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Archives of Toxicology, Supplement 4
Further Studies in the Assessment of Toxic Actions
Proceedings of the European Society of Toxicology Meeting Held in Dresden, June 11-13, 1979
Edited by
P. L. Chambers and W. Klinger
With 147 Figures
Springer-Verlag Berlin Heidelberg New York 1980
Dr. PHILIP L. CHAMBERS University of Dublin, Department of Pharmacology, Trinity College, Dublin 2, Ireland
Professor Dr. WOLFGANG KLINGER Friedrich-Schiller-UniversiHit Jena, Institut flir Pharmakologie und Toxikologie, DDR-6900 Jena, GDR
ISBN-13: 978-3-540-10191-8 e-ISBN-13: 978-3-642-67729-8 DOl: 10.1007/978-3-642-67729-8
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law, where copies are made for other than private use, a fee is payable to the publisher, the amount of the fee to be determined by agreement with the publisher. © by Springer-Verlag Berlin Heidelberg 1980
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
2123/3130543210.
Contents
Testing for Mutagenicity and Carcinogenicity 1
Assessment of Mutagenicity Tests G. ROHRBORN ................................................... 3
Testing of Medicines for Their Mutagenic Potency. Proposition from a French Working Party (Abstract) G. RAYNAUDand D. MARZINetal. ................................... 10
Monitoring the Occupational Exposure to Mutagens by the Cytogenetic Analysis of Human Peripheral Lymphocytes in vivo R. J. SRAM and N. P. KULESHOV ..................................... 11
Elevated Mitotic Number in the Adrenal Cortex as a Reflection of Early Events in Growth Induction by Carcinogens and Promoters - A Possible Short -Term Assay M. DANZ and H. URBAN ........................................... 19
Sister Chromatid Exchanges in Chinese Hamster Embryonic Liver Cells Exposed Transplacentally to Bromodeoxyuridine (BrdU) and Chemical Mutagens A. BASLER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Differences in Carcinogenicity After Transplacental and Postnatal Administration of Drugs and Pesticides R. WARZOK, J. MENDEL, R. THUST, E.-M. BLAUFUSS, H. BATKA, and H. SCHWARZ ................................................... 25
Combination Effects in Chemical Carcinogenesis D. SCHMAHL. With 2 Figures ....................................... 29
Chromosome Aberration Tests with Chinese Hamster Cells in vitro with and without Metabolic Activation - A Comparative Study on Mutagens and Carcinogens M. ISHIDATE, Jr., and K. YOSHIKAWA. With 1 Figure. . . . . . . . . . . . . . . . . . . . . 41
VI Contents
Ligand Binding of Safrole to Cytochrome P-450 M. DELAFORGE, C. IOANNIDES, and D. V. PARKE. With 2 Figures
Testing of Drugs for Combined Mutagenesis with Sodium Nitrite in the Hostmediated Assay
45
R. BRAUN, J. SCHONEICH, and D. ZIEBARTH. With 1 Figure ................ 49
Biotransformation and Spectral Interaction of Xenobiotics with Subcellular Fractions from Drosophila Melanogaster A. J. BAARS, J. A. ZIJLSTRA, M. JANSEN, E. VOGEL, and D. D. BREIMER. With 1 Figure ........................................................ 54
Mutagenicity of DNOC in Drosophila Melanogaster J. MOLLER and R. HABERZETIL .................................... 59
Standardization of Clastogenicity and SCE Assays on Mammalian Cells in vitro - Results and Problems (Abstract) R. THUST, J. MENDEL, S. KNEIST, and R. WARZOK ...................... 62
Influence of Experimental Factors on the Mutagenicity of Vinylic Monomers F. PONCELET, C. DE MEESTER, M. DUVERGER-VAN BOGAERT, M. LAMBOTIE-VANDEPAER, M. ROBERFROID, and M. MERCIER. With 2 Figures. . . . . . . . . . . 63
