In combination with mestranol, similarly to ethynerone and anagestone acetate (and certain other progestogens, including progesterone and several other 17α-hydroxyprogesterone derivatives), chloroethynylnorgestrel was found to produce striking mammary tumors in beagledogs after administration at very high dosages (10- to 25-fold human clinical dosages) for prolonged periods of time.[1][3][4] This resulted in the discontinuation of its development, along with that of ethynerone and anagestone acetate, as well as the removal of several progestins, including chlormadinone acetate, medroxyprogesterone acetate, and megestrol acetate, from various markets as contraceptives (although medroxyprogesterone acetate has since been reintroduced).[1][5] Subsequent research revealed that the risk is species-dependent and unique to canines and that there is no similar risk for humans.[6]
^ abGeil RG, Lamar JK (September 1977). "FDA studies of estrogen, progestogens, and estrogen/progestogen combinations in the dog and monkey". Journal of Toxicology and Environmental Health. 3 (1–2): 179–193. Bibcode:1977JTEH....3..179G. doi:10.1080/15287397709529557. PMID411941.
^Streffer C, Bolt H, Follesdal D, Hall P, Hengstler JG, Jacob P, Oughton D, Prieß K, Rehbinder E, Swaton E (11 November 2013). "Interspecies Extrapolation". Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation. Springer Science & Business Media. pp. 135–. ISBN978-3-662-08422-9.
^Neumann F, Düsterberg B, Laurent H (6 December 2012). "Development of progestogens.". In Runnebaum B, Rabe T, Kiesel L (eds.). Female Contraception: Update and Trends. Springer Science & Business Media. pp. 134–. ISBN978-3-642-73790-9.