A new perspective on deoxynivalenol and growth suppression.

Deoxynivalenol (DON) is a secondary metabolite of Fusarium culmorum and Fusarium graminearum and is one of the most common mycotoxin contaminants of wheat, barley, maize, and cereal-based food products (Canady et al., 2001; Schothorst and van Egmond, 2004). Like other trichothecenes, DON induces a spectrum of effects in farm and laboratory animals including emesis (DON has the trivial name ‘‘vomitoxin’’ because high doses cause emesis in swine), immunotoxic effects, and suppression of appetite and growth. A dietary no-observed effect level (NOEL) of 1 ppm DON was established in a 2-year mouse feeding study (Iverson et al., 1995). The NOEL corresponded to an average daily intake of 100 lg DON/kg body weight. The critical finding for establishing the NOEL was growth suppression, which occurred in both sexes at dietary concentrations 5 ppm DON and could not be explained on the basis of decreased feed consumption. A provisional maximum tolerated daily intake (PMTDI) for DON of 1 lg /kg body weight was subsequently established by the World Health Organization Joint Expert Committee on Food Additives on the basis of the NOEL (Canady et al., 2001). Surveys in Europe (Schothorst and van Egmond, 2004; Turner et al., 2008) have revealed that DON intake by cereal consumers, while mostly well below the PMTDI, sometimes approach or exceed the PMTDI in some segments of the population, including young children. It is therefore important to understand the mechanisms by which DON suppresses growth in animal models, particularly at low doses that do not cause inappetence and to determine its relevance to humans. The experimental approach and findings reported by Amuzie et al. (2009) in this issue offers significant new insight about the mechanisms contributing to growth inhibition by DON in a critical animal model. Specifically, they have now shown that DON suppresses growth in mice by reducing growth hormone (GH) signaling through mechanisms mediated by insulin-like growth factor 1 (IGF1) and insulinlike growth factor acid-labile substance (IGFALS). This report is particularly interesting because the findings for the first time provide evidence for a mechanism of growth inhibition that links the well-established role of DON as a modulator of cytokine expression with disruption of GH signaling.