Synthesis, biologic and toxic effects of the major 2,3,7,8-tetrachlorodibenzo-p-dioxin metabolites in the rat. 1986

G Mason, and S Safe

The two major mammalian metabolites of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), namely 2-hydroxy-3,7,8-trichlorodibenzo-p-dioxin and 2-hydroxy-1,3,7,8-tetrachlorodibenzo-p-dioxin, have been synthesized. The compounds were individually administered to immature male Wistar rats and their effects on body weight loss, thymic atrophy, liver and spleen weights and their activities as inducers of hepatic microsomal benzo[a]pyrene hydroxylase, 4-chlorobiphenyl hydroxylase and ethoxyresorufin O-deethylase were determined using dose levels of 100, 1000 and 5000 micrograms/kg. The 2 metabolites did not affect organ or body weights after 14 days of exposure and only 2-hydroxy-3,7,8-trichlorodibenzo-p-dioxin was active as an inducer of the microsomal monooxygenases at dose levels of 1000 and 5000 micrograms/kg. A comparison of the relative enzyme induction activities of 2,3,7,8-TCDD and 2-hydroxy-3,7,8-trichlorodibenzo-p-dioxin indicates that the former compound was greater than 3 orders of magnitude more active than the metabolite.

UI MeSH Term Description Entries
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D004147 Dioxins A family of compounds that contain the 1,4-dioxin structure. Many specific dioxin derivatives are listed as CARCINOGENS; TERATOGENS; or MUTAGENS. Dioxin
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000072317 Polychlorinated Dibenzodioxins Dibenzodioxin derivatives that contain multiple chloride atoms bound to the benzene ring structures. TCDD,Tetrachlorodibenzodioxin,2,3,7,8-Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo-p-dioxins,Dibenzo(b,e)(1,4)dioxin, 2,3,7,8-tetrachloro-,PCDD,Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzodioxin,Polychlorodibenzo-4-dioxin,Polychlorodibenzo-p-dioxin,Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo p dioxins,Dibenzo-p-dioxins, Chlorinated,Dibenzo-p-dioxins, Polychlorinated,Dibenzodioxin, Polychlorinated,Dibenzodioxins, Polychlorinated,Polychlorinated Dibenzo p dioxins,Polychlorodibenzo 4 dioxin,Polychlorodibenzo p dioxin,Tetrachlorodibenzo p dioxin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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