Summary Many of the physiological changes associated with thermoregulation, such as alveolar ventilation and the redistribution of blood flow to organs, can influence the kinetics of chemical compounds in the human body. Although some preventive measures may protect workers against the direct effects of heat, they cannot prevent thermoregulatory processes from occurring. Concomitant exposure to heat and volatile chemicals can result in variations in absorption through inhalation and the kinetics of these compounds, thus skewing the evaluation of biomonitoring data. In this study, the influence of temperature on various physiological parameters and on the kinetics of three volatile industrial solvents (toluene, acetone and dichloromethane) were evaluated in male volunteers exposed to different temperatures, with or without solvents, in an inhalation chamber. First, body temperatures (TEMP) and more than 20 cardiopulmonary parameters (CARDP) were measured in the subjects during four-hour exposure sessions at wet-bulb globe temperature (WBGT) values of 21, 25 and 30°C. In the second step, these exposure sessions were replicated, this time in the presence of each of the solvents being studied. The male subjects were then exposed at the same time to heat and solvent concentrations equal to time-weighted average exposure values (TWAEV) in force in Québec (45, 50 and 500 ppm for the toluene, dichloromethane and acetone, respectively). Samples of alveolar air, blood and urine were taken to determine the concentrations of solvents or their metabolites. The TEMP and the CARDP measured during the first step and the rate of perfusion to the organs were used to develop a physiologically-based toxicokinetic model (PBPK) in order to predict the biological concentrations of solvent according to exposure concentration under thermal stress. The average internal temperature varied little between the different exposure temperatures (less than 0.2°C). Oxygen consumption rates (0.370 ± 0.084, 0.393 ± 0.098, 0.396 ± 0.131 L/min), energy expenditure rates (1.80 ± 0.41, 1.91 ± 0.48, 1.92 ± 0.64 kcal/min), heart rate 70.75 ± 5.90, 77.22 ± 5.70, 82.56 ± 4.13 beats/min), and cardiac output (Qc; 5.89 ± 0.60, 6.05 ± 0.69, 6.07 ± 0.91 L/min) increased according to exposure to WBGT of 21, 25 and 30°C, respectively. The highest (VA; 6.75 ± 1.75 L/min) and lowest (5.75 ± 5.75 L/min) alveolar ventilation rates were observed at WBGT of 25 and 30°C, respectively, compared to a rate of 6.24 ± 1.64 L/min at a WBGT of 21°C. The same was found for ventilation per minute rates ranked in the same order (9.98 ± 2.23 and 8.44 ± 2.67 L/min compared to 9.28 ± 2.23 L/min). The individual (from 0.91 to 1.16, from 0.98 to 1.20, and from 0.76 to 1.15) and average (1.05, 1.10 and 0.93), VA/Qc ratios for WBGT exposure of 21, 25 and 30°C, respectively, were normal. Polypnea, characterized by rapid, shallow breathing (thus, reduced tidal volumes), was observed in most of the subjects (seven out of nine subjects) at a WBGT of 30°C. In urine, a decrease in acetone concentrations was observed at the end of exposure, but not in samples taken two hours later. Blood concentrations of the three solvents inhaled increased from 4 to 85% at the end of the exposure period at a WBGT of 30°C compared to concentrations measured at the end of the exposure period at a WBGT of 21°C. These increases appear not only to be in line with the decreased liver perfusion rate, but are also directly influenced by the body characteristics of the participants. Based on our observations, obese individuals may be at greater risk of presenting substantial elevations in blood concentrations of parent substances in the presence of thermal stress. In addition, the blood concentrations measured at the end of exposures are strongly correlated with exposure temperature. The decrease of alveolar ventilation values in the presence of heat is in contrast with the increase of blood concentrations. These values were therefore re-evaluated by adjusting the VA using the PBPK model on blood concentrations of acetone. In general, the PBPK model developed is good at predicting the experimental average concentrations measured in various biological matrices. According to that model, an eight-hour exposure to TWAEV at a WBGT of 30°C for toluene, dichloromethane and acetone would result in blood concentration increases of between 20 and 28% compared to an exposure at a WBGT of 21°C. In urine, a slight increase (5.09%) in excretion of o-Cresol is expected, as well as an increase in acetone (approximately 20%). Yet, no increase was observed experimentally for urinary acetone. However, these values remain well below the reference values. Simulations have shown that the allocation of work in a work/rest cycle of 75%, as recommended by the American Conference of Governmental Industrial Hygienists (ACGIH) for an acclimatized individual performing light tasks at a WBGT of 31°C counteracts the effect of co-exposure to heat and VOC for the substances that have marginally accumulated in the organism. In short, the interpretation of the biological exposure index values should take into account the exposure temperature, especially for the interpretation of blood concentrations. Future studies are recommended to further investigate the impact of thermal stress in workers, with cohorts of over 30 volunteers, for different BMI categories, in order to obtain statistically comparable data. These studies should be carried out with low blood soluble VOC in order to better assess the impact of a change in cardiac output during thermal stress.