Diethylstilbestrol toxicity

EPA. 1986c. Final report on the evaluation of four toxic chemicals in an in vivo/in vitro toxicological screen Acrylamide, chlordecone, cyclophosphamide, and diethylstilbestrol. Research Triangle Park, NC U.S. Environmental Protection Agency, Health Effects Research Laboratory. EPA-600-1-86-002. 

Simmons JE, Berman E, Jackson M, et al. 1987. In vitro and in vivo toxicity A comparison of acrylamide, cyclophosphamide, chlordecone, and diethylstilbestrol. J Environ Sci Health A22(7) 639-64. 

Another feature of developmental toxicity is raised by the experience we have had with the drug DES - diethylstilbestrol. This is an... 

A series of investigations initiated during this period led to the conclusion that DBS use by the mothers of these young women was the causative factor. Diethylstilbestrol is a developmental toxicant, because its effect was the result of exposures received in utero, but that effect - a rare form of vaginal cancer - was not fully expressed for about two decades following the exposure (the age at which the incidence of the disease peaked was later shown to be 19). The DES produced not only cancer but abnormalities of the sexual organs in both male and female offspring, most of which were not expressed until the children passed the age of puberty. 

The typical dose-response curve for a developmental toxicant is steep and covers less than one to three orders of magnitude below the dose that kills or malforms half the embryos. However, the threshold and shape of a dose-response curve for a particular teratogen may differ, depending on the gestational time of exposure and the type of embryotoxicity that is measured. Furthermore, the dose at which an agent causes malformations may be above, below, or equivalent to the embryolethal threshold. Toxicants that cause little or no maternal toxicity, even at elevated doses, but adversely affect the conceptus are especially dangerous (e.g., thalidomide, diethylstilbestrol). 

Androgen-dependent carcinoma. Diethylstilbestrol (stilboestrol) is rarely used to treat prostate cancer because of its adverse effects. It is occasionally used in postmenopausal women with breast cancer. Toxicity is common. 

Purpura, edema, leg cramps, gynecomastia, porphyria cutanea tarda, and chloasma may be associated with the chronic use of diethylstilbestrol. Various cancers in premenopausal women have been shown to occur. Other chronic toxic effects include thrombocytopenia, gynecomastia, and fluid retention. 

See also Androgens Diethylstilbestrol Environmental Hormone Disruptors Radiation Toxicology, Ionizing and Nonionizing Reproductive System, Female Reproductive System, Male Toxicity Testing, Reproductive. 

Approximately equimolar mixtures of trideuterated diethylstilbestrol and unlabeled diethylstilbestrol also have been used to study the metabolic activation of diethylstilbestrol to potentially toxic metabolites by rat liver homogenates. 0 Reactive polar metabolites were converted to non-polar metabolites by enzymatic methylation. The ion-doublets arising in the mass spectra of these derivatives guaranteed that these compounds were metabolites of the substrate and also helped to establish their structures. 

DES (diethylstilbestrol), xiii, 106, 115, 206 detoxification, 34 developmental toxicity, 103 dibenz(a,h)anthracene, 112 diet, 5, 13-14,106 as exposure pathway, 13-14 chemical composition of, 5 effect on absorption of chemicals, 29 natural carcinogens in, 229-31 role in cancer, 116—20, 154-6 role in cancer prevention, 230 Dioscorides, 39 dioxin, xiii, 54, 164, 180 distribution of chemicals in body, 31-2 DNA damage, 150-3, 156 Doll, R. (Sir), 117-20, 155, 177 Donora, Pennsylvania, 81 dose, 16,39,48,71 absorbed, 27-31, 161 acute, 160... 

Comparative Dose Response Data There are only a limited number of cases in which it has been possible, even on a crude level, to compare animal and human dose responses to the same carcinogens. The paucity of data in this area is related to the fact that in most epidemiological studies the actual doses of the toxic substance is not known with certainty and that while complete dose response curves can be obtained in animal studies, such studies are very expensive. A systematic attempt to estimate human exposures and compare human and animal dose response relationships for several known carcinogens has been made and is contained in a report by the National Academy of Sciences and National Research Council on Environmental Studies Board on Pest Control.The carcinogens for which responses were compared in the study were benzidine chlornaphazine diethylstilbestrol aflatoxin Bl vinyl chloride, and cigarette smoke. 

Intravenous 50 mg weekly Phenoxymethylpenicillin 250 mg on alternate days Dermatomyositis (also treated with prednisone and prostatic cancer treated with diethylstilbestrol (stilboestrol) also treated with furosemide) Methotrexate toxicity within week of starting phenoxymethylpenicillin treated with folinic acid and fluid replacement (and nafcillin and tobramycin) 9... 

Reproductive toxicant May damage fertility or the unborn child lA, IB Danger Known or presumed human reproductive toxicant Diethylstilbestrol, thalidomide, ethanol, organomercury compounds, lead, cocaine, 1,2-dibromo-3-chloropropane... 

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