Receptors and Other Targets for Toxic Substances: Proceedings of the European Society of Toxicology, Meeting Held in Budapest, June 11-14, 1984

ISBN-13: 9783540136705 / Angielski / Miękka / 1985 / 520 str.

P. L. Chambers; E. Cholnoky; C. Chambers

Opis

Trichloroethylene (TRI), administered orally at high doses for 18 months has been shown to increase the incidence of hepatocellular carcinoma in B6C3F 1 mice but not Osborne-Mendel rats (NCI, 1976). The interpretation of these studies has been confounded due to the presence of epoxide stabilizers in the TRI. However more recent studies have demonstrated that pure TRI also causes hepatocellular carcinoma in B6C3F mice (NTP, 1983) and Aldedey Park (Swiss) mice (Elcombe 1 and Pratt, unpublished data). Furthermore, no increase in the incidence of hepatocellular carcinoma was observed in Fisher 344 rats administered pure TRI (NTP, 1983). TRI has been extensively examined for mutagenic potential, but many studies were bedeviled by the presence of mutagenic epoxide stabilizers. However, in general, TRI has been found to be only 'marginally' mutagenic or non-mutagenic (Greim et ai., 1975; Simmon et ai., 1977; Bronzetti et ai., 1978; Waskell, 1978; Bartsch et ai., 1979; Slacik-Erben et ai., 1980). Covalent binding of trichloroethylene or its metabolites to protein, RNA and DNA has been illustrated in vitro (Van Duuren and Banerjee, 1976; Bolt et ai.,1977; Bolt and Filser, 1977; Uehleke and Poplawski-Tabarelli, 1977; Banerjee and Van Dauren, 1978). However, in vivo, only extremely low (indistinguishable from protein binding) or zero binding of TRI metabolites to DNA has been reported (Parchman and Magee, 1982; Stott et ai., 1982).

