For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 280)
Conjugated oestrogens
CAS No.: N/A
Chem. Abstr. Name: N/A
Sodium oestrone sulphate
CAS No.:
Chem. Abstr. Name: 3-(Sulfooxy)estra-1,3,5(10)-trien-17-one sodium salt
Sodium equilin sulphate
CAS No.:
Chem. Abstr. Name: 3-(Sulfooxy)estra-1,3,5(10),7-tetraen-17-one sodium salt
Piperazine oestrone sulphate
CAS No.: 17280-37-7
Chem. Abstr. Name: 3-(Sulfooxy)estra-1,3,5(10)-trien-17-one compd. with piperazine (1:1)
Oestradiol-17 b
CAS No.:
Chem. Abstr. Name: (17 b)-Estra-1,3,5(10)-triene-3,17-diol
Oestradiol 3-benzoate
CAS No.:
Chem. Abstr. Name: Estra-1,3,5(10)-triene-3,17-diol(17b)-3-benzoate
Oestradiol dipropionate
CAS No.:
Chem. Abstr. Name: Estral,3,5(10)-triene-3,17-diol(17b)-dipropionate
Oestradiol-17b-valerate
CAS No.:
Chem. Abstr. Name: (17b)-Estra-1,3,5-triene-3,17-diol 17-pentanoate
Polyoestradiol phosphate
CAS No.:
Chem. Abstr. Name: (17b)-Estra-1,3,5(10)-triene-3,17-diol polymer with phosphoric acid
Oestriol
CAS No.:
Chem. Abstr. Name: O(16 a,17 b)-Estra-1,3,5(10)-triene-3,16,17-triol
Oestrone
CAS No.:
Chem. Abstr. Name: 3-Hydroxyestra-1,3,5(10)-trien-17-one
Oestrone benzoate
CAS No.:
Chem. Abstr. Name: 3-(Benzoyloxy)estra-1,3,5(10)-trien-17-one
Ethinyloestradiol
CAS No.:
Chem. Abstr. Name: (17a)-19-Norpregna-1,3,5(10)-trien-20yne-3,17-diol
Mestranol
CAS No.:
Chem. Abstr. Name: (17a)-3-Methoxy-19-norpregna-1,3,5(10)-trien-20-yn-17-ol
Oestrogen replacement therapy
A. Evidence for carcinogenicity to humans (sufficient)
A number of studies, utilizing a variety of designs, have shown a consistent, strongly positive association between exposure to a number of oestrogenic substances and risk of endometrial cancer, with evidence of positive dose-response relationships both for strength of medication and duration of use [ref: 1]. Consistent findings have also been seen in more recent studies [ref: 2-16]. The rise and fall of incidence of endometrial cancer in several areas of the USA was compatible with trends in oestrogen use [ref: 1,15].
Of the 20 epidemiological studies of oestrogen replacement therapy and breast cancer risk [ref: 16-35], nine show a positive relation between oestrogen use and breast cancer [ref: 17-20,22-24,28,33]. The increased risks tend to be small; for example, a 50% increase was found with 20 years of menopausal oestrogen replacement therapy use [ref: 24]. All except one [ref: 33] of the positive studies involved use of population controls (eight of the nine studies with population controls gave positive results), and most showed increased risk after prolonged use or after ten or more years since initial exposure. One study showed a positive association with current oestrogen use [ref: 28].
One possible reason that studies with hospital controls gave negative results and those with population controls positive results is that oestrogen replacement therapy may be used more frequently in hospitalized women than in the general population. However, in two studies involving use of both hospital and population control groups, one giving positive [ref: 29] and the other largely negative [ref: 25] results, similar results were obtained when hospital and population controls were used to estimate the relative risk. Three of the studies with negative results [ref: 26,27,34] probably did not permit the authors to address satisfactorily the question of long-term use of oestrogen replacement therapy. The large hospital-based study that showed a positive finding used as controls subjects with a large spectrum of acute conditions unrelated to any of the known or suspected risk factors for breast cancer [ref: 33].
One cohort study of 1439 women initially treated for benign breast disease showed increased risk for women who took exogenous oestrogens after biopsy, but not for those who had taken them before biopsy. The increased risk in the former group appeared to be associated with epithelial hyperplasia or calcification in the initial lesion [ref: 35].