Modification of Mutagenic Activity of Anticancer Drugs (Abstract) J. REVAZOVA, L. RADCHENKO, and G. MURAVNIK ........ . . . . . . . . . . . . . . 67
Mutagenic Activity in Foundry Air E. SKYTIA, R. SCHIMBERG, and H. V AINIO. With 2 Figures
The Effect of Carcinogens and Non-Carcinogens on Some Biochemical Features of the Mouse Lung Tissue (Abstract)
68
1. ARANY, P. RADY, F. BOJAN, and P. KERTAI ............ . . . . . . . . . . . . . . 73
Attempt to Develop New Mouse Colony with High Susceptibility to Carcinogens F. BOJAN and P. KERTAI ........................................... 74
Metabolizing Activities of Postmitochondrial Liver Fractions (S-9) on Benzo[ a]Pyrene and Dimethylnitrosamine B. TEICHMANN, G. BUTSCHAK, G. SCHEUNIG, and S. KOHLER. With 2 Figures 77
Reduced Induction of Pyruvate Kinase After Feeding 2-Acetylaminofluorene W. FISCHER and E. GRUND. With 1 Figure ............................ 81
Chemical Carcinogens: Screening, Testing, Risk Assessment for Man (Abstract) T. SCHRAMM and B. TEICHMANN ................................... 83
Studies on the Detection of Chemical Carcinogens Using a Mammalian Cell Transformation Assay. A Correlated Study of BHK Cell Transformation and Bacterial Mutagenicity R. STROBEL, W. GREB, and G. ROHRBORN. With 3 Figures. . . . . . . . . . . . . . . 84
Contents VII
Chronic and Carcinogenic Study of Trinitroglycerin in Rats, Mice and Dogs (Abstract) J. C. DACRE, c.-c. LEE, H. V. ELLIS III, and c.-B. HONG .. ~ . . . . . . . . . . . . . 88
Induction of Pituitary Tumours and Hyperprolactinemia in Female Rats by Estrogens. The Effect of Apomorphine, Reserpine and L-DOPA M. KOCH, M. OETTEL, H. LAUTERBACH, and H. FREUND ................ 89
Testing for Influence on the Immunological System ....................... 93
Immunotoxicity Assessment: Screening and Function Studies J. G. VOS. With 4 Figures .......................................... 95
Immunopharmacology and its Toxicological Problems J. STERZL. With 8 Figures .......................................... 109
Some Approaches to Experimental Testing of Drugs for Immunotoxicity R. OVTCHAROV, G. GUENTCHEVA, and S. MICHAILOVA. With 7 Figures 120
Biotransformation and Immunotoxicity P. LANGE, G. HENNIGHAUSEN, and U. KARNSTEDT. With 2 Figures
Effects of Toxicants on T-cell Sub populations as Determined by Lymphokine Activity
132
D. L. ARCHER, B. G. SMITH, and H. M. JOHNSON ....................... 138
A Simple Technique of Testing for the Influence of Metal Salts and Other Chemicals on Macrophages and Thymocytes in vitro G. HENNIGHAUSEN and P. LANGE. With 2 Figures. . . . . . . . . . . . . . . . . . . . . .. 143
Toxicity of Organotin Compounds in Chicken and Rats M. RENHOF, U. KRETZER, T. SCHDRMEYER, H. SKOPNIK, and F. H. KEMPER. With 2 Figures ...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 148
Inhibition of Immune Response by Diisopropyl Phosphorofluoridate T. LiS and J. MIERZEJEWSKI. With 2 Figures ........................... 151
Thymocyte Stimulating Activity of the Serum of Rats in the Early Phase After 2-Acetylaminofluorene (AAF)-Treatment R. BRAUER, M. DANZ, H. URBAN, and G. WALDMANN. With 1 Figure. . . . .. 156
Lysozyme (Muramidase) and Hemolytic Complement (CHsoU) in Sera of Beagle Dogs and Minipigs after Longterm Application of Different Preparations of Estrogens and Gestagens A. STELZNER, G. KLINGER, M. OETTEL, H. HOFFMANN, H.-G. HILLESHEIM, K.-H. CHEMNITIUS, E. SCHIMKE, and M. ZIEGER ...................... 159
The Effect of Acute Administration of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) on Humoral Antibody Production and Cell-Mediated Activities in Mice A. VECCHI, A. MANTOV ANI, M. SIRONI, W. LUINI, F. SPREAFICO, and S. GARA TTINI. With 1 Figure ........................................ 163
