Modeling the impact of heat stress on the toxicokinetics of toluene and acetone

Auteurs

Axelle Marchand, Centre de recherche en santé publique, Université de Montréal, C.P. 6128 Succ. Centre–ville, Montreal, H3C 3J7, QC, Canada, Department of Environmental and Occupational Health, ESPUM, Université de Montréal, C.P. 6128 Succ. Centre–ville, Montreal, H3C 3J7, QC, Canada, Chair in Toxicological Risk Assessment and Management, Université de Montréal, Montreal, QC, Canada
Jessie Ménard, Centre de recherche en santé publique, Université de Montréal, C.P. 6128 Succ. Centre–ville, Montreal, H3C 3J7, QC, Canada, Chair in Toxicological Risk Assessment and Management, Université de Montréal, Montreal, QC, Canada
Pierre Brochu, Québec, QC, Canada
Sami Haddad, Centre de recherche en santé publique, Université de Montréal, C.P. 6128 Succ. Centre–ville, Montreal, H3C 3J7, QC, Canada, Chair in Toxicological Risk Assessment and Management, Université de Montréal, Montreal, QC, Canada

Type de document

Études primaires

Année de publication

2024

Langue

Anglais

Titre de la revue

Archives of Toxicology

Première page

471

Dernière page

479

Résumé

Many workers can be exposed simultaneously to heat and volatile chemicals. In a controlled human exposure study, it was observed that an increase in ambient temperature was associated with increased blood concentrations for acetone and toluene. Based on the expected changes in physiological parameters that occur with an increase in ambient temperature, we aimed to develop a PBPK model for acetone and toluene that could account for the impact of temperature on the kinetics of these solvents. Changes in temperature-dependent physiological parameters (i.e. blood flows, cardiac output, alveolar ventilation) based on recent measurements in volunteers were introduced in the PBPK models to simulate observed blood concentrations for different temperature exposure conditions. Because initial simulations did not adequately predict solvent kinetics at any temperature, the most sensitive parameter (alveolar ventilation; Qp) was, therefore, optimized on experimental acetone blood concentrations to obtain a relationship with temperature. The new temperature-dependent Qp relationship gave Qp values consistent with the literature and estimated a mean increase of 19% at 30 °C (wet bulb globe temperature) compared to 21 °C. The integration of a new temperature-dependent Qp relationship in the PBPK toluene model yielded adequate simulations of the experimental data for toluene in blood, exhaled air and urine. With further validation with other solvents, the temperature-dependant PBPK model could be a useful tool to better assess the risks of simultaneous exposure to volatile chemicals and heat stress and interpret biomonitoring data in workers as well as in the general population. TRN: NCT02659410, Registration date: January 15, 2016. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Mots-clés

Solvant, Solvent, Toxicocinétique, Toxicokinetics, Métabolisation, Metabolic process, Lieu de travail chaud, Hot workplace, Toluène, Toluene, CAS 108883, Acétone, Acetone, CAS 67641

Numéro de projet IRSST

2013-0012

Citation recommandée

Marchand, A., Ménard, J., Brochu, P. et Haddad, S. (2024). Modeling the impact of heat stress on the toxicokinetics of toluene and acetone. Archives of Toxicology, 98(2), 471-479. https://doi.org/10.1007/s00204-023-03646-6