ZEARALENONE
Overview
Functional Class
Food Contaminant
MYCOTOXIN
MYCOTOXIN
Evaluations
Evaluation year: 2000
Comments:
Zearalenone has been tested for genotoxicity in a variety of test systems; the results were negative, except for the induction of chromosomal aberrations after exposure of mammalian cells in vitro to very high concentrations. Hepatocellular adenomas and pituitary tumours were observed in carcinogenicity studies in mice, but only at doses greatly in excess of the concentrations that have hormonal effects, i.e. ≥ 8-9 mg/kg bw/d. The Committee concluded that these tumours were due to the estrogenic effects of zearalenone and that the safety of zearalenone could be evaluated on the basis of the dose that had no hormonal effect in pigs, the most sensitive species. Using a safety factor of about 100, the Committee established a PMTDI for zearalenone of 0.5 µg/kg bw/d, based on the NOEL of 40 µg/kg bw/d in the 15-day study in pigs. The Committee also considered the LOEL of 200 µg/kg bw per day in this study and the previously established ADI of 0-0.5 µg/kg bw for the metabolite alpha-zearalanol, evaluated as a veterinary drug. The Committee recommended that the total intake of zearalenone and its metabolites (including alpha-zearalanol) should not exceed this value.
Intake:
Average dietary intakes of zearalenone from cereals and legumes in the GEMS/Food regional diets: 0.03 µg/kg bw/d (European diet) and 0.06 µg/kg bw/d (Middle Eastern diet); estimated on the basis of individual dietary records: are 0.02 µg/kg bw/d-0.03 µg/kg bw/d. Theoretical maximum daily intake of alpha-zearalanol when used as a veterinary drug: 0.02 µg/kg bw/d.
Tolerable Intake:
PMTDI: 0.5 µg/kg bw/d for total intake of zearalenone and its metabolites (including alpha-zearalanol)
Meeting:
53
Report:
Tox Monograph:
Toxicological study
Pivotal Study:
15-day feeding study in gilts on Days 5-20 of the estrous cycle (Edwards et al., 1987a): Sexually mature gilts given 2 kg of feed containing zearalenone at 0, 1, 5, or 10 mg/kg of diet (equivalent to 0, 0.04, 0.2, and 0.4 mg/kg bw/d) on days 5-20 of estrus. Effects: inter-estrus interval increased in gilts fed 5 and 10 mg/kg zearalenone in the diet. The inter-estrus interval was not
affected in gilts given 1 mg/kg in the diet. Increased plasma concentrations of progesterone and prolonged maintenance of corpora lutea were observed in the gilts with prolonged cycles. The corpora lutea regressed when zearalenone was withdrawn from the diet
Animal Specie:
Female pigs
Effect:
Increased inter-estrus interval, concentrations of progesterone and prolonged maintenance of corpora lutea
NOEL:
40 µg/kg bw/day
LOEL:
200 µg/kg bw/day
PMTDI:
0.5 µg/kg bw/d for total intake of zearalenone and its metabolites (including alpha-zearalanol)
Point of departure:
NOEL: 40 µg/kg bw/day