Modeling the emetic potencies of food-borne trichothecenes by benchmark dose methodology

Abstract

Trichothecene mycotoxins commonly co-contaminate cereal products. They cause immunosuppression, anorexia, and emesis in multiple species. Dietary exposure to such toxins often occurs in mixtures. Hence, if it were possible to determine their relative toxicities and assign toxic equivalency factors (TEFs) to each trichothecene, risk management and regulation of these mycotoxins could become more comprehensive and simple. We used a mink emesis model to compare the toxicities of deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, nivalenol, fusarenon-X, HT-2 toxin, and T-2 toxin. These toxins were administered to mink via gavage and intraperitoneal injection. The United States Environmental Protection Agency (EPA) benchmark dose software was used to determine benchmark doses for each trichothecene. The relative potencies of each of these toxins were calculated as the ratios of their benchmark doses to that of DON. Our results showed that mink were more sensitive to orally administered toxins than to toxins administered by IP. T-2 and HT-2 toxins caused the greatest emetic responses, followed by FX, and then by DON, its acetylated derivatives, and NIV. Although these results provide key information on comparative toxicities, there is still a need for more animal based studies focusing on various endpoints and combined effects of trichothecenes before TEFs can be established.

Intestinal toxicity of the type B trichothecene mycotoxin fusarenon-X: whole transcriptome profiling reveals new signaling pathways

“…The toxicity rankings for FX and DON based on the histo-morphometric analysis indicate greater intestinal toxicity of FX, which is in accordance with the few available comparative toxicity studies of these toxins, including cytotoxicity toward intestinal cell lines 36 , 37 , emesis 16 , 17 , and anorexia 38 .…”

Effects of chronic deoxynivalenol exposure on p53 heterozygous and p53 homozygous mice

“…The range of BMDLs derived from these endpoints (0.07e0.42 mg/kg bw/d or 70e420 mg/kg bw/d) was consistent with the NOEL of 100 mg/ kg bw/day derived by JECFA based on decreased body weight gain in the mouse 2-year DON feeding study (Iverson et al, 1995;JECFA, 2001JECFA, , 2011, although the BMDL 10 for decreased weight gain in the present study (0.42 mg or 420 mg/kg bw/d) was higher than the NOEL for decreased weight gain based on DON consumption (90 mg DON/kg bw/day; Table 1), and higher than the NOEL derived by JECFA based on decreased body weight gain in the mouse 2-year DON feeding study (100 mg/kg bw/day) (Iverson et al, 1995;JECFA, 2001JECFA, , 2011. In comparison, the BMD for emesis in mink due to gavage administration of DON (24 mg/kg bw/d) was 12e22-fold lower than the BMDs for the most sensitive endpoints in the present study (300e530 mg/kg bw/d), confirming that the potency of DON as an emetic agent is higher than its potency as a anorectic agent (Male et al, 2016).…”

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

“…() data, Male et al. (), reported BMD 10 values of 0.198 and 0.040 mg/kg bw for 3‐Ac‐DON and 15‐Ac‐DON, respectively. The BMD analysis of the CONTAM Panel following the EFSA guidance (EFSA Scientific Committee, ), resulted in the BMD 10 values of 0.14 and 0.007 mg/kg bw and BMDL 10 values of 0.05 and 0.004 mg/kg bw for 3‐Ac‐DON and 15‐Ac‐DON, respectively (Appendix G).…”