Subchronic (13-week) toxicity of heptachlorodibenzo-p-dioxin in male Sprague-Dawley rats. 1994

M Viluksela, and B U Stahl, and K K Rozman
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417.

A 13-week oral toxicity study with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) was performed in Sprague-Dawley rats. Rats received HpCDD at five different dose levels or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at one dose level. The doses were divided into 4 daily loading doses and 6 biweekly maintenance doses. At the end of the 13-week dosing period half of the rats were scheduled for necropsy and the other half after another 13-week off-dose period. This preliminary report contains only data from male rats during the 13-week main study period. At the two highest doses of HpCDD and in the TCDD dosage group the body weight or body weight gain was reduced. Mortality was 15, 50 and 5%, respectively. Wasting syndrome was the primary cause of death, but some rats died of hemorrhage without wasting, which may be related to the dose-dependent decrease in platelet counts. Phosphoenolpyruvate carboxykinase (PEPCK), the rate limiting enzyme of gluconeogenesis, was decreased only at the two highest dose levels of HpCDD and in the TCDD group, all of which also showed mortality. Ethoxyresorufin O-deetylase (EROD) was induced dose-dependently in all treated groups. Serum total thyroxine (T4) concentrations were decreased beginning at the middle dose of HpCDD. The study demonstrates that the toxicity observed after subchronic exposure to HpCDD is very similar to that of TCDD. Most importantly, most of the effects after subchronic and acute dose exposure are identical, confirming the validity of 0.007 as the toxic equivalency factor for HpCDD.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010088 Oxidoreductases The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9) Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D010729 Phosphoenolpyruvate Carboxykinase (GTP) An enzyme of the lyase class that catalyzes the conversion of GTP and oxaloacetate to GDP, phosphoenolpyruvate, and carbon dioxide. This reaction is part of gluconeogenesis in the liver. The enzyme occurs in both the mitochondria and cytosol of mammalian liver. (From Dorland, 27th ed) EC 4.1.1.32. GTP-Dependent Phosphoenolpyruvate Carboxykinase,Carboxykinase, GTP-Dependent Phosphoenolpyruvate,GTP Dependent Phosphoenolpyruvate Carboxykinase,Phosphoenolpyruvate Carboxykinase, GTP-Dependent
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
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
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
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
D005260 Female Females

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