[Frontiers in Bioscience E2, 293-311, January 1, 2010]

Response of the thermoregulatory system to toxic insults

Christopher J. Gordon

Toxicology Assessment Division, Neurotoxicology Branch,National Health Effects and Environmental Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Introduction
3. Thermoregulatory profile
4. Impact of environmental temperature on toxic response
4.1. Ideal ambient temperature to study thermoeffector function
4.2. Temperature and biological dose of a toxicant
4.3. Magnitude and duration of a toxicological response
5. Acute thermoregulatory responses to toxicants
5.1. Forced and regulated changes in temperature
5.2. Is toxicant induced hypothermia forced or regulated?
5.3. Importance of behavioral thermoregulation
5.4. Mechanism of action
5.5. Recommended approach to study thermoregulatory effects of toxicants
6. Thermoregulatory effects of alcohol
7. Toxic chemicals eliciting hyperthermia
8. Advantages of a hypothermic response
9. Delayed and chronic effects
10. Scaling thermoregulatory responses to toxic agents
11. Acknowledgements
12. References

1. ABSTRACT

The physiological response to environmental toxicants and drugs is modulated by the thermoregulatory system. Environmental and body temperature can affect the entry of toxicants into the body through pulmonary, cutaneous, and gastrointestinal routes. Thermoregulation can ultimately influence the metabolic clearance of chemicals and their toxicity, including lethality. The thermoregulatory response following acute exposure to many toxic chemicals involves a regulated hypothermic response, characterized by activation of autonomic thermoeffectors to raise heat loss and a behavioral preference for cooler temperatures. Moderate hypothermia in rodents improves recovery and survival following toxic exposure. In relatively large mammals, including humans, the hypothermic response is minimal. Fever-like responses are often seen in humans and other large mammals exposed to many toxicants. Fever is also observed in rodents exposed to some toxicants provided that core temperature can be monitored without disturbing the animal (e.g., telemetry). Overall, the universal effects of temperature on chemical toxicity call for researchers to have a better understanding of how body and ambient temperature affect the physiological response to environmental toxicants.