VIII Contents
Quantitative Development of Immunoglobulin (IgG) During Life-Span of Male and Female Laboratory Rat (Abstract) R. SCHADE. . . . . . . . .. . . .. . . . . . . . . .. . . . . . . . . . . . . . . . . . .. . . .. . . .. . .. 166
Studies on the Action of Dimethoate on the Immune System B. llEFENBACH and P. LANGE. With 3 Figures. . . . . . . . . . . . . . . . . . . . . . . .. 167
The Effect of DDVP, an Organophosphorus Pesticide, on the Humoral and CellMediated Immunity of Rabbits I. DESI, L. VARGA, and I. FARKAS. With 2 Figures ...................... 171
The Relationship Between the Length of the Alkyl Chain of Dialkyltin Compounds and their Effects on Thymus and Bile Ducts in Mice G. HENNIGHAUSEN , P. LANGE, and J. MERKORD ....................... 175
Allergic Encephalomyelitis in Rats - Toxicity Assay for Pertussis Vaccines H. RONNEBERGER and O. ZWISLER .................................. 179
Testing for Nephrotoxicity .......................................... 185
Some Aspects of Testing Drugs for Nephrotoxicity in Rats I. BEREZOVSKAYA, A. BELOSHAPKO, M. VLASOVA, A. KINZYRSKY, and V. RYMARTSEV. With 2 Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 187
Nephrotoxicity of Drugs, Evaluated by Renal Enzyme Excretion Studies W. RAAB. With 1 Figure ........................................... 194
Urinary Enzyme Excretion and Changes in Renal Functions Induced by Toxic Substances or by Renal Ischemia in Rats F. ANSERMET, C. MIEVILLE, and J. DIEZI. With 2 Figures ............ . . . .. 201
Stimulation of Kidney Function in Rats Injured by Nephrotoxic Agents M. STOPP, C. FLECK, C. WEISE, and H. BRAUNLICH. With 6 Figures. . . . . . .. 208
Relationship Between Exposure to Heavy Metals and Prevalence of Renal Dysfunction J. P. BUCHET, R. LAUWERYS, H. ROELS, and A. BERNARD. . . . . . . . . . . . . .. 215
Nephrotoxicity of the Flame Retardant Tris (2,3-Dibromopropyl) Phosphate E. DYBING and E. SCDDERLUND. With 2 Figures. . . . . . . . . . . . . . . . . . . . . . . .. 219
Paper Presented by the Young Scientists Award Winner 1979: Evaluation of Renal Dysfunction Induced by Cadmium in Man by Determination of Enzymes and Specific Proteins in Urine A. BERNARD. With 3 Figures ....................................... 223
Testing of Drugs for Nephrotoxicity. General Principles and Minimal Criteria H. BRAuNLICH ................................................... 233
Contents
Testing for Embryotoxicity
Hydroxyurea as a Reference Standard in Teratological Screening. Comparison of the Embryotoxic and Teratogenic Effects Following Single Intraperitoneal or Repeated Oral Administrations to Pregnant Rats
IX
237
V. ALIVERTI, L. BONANOMI, and E. GIAVINI. With 1 Figure .............. 239
Embryotoxic Effects of Post-Coital Fertility Inhibiting Steroids M. OETIEL, A. KURISCHKO, J. STRECKE, and M. KOCH. .... . .... . .... .. 248
Subtle Consequences of Prenatal Exposure to Low Carbon Disulphide Levels S. T ABACOVA and L. BALABAEV A ................................... 252
Behaviour Teratology Tests (Abstract) T. VERGIEV A and CH. ZAIKOV ...................................... 255
Testing for Embryotoxicity R. BASS and D. NEUBERT. With 2 Figures 256
Morphogenetic Systems and Screening for Embryotoxicity R. JELINEK and Z. RYCHTER. With 4 Figures. . . . . . . . . . . . . . . . . . . . . . . . . .. 267
The State and Future Requirements of Teratogenic Testing D. WENDLER. With 6 Figures ....................................... 274
Behavioural Tests in Peri- and Post-Natal Toxicity Study in Rats of Trithiozine [4-(3 ,4,5-trimethoxythiobenzoyl)-tetrahydro-1 ,4-oxazine] O. FORMENTI and A. GAMBA ....................................... 284
