Defining Human Thermoregulation Limits: A Critical Evaluation of Predictive Models using Healthy Young Adults

Background: 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. Methods: This study evaluated their predictive accuracy by exposing 36 healthy young adults (20 males & 16 females) to five counterbalanced 8-hour 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, 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 (Trec) was continuously monitored. Results: Contrary to model predictions, all five conditions remained compensable (Trec rise rate ≤ 0.1 °C/h), with mean peak Trec well below heatstroke thresholds (38.2 ± 0.4 °C). At 44°C/29.2%RH, females exhibited significantly lower Trec than males (p < 0.05); however, no sex differences in steady-state Trec 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. Conclusions: 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.