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NTP-CERHR expert panel report on the reproductive and developmental toxicity of genistein.

Rozman-KK; Bhatia-J; Calafat-AM; Chambers-C; Culty-M; Etzel-RA; Flaws-JA; Hansen-DK; Hoyer-PB; Jeffery-EH; Kesner-JS; Marty-S; Thomas-JA; Umbach-D
Birth Defects Res B Dev Reprod Toxicol 2006 Dec; 77(6):485-638
There are no human data available on developmental or reproductive toxicity of purified genistein. Available experimental data are sufficient to conclude that purified genistein can produce reproductive or developmental toxicity in rats and mice. * LOAELs for various developmental endpoints (e.g., histologic vs. non-histologic) in available rat and mouse studies were highly variable with some biomarkers being very sensitive and others less sensitive. * In a single multigenerational study, a developmental BMDL10 of 20-26 mg/kg bw/day (LOEL 7-9 mg/kg bw/day) was reported for a non-consistent decrease in body weight in male Sprague-Dawley rat pup weight during lactation in the F1 and F3 generations. This marginal decrease was restored by the time the study terminated and was not seen in the F2 and F4 generations. Pup body weights were consistently decreased in F1 and F2 generations at estimated dietary doses of 35-44 mg/kg bw/day. * A LOAEL of 35 mg/kg bw/day (male) and 44 mg/kg bw/day (female) for reproductive/developmental toxicity was identified based on decreased anogenital distance in male and female rat pups, abnormal estrous cyclicity, decreased age and body weight at vaginal opening in female pups, and increased age at testicular descent in male pups. In a large multigenerational study, exposure to purified genistein occurred throughout fetal development as well as during adulthood. This experimental design made it extremely difficult for the Expert Panel to clearly separate developmental toxic effects from reproductive toxic effects. The Expert Panel viewed some of these diverse endpoints as a continuum from the maternal exposure (oral) to the effects observed in multigenerational offspring. Even though there is a paucity of available human data on exposure to purified genistein, the Expert Panel expresses negligible concern for reproductive and developmental effects from exposure of adults in the general population. The most highly reported exposed human population is Japanese adults with ingestion of approximately 0.43 mg/kg bw/day. However, adverse effects in rodent studies were not observed at levels below 35-44 mg/kg bw/day. Therefore, the Expert Panel feels that under current exposure conditions, adults would be unlikely to consume sufficient daily levels of genistein to cause adverse reproductive or developmental effects. The Expert Panel expresses negligible concern6 for adverse effects in neonates and infants who may consume up to 0.01-0.08 mg/kg bw/day of genistein aglycone contained in soy formula (it is noteworthy that about 1% of total genistein in soy formula is present as the aglycone; see Table 6 in the CERHR Soy Report).
Health-hazards; Reproductive-hazards; Reproductive-system-disorders; Reproductive-effects; Hormones; Hormone-activity; Glycols; Foodstuff; Food; Food-additives
Michael D. Shelby, PhD, NIEHS EC-32, PO Box 12233, Research Triangle Park, NC 27709
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Journal Article
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NIOSH Division
Priority Area
Disease and Injury: Fertility and Pregnancy Abnormalities
Source Name
Birth Defects Research Part B: Developmental and Reproductive Toxicology