References
1. IARC Monographs, 21, 95-102, 147-159, 1979
2. Buring, J.E., Bain, C.J. & Ehrmann, R.L. (1986) Conjugated estrogen use and risk of endometrial cancer. Am. J. Epidemiol., 124, 434-441
3. Ewertz, M., Machado, S.G., Boice, J.D., Jr & Jensen, O.M. (1984) Endometrial cancer following treatment for breast cancer: A case-control study in Denmark. Br. J. Cancer, 50, 687-692
4. Henderson, B.E., Casagrande, J.T., Pike, M.C., Mack, T., Rosario, I. & Duke, A. (1983) The epidemiology of endometrial cancer in young women. Br. J. Cancer, 47, 749-756
5. Hulka, B.S., Fowler, W.C., Jr, Kaufman, D.G., Grimson, R.C., Greenberg, B.G., Hogue, C.J.R., Berger, G.S. & Pulliam, C.C. (1980) Estrogen and endometrial cancer: Cases and two control groups from North Carolina. Am. J. Obstet. Gynecol., 137, 92-101
6. Kelsey, J.L., LiVolsi, V.A., Holford, T.R., Fischer, D.B., Mostow, E.D., Schwartz, P.E., O'Connor, T. & White, C. (1982) A case-control study of cancer of the endometrium. Am. J. Epidemiol., 116, 333-342
7. La Vecchia, C., Franceschi, S., Gallus, G., DeCarli, A., Colombo, E., Mangioni, C. & Tognoni, G. (1982) Oestrogens and obesity as risk factors for endometrial cancer in Italy. Int. J. Epidemiol., 11, 120-126
8. La Vecchia, C., Franceschi, S., DeCarli, A., Gallus, G. & Tognoni, G. (1984) Risk factors for endometrial cancer at different ages. J. natl Cancer Inst., 73, 667-671
9. Öbrink, A., Bunne, G., Collén, J. & Tjernberg, B. (1981) Estrogen regimen of women with endometrial carcinoma. A retrospective case-control study at Radiumhemmet. Acta obstet. gynecol. scand., 60, 191-197
10. Shapiro, S., Kaufman, D.W., Slone, D., Rosenberg, L., Miettinen, O.S., Stolley, P.D., Rosenshein, N.B., Watring, W.G., Leavitt, T., Jr & Knapp, R.C. (1980) Recent and past use of conjugated estrogens in relation to adenocarcinoma of the endometrium. New Engl. J. Med., 303, 485-489
11. Shapiro, S., Kelly, J.P., Rosenberg, L., Kaufman, D.W., Helmrich, S.P., Rosenshein, N.B., Lewis, J.L., Jr, Knapp, R.C., Stolley, P.D. & Schottenfeld, D. (1985) Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. New Engl. J. Med., 313, 969-972
12. Spengler, R.F., Clarke, E.A., Woolever, C.A., Newman, A.M. & Osborn, R.W. (1981) Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases. Am. J. Epidemiol., 114, 497-506
13. Stavraky, K.M., Collins, J.A., Donner, A. & Wells, G.A. (1981) A comparison of estrogen use by women with endometrial cancer, gynecologic disorders, and other illnesses. Am. J. Obstet. Gynecol., 141, 547-555
14. Weiss, N.S., Farewell, V.T., Szekely, D.R., English, D.R. & Kiviat, N. (1980) Oestrogens and endometrial cancer: effect of other risk factors on the association. Maturitas, 2, 185-190
15. Marrett, L.D., Meigs, J.W. & Flannery, J.T. (1982) Trends in the incidence of cancer of the corpus uteri in Connecticut, 1964-1969, in relation to consumption of exogenous estrogens. Am. J. Epidemiol., 116, 57-67
16. Vakil, D.V., Morgan, R.W. & Halliday, M. (1983) Exogenous estrogens and development of breast and endometrial cancer. Cancer Detect. Prev., 6, 415-424
17. Hoover, R., Gray, L.A., Sr, Cole, P. & MacMahon, B. (1976) Menopausal estrogens and breast cancer. New Engl. J. Med., 295, 401-405
18. Ross, R.K., Paganini-Hill, A., Gerkins, V.R., Mack, T.M., Pfeffer, R., Arthur, M. & Henderson, B.E. (1980) A case-control study of menopausal estrogen therapy and breast cancer. J. Am. med. Assoc., 243, 1635-1639
19. Hoover, R., Glass, A., Finkle, W.D., Azevedo, D. & Milne, K. (1981) Conjugated estrogens and breast cancer risk in women. J. natl Cancer Inst., 67, 815-820
