Table Of ContentArchives of Toxicology, Supplement 17
Toxicology
in Transition
Proceedings of the
1994 EUROTOX Congress
Meeting Held in Basel, Switzerland, August 21-24, 1994
Edited by the Publication Committee
G. H. Degen, J. P. Seiler and P. Bentley
With 104 Figures and 59 Tables
, Springer
Gisela H. Degen
Institut fUr Arbeitsphysiologie an der Universitat Dortmund
Ardeystr.67
0-44139 Dortmund
Jurg P. Seiler
Interkantonale Kontrollstelle fUr Heilmittel
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Philip Bentley
Ciba-Geigy Ltd.
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Contents
Genetically Modified Cells and Animals in Toxicological Research
Concepts, potentials, methods for constructing transgenic cells
and animals -Introduction
K. Biirki ................................................................................................................. 3
Use of recombinant cells in metabolic and mechanistic studies
(analysis of pathways)
W. A. Schmalix and f. D6hmer... ......................................................................... 8
Applications for transgenic animals in toxicology
D. Brusick ............................................................................................................ 23
The Benchmark Dose Concept
Principles, benefits and limitations of the NOEL approach
D.l. Esdaile .......................................................................................................... 37
Comparison of benchmark doses (BMD) with no-observed-adverse
effect-levels (NOAEL) and low-observed-adverse-effect-levels (LOAEL)
for subchronic studies
R. S. Nair. M. W. Stevens. M. A. Martens. and f. Ekuta..................................... 44
Bioindicators in Ecotoxicology
Bioindicators in ecotoxicology: an overview
f. Lopez-Barea........ ... ................ ................................................................. ........ 57
Use of cytochrome P450 lA in fish as a biomarker of aquatic pollution
A. Goksf/Jyr ..... ....... ..... ....... ..... ..... .............. ..... ..... ....... ....... ... ......... ..... ....... ..... ..... 80
Receptor-mediated toxicity
Cellular and molecular biology of aryl hydrocarbon
(Ah) receptor-mediated gene expression
S. Safe and V. Krishnan......... ........................ ..................................................... 99
Inhibitors of the sodium pump: toxins, then drugs, and now hormones
f.-D. Horisberger .............................................................................................. 116
Rodent responses to peroxisome proliferators -
a receptor-mediated phenomenon?
f. D. Tugwood .................................................................................................... 125
VI
Role of second messengers in mineral particle-induced production
of reactive oxygens species by phagocytes
K. Savolainen and M. Ruotsalainen .................................................................... 134
Estrogenic effects of some xenobiotics
M. Vargova, M. Gajdova, J. Jakubovsky, and L. Ws6lova ............................... 148
In Vitro tests in regulatory toxicology
In Vitro methods in regulatory toxicology: the crucial
significance of validation
M. Balls ............................................................................................................. 155
Scientific, ethical and legal aspects of the acceptance of
in vitro methods in regulatory toxicology
E. Walunl ............................................................................................................ 163
The validation and use of in vitro teratogenicity tests
R. Bechter ........................................................................................................... 170
In Vitro methods in regulatory toxicology
R. Bass ............................................................................................................ 192
In Vitro tests in regulatory toxicology: symposium chairman's summing-up
M. Balls .............................................................................................................. 205
Ex Vivo and in Vitro Models in acetaminophen hepatotoxicity studies.
Relationship between glutathione depletion, oxidative stress and disturbances
in calcium homeostasis and energy metabolism
S. Ellouk-Achard, V. Levesse, C. Martin, C. Pham-Huy, H. Dutertre-
Catella, M. Thevenin, 1.-M. Warnet, and 1. R. Claude .................................... 209
Rabbit renal proximal tubule suspensions as a model for nephrotoxicity
evaluation of native or in situ metabolized B-Iactam antibiotics
H. Dutertre-Catella, C. Martin, M. Debray, C. Pham-Huy, M. Thevenin,
1.M. Warnet, R. A. Podevin, and 1. R. Claude ................................................ 215
Neurobehavioral abnormalities induced by substance abuse
Neurobehavioral abnormalities induced by prenatal exposure to
substances of abuse -stating the problem
J. Elsner .............................. .............................................................................. 221
Prenatal exposure to marihuana and tobacco during infancy, early
and middle childhood: effects and an attempt at synthesis.
