4,15-DAS; (3α,4β)-3-HYDROXY-12,13-EPOXYTRICOTHEC-9-ENE-4,15-DIYL DIACETATE
Evaluation year: 2016
The Committee concluded that there are insufficient toxicological data available to derive a point of departure for the risk assessment of 4,15-DAS alone. There are limitations in the available short-term toxicity studies and no data from chronic exposure and reproductive and developmental toxicity studies. 4,15-DAS and T-2/HT-2 toxin are structurally similar, and there is evidence that they cause similar effects at the biochemical and cellular levels, have similarities in toxic effects in vivo and have an additive dose effect when co-exposure occurs. Therefore, the evidence was considered sufficient by the Committee to support including 4,15-DAS in the group provisional maximum tolerable daily intake (PMTDI) for T-2 and HT-2 toxin established at the forty-seventh JECFA meeting. The inclusion of 4,15-DAS in the group PMTDI of 0.06 µg/kg bw is considered to be a conservative approach when taking into consideration the observation that T-2 toxin was consistently more potent than 4,15-DAS when comparing similar in vitro and in vivo end-points. The Committee noted that only total lower-bound dietary exposure estimates for Europe were available for the sum of T-2, HT-2 and 4,15-DAS. From these estimates, the sum of the total lower-bound dietary exposure estimates for 4,15-DAS of up to 0.0028 µg/kg bw per day and the total dietary exposures estimated for T-2 plus HT-2 of 0.016 µg/kg bw per day results in a total lower-bound mean dietary exposure of 0.019 µg/kg bw per day and in a total lower-bound high dietary exposure estimated at 0.038 µg/kg bw per day (twice the mean ). The Committee concluded that these total lower-bound estimates for Europe do not exceed the group PMTDI for T-2, HT-2 and 4,15-DAS.
PMTDI 60 ng/kg bw per day for 4,15-DAS, T-2 and HT-2 toxins, alone or in combination