Spis treści

On the Occasion of the 25th Meeting of the European Society of Toxicology.- Young Scientists Award Lecture 1984: Species Differences in Carcinogenicity and Peroxisome Proliferation due to Trichloroethylene: A Biochemical Human Hazard Assessment.- The Role of the Receptor in Toxicology.- The Role of Immunoreceptors.- The Role of the Estrogen Receptor in Diethylstilbestrol Toxicity.- The Role of Receptors in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD Toxicity).- The Oncogene and its Potential Role in Carcinogenesis.- Brain Glucocorticoid Receptors and Their Role in Behavioural Teratogenicity of Synthetic Glucocorticoids.- Effect of Dithiocarbamate-Fungicides and Thiurams on Haloperidol Binding in Rat Brain.- Toxic Effects on the Gastrointestinal Tract.- Mucosal Biotransformation of Toxins in the Gut.- Intestinal Excretion of Toxic Substances.- Biochemical Changes of Intestinal Epithelial Cells Induced by Cytostatic Agents in Rats.- Intestinal Pathology in the Dog Induced by Sublethal Doses of Amiodarone.- Distribution of Glutathione and its Related Enzymes in Small Intestinal Mucosa of Rats.- Induction of Forestomach Lesions by Butylhydroxyanisole and Structurally Related Substances.- The Effect of Cyclophosphamide and Vincristine on Intestinal Protein Loss in Rats.- The Induction and Assessment of Rat Gastric Mucosal Lesions.- The Technique of Gastric Endoscopy and Biopsy in the Dog.- The Incidence of Neoplasms in Syrian Hamsters with Particular Emphasis on Intestinal Neoplasia.- Toxic Effects on Haemostasis and Blood.- Thrombogenic Effects of Xenobiotics.- Toxicologically Relevant Disturbances of Haemostasis.- Effects of Organic Solvents on Erythrocyte Membrane Acetylcholine Esterase Activity.- Changes of Haemostaseological Variables in Carbon Tetrachloride Poisoning in Rats.- Influence of Antithrombin III on Carbon Tetrachloride Intoxication of Rabbits.- Increased Serum Alkaline Phosphatase Activity in Beagle Dogs: Mechanism, Diagnostic Considerations.- Interaction of Rodenticides and Humic Acids — Effects on Prothrombin Activity.- Interpretation of Concentrations of Toxic Agents during Drug Safety Studies.- Reasons for Monitoring Kinetics in Safety Evaluation Studies.- A Decision Tree Approach for the Application of Drug Metabolism and Kinetic Studies to In Vivo and In Vitro Toxicological and Pharmacological Testing.- Theoretical Aspects Pertinent to the Interpretation of Concentration Data.- How to Identify Compounds Posing Problems in Absorption, Distribution and Elimination.- A Questionnaire Assessing the Involvement of Toxicologists in Metabolism and Kinetics.- A Stochastic Approach in the Evaluation of Plasma Curves with Enterohepatic Recycling.- Endotoxin and Pharmacokinetics of Rifampicin.- Local Toxicity and Pharmacokinetics After Intramuscular or Intralipomatous Injection of Different Drugs in Pigs.- Distribution of Metabolites of the Potent ?-Adrenoceptor Blocking Drug B 24/76 in Different Tissues of Rats under Toxic Conditions.- Functional and Morphological Changes in the Inner Ear.- Principles in Cochlear Toxicity.- Link Between Functional and Morphological Changes in the Inner Ear — Functional Changes Produced by Ototoxic Agents and Their Interactions.- Toxic Effects of Pesticides.- The Effect of Maneb, Zineb and Ethylenethiourea on the Humoral Activity of the Pituitary-Thyroid Axis in Rat.- Toxicokinetics of the Herbicide Dichlorprop and its Leucinate and Their Action on Liver Mixed Function Oxidases.- Organochlorines and Mercury in Blood of a Fish-Eating Population at the River Elbe in Schleswig-Holstein, FRG.- Pesticide-Drug Interaction in Rats.- Dithiocarbamate Fungicides Decrease Histochemical Reactivity of Cholinesterases in the Gut Wall of Rat.- Biochemical Study of Muscle Samples from Chicken Embryos Affected by Wofatox 50 EC.- Investigation of Adrenal Steroid and 25-hydroxy-cholecalcipherol in Human Gramoxone Poisoning.- Group Intoxication with Gramoxone (Paraquat) Toxicological and Pathohistological Aspects.- The Genetic Control of Paraquat Sensitivity of H-2 Congenic and Recombinant Mice.- The Effect of Light on the Toxicity of Paraquat in the Mouse.- Changes of the Serum Superoxide Dismutase Content of Gramoxone Poisoned Patients, Measured by Anti-SOD Monoclonal Antibody.- Cardiodepression in Organophosphate Poisonings.- The Effect of Organophosphoric Pesticides on T- and B-Lymphocytes and Antibody Production in Mice.- Toxicity Study of the Insecticide Ekalux 25 EC in Rats.- Effect of Different Antidotes in Ekalux 25 EC Poisoned Male Rats.- Assessment of Acute Neurotoxic Effects of Different Kinds of Pesticides in Mice.- Subacute and Subchronic Toxicity of Dietary Bendiocarb in Rats.- Effect of Lethal Dose of Trichlorphon on Different Biochemical and Physiological Parameters of Common Carp (Cyprinus Carpio L.).- Chlorate Poisoning: Mechanism of Toxicity.- Effect of Nabam and Ethylenethiourea on the Urinary Output of Rats.- Decis and Perocin Influence on the Activity of Serum Monoamine-Oxidase in Greenhouse Workers.- Immunotoxicological Investigation of the Effects of a Pesticide; Cypermethrin.- Heavy Metal Toxicity.- Effect of Some Heavy Metal Salts on Hepatic Mono-Oxygenases After Subchronic Exposure.- Intestinal Absorption of Aluminium in Rats.- The Formation of Glutathione-Chromium Complexes and Their Possible Role in Chromium Disposition.- Long-Term Exposure to Cadmium and Cardiovascular Alterations in the Rabbit.