T-2, HT-2 and DAS TOXINS
Overview
Synonyms
Trichothecenes (T-2, HT-2)
4,15-Diacetoxyscirpenol (DAS)
CAS number
(T-2) 26934-87-2; (HT-2) 21259-20-1
Functional Class
Food Contaminant
MYCOTOXIN
MYCOTOXIN
Evaluations
Evaluation year: 2022
Comments:
The Committee established a group ARfD for T-2, HT-2 and DAS of
320 ng/kg bw (rounded down).
The Committee established a group TDI of 25
ng/kg bw for T-2, HT-2 and DAS, alone or in combination. The previous group provisional maximum tolerable daily intake (PMTDI) of 60 ng/kg bw for T-2 and HT-2, established at the fifty-sixth meeting and amended at the eighty-third meeting to include DAS, was withdrawn.
Intake:
There is insufficient information available to estimate combined acute exposure
to T-2, HT-2 and DAS. The dietary exposure estimates for T-2 and HT-2 calculated by the Committee at its ninetieth meeting are below the acute reference dose (ARfD) of 320 ng/kg bw. UB estimates of acute dietary exposure to the sum of T-2 and HT-2 (first tier) indicate no health concern, but estimates of dietary exposure to DAS in combination with T-2 and HT-2 should be carried out at a future meeting of the Committee when sufficient and suitable data on DAS become available.
The estimates of chronic dietary exposure to the sum of T-2 and HT-2 derived from the literature for the general population for the lower bound (LB) mean ranged from 0.3 to 53 ng/kg bw per day and for the LB 95th percentile from 1.9 to 210 ng/kg bw per day.
Meeting:
93
Report:
Toxicological study
Pivotal Study:
The Committee concluded that the most sensitive, reliable and reproducible effects observed following repeated dietary exposure were reported in the 3-week toxicity study in juvenile pigs. This study adequately characterized the test material and background exposure to common mycotoxins detected in feed and examined critical toxicological effects at relatively low doses (for example, <25 µg/kg bw per day). The Committee also noted that juvenile pigs have been identified previously as a species sensitive to the emetic and haematotoxic effects of trichothecenes. Dose–response analysis of body weights, daily body weight gain and daily feed intake was conducted and a BMDL10 of 1.8 µg/kg bw per day based on reduced daily body weight gain was selected as the most appropriate point of departure for establishing a health-based guidance value. Considering that the critical effect (i.e. nausea-induced reductions in feed intake resulting in decreased body weight gain) is likely to be Cmax-dependent and given the Committee’s low confidence in the overall toxicological database, a composite uncertainty factor of 72 was considered appropriate (eightfold as for the group ARfD; threefold for extrapolation from subacute to chronic exposure and threefold for other uncertainties in the database).
PMTDI:
25 ng/kg bw r T-2, HT-2 and DAS, alone or in combination
Evaluation year: 2016
Comments:
At the eighty-third JECFA meeting the Committee included 4,15-diacetoxyscirpenol in the group provisional maximum tolerable daily intake (PMTDI) for T-2 and HT-2 toxin established at the forty-seventh JECFA meeting.
Tolerable Intake:
PMTDI 60 ng/kg bw per day for T-2, HT-2 and 4,15-diacetoxyscirpenol toxins, alone or in combination
Meeting:
83
Report:
Tox Monograph:
Evaluation year: 2002
Comments:
The Committee concluded that there was substantial evidence for the immunotoxicity and haematotoxicity of T-2 toxin in several species, and that these are critical effects after short-term intake. The one available long-term study was not suitable for establishing a tolerable intake. The Committee used the LOEL of 0.029 mg/kg bw/d for changes in white and red blood cell counts identified in the 3-week dietary study in pigs as the point of departure for the risk assessment. This LOEL was considered to be close to a NOEL, as the effects on blood cell counts were subtle and reversible. The Committee further concluded that the toxic effects of T-2 toxin and its metabolite HT-2 toxin could not be differentiated, and that the toxicity of T-2 toxin in vivo might be due at least partly to effects of HT-2 toxin. The Committee used the LOEL from the pig study and a safety factor of 500 to derive a group PMTDI of 60 ng/kg bw per day for T-2 and HT-2 toxins, alone or in combination. The safety factor of 500 accounted for the lack of a clear NOEL in the 3-week study in pigs; deficiencies in the database, including insufficient study of long-term administration of T-2 toxin; and sex, species, and individual variations in sensitivity. The total of the average intakes of T-2 toxin and HT-2 toxin (8 ng/kg bw/d and 9 ng/kg bw/d, respectively) was not expected to exceed the group PMTDI.
Intake:
Average intakes of T-2 toxin and HT-2 toxin: 8 ng/kg bw/d and 9 ng/kg bw/d, respectively
Tolerable Intake:
PMTDI 60 ng/kg bw per day for T-2 and HT-2 toxins, alone or in combination
Meeting:
56
Report:
Tox Monograph:
Toxicological study
Pivotal Study:
3-week dietary study in pigs (Rafai et al., 1995): 7-week-old pigs were fed a diet providing an average T-2 toxin intake equal to 0.029, 0.062, 0.10, or 0.13 mg/kg bw per day. On the first and fourth days of administration, the pigs were immunized by an intramuscular injection of horse globulin. The titre of anitibodies to this antigen was significantly lower in T-2 toxin-treated than in control pigs at 14 and 21 days at all doses tested. The leukocyte count and the proportion of leukocytes made up by T-lymphocytes was lower in all treated groups. A decreased proliferative response to phytohaemagglutinin and concanavalin A was observed at all doses of T-2 toxin at 21 days. A dose-related decrease in feed intake was observed at all doses, and decreased weight gain was observed at doses of 0.062 mg/kg bw per day and above. The haemoglobin concentration was decreased in a dose-related manner at these doses. A reduction in erythrocyte count was observed at 0.10 and 0.13 mg/kg bw per day, and the erythrocyte volume fraction was reduced at 0.13 mg/kg bw per day. The Committee noted that, as pair-fed animals were not used as controls, the potential confounding effects of feed intake and differences in weight gain on the observed end-points could not be evaluated. A NOEL was not identified.
Animal Specie:
Pig
Effect:
Changes in white and red blood cell counts
NOEL:
not identified
LOEL:
0.029 mg/kg bw/day for T-2 toxin
PMTDI:
60 ng/kg bw per day for T-2 and HT-2 toxins, alone or in combination
Point of departure:
LOEL: 0.029 mg/kg bw/day