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A dosimetric analysis of behavioral effects of acute toluene exposure in rats and humans.
Toxicol Sci. 1998 Jun; 43(2):186-95.TS

Abstract

The literature on behavioral effects of exposure to toluene is difficult to assess due, in part, to a wide variety of exposure conditions employed and outcomes measured. This study investigated whether previous experiments would be more consistent with each other if toluene exposure parameters were expressed not as concentration and duration, but as estimated amount of toluene in tissues. A physiologically based pharmacokinetic (PBPK) model was used to estimate concentration of toluene in arterial blood (CaTOL) from published studies in rats and humans exposed acutely to toluene vapor. Data for rats were selected from studies of avoidance behavior using both rate of responding and measures of successful responding. Data for humans were from studies of choice reaction time (CRT). Behavioral measures were converted to proportion of baseline to place them on a common scale across experiments. A meta-analysis was done to fit dose-effect curves using CaTOL and the rescaled effects. Results demonstrated that effects were an orderly function of CaTOL and were not influenced by concentration or duration of exposure, except as exposure influenced CaTOL. In rats, response rates first increased, reached a peak, and then declined as CaTOL increased. Successful avoidance in rats and CRT in humans always declined as CaTOL increased. In rats, response rates were increased by 10% at CaTOL approximately 13 ml/L. In humans, reaction times increased by 10% at CaTOL approximately 3 ml/L. Cross-species comparisons were made with the following caveats: PBPK uncertainties, few human data, and poor task comparability.

Authors+Show Affiliations

U.S. Environmental Protection Agency, Human Studies Division, Research Triangle Park, North Carolina 27711, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

9710960

Citation

Benignus, V A., et al. "A Dosimetric Analysis of Behavioral Effects of Acute Toluene Exposure in Rats and Humans." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 43, no. 2, 1998, pp. 186-95.
Benignus VA, Boyes WK, Bushnell PJ. A dosimetric analysis of behavioral effects of acute toluene exposure in rats and humans. Toxicol Sci. 1998;43(2):186-95.
Benignus, V. A., Boyes, W. K., & Bushnell, P. J. (1998). A dosimetric analysis of behavioral effects of acute toluene exposure in rats and humans. Toxicological Sciences : an Official Journal of the Society of Toxicology, 43(2), 186-95.
Benignus VA, Boyes WK, Bushnell PJ. A Dosimetric Analysis of Behavioral Effects of Acute Toluene Exposure in Rats and Humans. Toxicol Sci. 1998;43(2):186-95. PubMed PMID: 9710960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A dosimetric analysis of behavioral effects of acute toluene exposure in rats and humans. AU - Benignus,V A, AU - Boyes,W K, AU - Bushnell,P J, PY - 1998/8/26/pubmed PY - 1998/8/26/medline PY - 1998/8/26/entrez SP - 186 EP - 95 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 43 IS - 2 N2 - The literature on behavioral effects of exposure to toluene is difficult to assess due, in part, to a wide variety of exposure conditions employed and outcomes measured. This study investigated whether previous experiments would be more consistent with each other if toluene exposure parameters were expressed not as concentration and duration, but as estimated amount of toluene in tissues. A physiologically based pharmacokinetic (PBPK) model was used to estimate concentration of toluene in arterial blood (CaTOL) from published studies in rats and humans exposed acutely to toluene vapor. Data for rats were selected from studies of avoidance behavior using both rate of responding and measures of successful responding. Data for humans were from studies of choice reaction time (CRT). Behavioral measures were converted to proportion of baseline to place them on a common scale across experiments. A meta-analysis was done to fit dose-effect curves using CaTOL and the rescaled effects. Results demonstrated that effects were an orderly function of CaTOL and were not influenced by concentration or duration of exposure, except as exposure influenced CaTOL. In rats, response rates first increased, reached a peak, and then declined as CaTOL increased. Successful avoidance in rats and CRT in humans always declined as CaTOL increased. In rats, response rates were increased by 10% at CaTOL approximately 13 ml/L. In humans, reaction times increased by 10% at CaTOL approximately 3 ml/L. Cross-species comparisons were made with the following caveats: PBPK uncertainties, few human data, and poor task comparability. SN - 1096-6080 UR - https://www.unboundmedicine.com/medline/citation/9710960/A_dosimetric_analysis_of_behavioral_effects_of_acute_toluene_exposure_in_rats_and_humans_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1006/toxs.1998.2458 DB - PRIME DP - Unbound Medicine ER -