Abstract

PIP: This monograph on diethylstilbestrol (DES) and its dipropionate includes chemical and physical data (synonyms and trade names), structural and molecular formulae and molecular weight of DES, chemical and physical properties of DES, and the production, use, occurrence, and analysis of DES. Production of DES, which is not known to occur naturally, can be effected by using the following starting materials in its preparation: deoxyanisoin, para-anisaldehyde, anisole, or anethole hydrobromide. All known methods of analyzing the purity of DES are provided tabularly. DES has been used in human medicine for treating menopausal symptoms, as a postcoital emergency contraceptive, for prevention of postpartum breast engorgement, for chemotherapy of advanced carcinoma of the breast and prostate, and for treating dysfunctional uterine bleeding. It also has various veterinary uses, mainly as growth promoter in poultry and beef cattle. Although DES and its dipropionate do not occur naturally, humans are exposed to the agent occupationally, via food residues, and in water sources. Biological data relevant to the evaluation of carcinogenic risk to humans are also presented in brief. Experimental data include studies of various species and administration routes. In mice, DES exposure produced increased incidence of mammary and lymphoid tumors in both sexes; in rats, DES exposure raised incidences of pituitary, mammary, and bladder tumors. In hamsters, renal tumors had higher incidences after DES exposure: hamster offspring also showed tumors occurring in accessory sex organs. It is concluded that sufficient evidence exists for DES's carcinogenicity in experimental animals. DES is causally related to cancer occurring in humans, especially for human female offspring where a risk on the order of .14-1.4/1000 exposed daughters of vaginal or cervical clear cell adenocarcinoma was found.