Mycotoxins are food-borne toxins produced by molds which are commonly found on animal feeds of economic significance. Toxic doses of these compounds vary widely across livestock species, and even within a species when considered across all stages of development and production. This variation is due to the wide range of exposure, biotransformation events, and environmental interactions (including co-exposure to other toxins) experienced by the diverse animals kept by man for work and food production. The general consensus that certain classes of livestock are more or less resistant to select mycotoxins has led to the diversion of toxic feeds to resistant species while avoiding more sensitive animals. Unfortunately, the reasons for these differences are, in many cases, not fully understood, and thus there is little information to promote resistance to these dietary toxins.
The work presented here evaluates several components of this issue: reduced toxicity in a species of interest, metabolism of mycotoxins which may explain this resistance, and onset and persistence of toxicity in a resistant species due to environmental cofactors. To address these issues, Chapter 2 evaluates the toxicity of the ergot alkaloid ergovaline in a model species of domestic poultry. The previously documented reduced sensitivity in this species is partially confirmed, while thermodysregulation is identified as a toxicological outcome at doses relevant to commercial exposure. Despite changes in body temperature dynamics, poultry maintain productivity at ergot alkaloid doses far higher than almost any other investigated species. An explanation for this tolerance is explored in Chapter 3, in which the metabolic end-products of ergovaline in feces, urates and duodenal fluid from resistant animals are characterized, and several metabolites identified which may inhibit toxicity of these compounds. Onset and persistence of toxicity in another resistant species (beef cattle) is investigated in Chapter 4, in which the immunotoxicity of co-occurring fusariotoxins (deoxynivalenol and fumonisins) are evaluated in animals which have reached a critical state of dietary exposure and physiological stressors observed in commercial settings. Despite previous documentation that ruminants such as cattle detoxify these compounds, fusariotoxins in finishing feedlot steers show marked immunomodulatory effects. These toxic effects outlast the treatment period, indicating that not only are beef cattle susceptible to these compounds, but that this susceptibility may lead to long-lasting changes in the immune status of these animals even after the dietary source has been removed.
The highly conserved molecular targets of many mycotoxins prevent any animal from fully escaping their toxicity. Identification and support of resistance pathways is necessary to prevent apparent toxicity, even in animals which have been previously identified as resistant.