Toxicological mechanisms and potential health effects of deoxynivalenol and nivalenol

Produced by the mould genus Fusarium , the type B trichothecenes include deoxynivalenol (DON), nivalenol (NIV) and their acetylated precursors. These mycotoxins often contaminate cereal staples, posing a potential threat to public health that is still incompletely understood. Understanding the mechanistic basis by which these toxins cause toxicity in experimental animal models will improve our ability to predict the specific thresholds for adverse human effects as well as the persistence and reversibility of these effects. Acute exposure to DON and NIV causes emesis in susceptible species such as pigs in a manner similar to that observed for certain bacterial enterotoxins. Chronic exposure to these mycotoxins at low doses causes growth retardation and immunotoxicity whereas much higher doses can interfere with reproduction and development. Pathophysiological events that precede these toxicities include altered neuroendocrine responses, upregulation of proinflammatory gene expression, interference with growth hormone signalling and disruption of gastrointestinal tract permeability. The underlying molecular mechanisms involve deregulation of protein synthesis, aberrant intracellular cell signalling, gene transactivation, mRNA stabilisation and programmed cell death. A fusion of basic and translational research is now needed to validate or refine existing risk assessments and regulatory standards for DON and NIV. From the perspective of human health translation, biomarkers have been identified that potentially make it possible to conduct epidemiological studies relating DON consumption to potential adverse human health effects. Of particular interest will be linkages to growth retardation, gastrointestinal illness and chronic autoimmune diseases. Ultimately, such knowledge can facilitate more precise science-based risk assessment and management strategies that protect consumers without reducing availability of critical food sources.