Quantcast
Environmental Health Perspectives Free Trail Issue
Author Keyword Title Full
About EHP Publications Past Issues News By Topic Authors Subscribe Press International Inside EHP Email Alerts spacer
Environmental Health Perspectives (EHP) is a monthly journal of peer-reviewed research and news on the impact of the environment on human health. EHP is published by the National Institute of Environmental Health Sciences and its content is free online. Print issues are available by paid subscription.DISCLAIMER
spacer
NIEHS
NIH
DHHS
spacer
Current Issue

EHP Science Education Website




Comparative Toxicogenomics Database (CTD)

spacer
Environmental Health Perspectives Volume 111, Number 12, September 2003 Open Access
spacer
The OECD Program to Validate the Rat Uterotrophic Bioassay. Phase 2: Dietary Phytoestrogen Analyses

William Owens,1 John Ashby,2 Jenny Odum,2 and Lesley Onyon3

1Procter & Gamble, Cincinnati, Ohio, USA; 2Syngenta Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom; 3Environmental Health and Safety Division, Organization for Economic Cooperation and Development, Paris, France

Abstract
Many commercial laboratory diets have detectable levels of isoflavones (e.g., phytoestrogens such as genistein [GN]) that have weak estrogenic activity both in vitro and in vivo. During validation studies of the uterotrophic bioassay, diet samples from 20 participating laboratories were collected and analyzed for three major phytoestrogens: GN, daidzein (DN) , and coumestrol (CM) . Soy phytoestrogens GN and DN were found at total phytoestrogen levels from 100 to 540 µg/g laboratory diet ; a forage phytoestrogen, CM, ranged from nondetectable to 4 µg/g laboratory diet. The phytoestrogen levels were compared with both baseline uterine weights of the control groups and with the relative uterine weight increase of groups administered two weak estrogen agonists: bisphenol A (BPA) and nonylphenol (NP) . The comparison uses a working assumption of additivity among the phytoestrogens, despite several significant qualifications to this assumption, to estimate total genistein equivalents (TGE) . Some evidence was found that phytoestrogen levels in the diet > 325-350 µg/g TGE could diminish the responsiveness of the uterotrophic bioassay to weak agonists. This was especially true for the case of the intact, immature female version of the uterotrophic bioassay, where higher food consumption relative to body weight leads to higher intakes of dietary phytoestrogens versus ovariectomized adults. This dietary level is sufficient in the immature female to approach a biological lowest observable effect level for GN of 40-50 mg/kg/day. These same data, however, show that low to moderate levels of dietary phytoestrogens do not substantially affect the responsiveness of the assay with weak estrogen receptor agonists such as NP and BPA. Therefore, laboratories conducting the uterotrophic bioassay for either research or regulatory purposes may routinely use diets containing levels of phytoestrogens < 325-350 µg/g TGE without impairing the responsiveness of the bioassay. Key words: , , , , , , , , . Environ Health Perspect 111:1559-1567 (2003) . doi:10.1289/ehp.5949 available via http://dx.doi.org/ [Online 23 January 2003]


The full version of this article is available for free in HTML or PDF formats.
spacer
 
Open Access Resources | Call for Papers | Career Opportunities | Buy EHP Publications | Advertising Information | Subscribe to the EHP News Feeds News Feeds | Inspector General USA.gov