Inhalation pharmacokinetics of ethylbenzene in B6C3F1 mice
- Departement de sante environnementale et sante au travail, Faculte de medecine, Universite de Montreal, 2375 Cote Ste Catherine, Bureau 4105, Montreal, PQ, H3T 1A8 (Canada)
The objective of the present study was to characterize the inhalation pharmacokinetics of ethylbenzene (EB) in male and female B6C3F1 mice following single and repeated exposures. Initially, groups of 28 male and female mice were exposed for 4 h to 75, 200, 500, or 1000 ppm in order to determine potential non-linearity in the kinetics of EB. Then, groups of male and female mice were exposed for 6 h to 75 ppm and 750 ppm (corresponding to the NTP exposures) for 1 or 7 consecutive days, to evaluate whether EB kinetics was altered during repeated exposures, The maximal blood concentration (C {sub max}; mean {+-} SD, n = 4) observed in female mice at the end of a 4-h exposure to 75, 200, 500, and 1000 ppm was 0.53 {+-} 0.18, 2.26 {+-} 0.38, 19.17 {+-} 2.74, and 82.36 {+-} 16.66 mg/L, respectively. The areas under the concentration vs. time curve (AUCs) following 4-h exposure to 75, 200, 500, and 1000 ppm were 88.5, 414.0, 3612.2, and 19,104.1 mg/L/min, respectively, in female mice, and 116.7, 425.7, 3148.3, and 16,039.1 mg/L/min in male mice. The comparison of C {sub max} and the kinetic profile of EB in mice exposed to 75 ppm suggests that they are similar between 1-day and 7-day exposures. However, at 750 ppm, the rate of EB elimination would appear to be greater after repeated exposures than single exposure, the pattern being evident in both male and female mice. Overall, the single and repeated exposure pharmacokinetic data collected in the present study suggest that EB kinetics is saturable at exposure concentrations exceeding 500 ppm (and therefore at 750 ppm used in the NTP mouse cancer bioassay) but is in the linear range at the lower concentration used in the bioassay (75 ppm). These data suggest that consideration of the nature and magnitude of non-linear kinetics and induction of metabolism during repeated exposures is essential for the conduct of a scientifically sound analysis of EB cancer dose-response data collected in B6C3F1 mice.
- OSTI ID:
- 20783401
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 210, Issue 1-2; Other Information: DOI: 10.1016/j.taap.2005.07.001; PII: S0041-008X(05)00402-3; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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