For definition of Groups, see Preamble Evaluation.

VOL.: 66 (1996) (p. 241)

CAS No.: 82413-20-5
Chem. Abstr. Name: (E)-3-(1-(4(2-(Dimethylamino)ethoxy)phenyl)-2-phenyl-1-butenyl)phenol

CAS No.: 97752-20-0
Chem. Abstr. Name: (E)-3-(1-(4(2-(Dimethylamino)ethoxy)phenyl)-2-phenyl-1-butenyl)phenol,
2-hydroxy-1,2,3-propanetricarboxylate(1:1)

5.1 Exposure data

Droloxifene is a phenolic analogue of tamoxifen which is undergoing clinical trials for the treatment of metastatic breast cancer, but is not yet registered in any country.

5.2 Human carcinogenicity data

No data were available to the Working Group.

5.3 Animal carcinogenicity data

Droloxifene was tested for carcinogenicity by oral administration in one study in rats. No increase in the incidence of tumours was reported. Droloxifene was studied in two experiments in rats for its modulation of chemically induced mammary tumours. In one study with 7,12-dimethylbenz[a]anthracene, inhibition of mammary tumours was observed, while in another study with N-methyl-N-nitrosourea, there was no effect or a slight increase in the incidence of mammary tumours.

5.4 Other relevant data

Droloxifene is well absorbed in humans after oral doses. It undergoes both oxidative metabolism and direct glucuronidation, and the elimination half-life is about 24 h. Metabolites were identified in rats and mice that were not found in humans. Toxic effects were infrequent in a phase II trial in postmenopausal women with metastatic breast cancer. Short- (four weeks) and longer- (six months) term toxicity studies in rats at doses of up to 200 mg/kg bw showed biochemical changes but little toxicity. Droloxifene did not induce cell transformation in vitro or form DNA adducts in rat liver in vivo.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of droloxifene.

There is inadequate evidence in experimental animals for the carcinogenicity of droloxifene.

Overall evaluation

Droloxifene is not classifiable as to its carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation

Synonyms for Droloxifene

• (E)-1-(4'-(2-Dimethylaminoethoxy)phenyl)-1-(3-hydroxyphenyl)-2-phenylbut-1-ene
• trans-1-(4-b-Dimethylaminoethoxyphenyl)-1-(3-hydroxyphenyl)-2-phenylbut-1-ene
• 3-Hydroxytamoxifen

• (E)-1-(4'-(2-Dimethylaminoethoxy)phenyl)-1-(3-hydroxyphenyl)-2-phenylbut-1-ene citrate
• trans-1-(4-b-Dimethylaminoethoxyphenyl)-1-(3-hydroxyphenyl)-2-phenylbut-1-ene citrate
• E-Droloxifene
• FK 435
• 3-Hydroxytamoxifen citrate
• K 060
• K 060E
• K 21.060E

    See Also:
       Toxicological Abbreviations