Objective:
To improve understanding of mechanisms, biomarkers, and thresholds for trichothecene-induced health effects for application to risk assessment. Test the hypothesis that DON-induced growth retardation results from DON-induced cytokine-mediated SOCS-3 upregulation, which inhibits hepatic GH signaling, leading to reductions of growth factor(s) and weight gain.

Approach:
Relate acute DON-induced SOCS upregulation to GH impairment by (a) assessing the capacity of DON to inhibit GH-induction of acid-labile subunit (ALS) of the insulin-like growth factor 1 (IGF-1) ternary complex and (b) demonstrating DON's impairment of GH's activation of its receptor, and (c) relating post DON exposure kinetics SOCS-3 upregulation to ALS downregulation kinetics. Determine the sensitivity of SOCS-3, ALS, IGF-1 proteins to act as biomarkers of DON's growth effects by (a) comparing the minimal dietary DON concentrations required to alter these biomarkers and (b) identifying the NOAEL for the most sensitive biomarker. Determine the influence of age and gender on DON-induced biomarker alteration.