(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL: 66, (1996) (p. 367)

CAS No: 89778-26-7
Chem. Abstr. Name: (Z)-2-[4-(4-Chloro-1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine

CAS No: 89778-27-8
Chem. Abstr. Name: (Z)-2-[4-(4-Chloro-1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine,
2-hydroxy-1,2,3-propanetricarboxylate (1:1)

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Toremifene, a chlorinated analogue of tamoxifen, was first marketed in 1990 and by 1995 was registered in five countries. It is currently undergoing further clinical trials for the treatment of metastatic breast cancer as well as trials for use as adjuvant therapy.

5.2 Human carcinogenicity data

No data were available to the Working Group.

5.3 Animal carcinogenicity data

Toremifene was tested for carcinogenicity in one study by oral administration to male and female rats and in four studies of limited duration in female rats. No increase in tumour incidence was observed in these studies. In the one study of long duration, toremifene decreased the incidence of tumours in some hormone-dependent tissues, notably mammary gland.

In one study in female rats, toremifene increased the incidence of kidney tumours and the proportion of malignant liver tumours induced by N-nitrosodiethylamine.

In four other experiments in rats, toremifene inhibited the development of 7,12-dimethylbenz[a]anthracene- or N-methyl-N-nitrosourea-induced mammary tumours.

5.4 Other relevant data

Toremifene is well absorbed in humans. The major metabolites result from N-demethylation, hydroxylation and deamination, and are excreted predominantly in faeces. The elimination half-life is about six days. The metabolism is qualitatively similar, but quantitatively different, in rats.

In a single study, no teratogenic effect of toremifene was found in rats.

Toremifene induced micronucleus formation in one study that used genetically engineered cell lines. Low levels of DNA adducts were detected in rat liver in one of three studies. Low levels of DNA adduct formation have also been reported in human lymphocytes in vitro.

5.5 Evaluation

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

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

Overall evaluation

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

For definition of the italicized terms, see Preamble Evaluation

Synonyms for Toremifene

Synonyms for Toremifene citrate

Last updated 05/23/97

    See Also:
       Toxicological Abbreviations