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

518 Pages·1986·10.952 MB·English

by  J. S. Schou (auth.), Philip L. Chambers, Eszter Cholnoky, Claire M. Chambers (eds.)

Archives of Toxicology, Supplement 8
Receptors
and Other Targets
for Toxic Substances
Proceedings of the
European Society ofT oxicology
Meeting Held in Budapest, June 11-14, 1984
Edited by
P. L. Chambers, E. Cholnoky and C. M. Chambers
With 120 Figures
Springer-Verlag Berlin Heidelberg New York Tokyo
CLAIRE M. CHAMBERS and PHILIP L. CHAMBERS
University of Dublin, Department of Pharmacology and Therapeutics,
Trinity College, Dublin 2, Ireland
ESZTER CHOLNOKY
Chemical Works of Gedeon Richter Ltd., Pharmacological Research Centre,
Toxicological Service, P.O. Box 27, 1475 Budapest, Hungary
ISBN -13:978-3-540-13670-5 e-ISBN-13 :978-3-642-69928-3
DOl: 10.1007/978-3-642-69928-3
Library of Congress Cataloging in Publication Data. European Society of Toxicology. Meeting (1984: Budapest,
Hungary) Receptors and other targets for toxic substances. (Archives of toxicology. Supplement; 8) I. Poisons
Metabolism-<::ongresses. 2. Poisons-Physiological effect-<::ongresses. 3. Drug receptors-{;ongresses. I. Chambers, P.
L. (Philip L.), 1931. II. Cholnoky, E. (Eszter), 1928. III. Chambers, C. M. (Claire M.). IV. Title. V. Series
[DNLM: I. Poisons-metabolism-<:ongresses. 2. Receptors, Drug-metabolism-<:ongresses. WI AR496A v.8/QV 600
E896r 1984] RA1l90.E8 Suppl. vol. 8 [RA1216] 615.9 s 85-14880
ISBN-13:978-3-540-13670-5 (U.S.) [615.9]
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© by Springer-Vedag Berlin Heidelberg 1985
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2127/3020-543210
Contents
On the Occasion of the 25th Meeting of the European Society of Toxicology
J. S. SCHOU ..................................................................... .
Young Scientists Award Lecture 1984:
Species Differences in Carcinogenicity and Peroxisome Proliferation due to Trichloroethylene:
A Biochemical Human Hazard Assessment
C. R. ELCOMBE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
The Role of the Receptor in Toxicology
The Role of Immunoreceptors
D. R. STANWORTH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
The Role of the Estrogen Receptor in Diethylstilbestrol Toxicity
K. S. KORACH and J. S. McLACHLAN ............................................... 33
The Role of Receptors in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD Toxicity)
L. DENCKER ..................................................................... 43
The Oncogene and its Potential Role in Carcinogenesis
F. WONG-STAAL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Brain Glucocorticoid Receptors and Their Role in Behavioural Teratogenicity of Synthetic
Glucocorticoids
o. BENE§ovA and A. PAvLiK....................................................... 73
Effect of Dithiocarbamate-Fungicides and Thiurams on Haloperidol Binding in Rat Brain
H. KOMULAlNEN and K. SAVOLAINEN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Toxic Effects on the Gastrointestinal Tract
Mucosal Biotransformation of Toxins in the Gut
o. HANNINEN .................................................................... 83
Intestinal Excretion of Toxic Substances
K. ROZMAN ..................................................................... 87
VI Contents
Biochemical Changes of Intestinal Epithelial Cells Induced by Cytostatic Agents in Rats
J. KRALOVANSZKY and N. PRAJDA .................................................. 94
Intestinal Pathology in the Dog Induced by Sublethal Doses of Amiodarone
P. VIC, D. GoUY, F. LACHERETZ, B. VERSCHUERE, M. CROS, B. REMANDET, J. BERTHE, and
G. MAZUE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Distribution of Glutathione and its Related Enzymes in Small Intestinal Mucosa of Rats
T. OGASAWARA, H. HOENSCH, and E. E. OHNHAUS .................................... 110
Induction of Forestomach Lesions by Butylhydroxyanisole and Structurally Related Substances
H.-J. ALTMANN, W. GRUNOW, P. W. WESTER, and U. MOHR ........................... 114
The Effect of Cyclophosphamide and Vincristine on Intestinal Protein Loss in Rats
T. BERO and T. JAVOR ............................................................ 117
The Induction and Assessment of Rat Gastric Mucosal Lesions
G. K. SALMON ................................................................... 122
The Technique of Gastric Endoscopy and Biopsy in the Dog
