Thermal Stress and Toxicity

Abstract

Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at sub-thermoneutral temperatures of ~22∘C. When exposed to chemical toxicants under these relatively cool conditions, rodents typically undergo a regulated hypothermic response, characterized by preference for cooler ambient temperatures and controlled reduction in core temperature. Reducing core temperature delays the clearance of most toxicants from the body; however, a mild hypothermia also improves recovery and survival from the toxicant. Raising ambient temperature to thermoneutrality and above increases the rate of clearance of the toxicant but also exacerbates toxicity. Furthermore, heat stress combined with work or exercise is likely to worsen toxicity. Body temperature of large mammals, including humans, does not decrease as much in response to exposure to a toxicant. However, heat stress can nonetheless worsen toxic outcome in humans through a variety of mechanisms. For example, heat-induced sweating and elevation in skin blood flow accelerates uptake of some insecticides. Epidemiological studies suggest that thermal stress may exacerbate the toxicity of airborne pollutants such as ozone and particulate matter. Overall, translating results of studies in rodents to that of humans is a formidable task attributed in part to the interspecies differences in thermoregulatory response to the toxicants and to thermal stress.

A hot lunch for herbivores: physiological effects of elevated temperatures on mammalian feeding ecology

“…Below the lower critical temperature (LCT) of the TNZ, heat lost to the environment is greater than that generated through basal metabolism, so the animal initiates both a reduction in heat loss (e.g. peripheral vasoconstriction and piloerection) and an increase in heat generation (Gordon, Johnstone & Aydin, 2014). Heat may be generated by shivering thermogenesis, non-shivering thermogenesis, or activity (Rezende & Bacigalupe, 2015).…”

“…Woodrats also demonstrate temperature-dependent changes in diet selection to reduce intake of PSMs at high ambient temperatures (Kurnath et al, 2016). Studies suggest that reduced detoxification capacity in the liver at high ambient temperatures could be due to one or more of the following: a decrease in expression of genes coding for enzymes involved in detoxification; reduced activity of critical enzymatic reactions; or lower liver mass (Dearing, 2013;Gordon et al, 2014). As ambient temperature increases, the physiological capacity of herbivores to deal with PSMs therefore decreases.…”

“…In this case, the heat load from flight and feeding may be more than the ambient heat load during the day. It is common for large herbivores to store heat internally (thus sparing water from being used for cooling) until the ambient temperature favours heat dissipation (Gordon et al, 2014;Hetem et al, 2016), highlighting how FcT can be constrained by heat dissipation. Unfortunately, there has been little research to date investigating the use of FcT for energy balance in wild herbivores, or the implications of HDL in this context.…”

Ambient temperature influences tolerance to plant secondary compounds in a mammalian herbivore

“…Evidence from pharmacological [15,16] and agricultural studies [17 -19] suggests that chemical toxicity is temperature-dependent, whereby compounds became more toxic at warmer temperatures. The mechanism, referred to as temperature-dependent toxicity, is the likely result of reduced liver function through changes in toxin clearance time, enzymatic reactions or gene expression of crucial detoxification pathways [20,21]. In addition to artificial systems, there is evidence for temperature-dependent toxicity from an ecologically and evolutionarily relevant context.…”

Nutrition and energetics in rodent longevity research

“…However, environmentalor ambient temperature (T a ) is variable and frequently below T b , significantly impacting the metabolic requirements necessary to maintain a stable T b (Gordon et al , 1998). When the T a rises near or above T b , the ability to dissipate excess heat is reduced, resulting in a thermal stress, triggering adaptive responses to cool the body (Gordon et al , 2014). Conversely, when T a drops significantly below the T b , additional heat production is needed to counter the thermal loss of T b to the environment, accompanied by an inverse, proportional increase in metabolism and caloric intake (Cannon & Nedergaard, 2004).…”