Influence of Thalidomide on Alkaline (AP) and Acid (ACP) Phosphatase Activities in Rat Fetuses and Mothers (Abstract) A. Dl'.UZNIEWSKI, L. GASTOl'.-LEWINSKA, A. GR6DECKA, and B. KRASNICKA 288
Experiences with a Three Step Test Scheme for Embryotoxicity and Teratogenicity H. HEINECKE, S. KLAUS, and J. GOTTNER. With 1 Figure................. 289
Postnatal Effects of Oral Administration of Ethylenethiourea to Rats During Late Pregnancy H. J. LEWERENZ and D. W. R. BLEYL ................................ 292
Activity of Some Mixed Function Oxidases in Prenatally Carbon Disulphide (CS2)
Treated Rats B. NIKIFOROV and S. TABACOVA .................................... 296
Free Communications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 299
Endocrine Aspects of Ozone Exposure in Rats G. K. CLEMONS and J. F. GARCIA. With 1 Figure 301
x Contents
Significance of Mode of Exposure in Aerosol Inhalation Toxicity Studies - Head only Versus Whole Body Exposure K. SACHSSE, K. ZBINDEN, and L. ULLMANN. With 2 Figures ............... 305
Pharmacokinetic Studies with 3H-Cytisine H.-P. KLOCKING, M. RICHTER, and G. DAMM 312
Kinetics of Benzene Metabolism in Rats in Inhalation Exposure I. GUT and E. FRANTfK. With 2 Figures ............................... 315
Estimation of Occupational Exposure to Phenoxy Acids (2,4-D and 2,4,5-T) B. KOLMODIN-HEDMANN and K. ERNE. With 2 Figures. . . . . . . . . . . . . . . . .. 318
Acrylonitrile Metabolism in the Rat J. KOPECKY, I. GUT, J. NERUDovA, D. ZACHARDovA, V. HOLECEK, and J. FILIP ......................................................... 322
Changes of Pharmacokinetics and Metabolism of Sulfadimidine in Endotoxin Pretreated Rabbits R. LAPKA, M. LANGMEIEROV A, J . VANECEK, and H. RASKOV A. With 2 Figures 325
Effect of Hydrocortisone on Oxidative Degradation of Hexobarbital and Ethylmorphine L. TANCHEVA and T. STOYTCHEV. With 1 Figure. . . . . . . . . . . . . . . . . . . . . .. 328
Study of the Protective Effect of an Anabolic Steroid, 19-Nortestosterone Phenylpropionate (19-NTPP), on the Fatty Liver Induced by High Doses of Rifampicin in the Rat A. PIRIOU, A. JACQUESON, M. THEVENIN, J.-M. WARNET, and J. R. CLAUDE 331
Comparative in vitro Investigations on the Dialysability of Hypnotic and Psychotropic Drugs by Hemodialysis and Controlled Sequential Ultradiffusion A. BALOGH, R. FONFSroCK, L. KANGAS, U. DEMME, H. SPERSCHNEIDER, A. TRAEGER, G. STEIN, and A. PEKKARINEN. With 1 Figure. . . . . . . . . . . . . .. 335
The Excretion of Ascorbic Acid and Hippuric Acid in the Urine of Rats with Liver Injury E. BIEN, G. SKORKA, R. KONDIGER, and R. MOLLER. With 1 Figure .. . . . . . .. 338
Evaluation of Liver Function Tests After Administration of Aminophenazone E. BIEN, G. SKORKA, and P. BUNTROCK ". . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 341
Effects of Some Cholephilic Agents on Hepatic Mitochondrial Respiration and Biliary Excretion E. FISCHER, Z. GREGUS, and F. VARGA .............................. 343
The Fate of Propoxur in Rat W. Foss and J. KRECHNIAK. With 2 Figures
Different Role of Biotransformation in the Elimination of Some Important Pharmaceuticals and Industrial Xenobiotics
346
I. GUT. .... ..... . .... . . .. . . ... . .... ..... . ..... ...... ... . ..... . .. 350
Contents XI
The Effect of Heavy Metals (Lead, Manganese, Mercury) on the Concentration of Free Amino Acids in the Liver of Rats L. HALATCHEVA and P. NIKOLOVA. With 1 Figure. . . . . . . . . . . . . . . . . . . . .. 355
