DEOXYNIVALENOL

Comments:

The Committee reviewed several new studies on metabolism and toxicokinetics, acute toxicity, genotoxicity, mechanisms of toxicity and developmental toxicity of DON and/or its acetyl derivatives. (3-Ac-DON and 15-Ac-DON). The Committee concluded that the toxicity of the acetylated derivatives is equal to that of DON, based on their acute lethality in mice and data demonstrating conversion of the acetylated metabolites to DON in vivo. Based on this determination, the Committee extended the previously-derived PMTDI for DON of 1 μg/kg bw to include its acetylated derivatives. There is insufficient information to include DON-3-glucoside in the group PMTDI. The Committee also derived an acute RfD value of 8 μg/kg bw for DON and its acetylated derivatives, using the lowest BMDL10 of 0.21 mg/kg bw per day for emesis in pigs and an uncertainty factor of 25, which is the value used by JMPR for acute Cmax-dependent effects. All of the mean estimates of national exposure to DON were below the group PMTDI of 1 μg/kg bw. For acute dietary exposure, the high-intake estimate of 9 μg/kg bw/d was close to the group ARfD.

Intake:

For acute dietary exposure, the estimate of 9 μg/kg-bw per day, based on high consumption of bread and a regulatory limit for DON of 1 mg/kg food. The acetylated derivatives were not included in the estimates of dietary exposure to DON. Inclusion of acetylated derivatives would not be expected to significantly change the estimates of dietary exposure to DON due to extremely low levels (< 10% of DON levels).

Tolerable Intake:

PMTDI: 1 μg/kg bw/d for DON & acetylated metabolites; ARfD: 8 μg/kg bw for DON & acetylated metabolites

Meeting:

72

Report: 

Tox Monograph: 

Comments:

The Committee established a provisional maximum tolerable daily intake (PMTDI) of 1 μg/kg bw on the basis of the no observed-effect level (NOEL) of 100 μg/kg bw per day for decreased body weight gain reported in a 2-year feeding study in mice and application of a safety factor of 100. The Committee concluded that intake at this level would not result in effects of DON on the immune system, growth or reproduction. The Committee noted that the available data did not suggest that DON presents a carcinogenic hazard. Estimation of the dietary intake of deoxynivalenol on the basis of the single weighted mean concentrations and the GEMS/Food regional diets resulted in values that exceeded the PMTDI for four of the five regional diets. The Committee noted that there was considerable uncertainty in the intake estimates because of uncertainties in the values for concentration and consumption used in the assessment. Furthermore, food processing would be expected to reduce the levels of deoxynivalenol to varying extents, which would result in lower estimates of dietary intake.

Intake:

0.77 µg/kg bw per day in the African diet to 2.4 µg/kg bw per day in the Middle Eastern diet. Large uncertainties in exposure estimates were noted. High intakes values may be approximated by multiplying the average intake by a factor of two for a single food and three for the total diet. Possible reductions in the concentrations of deoxynivalenol resulting from processing were not taken into consideration in this assessment.

Report: 

Tox Monograph: