Defining human thermoregulation limits: a critical evaluation of predictive models using healthy young adults

The core temperature inflection point (CTIP) method (also known as humidity-ramp protocol) and biophysical modeling are widely used to determine human thermoregulation limits, yet their validity under prolonged heat exposure remains unverified. This study evaluated the predictive accuracy by exposing 36 healthy young adults (20 males and 16 females) to five counterbalanced 8-h indoor heat trials in a controlled chamber (36°C/74.5%RH, 40°C/55.0%RH, 44°C/29.2%RH, 47°C/35.6%RH, and 50°C/24.5%RH). These conditions were selected based on prior CTIP and biophysical model predictions of human thermoregulation limits. Participants engaged in sedentary office tasks (1.29-1.67 METs), wore standardized summer clothing (0.39-0.40 clo), and had ad libitum access to an electrolyte drink, with a 500-kcal sandwich provided at midday. Rectal temperature (T_rec) was continuously monitored. Contrary to model predictions, all five conditions remained compensable (T_rec rise rate ≤ 0.1°C/h), with mean peak T_rec well below heatstroke thresholds (38.2 ± 0.4°C). At 44°C/29.2%RH, females exhibited significantly lower T_rec than males (P < 0.05); however, no sex differences in steady-state T_rec responses were observed across other conditions (all P > 0.10). All exposures were compensable, aligning with the broader literature indicating minimal sex-based variability under such conditions. Collectively, CTIP and biophysical models substantially underestimated human thermoregulation limits, leading to overpredicted heat risk across all trials. These findings challenge the reliability of current predictive methods, suggesting human tolerance may exceed existing estimates. Refining these models is essential for improving heat risk assessment and informing public and occupational health guidelines in a warming climate.NEW & NOTEWORTHY This study reveals that widely used methods-core temperature inflection point and biophysical models-substantially underestimate human thermoregulation limits during prolonged heat exposure. Despite predictions of uncompensable heat stress, all five 8-h trials remained compensable, with core temperatures well below critical thresholds. These findings challenge the accuracy of current predictive tools and highlight the need to refine models to better assess heat risk in real-world, prolonged exposure scenarios.