Empirical Relations Predicting Human and Rat Tissue:Air Partition Coefficients of Volatile Organic Compounds

Meulenberg, Cécil J. W.; Vijverberg, Henk P.M.

doi:10.1006/taap.2000.8929

Cited by 87 publications

(87 citation statements)

References 35 publications

(20 reference statements)

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“…Based on a model, Meulenberg and Vijverberg (2000) predicted that tissue: air partition coefficients for all three TMB isomers would be similar in humans and rats, indicating that the TMB isomers are likely to have similar tissue distribution patterns in both species and that the results of studies in rats would probably be reflective of systemic distribution in humans. Estimated fat/air partition coefficients were at least 10-fold greater than those for other tissues and 100-fold greater than the blood/air partition coefficients, indicating a propensity for distribution to adipose tissue.…”

Section: Distributionmentioning

confidence: 99%

Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum processing streams, containing only carbon and hydrogen atoms, with carbon numbers ranging from approximately C5-C20 and boiling between approximately 35-370°C. Many of the hydrocarbon solvents have complex and variable compositions with constituents of 4 types, alkanes (normal paraffins, isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one-and tworing species). Because of the compositional complexity, hydrocarbon solvents are now identified by a nomenclature ("the naming convention") that describes them in terms of physical/ chemical properties and compositional elements. Despite the compositional complexity, most hydrocarbon solvent constituents have similar toxicological properties, and the overall toxicological hazards can be characterized in generic terms. To facilitate hazard characterization, the solvents were divided into 9 groups (categories) of substances with similar physical and chemical properties. Hydrocarbon solvents can cause chemical pneumonitis if aspirated into the lung, and those that are volatile can cause acute CNS effects and/or ocular and respiratory irritation at exposure levels exceeding occupational recommendations. Otherwise, there are few toxicologically important effects. The exceptions, n-hexane and naphthalene, have unique toxicological properties, and those solvents containing constituents for which classification is required under the Globally Harmonized System (GHS) are differentiated by the substance names. Toxicological information from studies of representative substances was used to fulfill REACH registration requirements and to satisfy the needs of the OECD High Production Volume (HPV) initiative. As shown in the examples provided, the hazard characterization data can be used for hazard classification and for occupational exposure limit recommendations. Introduction Scope and purpose of the documentThe present document summarizes information on the physical/ chemical properties and toxicological hazards of hydrocarbon solvents and provides examples of the ways in which the information on hazard characterization can be used for hazard classification and to set occupational exposure limits. Many of the toxicological studies were published separately, but the results are summarized herein and referenced in the appendices.Hydrocarbon solvents are liquid hydrocarbon fractions that are primarily produced by the distillation of petroleum feed stocks or their synthetic analogs (e.g., Fischer-Tropsch derived materials), sometimes followed by additional processing steps such as solvent extraction, hydrodesulfurization, or hydrogenation. 1 Most hydrocarbon solvents are complex substances with variable compositions and are best described as UVCB 2 (unknown and variable composition) substances, but some are single constituent (mono-constituent) substances. The complex and variable nature of these solvents is the consequence of their manufacturing processes. In short, most hydroca...

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Section: Distributionmentioning

confidence: 99%

Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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“…Styrene partition coefficients were assumed to be age-independent. They were taken from Meulenberg and Vijverberg (2000) to be 55.6, 2.50, 57.3, 1.82, and 1.02 for blood:air, liver:blood, fat:blood, brain:blood, and kidney:blood, respectively. For the muscle/skin compartment, the reported partition coefficient of 1.29 for muscle:blood was used.…”