20. Hulka, B.S., Chambless, L.E., Deubner, D.C. & Wilkinson, W.E. (1982) Breast cancer and estrogen replacement therapy. Am. J. Obstet. Gynecol., 143, 638-644
21. Gambrell, R.D., Jr, Maier, R.C. & Sanders, B.I. (1983) Decreased incidence of breast cancer in postmenopausal estrogen-progestogen users. Obstet. Gynecol., 62, 435-443
22. Hiatt, R.A., Bawol, R., Friedman, G.D. & Hoover, R. (1984) Exogenous estrogen and breast cancer after bilateral oophorectomy. Cancer, 54, 139-144
23. McDonald, J.A., Weiss, N.S., Daling, J.R., Francis, A.M. & Polissar, L. (1986) Menopausal estrogen use and the risk of breast cancer. Breast Cancer Res. Treat., 7, 193-199
24. Brinton, L.A., Hoover, R. & Fraumeni, J.F., Jr (1986) Menopausal oestrogens and breast cancer risk: an expanded case-control study. Br. J. Cancer, 54, 825-832
25. Nomura, A.M.Y., Kolonel, L.N., Hirohata, T. & Lee, J. (1986) The association of replacement estrogens with breast cancer. Int. J. Cancer, 37, 49-53
26. Sartwell, P.E., Arthes, F.G. & Tonascia, J.A. (1977) Exogenous hormones, reproductive history, and breast cancer. J. natl Cancer Inst., 59, 1589-1592
27. Ravnihar, B., Seigel, D.G. & Lindtner, J. (1979) An epidemiologic study of breast cancer and benign breast neoplasias in relation to the oral contraceptive and estrogen use. Eur. J. Cancer, 15, 395-405
28. Jick, H., Walker, A.M., Watkins, R.N., D'Ewart, D.C., Hunter, J.R., Danford, A., Madsen, S., Dinan, B.J. & Rothman, K.J. (1980) Replacement estrogens and breast cancer. Am. J. Epidemiol., 112, 586-594
29. Kelsey, J.L., Fischer, D.B., Holford, T.R., LiVolsi, V.A., Mostow, E.D., Goldenberg, I.S. & White, C. (1981) Exogenous estrogens and other factors in the epidemiology of breast cancer. J. natl Cancer Inst., 67, 327-333
30. Sherman, B., Wallace, R. & Bean, J. (1983) Estrogen use and breast cancer. Interaction with body mass. Cancer, 51, 1527-1531
31. Kaufman, D.W., Miller, D.R., Rosenberg, L., Helmrich, S.P., Stolley, P., Schottenfeld, D. & Shapiro, S. (1984) Noncontraceptive estrogen use and the risk of breast cancer. J. Am. med. Assoc., 252, 63-67
32. Horwitz, R.I. & Stewart, K.R. (1984) Effect of clinical features on the association of estrogens and breast cancer. Am. J. Med., 76, 192-198
33. La Vecchia, C., Decarli, A., Parazzini, F., Gentile, A., Liberati, C. & Franceschi, S. (1986) Non-contraceptive oestrogens and the risk of breast cancer in women. Int. J. Cancer, 38, 853-858
34. Wingo, P.A., Layde, P.M., Lee, N.C., Rubin, G. & Ory, H.W. (1987) The risk of breast cancer in postmenopausal women who have used estrogen replacement therapy. J. Am. med. Assoc., 257, 209-215
35. Thomas, D.B., Persing, J.P. & Hutchison, W.B. (1982) Exogenous estrogens and other risk factors for breast cancer in women with benign breast diseases. J. natl Cancer Inst., 69, 1017-1025
Conjugated oestrogens
A. Evidence for carcinogenicity to animals (limited)
Conjugated oestrogens were tested inadequately in rats by oral administration in one study [ref: 1]. In male hamsters castrated as adults, equilin administered as a subcutaneously implanted pellet produced renal tumours in 6/8 treated animals. In contrast, d-equilenin administered similarly did not induce renal tumours [ref: 2,3].
B. Other relevant data
No data were available on the genetic and related effects of conjugated oestrogens in humans.
A commercial preparation of conjugated oestrogens did not induce chromosomal aberrations in human lymphoblastoid cells in vitro or in Chinese hamster V79 cells exposed in diffusion chambers implanted into mice after oestrogen treatment. It was not mutagenic to bacteria [ref: 4].
