Inhalation of Butanols: Changes in the Cytochrome P-450 Enzyme System

Aarstad, Kjell; Zahlsen, Kolbjørn; Nilsen, Odd G.

doi:10.1007/978-3-642-69928-3_93

Cited by 14 publications

(4 citation statements)

References 4 publications

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“…As described in Leavens and Borghoff (2009), data from a mouse study (McComb and Goldstein, 1979) was used for estimating the extent of metabolic induction from repeated exposures to TBA. While TBA has been shown to induce metabolic enzymes in rats (Aarstad et al, 1985), literature data are not available to evaluate interspecies extrapolation; therefore, the mouse data from McComb and Goldstein (1979) were used for the rat. In addition to possible interspecies differences, the induction of metabolism would be expected to be concentration dependent (Aarstad et al, 1985); however, there are insufficient data in the literature to establish a correlation that could be incorporated into the model at this time.…”

Section: Discussionmentioning

confidence: 99%

“…While TBA has been shown to induce metabolic enzymes in rats (Aarstad et al, 1985), literature data are not available to evaluate interspecies extrapolation; therefore, the mouse data from McComb and Goldstein (1979) were used for the rat. In addition to possible interspecies differences, the induction of metabolism would be expected to be concentration dependent (Aarstad et al, 1985); however, there are insufficient data in the literature to establish a correlation that could be incorporated into the model at this time. Other potential sources (1983) TBA toxicokinetics report, the final TBA blood concentrations were only 100-fold higher following a dose of 500 mg kg À1 bw than following a dose of 1 mg kg À1 bw.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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“…However, these data were contained in a meeting abstract and were not subsequently published in a peer-reviewed journal. Aarstad et al (1985) noted in a meeting proceeding that inhalation exposure to 2000 ppm TBA for 3 days caused a small increase in cytochrome P450 activity in Sprague-Dawley rats (128% of control). A similar increase was not observed in rats exposed to 500 ppm for 5 days.…”

Section: Female Mouse Thyroid Follicular Cell Tumor Datamentioning

confidence: 99%

Acute toxicity and cancer risk assessment values for tert-butyl acetate

Budroe

Brown

Salsmon

et al. 2004

Regulatory Toxicology and Pharmacology

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“…In a study using male Sprague-Dawley rats exposed to 2000 ppm, the most pronounced effect was on cytochrome P-450 (hepatic), which was elevated 28% (Aarstad et al 1985).…”

Section: Toxicity -Health Effectsmentioning

confidence: 99%

Exposure Based Health Issues Project Report: Phase I of High Level Tank Operations, Retrieval, Pretreatment, and Vitrification Exposure Based Health Issues Analysis

Stenner¹,

Bowers²,

Kenoyer³

et al. 2001

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National Laboratory (PNNL) staff in helping put this document together in its final form. Lauri Marquardt, Scott Somers, and Rick Melbihess of CHG provided invaluable technical knowledge and insights into the current operations at the Hanford tank farms and the industrial hygiene challenges involved with protection of the workers. Jim Huckaby of PNNL provided his insight into gas and vapor generation and high-probability release points associated with the single-shell tanks. Our thanks go to Charles Olaiya and Richard Grill of the ORP for their discussions on the important aspects of this work, their guidance for the prioritization of efforts, and for their support of the project. We also want to thank Mary Ann McKinney of HEHF for her excellent job of performing a high-quality and timely technical review of the document.

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Inhalation of Butanols: Changes in the Cytochrome P-450 Enzyme System

Cited by 14 publications

References 4 publications

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

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

Acute toxicity and cancer risk assessment values for tert-butyl acetate

Exposure Based Health Issues Project Report: Phase I of High Level Tank Operations, Retrieval, Pretreatment, and Vitrification Exposure Based Health Issues Analysis

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