Tags

Type your tag names separated by a space and hit enter

A dosimetric analysis of the acute behavioral effects of inhaled toluene in rats.
Toxicol Sci. 2007 Sep; 99(1):181-9.TS

Abstract

Knowledge of the appropriate metric of dose for a toxic chemical facilitates quantitative extrapolation of toxicity observed in the laboratory to the risk of adverse effects in the human population. Here, we utilize a physiologically based toxicokinetic (PBTK) model for toluene, a common volatile organic compound (VOC), to illustrate that its acute behavioral effects in rats can be quantitatively predicted on the basis of its concentration in the brain. Rats previously trained to perform a visual signal detection task for food reward performed the task while inhaling toluene (0, 1200, 1600, 2000, and 2400 ppm in different test sessions). Accuracy and speed of responding were both decreased by toluene; the magnitude of these effects increased with increasing concentration of the vapor and with increasing duration of exposure. Converting the exposure conditions to brain toluene concentration using the PBTK model yielded a family of overlapping curves for each end point, illustrating that the effects of toluene can be described quantitatively by its internal dose at the time of behavioral assessment. No other dose metric, including inhaled toluene concentration, duration of exposure, the area under the curve of either exposure (ppm h), or modeled brain toluene concentration (mg-h/kg), provided unambiguous predictions of effect. Thus, the acute behavioral effects of toluene (and of other VOCs with a similar mode of action) can be predicted for complex exposure scenarios by simulations that estimate the concentration of the VOC in the brain from the exposure scenario.

Authors+Show Affiliations

Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. bushnell.philip@epa.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17548890

Citation

Bushnell, Philip J., et al. "A Dosimetric Analysis of the Acute Behavioral Effects of Inhaled Toluene in Rats." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 99, no. 1, 2007, pp. 181-9.
Bushnell PJ, Oshiro WM, Samsam TE, et al. A dosimetric analysis of the acute behavioral effects of inhaled toluene in rats. Toxicol Sci. 2007;99(1):181-9.
Bushnell, P. J., Oshiro, W. M., Samsam, T. E., Benignus, V. A., Krantz, Q. T., & Kenyon, E. M. (2007). A dosimetric analysis of the acute behavioral effects of inhaled toluene in rats. Toxicological Sciences : an Official Journal of the Society of Toxicology, 99(1), 181-9.
Bushnell PJ, et al. A Dosimetric Analysis of the Acute Behavioral Effects of Inhaled Toluene in Rats. Toxicol Sci. 2007;99(1):181-9. PubMed PMID: 17548890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A dosimetric analysis of the acute behavioral effects of inhaled toluene in rats. AU - Bushnell,Philip J, AU - Oshiro,Wendy M, AU - Samsam,Tracey E, AU - Benignus,Vernon A, AU - Krantz,Quentin Todd, AU - Kenyon,Elaina M, Y1 - 2007/06/04/ PY - 2007/6/6/pubmed PY - 2007/10/5/medline PY - 2007/6/6/entrez SP - 181 EP - 9 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 99 IS - 1 N2 - Knowledge of the appropriate metric of dose for a toxic chemical facilitates quantitative extrapolation of toxicity observed in the laboratory to the risk of adverse effects in the human population. Here, we utilize a physiologically based toxicokinetic (PBTK) model for toluene, a common volatile organic compound (VOC), to illustrate that its acute behavioral effects in rats can be quantitatively predicted on the basis of its concentration in the brain. Rats previously trained to perform a visual signal detection task for food reward performed the task while inhaling toluene (0, 1200, 1600, 2000, and 2400 ppm in different test sessions). Accuracy and speed of responding were both decreased by toluene; the magnitude of these effects increased with increasing concentration of the vapor and with increasing duration of exposure. Converting the exposure conditions to brain toluene concentration using the PBTK model yielded a family of overlapping curves for each end point, illustrating that the effects of toluene can be described quantitatively by its internal dose at the time of behavioral assessment. No other dose metric, including inhaled toluene concentration, duration of exposure, the area under the curve of either exposure (ppm h), or modeled brain toluene concentration (mg-h/kg), provided unambiguous predictions of effect. Thus, the acute behavioral effects of toluene (and of other VOCs with a similar mode of action) can be predicted for complex exposure scenarios by simulations that estimate the concentration of the VOC in the brain from the exposure scenario. SN - 1096-6080 UR - https://www.unboundmedicine.com/medline/citation/17548890/A_dosimetric_analysis_of_the_acute_behavioral_effects_of_inhaled_toluene_in_rats_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfm146 DB - PRIME DP - Unbound Medicine ER -