Weak estrogenic activity from continuous-release pellets.
In the process of evaluating a proprietary compound for weak estrogenic activity, two different types of dosing regimens were used, repeated daily dosing (three times/d) and continuous-release pellets. In studies using the proprietary compound, rats that were dosed via intraperitoneal injection showed no estrogenic responses, while those receiving the test compound via continuous-release pellets displayed several estrogenic responses. Because of the conflicting results, the control pellets were evaluated for estrogenic activity in the same battery of tests using the same number of pellets. In studies using only the control pellets, several estrogenic responses were observed including increased uterine weight, uterine stromal cell proliferation, estrous conversion, uterine progesterone receptor content, and decreased uterine estrogen receptor content. Animals receiving no pellet implant showed no estrogenic responses. In addition, a methylene chloride/DMSO extract of the control pellets promoted expression of a reporter gene controlled by the estrogen receptor and demonstrated competition with 17 beta-estradiol for binding to the human estrogen receptor. It is concluded that component(s) of the control pellets possess weak estrogenic activity.
O'Connor
J C
JC
Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours & Company, Newark, Delaware.
Cook
J C
JC
Van Pelt
C S
CS
Arnold
S F
SF
Obourn
J D
JD
D000818:Animals; D001667:Binding, Competitive; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004967:Estrogens / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism
D003692:Delayed-Action Preparations; D004967:Estrogens; D011960:Receptors, Estrogen