References
1. IARC Monographs, 21, 147-159, 1979
2. Li, J.J., Li, S.A., Klicka, J.K., Parsons, J.A. & Lam, L.K.T. (1983) Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney. Cancer Res., 43, 5200-5204
3. Li, J.J. & Li, S.A. (1984) Estrogen-induced tumorigenesis in hamsters: roles for hormonal and carcinogenic activities. Arch. Toxicol., 55, 110-118
4. IARC Monographs, Suppl. 6, 187, 1987
Oestradiol-17b and esters
A. Evidence for carcinogenicity to animals (sufficient)
Oestradiol-17b and its esters were tested in mice, rats, hamsters and guinea-pigs by oral and subcutaneous administration. Administration to mice increased the incidences of mammary, pituitary, uterine, cervical, vaginal, testicular, lymphoid and bone tumours [ref: 1-5]. In rats, there was an increased incidence of mammary and/or pituitary tumours [ref: 1,6]. Oestradiol-17b produced a nonstatistically significant increase in the incidence of foci of altered hepatocytes and hepatic nodules induced by partial hepatectomy and administration of N-nitrosodiethylamine in rats [ref: 7]. In hamsters, a high incidence of malignant kidney tumours occurred in intact and castrated males [ref: 1,8-10] and in ovariectomized females, but not in intact females [ref: 1]. In guinea-pigs, diffuse fibromyomatous uterine and abdominal lesions were observed [ref: 1].
B. Other relevant data
No data were available on the genetic and related effects of oestradiol-17b in humans.
Oestradiol-17b did not induce chromosomal aberrations in bone-marrow cells of mice treated in vivo. Unusual nucleotides were found in kidney DNA of treated hamsters. It induced micronuclei but not aneuploidy, chromosomal aberrations or sister chromatid exchanges in human cells in vitro. In rodent cells in vitro, it induced aneuploidy and unscheduled DNA synthesis but was not mutagenic and did not induce DNA strand breaks or sister chromatid exchanges. Oestradiol-17b was not mutagenic to bacteria [ref: 11].
References
1. IARC Monographs, 21, 279-326, 1979
2. Huseby, R.A. (1980) Demonstration of a direct carcinogenic effect of estradiol on Leydig cells of the mouse. Cancer Res., 40, 1006-1013
3. Highman, B., Roth, S.I. & Greenman, D.L. (1981) Osseous changes and osteosarcomas in mice continuously fed diets containing diethylstilbestrol or 17b-estradiol. J. natl Cancer Inst., 67, 653-662
4. Highman, B., Greenman, D.L., Norvell, M.J., Farmer, J. & Shellenberger, T.E. (1980) Neoplastic and preneoplastic lesions induced in female C3H mice by diets containing diethylstilbestrol or 17b-estradiol. J. environ. Pathol. Toxicol., 4, 81-95
5. Nagasawa, H., Mori, T. & Nakajima, Y. (1980) Long-term effects of progesterone or diethylstilbestrol with or without estrogen after maturity on mammary tumorigenesis in mice. Eur. J. Cancer, 16, 1583-1589
6. Inoh, A., Kamiya, K., Fujii, Y. & Yokoro, K. (1985) Protective effects of progesterone and tamoxifen in estrogen-induced mammary carcinogenesis in ovariectomized W/FU rats. Jpn. J. Cancer Res. (Gann), 76, 699-704
7. Yager, J.D., Campbell, H.A., Longnecker, D.S., Roebuck, B.D. & Benoit, M.C. (1984) Enhancement of hepatocarcinogenesis in female rats by ethinyl estradiol and mestranol but not estradiol. Cancer Res., 44, 3862-3869
8. Li, J.J., Li, S.A., Klicka, J.K., Parsons, J.A. & Lam, L.K.T. (1983) Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney. Cancer Res., 43, 5200-5204
9. Li, J.J. & Li, S.A. (1984) Estrogen-induced tumorigenesis in hamsters: roles for hormonal and carcinogenic activities. Arch. Toxicol., 55, 110-118
10. Liehr, J.G., Stancel, G.M., Chorich, L.P., Bousfield, G.R. & Ulubelen, A.A. (1986) Hormonal carcinogenesis: separation of estrogenicity from carcinogenicity. Chem.-biol. Interactions, 59, 173-184
11. IARC Monographs, Suppl. 6, 437-439, 1987
Oestriol
A. Evidence for carcinogenicity to animals (limited)
Oestriol was tested by subcutaneous implantation in castrated mice and in rats and hamsters. It increased the incidence and accelerated the appearance of mammary tumours in both male and female mice and produced kidney tumours in hamsters [ref: 1].
