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A descriptive and mechanistic study of the interaction between toluene and xylene in humans.
Int Arch Occup Environ Health. 1993; 65(1 Suppl):S135-7.IA

Abstract

This study was undertaken to characterize the mechanism of toxicokinetic interaction between toluene (TOL) and m-xylene (XYL) in the rat using physiologically-based toxicokinetic (PBTK) modeling approach. First, the metabolic rate constants were determined by conducting closed-chamber inhalation exposures with individual solvents (Vmax: TOL = 4.8, XYL = 8.4 mg/hr/kg; Km: TOL = 0.55, XYL = 0.2 mg/l). Then, using the same experimental set-up, rats were exposed to different binary mixtures of TOL and XYL. PBTK analysis of the data showed competitive inhibition as the plausible mechanism of TOL/XYL interaction. This mechanistic modeling study suggests that the interaction between TOL and XYL is likely to be observed when the exposure concentration exceeds 50 ppm of each solvent.

Authors+Show Affiliations

Tardif R
Départment de Médecine du travail et hygiène du milieu, Faculté de Médecine, Université de Montréal, Québec, Canada.
Laparé S
No affiliation info available
Krishnan K
No affiliation info available
Brodeur J
No affiliation info available

MeSH

AnimalsAtmosphere Exposure ChambersDose-Response Relationship, DrugDrug InteractionsEnvironmental ExposureHumansMaleModels, BiologicalRatsRats, Sprague-DawleyTolueneXylenes

Pub Type(s)

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

Language

eng

PubMed ID

8406910

Citation

Tardif, R, et al. "A Descriptive and Mechanistic Study of the Interaction Between Toluene and Xylene in Humans." International Archives of Occupational and Environmental Health, vol. 65, no. 1 Suppl, 1993, pp. S135-7.
Tardif R, Laparé S, Krishnan K, et al. A descriptive and mechanistic study of the interaction between toluene and xylene in humans. Int Arch Occup Environ Health. 1993;65(1 Suppl):S135-7.
Tardif, R., Laparé, S., Krishnan, K., & Brodeur, J. (1993). A descriptive and mechanistic study of the interaction between toluene and xylene in humans. International Archives of Occupational and Environmental Health, 65(1 Suppl), S135-7.
Tardif R, et al. A Descriptive and Mechanistic Study of the Interaction Between Toluene and Xylene in Humans. Int Arch Occup Environ Health. 1993;65(1 Suppl):S135-7. PubMed PMID: 8406910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A descriptive and mechanistic study of the interaction between toluene and xylene in humans. AU - Tardif,R, AU - Laparé,S, AU - Krishnan,K, AU - Brodeur,J, PY - 1993/1/1/pubmed PY - 1993/1/1/medline PY - 1993/1/1/entrez SP - S135 EP - 7 JF - International archives of occupational and environmental health JO - Int Arch Occup Environ Health VL - 65 IS - 1 Suppl N2 - This study was undertaken to characterize the mechanism of toxicokinetic interaction between toluene (TOL) and m-xylene (XYL) in the rat using physiologically-based toxicokinetic (PBTK) modeling approach. First, the metabolic rate constants were determined by conducting closed-chamber inhalation exposures with individual solvents (Vmax: TOL = 4.8, XYL = 8.4 mg/hr/kg; Km: TOL = 0.55, XYL = 0.2 mg/l). Then, using the same experimental set-up, rats were exposed to different binary mixtures of TOL and XYL. PBTK analysis of the data showed competitive inhibition as the plausible mechanism of TOL/XYL interaction. This mechanistic modeling study suggests that the interaction between TOL and XYL is likely to be observed when the exposure concentration exceeds 50 ppm of each solvent. SN - 0340-0131 UR - https://www.unboundmedicine.com/medline/citation/8406910/A_descriptive_and_mechanistic_study_of_the_interaction_between_toluene_and_xylene_in_humans_ DB - PRIME DP - Unbound Medicine ER -