Comparison of murine anorectic responses to the 8-ketotrichothecenes 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, fusarenon X and nivalenol
文摘
While induction of food refusal by the trichothecene mycotoxin deoxynivalenol (DON) has been described in several animal models, much less is known about the anorectic effects of structurally related 8-ketotrichothecenes, 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX) and nivalenol (NIV). Here, we compared the capacities of these congeners to induce anorexia in the mouse. As previously observed for DON, anorectic responses to 3-ADONand 15-ADON in the B6C3F1 female mouse following both intraperitoneal (IP) and oral exposure were transient, lasting only a few hours, with food intake recovering to control levels within 16xA0;h. For both ADONs, the no observed adverse effect levels (NOAEL) and lowest observed adverse effect levels (LOAEL) were 0.5 and 1xA0;mg/kg bw following IP exposure, respectively, and 1 and 2.5xA0;mg/kg bw after oral exposure, respectively. In contrast, food refusal persisted from 48 to 96xA0;h following IP and oral exposure to FX and NIV. For both IP and oral FX exposure, the NOAEL was 0.025xA0;mg/kg bw and LOAEL was 0.25xA0;mg/kg bw, whereas the NOAELs and LOAELs for NIV were 0.01 and 0.1xA0;mg/kg bw, respectively, after IP exposure and 0.1 and 1xA0;mg/kg bw, respectively, following oral exposure. Both these data and a prior DON study suggest that anorectic responses to 8-ketotrichothecenes were always greater when administered IP as compared to oral exposure and follow an approximate rank order of NIVxA0;>xA0;FXxA0;>xA0;DONxA0;?#xA0;3-ADONxA0;?#xA0;15-ADON for IP exposure and FXxA0;>xA0;NIVxA0;>xA0;DONxA0;?#xA0;3-ADONxA0;?#xA0;15-ADON for oral exposure. Toxic potency data such as is described here will be applicable to future comparative risk assessments for this important group of trichothecene mycotoxins.