Metabolic fates of diethylstilboestrol sulphates in the rat

Abstract

The metabolic fates and modes of excretion of diethylstilboestrol mono [35S] Diethylstilboestrol has been used as a synthetic oestrogen in humans and in food-producing animals. It has been shown to have carcinogenic properties in a number of animal species (Umberger, 1975) and its use has been associated with the occurrence of tumours in humans (Herbst et al., 1972).The metabolic fate of diethylstilboestrol has been studied in several animal species (Abou-EI-Makarem et al., 1967) and it has been shown that biliary excretion as a glucuronic acid conjugate represents a major pathway for elimination (Klaasen, 1973). The disulphate ester of diethylstilboestrol, which is approximately half as active as diethylstilboestrol itself with respect to oestrogenic activity (Bishop et al., 1951), has been used as a water-soluble form of the synthetic oestrogen. Nevertheless, the metabolism of sulphated forms of diethylstilboestrol has not been reported.

Biliary excretion of some anionic derivatives of diethylstilboestrol and phenolphthalein in the guinea pig

“…Phenolphthalein di[35S]sulphate was excreted unchanged in bile. These findings are discussed in relation to studies carried out in the rat [Barford, Olavesen, Curtis & Powell (1977) Biochem. J.…”

“…[35S]sulphate and diethylstilboestrol di[35S]sulphate in the guinea pig differ markedly from those already established in the rat (Barford et al, 1977). The salient differences shown in Scheme 1 are explicable in terms of the enzyme activities of guinea-pig liver and rat liver respectively.…”

“…Potassium diethylstilboestrol mono[5S]sulphate (8.9 mCi/mmol) and potassium diethylstilboestrol di[35S]sulphate (1l.OmCi/mmol) were prepared by the methods of Barford et al (1977). Potassium phenolphthalein di[35S]sulphate (8.9mCi/mmol) was prepared as described by Powell et al (1975).…”

Biliary excretion of some anionic derivatives of diethylstilboestrol and phenolphthalein in the guinea pig

“…Phenolphthalein di[35S]sulphate was excreted unchanged in bile. These findings are discussed in relation to studies carried out in the rat [Barford, Olavesen, Curtis & Powell (1977) Biochem. J.…”

“…[35S]sulphate and diethylstilboestrol di[35S]sulphate in the guinea pig differ markedly from those already established in the rat (Barford et al, 1977). The salient differences shown in Scheme 1 are explicable in terms of the enzyme activities of guinea-pig liver and rat liver respectively.…”

“…Potassium diethylstilboestrol mono[5S]sulphate (8.9 mCi/mmol) and potassium diethylstilboestrol di[35S]sulphate (1l.OmCi/mmol) were prepared by the methods of Barford et al (1977). Potassium phenolphthalein di[35S]sulphate (8.9mCi/mmol) was prepared as described by Powell et al (1975).…”

Delayed Adverse Effects of Neonatal Exposure to Diethylstilbestrol and Their Dose Dependency in Female Rats

“…A concern that twenty-four hours after a single treatment is too soon to detect any estrogenic activity in uterotrophic assay might exist, because uterine weights are usually measured twenty-four hours after a three-day treatment with a test substance in a uterotrophic assay (OECD 2007). However, a previous study that demonstrated, using radioautography, that DES di [ 35 S] sulfate injected intraperitoneally at 1 mg/rat distributed in the whole body within twenty-four hours (Barford et al 1977) could be support that the concern could be excluded.…”

“…TOXICOLOGIC PATHOLOGY distributed in the whole body within twenty-four hours (Barford et al 1977) could be support that the concern could be excluded.…”

Biliary excretion of some anionic derivatives of diethylstilboestrol and phenolphthalein in the guinea pig

“…Phenolphthalein di[35S]sulphate was excreted unchanged in bile. These findings are discussed in relation to studies carried out in the rat [Barford, Olavesen, Curtis & Powell (1977) Biochem. J.…”

“…[35S]sulphate and diethylstilboestrol di[35S]sulphate in the guinea pig differ markedly from those already established in the rat (Barford et al, 1977). The salient differences shown in Scheme 1 are explicable in terms of the enzyme activities of guinea-pig liver and rat liver respectively.…”

“…Potassium diethylstilboestrol mono[5S]sulphate (8.9 mCi/mmol) and potassium diethylstilboestrol di[35S]sulphate (1l.OmCi/mmol) were prepared by the methods of Barford et al (1977). Potassium phenolphthalein di[35S]sulphate (8.9mCi/mmol) was prepared as described by Powell et al (1975).…”

Delayed Adverse Effects of Neonatal Exposure to Diethylstilbestrol and Their Dose Dependency in Female Rats

“…A concern that twenty-four hours after a single treatment is too soon to detect any estrogenic activity in uterotrophic assay might exist, because uterine weights are usually measured twenty-four hours after a three-day treatment with a test substance in a uterotrophic assay (OECD 2007). However, a previous study that demonstrated, using radioautography, that DES di [ 35 S] sulfate injected intraperitoneally at 1 mg/rat distributed in the whole body within twenty-four hours (Barford et al 1977) could be support that the concern could be excluded.…”

“…TOXICOLOGIC PATHOLOGY distributed in the whole body within twenty-four hours (Barford et al 1977) could be support that the concern could be excluded.…”

Biliary excretion of some anionic derivatives of diethylstilboestrol and phenolphthalein in the guinea pig

“…Phenolphthalein di[35S]sulphate was excreted unchanged in bile. These findings are discussed in relation to studies carried out in the rat [Barford, Olavesen, Curtis & Powell (1977) Biochem. J.…”

“…[35S]sulphate and diethylstilboestrol di[35S]sulphate in the guinea pig differ markedly from those already established in the rat (Barford et al, 1977). The salient differences shown in Scheme 1 are explicable in terms of the enzyme activities of guinea-pig liver and rat liver respectively.…”

“…Potassium diethylstilboestrol mono[5S]sulphate (8.9 mCi/mmol) and potassium diethylstilboestrol di[35S]sulphate (1l.OmCi/mmol) were prepared by the methods of Barford et al (1977). Potassium phenolphthalein di[35S]sulphate (8.9mCi/mmol) was prepared as described by Powell et al (1975).…”

Delayed Adverse Effects of Neonatal Exposure to Diethylstilbestrol and Their Dose Dependency in Female Rats

“…A concern that twenty-four hours after a single treatment is too soon to detect any estrogenic activity in uterotrophic assay might exist, because uterine weights are usually measured twenty-four hours after a three-day treatment with a test substance in a uterotrophic assay (OECD 2007). However, a previous study that demonstrated, using radioautography, that DES di [ 35 S] sulfate injected intraperitoneally at 1 mg/rat distributed in the whole body within twenty-four hours (Barford et al 1977) could be support that the concern could be excluded.…”

“…TOXICOLOGIC PATHOLOGY distributed in the whole body within twenty-four hours (Barford et al 1977) could be support that the concern could be excluded.…”