The stress factor: temperature and toxicity.

For toxicologists, defining the toxicity of a substance focuses on determining the lethal dose for 50% of rodents under well-defined conditions, even though life itself is rarely carried out under anything like the ideal. Environmental physiology, on the other hand, focuses on understanding how organisms deal with the demands placed on them by stressors in the world around them. At the point where these two fields intersect, important biological insights may be found, as described in a report in the May 2003 issue of Environmental Research.

"Life and exposure to toxic chemicals do not occur under ideal environmental conditions," says author Christopher J. Gordon, a research physiologist at the National Health and Environmental Effects Research Laboratory (NHEERL) of the Environmental Protection Agency. "We have to consider that life goes on at many temperatures, humidities, and wind speeds." Organisms constantly adjust to changes in temperature, humidity, workload, and other factors that can cause stress using a variety of physiological and behavioral responses. Gordon says temperature is one of the best-studied and biggest factors in how a rodent responds to a toxic insult.

NHEERL research physiologist Penn Watkinson was testing software he had developed for analyzing electrocardiograms when he noticed how dramatic the effect of temperature can be. "Someone gave me a pesticide that they'd been working with, and it gave me everything I wanted: heart rate changes, blood pressure changes, acute and chronic effects, lethality, and arrhythmia," he says. "But I was getting effects at five milligrams per kilogram, and when I looked at the literature, it showed seventy-five milligrams per kilogram as a no-effect level."

Yet, testers had never held rodents' temperatures constant. As a physiologist, Watkinson knew that rodents actively control their body temperature as a survival mechanism. By holding his animals' temperature constant, it turns out he was "just knocking their socks off" with the pesticide, he says. "What really happens in the toxicology world is the animals' body temperature is allowed to go down, so they're somewhat protected," he explains.

The hypothermic response will buy time for the rodent's body to detoxify harmful agents, but it may also slow the clearance of some chemicals. "If the rodent's temperature and metabolism decrease, then the retention of the toxicant may be longer in the animal, and it may cause a larger effect," says Matthew Campen, an associate research scientist at the Lovelace Respiratory Research Institute of Albuquerque, New Mexico, who has studied this phenomenon. "It can be a warning about using the rodent as the toxicological workhorse."

Epidemiologists, too, have noted an important temperature effect that bears watching. "Human mortality is clearly associated with ambient temperature effects," Gordon says. Despite broad use of heating and cooling to maintain comfortable indoor temperatures, population studies have shown strong ties between average outdoor temperature and mortality. Whether the connection is physiological or reflects seasonal changes in the persistence of toxicants (for example, in air pollution), learning to understand these temperature effects will stretch scientists beyond their traditional boundaries.