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Prenatal developmental toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats

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Author: Wolterbeek, A.P.M. · Roberts, A. · Korte, H. · Unkila, M. · Waalkens-Berendsen, D.H.
Institution: TNO Voeding
Source:Regulatory Toxicology and Pharmacology, 1, 40, 1-8
Identifier: 237922
doi: doi:10.1016/j.yrtph.2004.04.001
Keywords: Toxicology · Toxicology and Applied Pharmacology · 7 hydroxymatairesinol potassium acetate · acetic acid derivative · enterolactone · lignan derivative · unclassified drug · animal experiment · article · body weight · controlled study · corpus luteum · diet · dose response · drug dose regimen · female · fertility · fetus development · fetus resorption · food intake · gestation period · male · nonhuman · palatability · prenatal development · priority journal · rat · sex ratio · skeleton malformation · toxicity testing · Administration, Oral · Animal Feed · Animals · Animals, Outbred Strains · Chemistry, Pharmaceutical · Eating · Female · Fetus · Lignans · Male · Maternal Exposure · Molecular Structure · No-Observed-Adverse-Effect Level · Potassium Acetate · Pregnancy · Rats · Reproduction · Seeds · Sesamum · Animalia · Mammalia · Rattus norvegicus


Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan enterolactone was evaluated in a prenatal developmental toxicity study conducted in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4% (w/w) of 7-hydroxymatairesinol in the form of potassium acetate complex (HMRlignan; potassium acetate level approximately 20% w/w within the preparation) for days 0-21 of gestation. Test substance intake was calculated to be 0.14-0.18, 0.46-0.74, and 1.19-2.93g/kg body weight/day for the low, mid, and high-dose groups, respectively. The rats were sacrificed on day 21 of the gestation period and examined for standard parameters of reproductive performance (fecundity index, gestation index, number of corpora lutea, number of implantations, pre- and post-implantation loss, number of early- and late resorptions, number of live- and dead fetuses, sex-ration and the weight of the reproductive organs). The fetuses were examined for external, visceral, and skeletal alterations. The results from this study showed no effects on reproductive performance or any treatment related findings following external, visceral, and skeletal examination of the fetuses. However, approximately half of the mated dams of the high-dose failed to thrive due to an unexpected large decrease in their food intake, and were sacrificed early. Body weights of the remaining animals of the high-dose group were decreased. Food consumption was decreased in all treatment groups during the first three days of the gestation period as a result of decreased palatability of the feed. In conclusion, the no-observed-effect level (NOEL) for maternal effects was 1%, whereas the NOEL for fetal development following daily oral HMRlignan administration throughout the gestation was equivalent to 4% in the diet. © 2004 Elsevier Inc. All rights reserved.