- Lack of Substantial Neuroendocrine Changes in Short-Term High Dose Cadmium Treated Rats.- Effect of Cadmium on Proteins.- Interaction of Tin and Zinc in Some Processes of Heme Biosynthesis in Rabbits.- The Effect of Chronic Thallium Administration on Testicular Enzyme Activities in the Rat.- Miscellaneous Toxicological Studies.- The Effects of Methylglyoxal on Central Synaptic Transmission in the Isolated Nerve Cord of the Cockroach (Periplaneta Americana L.).- The Role of Bile Acids in the Effect of Ethinylestradiol on the Biliary Excretion Rate of Exogenous Organic Anions.- Substrate and Phenobarbital Induction of the Biliary Excretion of Exogenous Organic Anions in Rats.- The Biliary Elimination of Sulfamerazin in Rat and Man — A Comparison.- Preclinical Safety Studies with Temofel, a New Choleretic Compound.- Studies on Hyperoxaluria and Oxalate Stone Formation Induced by 2-Acetyl-3-PhenylTetrahydro-1,2,4-Oxadiazim-5-on.- The Biliary Elimination of Indomethacin in Man.- Increased Response of Cytochrome P-450 Dependent Biotransformation Reactions in Rat Liver to Repeated Administration of Inducers.- Influence of Pyrazolones on Hepatic Glutathione in Rats.- Comparative Study on the Sensitivity of Several Serum Enzymes in Detecting Hepatic Damage in Rats.- The Metabolism of Some Xenobiotics in Germ-free and Conventionalized Rats.- The Effect of Prostacyclin on the Liver.- Role of Vitamins in Biotransformation of Xenobiotics.- Possible Adrenal Involvement in Hydroxyurea Toxicity Defense Mechanisms.- Replacement Therapy Against Increased Hydroxyurea Toxicity in Pituitary or Adrenal Ablated Rats.- Testicular Toxicity of Antineoplastic Drugs During Postnatal Development of the Rat.- Free and Bound Testosterone in Male Heroin Addicts.- Effect of Single Treatment of Rats with Procarbazine on the Pituitary-Testicular Axis.- Toxic Effects of 3,7-Dimethylxanthine on Mature and Immature Male Rabbits.- Pharmokinetics of Metoprolol in Relation to Polymorphic Sparteine Oxidation.- Mutagenic Metabolites in Rat Urine After Dermal Exposure to 1,3-Diamino-Benzene.- Genotoxicity of Hexachlorobutadiene and Pentachlorobutenoic Acid: Correlation Between Induction of Unscheduled DNA Synthesis and Morphological Transformation in Syrian Hamster Embryo Fibroblasts.- Genotoxic Activity of Nitroimidazo(2,1-b)Thiazole Derivatives in Salmonella Typhimurium and Saccharomyces Cerevisiae Assays.- Serum Enzymes in Toxicity of Trichloroethylene After Subchronic Ethanol Pretreatment.- Oral Intake of a Toluene-Containing Thinner. Effects and Headspace Gas Chromatographic Analytical Diagnosis.- Circadian, Seasonal and Social Factors Influencing the Organic Solvent Toxicity.- Inhalation of Butanols: Changes in the Cytochrome P-450 Enzyme System.- Circulating Steroids in Male Rats Following Inhalation of n-Alcohols.- On the Embryotoxic Effects of Benzene and Its Alkyl Derivatives in Mice, Rats and Rabbits.- Biological Response to Nitrogen Oxide.- The Use of Whole Embryo Culture in the Study of Teratogenic Mechanisms.- Behavioural Tests in the Postnatal Period After Prenatal Administration of Cyclophosphamide to Wistar Rats.- Grip Strength Test and Infrared Thermometry as Non-Invasive Methods to Complement Acute Toxicity Data in Mice.- Behavioural Effects of Prenatal Exposure to Carbon Disulfide and to Aromatol in Rats.- Styrene Metabolism and Striatal Dopamine Depletion in Rabbits.- The Influence of Ethanol Pretreatment and Social Isolation on Dopamine Release and Locomotor Activity in Mice.- Metabolic Fate and Cardiovascular Effects of Arsenic in Rats and Rabbits Chronically Exposed to Trivalent and Pentavalent Arsenic.- Relationships Between the Myocardial Concentrations of Antracycline Antibiotics and Their Cardiotoxic Activity in the Rat.- On the Safety Evaluation of Extracts from Synthetic Polymers Used in Medicine.- Intramuscular Injection and Muscle Damage: Comparison Between Morphological and Enzymatic Changes After Irritants, Drugs and Solvents Administration in Rabbits.- A Six Month Dermal Irritation Test with Anthralins in the Göttingen Miniature Swine.- Separation of Immature and Adult Rat Hepatocytes into Distinct Subpopulations by Centrifugal Elutriation.- Tests for Local Toxicity of Intramuscular Drug Preparations. Comparison of in Vitro and in Vivo Methods.- Analysis of Cataract and Keratotic Damage Induced by 4-Diethylaminoethoxy-?-EthylBenzhydrol (RGH-6201) in Rats.- Applicability of Evans Blue Diffusion for Predicting Eye and Skin Irritancy to Chemicals in the Rat.- Prediction of Toxicity Using Quantitative Structure-Activity Relationships.- Structure-Activity-Adverse Effect Relationships of Condensated As-Triazine Derivatives.- A Mathematical Model Describing the Lethal Effects of High Temperature on Fish and Its Possible Application in the Planning of Toxicological Experiments.- In Vivo Formation of Carcinogenic Substance from Diethyl Pyrocarbonate in the Presence of Ammonia.- Subacute Oral Toxicity of Allyl Isothiocyanate in the Rat.- Preclinical Toxicity Studies with two Thymopoietin-Like Peptides.- Comparative Studies on the Effect of Some Macrolide Antibiotics on Their Own Demethylation.- Ecto-ATPase in Rat and Mouse Thymocytes Cytotoxic Effects of Various Chemical Substances in Vitro.- Toxicity of the Alkylating Agent Bendamustin.- The Leukemogenic Effect of Haloperidol in AKC3 F1 Hybrid Mice.- Author Index.