S. M. WHITEHEAD, G. P. CREAN, G. B. LESLIE, and D. WILD ........................... 123
The Incidence of Neoplasms in Syrian Hamsters with Particular Emphasis on Intestinal
Neoplasia
A. FABRY ....................................................................... 124
Toxic Effects on Haemostasis and Blood
Thrombogenic Effects of Xenobiotics
G. ZBINDEN and L. GRIMM ........................................................ 131
Toxicologically Relevant Disturbances of Haemostasis
H. P. KU)CKING ................................................................. 142
Effects of Organic Solvents on Erythrocyte Membrane Acetylcholine Esterase Activity
M. KORPELA and H. TAHTI ........................................................ 148
Changes of Haemostaseological Variables in Carbon Tetrachloride Poisoning in Rats
H. P. KU)CKING, H. MULLER, and F. MARKWARDT ................................... 152
Influence of Antithrombin III on Carbon Tetrachloride Intoxication of Rabbits
H. RONNEBERGER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
Increased Serum Alkaline Phosphatase Activity in Beagle Dogs: Mechanism, Diagnostic
Considerations
S. ELEK, I. LEMNT, I. POLGARI, and G. CSEH.. ........ .. .. ... .. ... .. .. ... ... .. ... ... . 160
Interaction of Rodenticides and Humic Acids - Effects on Prothrombin Activity
S. GOLBS and V. FUCHS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Contents VII
Interpretation of Concentrations of Toxic Agents during Drug Safety Studies
Reasons for Monitoring Kinetics in Safety Evaluation Studies
D. R. HAWKINS and L. F. CHASSEAUD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
A Decision Tree Approach for the Application of Drug Metabolism and Kinetic Studies to
In Vivo and In Vitro Toxicological and Pharmacological Testing
P. BACH and J. BRIDGES... ... ...... ...... .. .. . ..... ..... .. ..... .. ... ... ... ... ..... 173
Theoretical Aspects Pertinent to the Interpretation of Concentration Data
W. RIESS ..•.•...........••..........•.••.•..•.•.•..•........••.•.............•.. 189
How to Identify Compounds Posing Problems in Absorption, Distribution and Elimination
K. SCHMID ...................................................................... 196
A Questionnaire Assessing the Involvement of Toxicologists in Metabolism and Kinetics
W. RIESS ........................................................................ 205
A Stochastic Approach in the Evaluation of Plasma Curves with Enterohepatic Recycling
M. TARR and A. EORY ...........................•................................ 208
Endotoxin and Pharmacokinetics of Rifampicin
J. LAVICKY, L. CELEDA, Z. URBANOVA., J. KvETINA, J. VANECEK, and H. RASKOVA. ......... 211
Local Toxicity and Pharmacokinetics After Intramuscular or Intralipomatous Injection of
Different Drugs in Pigs
O. SVENDSEN, L. BLOM, T. AAES-J0RGENSEN and J.-J. LARSEN.. .. ....... ... .. ...... .. ... 216
Distribution of Metabolites of the Potent fJ-Adrenoceptor Blocking Drug B 24/76 in Different
Tissues of Rats under Toxic Conditions
I. AMON, A. BAUMANN, B. HARTMANN, K. P. HENSCHEL and A. MULLER ................. 218
Functional and Morphological Changes in the Inner Ear
Principles in Cochlear Toxicity
M. ANNIKO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Link Between Functional and Morphological Changes in the Inner Ear - Functional Changes
Produced by Ototoxic Agents and Their Interactions
R. D. BROWN, C. M. HENLEY, J. E. PENNY, and S. KUPETZ ............................ 240
Toxic Effects of Pesticides
The Effect of Maneb, Zineb and Ethylenethiourea on the Humoral Activity of the Pituitary
Thyroid Axis in Rat
A. LAISI, R. TUOMfNEN, P. MANNISTO, K. SAVOLAINEN, and J. MATTILA. . . . . . . . . . . . . . . . . . 253
Toxicokinetics of the Herbicide Dichlorprop and its Leucinate and Their Action on Liver Mixed
Function Oxidases
H. BEITZ, U. BANASIAK, S. GERICKE, and P. CLAUSING. ... .. .. ... ... .. .. .... .. ... ..... . 259
VIII Contents
Organochlorines and Mercury in Blood of a Fish-Eating Population at the River Elbe in
Schleswig-Holstein, FRG
A. LOMMEL, H. KRUSE, and O. WASSERMANN ......................................... 264
Pesticide-Drug Interaction in Rats
G. FENYVESI, M. BOTOS, and J. IVAN................. ..... ....... ........ .. ...... ... 269
Dithiocarbamate Fungicides Decrease Histochemical Reactivity of Cholinesterases in the Gut
Wall of Rat
K. SAVOLAINEN and H. HERVONEN .................................................. 272
