self-administered monitoring, a technique rarely used to obtain measurements from the general public (130 sets of measurements were obtained). Benzene exposures averaged 2.9 mg/m(3) (SD = 5.8 mg/m(3); median duration = 3 min) with a range of < 0.076-36 mg/m(3), and postexposure breath levels averaged 160 microg/m(3) (SD = 260 microg/m(3)) with a range of < 3.2-1,400 microg/m(3). Log-transformed exposures and breath levels were significantly correlated (r = 0.77, p < 0.0001). We used mixed-effects statistical models to gauge the relative influences of environmental and subject-specific factors on benzene exposure and breath levels and to investigate the importance of various covariates obtained by questionnaire. Model fitting yielded three significant predictors of benzene exposure, namely, fuel octane grade (p = 0.0011), duration of exposure (p = 0.0054), and season of the year (p = 0.032). Likewise, another model yielded three significant predictors of benzene concentration in breath, specifically, benzene exposure (p = 0.0001), preexposure breath concentration (p = 0.0008), and duration of exposure (p = 0.038). Variability in benzene concentrations was remarkable, with 95% of the estimated values falling within a 274-fold range, and was comprised entirely of the within-person component of variance (representing exposures of the same subject at different times of refueling). The corresponding range for benzene concentrations in breath was 41-fold and was comprised primarily of the within-person variance component (74% of the total variance). Our results indicate that environmental rather than interindividual differences are primarily responsible for benzene exposure and uptake during automobile refueling. The study also demonstrates that self-administered monitoring can be efficiently used to measure environmental exposures and biomarkers among the general public.

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“…has been implemented for the data in Table 1 (25). The internal dose microrelation (y II x) for mice was quantified in three steps: a) The PBPK model of Travis et al (17) was used to calculate the steadystate amounts of total benzene metabolites produced per day from different amounts of benzene administered per day. b) A nonlinear (Michaelis-Menten) regression model was used to quantify the relation between x, the administered daily dose of Figure 4.…”

Section: Results Of Monte-carlomentioning

confidence: 99%

“…{x} -> y} [5] This link can be quantified for benzene using any of several published PBPK models of the dynamics of benzene metabolism, distribution, and elimination (17,18 where the instantaneous rate of change ofy at time t is given by the formula…”

Section: Methods For a Biologically Based Causal Decomposition Of Dosmentioning

confidence: 99%

See 1 more Smart Citation

Reassessing Benzene Risks Using Internal Doses and Monte-Carlo Uncertainty Analysis

Cox¹

1996

Environmental Health Perspectives

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Pharmacokinetics of benzene

Cited by 103 publications

References 38 publications

Modeling Human Metabolism of Benzene Following Occupational and Environmental Exposures

Modeling Human Metabolism of Benzene Following Occupational and Environmental Exposures

Environmental and biological monitoring of benzene during self-service automobile refueling.

Reassessing Benzene Risks Using Internal Doses and Monte-Carlo Uncertainty Analysis

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