Involvement of Phenolic Metabolites in the Irreversible Protein-Binding of 14C_ Bromobenzene Catalysed by Rat Liver Microsomes S. HESSE, T. WOLFF, and M. MEZGER. With 3 Figures .................... 358
Effect of Acute Intoxication with Some Heavy Metals on Drug Metabolism M. KADIISKA and T. STOYTCHEV. With 1 Figure. . . . . . . . . . . . . . . . . . . . . . .. 363
Single Intravenous Dose Kinetics and Accumulation of Atenolol in Patients with Impaired Renal Function and on Hemodialysis W. KIRCH, M. SCHAFER, and M. BRAUN. With 2 Figures ................. 366
Hepatic Nuclear Protein Kinases in Young Rats Pretreated with 3-Methylcholanthrene J. SZEBERENYI, U. KLEEBERG, and J. GAAL. With 1 Figure ............... 370
Hepatic Nuclear Free and Engaged RNA-Polymerases in Young Rats Pretreated with 3-Methylcholanthrene U. KLEEBERG, J. SZEBERENYI, P. JUHASZ, A. TIGYI, and W. KLINGER. With 1 Figure ......................................................... 373
The Role of Metabolic Factors in the Interaction Between Opiates and Homopyrimidazoles in the Central Nervous System K. MAGYAR, L. G. HARSING, Jr., K. TEKES, and J. KNOLL. With 1 Figure 376
Research on Pharmacokinetics During Pregnancy H. NOSCHEL, G. PEIKER, R. VOIGT, P. MEINHOLD, B. MOLLER, S. SCHRODER, and A. BONOW ................................................... 380
Towards Standardization of the Reconstituted Mixed Function Oxidase Systems with Cytochrome P-450 M. M. SZUTOWSKI. With 1 Figure .................................... 385
Excretion of Nalidixic Acid via Mother's Milk A. TRAEGER and G. PEIKER. With 2 Figures
Effect of Insulin on the Biliary Excretion of Some Organic Anions in Rats
388
F. VARGA, J. MALLY, and E. FISCHER. With 2 Figures ................... 391
Aspects of Methodology Employed in the Investigation of Combined Chemical Effects on Acute Oral Toxicity P. CLAUSING and R. BIELEKE. With 1 Figure. . . . . . . . . . . . . . . . . . . . . . . . . .. 394
Modification of Toxicity of Violamycin BI (VBI) by Complex Formation with DNA, Metal Ions, and by Pretreatment with a-Tocopherol A. HARTL, E. KIRCHNER, W. F. FLECK, E. UNGER, and H. HOFFMANN. With 1 Figure ........................................................ 396
XII Contents
Comparative Studies on Cardiotoxicity of Some Anthracyc1ine Antitumor Antibiotics E. KIRCHNER, A HARTL, J. GUTINER, S. FRITSCH, and H. HOFFMANN. With 2 Figures ........................................................ 399
The Influence of Drugs on the Acute Toxicity of Cytisine H.-P. }(LOCKING, G. DAMM, and M. RICHTER .......................... 402
Requirements for Toxicological Evaluation of New Pesticides in Poland and the GDR (Abstract) R. KNAPEK and H. BEITZ .......................................... 405
Therapy of Acute Oral Poisonings by Organic Solvents: Treatment by Activated Charcoal in Combination with Laxatives W. LAASS. With 1 Figure ........................................... 406
Toxicity Evaluation of Water Soluble Substances of Dental Materials by Means of Cell Population in vitro G. NEUPERT and D. WELKER. With 1 Figure. ..... ..... .... . ... . ..... .. 410
Cardiotoxicity of Drugs Detected on Chicken Embryos M. PETERKA, R. JELINEK, and O. BENESOV A. With 1 Figure
The Effect of High Concentrations of Oxygen on Paraquat and Diquat Toxicity in Rats
413
I. S. PRATT, P. L. KEELING, and L. L. SMITH ........................... 415
Planning of Experiments for the Testing of Chronic Toxicity in Rats Taking into Account Biorhythms H. REX, D. KASTNER, and R. SCHADE.. .... . .... . .... . .... .... ..... .. 419
Acute and Cutaneous Toxicity of P-Chlorovinyl Ketones and Aldehydes in Rodents F. RIEMER, S. GRUTINER, G. HEGEWALD, A. STOLP, R. GUDIAN, E. SPIEGELBERGER, C. FIEBER, and A. GRISK