Biochemical Study of Muscle Samples from Chicken Embryos Affected by Wofatox 50 EC
E. DELI, L. SOMLYAY, and L. VARNAGY ..... ..... ..... ........ .... .. ........ ...... ... 277
Investigation of Adrenal Steroid and 25-hydroxy-cholecalcipherol in Human Gramoxone
Poisoning
J. BARsoNY and F. KERTESZ ....................................................... 280
Group Intoxication with Gramoxone (Paraquat) Toxicological and Pathohistological Aspects
L. HARSANYI, A. NEMETH, and A. LANG ............................................. 284
The Genetic Control of Paraquat Sensitivity of H-2 Congenic and Recombinant Mice
A. NEMETH, P. NEMETH, L. HARSANYI and A. LANG ................................... 285
The Effect of Light on the Toxicity of Paraquat in the Mouse
K. BARABAS, L. SZAB6, B. MATKOVICS, and G. BERENCSI .. .. ... ....... ........ ........ . 287
Changes of the Serum Superoxide Dismutase Content of Gramoxone Poisoned Patients,
Measured by Anti-SOD Monoclonal Antibody
P. NEMETH, L. RAcz, J. VARGA, A. LANG, A. NEMETH, and A. NEMETH.................. 288
Cardiodepression in Organophosphate Poisonings
G. MAROSI, J. IVAN, and L. NAGYMAJTENYI .......................................... 289
The Effect ofOrganophosphoric Pesticides on T -and B-Lymphocytes and Antibody Production
in Mice
B. TIEFENBACH and P. LANGE ...................................................... 292
Toxicity Study of the Insecticide Ekalux 25 EC in Rats
K. NAGY, M. BED6, M. Antal, J. SzEPVOLGYI, and A. J. N. ZSINKA 294
Effect of Different Antidotes in Ekalux 25 EC Poisoned Male Rats
J. M. SZEBERENYI and K. LEHOTZKY ................................................ 295
Assessment of Acute Neurotoxic Effects of Different Kinds of Pesticides in Mice
M. KARMos-VARSZEGI and I. DESI .................................................. 297
Subacute and Subchronic Toxicity of Dietary Bendiocarb in Rats
N. K. NESKOVIC, M. VUlcSA, V.RADoNnc, D. STOJlC, D. JANKOVIC, and S. LJ. VITOROVI .. . 298
Effect of Lethal Dose of Trichlorphon on Different Biochemical and Physiological Parameters
of Common Carp (Cyprinus Carpio L.)
Z. JENEY, G. JENEY and J. OLAM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
Contents IX
Chlorate Poisoning: Mechanism of Toxicity
C. S'I'JlFFEN and E. SINGELMANN .................................................... 300
Effect of Nabam and Ethylenethiourea on the Urinary Output of Rats
K. SAVOLAINEN, S.-L. PELTONEN, and O. MUONA...................................... 301
Decis and Perocin Influence on the Activity of Serum Monoamine-Oxidase in Greenhouse
Workers
Z. ZAPRIENOV, V. PENEVA, D. CoNEVSKI, A. BAINOVA, C. KOZUHAROVA, B. DRAGNEv, and
P. MOSHOEVA .................................................................... 303
Immunotoxicological Investigation of the Effects of a Pesticide; Cypermethrin
I. DEsI, L. VARGA, I. DOBRONYI, and G. SZKLENARIK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Heavy Metal Toxicity
Effect of Some Heavy Metal Salts on Hepatic Mono-Oxygenases After Subchronic Exposure
M. B. KADIISKA, T. S. STOYTCHEV and E. A. SERBINOVA ............................... 313
Intestinal Absorption of Aluminium in Rats
G. B. VAN DER VOET and F. A. DE WOLFF. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
The Formation of Glutathione-Chromium Complexes and Their Possible Role in Chromium
Disposition
H. J. WmGAND, H. OTTENWALDER, and H. M. BOLT .................................. 319
Long-Term Exposure to Cadmium and Cardiovascular Alterations in the Rabbit
M. CARMIGNANI and P. BoscoLO ................................................... 322
Lack of Substantial Neuroendocrine Changes in Short-Term
High Dose Cadmium Treated Rats
G. DE NATALE, A. LUCISANO, S. DAMIANO, D. CAPONE, and G. BASILE 327
Effect of Cadmium on Proteins
M. STANKOVIC, B. STANffiIC, and A. P. GRUJIN 329
Interaction of Tin and Zinc in Some Processes of Heme Biosynthesis in Rabbits
G. ZAREBA and J. CHMlELNICKA .................................................... 330
The Effect of Chronic Thallium Administration on Testicular Enzyme Activities in the Rat
C. GREGOTTI, L. FORMIGLI, A. DI NUCCI, P. POGGI, C. ROCCIO, R. SCELSI, L. MANZO,
and F. BERTE .............................................. :..................... 332
MisceUaneous Toxicological Studies
The Effects of Methylg1yoxal on Central Synaptic Transmission in the Isolated Nerve Cord
of the Cockroach (Periplaneta Americana L.)