B. Other relevant data
No data were available on the genetic and related effects of oestriol in humans. It did not induce aneuploidy in cultured lymphocytes from one pregnant woman; results for induction of sister chromatid exchange were inconclusive. No effect was seen in lymphocytes from one man [ref: 2].
References
1. IARC Monographs, 21, 327-341, 1979
2. IARC Monographs, Suppl. 6, 440-441, 1987
Oestrone
A. Evidence for carcinogenicity to animals (sufficient)
Oestrone was tested in mice by oral administration, in mice, rats and hamsters by subcutaneous injection and implantation, and in mice by skin painting. Its administration resulted in an increased incidence of mammary tumours in mice, in pituitary, adrenal and mammary tumours in rats, and in renal tumours in both castrated and intact male hamsters [ref: 1]. Oestrone implanted subcutaneously as a pellet produced renal tumours in 80% of treated male hamsters castrated as adults [ref: 2,3].
B. Other relevant data
No data were available on the genetic and related effects of oestrone in humans. It was not mutagenic to Chinese hamster cells in vitro [ref: 4].
References
1. IARC Monographs, 21, 343-362, 1979
2. Li, J.J., Li, S.A., Klicka, J.K., Parsons, J.A. & Lam, L.K.T. (1983) Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney. Cancer Res., 43, 5200-5204
3. Li, J.J. & Li, S.A. (1984) Estrogen-induced tumorigenesis in hamsters: roles for hormonal and carcinogenic activities. Arch. Toxicol., 55, 110-118
4. IARC Monographs, Suppl. 6, 442-443, 1987
Ethinyloestradiol
A. Evidence for carcinogenicity to animals (sufficient)
Ethinyloestradiol was tested in mice, rats, dogs and monkeys by oral administration and in rats by subcutaneous injection. In mice, it increased the incidences of pituitary tumours and of malignant mammary tumours in both males and females and produced malignant tumours of the uterus and cervix in females [ref: 1]. In rats, it increased the incidence of liver-cell tumours [ref: 1,2], pituitary chromophobe adenomas [ref: 2] and mammary adenocarcinomas [ref: 2,3]. Ethinyloestradiol administered as a subcutaneous injection of pellets produced a low but increased incidence of renal tumours in hamsters castrated as adults [ref: 4,5]. In rats, it induced foci of altered hepatocytes, a presumed preneoplastic lesion; when administered following initiation of hepatocarcinogenesis with N-nitrosodiethylamine, ethinyloestradiol enhanced the development of foci of altered hepatocytes and of hepatic nodules [ref: 6]. In female rats given partial hepatectomy and treated with N-nitrosodiethylamine, ethinyloestradiol potentiated the development of foci of altered hepatocytes and of hepatocellular carcinomas [ref: 7]. In N-nitrosodiethylamine-initiated rats, ethinyloestradiol increased the number of g-glutamyl transpeptidase-positive hepatic foci [ref: 8]. Dietary administration of ethinyloestradiol combined with subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl caused a high incidence of prostatic carcinomas in male rats [ref: 9]. In rats, ethinyloestradiol significantly enhanced the development of tumours of the liver and kidneys induced by several agents [ref: 10].
B. Other relevant data
No data were available on the genetic and related effects of ethinyloestradiol alone in humans. See, however, the summary of data for combined oral contraceptives.
Ethinyloestradiol did not induce chromosomal aberrations in human lymphocytes, chromosomal aberrations or mutation in Chinese hamster cells or unscheduled DNA synthesis in rat hepatocytes in vitro. Studies on cell transformation were inconclusive. It was weakly active in an assay for inhibition of intercellular communication in Chinese hamster V79 cells. It did not induce sex-linked recessive lethal mutations in Drosophila or mutation in yeast and did not induce mutation or DNA damage in bacteria [ref: 11].