Section: Styrene As Model Compoundmentioning

confidence: 99%

Elevated internal exposure of children in simulated acute inhalation of volatile organic compounds: effects of concentration and duration

et al. 2004

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When deriving health based exposure limits in recent years, attention has been drawn to susceptible subpopulations, in particular to children. We investigate the differences in kinetics between children and adults during inhalation of styrene as a typical category 3 volatile organic compound (VOC), i.e. a gas with a high rate of alveolar absorption (due to low reactivity and low water solubility). Internal exposure was simulated using a physiologically based kinetic model over a broad range of airborne concentrations (1 to 1000 ppm) and for an exposure time of up to eight hours according to the scenario in the acute exposure guideline level (AEGL) program. Age-specific anatomical and physiological parameters and compound-specific data were derived from the literature. The calculated concentrations in arterial blood are higher in children than in adults, and are highest in the newborn. For an 8-hour exposure to low concentrations, the calculated arterial concentration in the newborn is higher by a factor of 2.3 than in the adult. This is mainly due to the relatively high ventilation rate and the immature metabolism. With increasing airborne concentration, the ratio of arterial concentrations (newborn/adult) increases to a maximum of 3.8 at 130 ppm in ambient air, and declines with further increments of concentration to a value of 1.7. This is because the metabolism of the newborn becomes non-linear at lower concentrations than in adults. At high concentrations, metabolism is saturated in both age groups. For shorter exposures, the dose-dependency of the concentration ratios (newborn/adult) is less pronounced. This is the first article to show that the intraspecies uncertainty factor may vary with concentration and duration of exposure.

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“…However, there is indirect evidence – including evidence that ETBE causes α2u–globulin accumulation in the male rat kidney following inhalation exposure to ETBE (Medinsky et al ., 1999), as well as the reported high male rat kidney/air PC (Kaneko et al ., 2000) – suggesting that, besides solubility in the male rat kidney, there is another process affecting the uptake of ETBE into the tissue. Based on this specific information on MTBE, which is structurally similar to ETBE, along with the fact that other chemicals such as methanol, ethanol, 2‐propanol and 2‐methyl‐2 propanol have similar PCs in the liver and kidney (Meulenberg & Viverberg, 2000), assigning the same value to the kidney/blood PC and the liver/blood PC is warranted. As far as TBA binding to α2u–globulin, there is evidence in the literature to support this description (Williams & Borghoff, 2001).…”

Section: Methodsmentioning

confidence: 99%

Physiologically based pharmacokinetic model for ethyl tertiary‐butyl ether and tertiary‐butyl alcohol in rats: Contribution of binding to α2u–globulin in male rats and high‐exposure nonlinear kinetics to toxicity and cancer outcomes

Borghoff

Ring

Banton

et al. 2016

J of Applied Toxicology

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In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary‐butyl ether (ETBE), caused liver tumors in male rats, while tertiary‐butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary‐butyl ether, a structurally similar chemical, and verified against the literature and study report data. The model included ETBE and TBA binding to the male rat‐specific protein α2u–globulin, which plays a role in the ETBE and TBA kidney response observed in male rats. Metabolism of ETBE and TBA was described as a single, saturable pathway in the liver. The model predicted similar kidney AUC0–∞ for TBA for various exposure scenarios from ETBE and TBA cancer bioassays, supporting a male‐rat‐specific mode of action for TBA‐induced kidney tumors. The model also predicted nonlinear kinetics at ETBE inhalation exposure concentrations above ~2000 ppm, based on blood AUC0–∞ for ETBE and TBA. The shift from linear to nonlinear kinetics at exposure concentrations below the concentration associated with liver tumors in rats (5000 ppm) suggests the mode of action for liver tumors operates under nonlinear kinetics following chronic exposure and is not relevant for assessing human risk. Copyright © 2016 The Authors Journal of Applied Toxicology Published by John Wiley & Sons Ltd

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Empirical Relations Predicting Human and Rat Tissue:Air Partition Coefficients of Volatile Organic Compounds

Cited by 87 publications

References 35 publications

Characterization of the toxicological hazards of hydrocarbon solvents

Characterization of the toxicological hazards of hydrocarbon solvents

Elevated internal exposure of children in simulated acute inhalation of volatile organic compounds: effects of concentration and duration

Physiologically based pharmacokinetic model for ethyl tertiary‐butyl ether and tertiary‐butyl alcohol in rats: Contribution of binding to α2u–globulin in male rats and high‐exposure nonlinear kinetics to toxicity and cancer outcomes

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