P. L. CHAMBERS, M. G. DAVIES, and M. J. ROWAN. .. . . . . .. .. . . . .. . . . . . . . . . .. . . . . .. . . . 337
The Role of Bile Acids in the Effect of Ethinylestradiol on the Biliary Excretion Rate of
Exogenous Organic Anions
A. PFEiFENR6rn, E. FISCHER, and F. VARGA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
x Contents
Substrate and Phenobarbital Induction of the Biliary Excretion of Exogenous
Organic Anions in Rats
E. FISCHER and F. VARGA ......................................................... 345
The Biliary EliInination of Sulfamerazin in Rat and Man - A Comparison
T. GRAMAT'I1!, B. TEirnAAG, E. FISCHER, and F. VARGA ............... . . . . . . . . . . . . . . . . . 348
Preclinical Safety Studies with Temofel, a New Choleretic Compound
E. CHOLNOKY, D. DANYI, K. ANvos, E. L. HEGYI, E. HERENDY, and S. KNEFFEL 351
Studies on Hyperoxaluria and Oxalate Stone Formation Induced by 2-Acetyl-3-Phenyl
Tetrahydro-1,2,4-0xadiazim-5-on
K. ANYos, L. NOOT, R. S. LUKAcs, L. CSALAY, and E. CHOLNOKY ..................... 357
The Biliary Elimination of Indomethacin in Man
B. TERHAAG ..................................................................... 359
Increased Response of Cytochrome P-450 Dependent Biotransformation
Reactions in Rat Liver to Repeated Administration of Inducers
U. KLEEBERG, M. SOMMER, and W. KLINGER ......................................... 361
Influence of Pyrazolones on Hepatic Glutathione in Rats
E. BIEN and M. WrIT ............................................................. 366
Comparative Study on the Sensitivity of Several Serum Enzymes in Detecting
Hepatic Damage in Rats
M. BAUMANN and M. BERAUER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370
The Metabolism of Some Xenobiotics in Germ-free and Conventionalized Rats
R. MACHOLZ, M. KUJAWA, J. SCHULZE, H. J. LEWERENz, and W. SCHNAAK .............. 373
The Effect of Prostacyclin on the Liver
G. A. BALINT, G. KAUCSONY, A. PAP, and V. VARR6 ................................. 377
Role of Vitamins in Biotransformation of Xenobiotics
P. I. LUKlENKo, M. I. BusHMA, and L. I. SUSHKO ..................................... 379
Possible Adrenal Involvement in Hydroxyurea Toxicity Defense Mechanisms
P. PREZIOSI, A. NUNZIATA, S. MACRAE, E. RAGAZZONI, and M. VACCA.... ............... 380
Replacement Therapy Against Increased Hydroxyurea Toxicity in Pituitary
or Adrenal Ablated Rats
M. VACCA, N. DE GORI, R. DEL CARMINE, P. L. NAVARRA, and P. PREZIOSI 385
Testicular Toxicity of Antineoplastic Drugs During Postnatal Development of the Rat
R. BECHTER, R. H. MATTER, R. A. ETTLlN, and R. L. DIXON . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
Free and Bound Testosterone in Male Heroin Addicts
S. LAFISCA, G. BOLELLI, F. FRANCESCHETTI, A. DANIELl, F. TAGLIARO, M. MARlGO,
and C. FLAMIGNI ................................................................. 394
Effect of Single Treatment of Rats with Procarbazine on the Pituitary-Testicular Axis
R. A. ETTLlN, F. HAnZISELlMOVlC, and U. HENNES .................................... 398