Cardiotoxicity from Orphenadrine Intoxications in Humans
G. W. FISCHER,
E. MALIZIA, L. SARCINELLI, M. PASCARELLA, M. AMBROSINI, M. SMERIGLIO,
421
and A. RUSSO. With 1 Figure ........................................ 425
Morphological and Biochemical Criteria for Evaluating Cytotoxic Effects of Antiviral Substances K.-D. THIEL, U. EICHHORN, H. SCHWEIZER, and R. }(LOCKING. With 2 Figures 428
Toxicological Effects of Steam-Sterilized High Lactose Diets on Conventional and Gnotobiotic Rats D. W. R. BLEYL, J. SCHULZE, and F.-K. GRDTTE. With 1 Figure. . . . . . . . . . .. 431
Effects on Mice of Numbers of Animals per Cage: An 18-Month Study (Preliminary Results) M. CHVEDOFF, M. R. CLARKE, J. M. FACCINI, E. IRISARRI, and A. M. MONRO. With 1 Figure .................................................... 435
Contents XIII
Toxicological Tests on the Safety of Fermosin for Pigs, a Novel Microbial Feed from Petroleum Distillate W. NETSCH, A. BUSCH, G. HORNAWSKY, W. LAUE, H.-J. RUMMLER, and A. STREY. With 2 Figures .......................................... 439
Nutritional Toxicological Studies with Lannate: Interactions with Caffeine and Ethanol M. SELMECI-ANTAL, M. BARTA-BEDO, G. CONSTANTINOVITS, K. NAGY, and J. SZEPVOLGYI. With 1 Figure ....................................... 443
The Occurrence of Carcinogenic Polycyclic Hydrocarbons in Foodstuffs in Hungary K. So6s. With 1 Figure ............................................ 446
An Evaluation of the Toxicity of Thiuram in Combination with other Pesticides B. WYSOCKA-PARUSZEWSKA, A. OSICKA, J. BRZEZINSKI, and I. GRADOWSKA 449
Testicular Atrophy Produced by Phthalate Esters T. J. B. GRAY and K. R. BUTTERWORTH. With 1 Figure
Different Pituitary Prolactin Cell-Stimulating Effects of Various Estrogens in Female Rats
452
H. G. HILLESHEIM, P. GOHLER, and J. GOTTNER . . . . . . . . . . . . . . . . . . . . . . .. 456
Changes in the Gonads, Reproduction and Generations of White Rats Under the Effect of Some Pesticides L. IVANOVA-CHEMISHANSKA and G. ANTOV .............. . . . . . . . . . . .. 459
Clofibrate and the Development of Rats M. NYITRAY, E. SZASZOVSKY, and A. DRUGA. With 1 Figure 463
Drug-Induced Histological Changes in Rat Seminiferous Tubular Epithelium A. ZSCHAUER and C. HODEL ....................................... 466
The Influence of Haloperidol Pretreatment on the Morphine Toxicity K. ANDREAS, H.-D. FISCHER, E. RUDOLPH, and G. BROSGEN. With 2 Figures 471
Neurochemical Alterations in Rat Brain as a Test for Studying the Neurotoxicity of Organophosphorus Insecticides J. BRZEZINSKI and B. WYSOCKA-PARUSZEWSKA. With 2 Figures. . . . . . . . . .. 475
Effects of Preceding Sensibilization by Reserpine and Haloperidol on Toxicity of Dopaminergic Agonists J. SCHMIDT and K. H. WESTERMANN. With 3 Figures. . . . . . . . . . . . . . . . . . . . .. 479
The Use of Radionuclides for Evaluation of Dermal Irritation with Drugs (Abstract) I. CIFKovA, L. SPRINCL, and D. WAITZovA ............................ 482
Influence of Gold Salts on the Content of Trace Elements in Serum of Patients with Rheumatoid Arthritis Under Sanocrysin Treatment H. DAWCZYNSKI, K. WINNEFELD, E. TANNER, and E. TENNIGKEIT. With 1 Figure 483
XIV Contents
The Influence of Acetylsalicylic Acid, Phenylbutazone, Indomethacin and Flufenamic Acid on the Kinetics of Leukocytes During Acute Inflammation C. CARAMANIS and D. D. VARONOS. With 5 Figures ..................... 485
Influence of Liver Enzyme Induction Caused by Diphenylhydantoin and Diazepam on Bone Mass of Rats CH. TESSEROMATIS, P. GALANOPOULOU, and D. VARONOS. With 6 Figures. .. 492
Author Index 499
Subject Index 503
Indexed in Current Contents