References
1. IARC Monographs, 21, 233-255, 1979
2. Schardein, J.L. (1980) Studies of the components of an oral contraceptive agent in albino rats. I. Estrogenic component. J. Toxicol. environ. Health, 6, 885-894
3. Holtzman, S., Stone, J.P. & Shellabarger, C.J. (1981) Synergism of estrogens and X-rays in mammary carcinogenesis in female ACI rats. J. natl Cancer Inst., 67, 455-459
4. Li, J.J., Li, S.A., Klicka, J.K., Parsons, J.A. & Lam, L.K.T. (1983) Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney. Cancer Res., 43, 5200-5204
5. Li, J.J. & Li, S.A. (1984) Estrogen-induced tumorigenesis in hamsters: roles for hormonal and carcinogenic activities. Arch. Toxicol., 55, 110-118
6. Wanless, I.R. & Medline, A. (1982) Role of estrogens as promoters of hepatic neoplasia. Lab. Invest., 46, 313-320
7. Yager, J.D., Campbell, H.A., Longnecker, D.S., Roebuck, B.D. & Benoit, M.C. (1984) Enhancement of hepatocarcinogenesis in female rats by ethinyl estradiol and mestranol but not estradiol. Cancer Res., 44, 3862-3869
8. Yager, J.D., Roebuck, B.D., Paluszcyk, T.L. & Memoli, V.A. (1986) Effects of ethinyl estradiol and tamoxifen on liver DNA turnover and new synthesis and appearance of gamma glutamyl transpeptidase-positive foci in female rats. Carcinogenesis, 12, 2007-2014
9. Shirai, T., Fukushima, S., Ikawa, E., Tagawa, Y. & Ito, N. (1986) Induction of prostate carcinoma in situ at high incidence on F344 rats by a combination of 3,2'-dimethyl-4-aminobiphenyl and ethinyl estradiol. Cancer Res., 46, 6423-6426
10. Shirai, T., Tsuda, H., Ogiso, T., Hirose, M. & Ito, N. (1987) Organ specific modifying potential of ethinyl estradiol on carcinogenesis initiated with different carcinogens. Carcinogenesis, 8, 115-119
11. IARC Monographs, Suppl. 6, 293-295, 1987
Mestranol
A. Evidence for carcinogenicity to animals (sufficient)
Mestranol was tested in mice, rats, dogs and monkeys by oral administration. It increased the incidence of pituitary tumours and malignant mammary tumours in mice [ref: 1,2] and increased the incidence of malignant mammary tumours in female rats. Studies in monkeys were still in progress; although no tumour had been observed after seven years, no conclusive evaluation could be made [ref: 1]. Feeding of mestranol to rats following partial hepatectomy and treatment with N-nitrosodiethylamine enhanced the development of foci of altered hepatocytes and of hepatocellular carcinomas [ref: 3,4]. No significant increase in mammary tumour occurrence was seen in dogs treated with mestranol [ref: 5,6].
B. Other relevant data
No data were available on the genetic and related effects of mestranol alone in humans. See, however, the summary of data for combined oral contraceptives.
Mestranol did not induce DNA strand breaks in hepatocytes of rats or chromosomal aberrations in bone-marrow cells of mice treated in vivo. It did not induce chromosomal aberrations in human lymphocytes in vitro. It was weakly active in an assay for inhibition of intercellular communication in Chinese hamster V79 cells. It did not induce unscheduled DNA synthesis in cultured rat hepatocytes or sex-linked recessive lethal mutations in Drosophila. It was not mutagenic to bacteria [ref: 7].
References
1. IARC Monographs, 21, 257-278, 1979
2. El Etreby, M.F. & Neumann, F. (1980) Influence of sex steroids and steroid antagonists on hormone-dependent tumors in experimental animals. In: Iacobelli, S., King, R.J.B., Lindner, H.R. & Lippman, M.E., eds, Hormones and Cancer, New York, Raven Press, pp. 321-336
3. Yager, J.D., Jr & Yager, R. (1980) Oral contraceptive steroids as promoters of hepatocarcinogenesis in female Sprague-Dawley rats. Cancer Res., 40, 3680-3685
4. Yager, J.D., Campbell, H.A., Longnecker, D.S., Roebuck, B.D. & Benoit, M.C. (1984) Enhancement of hepatocarcinogenesis in female rats by ethinylestradiol and mestranol but not estradiol. Cancer Res., 44, 3862-3869
5. El Etreby, M.F. & Graf, K.-J. (1979) Effect of contraceptive steroids on mammary gland of beagle dog and its relevance to human carcinogenicity. Pharmacol. Ther., 5, 369-402
6. Kwapien, R.P., Giles, R.C., Geil, R.G. & Casey, H.W. (1980) Malignant mammary tumors in beagle dogs dosed with investigational oral contraceptive steroids. J. natl Cancer Inst., 65, 137-144
7. IARC Monographs, Suppl. 6, 369-371, 1987
Overall evaluation
Steroidal oestrogens are carcinogenic to humans (Group 1).
N.B. - This evaluation applies to the group of chemicals as a whole and not necessarily to all individual chemicals within the group.
For definition of the italicized terms, see Preamble Evaluation.
Also previous evaluations: Vol. 6 (1974); Vol. 21 (1979)
See Also:
Toxicological Abbreviations