This paper is one of several in this Special Issue of the International Journal of Hyperthermia that discusses the current state of knowledge about the human health risks of hyperthermia. This special issue emanated from a workshop sponsored by the World Health Organization in the Spring of 2002 on this topic. It is anticipated that these papers will help to establish guidelines for human exposure to conditions leading to hyperthermia. This comprehensive review of the literature makes it clear that much more work needs to be done to clarify what the thresholds for thermal damage are in humans. This review summarizes the basic principles that govern the relationships between thermal exposure (temperature and time of exposure) and thermal damage, with an emphasis on normal tissue effects. Methods for converting one time-temperature combination to a time at a standardized temperature are provided as well as a detailed discussion about the underlying assumptions that go into these calculations. There are few in vivo papers examining the type and extent of damage that occurs in the lower temperature range for hyperthermic exposures (e.g. 39-42degreesC). Therefore, it is clear that estimation of thermal dose to effect at these thermal exposures is less precise in that temperature range. In addition, there are virtually no data that directly relate to the thermal sensitivity of human tissues. Thus, establishment of guidelines for human exposure based on the data provided must be done with significant caution. There is detailed review and presentation of thermal thresholds for tissue damage (based on what is detectable in vivo). The data are normalized using thermal dosimetric concepts. Tables are included in an Appendix Database which compile published data for thresholds of thermal damage in a variety of tissues and species. This database is available by request (contact MWD or PJH), but not included in this manuscript for brevity. All of the studies reported are for single acute thermal exposures. Except for brain function and physiology (as detailed in this issue by Sharma et al) one notes the critical lack of publications examining effects of chronic thermal exposures as might be encountered in occupational hazards. This review also does not include information on the embryo, which is covered in detail elsewhere in this volume (see article by Edwards et al.) as well as in a recent review on this subject, which focuses on thermal dose.
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