P. A. Fried.. ....... ..... ..... ................... ....... ....... ... ....... .......... ......... ..... ............ ....... 233
Delayed developmental neuro-and immunotoxicity of benzodiazepines
M. SchlumpJ, R. Parmer, E. E. Butikofer, S.lnderbitzin, A. R. Salili, A . .A.
Schreiber, H. R. Ramseier, H. van Loveren, and W. Lichtensteiger .................. 261
VII
Changes of EEG of freely-moving rats caused by three generation
organophosphate treatment
L. NagynUlijtbzyi ................................................................................................ 288
Developmental neurotoxicity of carbon monoxide
M. R. Carratu. R. Cagiano. M. A. De Salvia. L. Trabace. and V. Cuomo .......... 295
Safety assessment of over the counter (OTC) products
The safety assessment of over the counter (OTC) products
B. Schnlid ........................................................................................................... 305
OTC pharmaceuticals and genotoxicity testing: the paracetamol,
anthraquinone, and griseofulvin cases
L. Miiller ........................................................................................................... 312
Safety assessment of OTC products: doxylamine succinate
1. A. Skare.......................................................... ............................... ................ 326
Safety assessment of OTC products: a regulatory view
P. Sjoberg ........................................................................................................... 341
Drug toxicity findings and no action taken
F. W. Wolff. ...................................................................................................... 346
Species specificity of organ toxicity
Species specificity of organ toxicity
W. Butler .............. ........................................................................... ............ ...... 351
Species specificity at the molecular level: the case of nitric oxide synthase
E. Felley-Bosco . ................................................................................................ 357
Mechanisms underlying species-specificity in target organ specificity
E. A. Lock. . ....................................................................................................... 367
Species specificity of organ toxicity: behavioral differences
G. Bignami. G. Dell 'Onw. and E. Alleva .......................................................... 375
Terrestrial ecotoxicity of chemical substances
Development of OECD test guidelines and hazard assessment
procedures for terrestrial effects
N. Grandy....... ............ ............... ..................... .................... .............. ................. 397
Development of guidance for terrestrial effects assessment
L. Sams¢e-Petersen and F. Pedersen ............................................................... 406
VIII
Application of quick and simple plant bioassays to assess the genotoxicity
of environmental pollutants -Detection of potential health hazards of air,
water and soil contaminants
T.-H. Ma ......................................................................................................... 420
Comparison of susceptibility to chemicals (pesticides) of species
used for human and environmental effect assessment
W. Pfluger ........................................................................................................ 434
Toxicological evaluation of pollutants in soil -concept of the
AGU and assessment of tolerable concentrations for metals
B. Liebl. U. Schwegler. E. Roscher. and G. Kerscher ..................................... 446
Immunodeficient mouse systems
scm
The (severe combined immnodeficiency) mouse -its
biology and use in immunotoxicological research
M. Lf/Jvik ............................................................................................................. 455
scm
The mouse as a tool to bridge the gap between animal
and human responses
H. Van Loveren and C. De Heer ........................................................................ 468
scm
The mouse and its use in immunopharmacological and
immunotoxicological investigations
C. H. Ladel. H. Puschner. and U. Bamberger .................................................. 472
Stereochemical effects
Chirality -from molecules to organisms
J. P. Seiler ......................................................................................................... 491
Interactions between the in vitro metabolism of xenobiotics and fatty acids.
The case of ibuprofen and other chiral profens.
J.M. Mayer. B. Testa. M. Roy-deVos. C. Audergon. and J.C. Etter ................ 499
Side effects and toxic reactions of chiral drugs: a clinical perspective
M. Eichelbaum ................................................................................................ 514
Analysis of (S)-and (R)-propanolol in human plasma and urine by a
specific immunoenzymtic assay versus HPLC
C. Pham-Huy. A. Sahui-Gnassi. F. Massicot. H. Galons. H. Dutertre-
Catella. B. Radenen. J.M. Warnet. H. T. Duc. and J. R. Claude .................. 522
Biological behavior of prestages of cancer cells
Biological behavior of prestages of cancer cells: an introduction
R. Schulte-Hermann ........................................................................................ 531
IX
Preneoplastic lesions in kidney and carcinogenesis by
non-genotoxic compounds
D. R. Dietrich and T. Rasollyi ...................................................................... 536
Early cellular alterations in chemical liver carcinogenesis as assessed
by immunohistochemical and molecular biological techniques
H. S. Huitfeldt .................................................................................................. 547
Late Manuscripts
The UK approach to the regulation and evaluation of novel foods
produced by biotechnology
D. A. Jonas ...................................................................................................... 557
Young Scientists Poster Award
Molecular mimikry of CF3CO-Iysine by lipoic acid I: the dehydrolipoamide
acetyltransferase subunit of the human pyruvate dehydrogenase as
autoantigen in halothane hepatitis
U. Christen and J. Gut ...................................................................................... 565
Molecular mimikry of CF3CO-Iysine by lipoic acid II: lipoic acid bearing
proteins as autoantigen in halothane hepatitis
N. Frey, V. Koch, and J. Gut ............................................................................. 566
Subject Index .............................................................................................. 567
Genetically Modified Cells and Animals in
Toxicological Research
(Chair: Dr. K. Biirla, Switzerland)
