Uterotrophic Bioassay in Rodents (UT assay) (OECD TG 440) (including OECD GD 71 on the procedure to test for anti-estrogenicity)

650. This assay is a short-term in vivo screening assay in female rodents for chemicals that interact with the estrogen receptor (ER). It is based on the increase in uterine weight (or uterotrophic response) that is elicited by ER agonists in animal models where endogenous estrogen levels are minimal. There are two variants of the assay; one uses immature animals, the other uses ovariectomised animals. The immature rodent assay may detect modalities acting via mechanisms other than ER, as the animals have an intact hypothalamic/pituitary/gonadal (HPG) axis, but the ability to detect these is limited. The assay may be conducted using rats or mice, but the there is more experience with the rat assay and this species was used in the OECD validation of this assay (OECD, 2006). Route of administration of test substance is via oral gavage or subcutaneous injection. This assay has been considered to be the “gold standard” bioassay screen for identifying ER agonists. A recently curated database of bioactivity with results from over 2 500 Uterotrophic Bioassays in rats and mice provides comprehensive information on this assay (Kleinstreuer et al., 2016).