Toxicology in Vitro An international journal published in association with BIBRA

Volume 8 1994

Volume Contents and Author Index

Pergamon

TOXICOLOGY IN VITRO

An international ,journal published in ussociation with BIBRA

Edir ors

DANIEL A~OSTA BAS .I. BLAAU~OEK Depurtment yf’ Phurnwcolog~ and Tosicolug.v, Rcseorch Institute of Tusicolog~~.

College of’ Phurmuc~~, University of Texm. Utrecht University. Yuleluan 2. Am/in. TX 78712. USA PO Bos 80.176. NL -3508

TD Utrecht. The Netherlunds

Associate Editor Review Editor STUART E. JAGGERS PHILIP A. BOTHAM

BIBRA Internutionul. Zenecu Centrul Tosicolug.v Luhorutor?: Woodrnunsterne Road. Curshulton. Alderkey Purk. Mucclesfield.

Surrey SM5 4DS. UK Cheshire SKI0 4TJ. UK

Editor Emeritus IAIN F. H. PURCHASE

Zenecu Central Tusicolozv Luhorutorv. Alderlev Park.

J. C. Barrett NIEHS, Research Triangle Park NC, USA

D. Beoford University of Surrey Guildford. Surrey, UK

J. Bradlaw FDA Washington, DC, USA

B. Ekwall University of Uppsala Uppsala, Sweden

R. Fahrig Fraunhofer-lnstitut fiir Toxikologie

und Aerosol-Forschung Hannover, Germany

J. L. Farber Thomas Jefferson University Philadelphia, PA, USA

S. D. Gangolli MRC Toxicology Unit Leicester, UK

T. J. B. Gray Sterling-Winthrop Research Centre Alnwick, UK

A. Guillouzo HBpital de Pontchaillou INSERM, Rennes, France

.*, Mucclesfield. Cheshire SKI0 2TJ. UK.

Managing Editor STELLA HILL

BIBRA Internutionul. Woodmunsterne Road, Carshulton, Surrer SM5 4DS, UK

International Editorial Board

G. C. Hard American Health Foundation Valhalla, NY, USA

S. Koontz Consumer Products Inc Skillman. NJ, USA

C. A. McQueen University of Arizona Tucson. AZ, USA

P. Maier Swiss Federal Institute of Technology

and University of Zurich Schwerzenbach, Switzerland

F. Marano Universite Paris 7 Paris, Cedex, France

M. Nagao National Cancer Center Research Institute Tokyo, Japan

K. Onozaki Nagoya City University Nagoya. Japan

J. A. Popp Sanofi Winthrop Inc., Collegeville, PA, USA

K. Ramos Texas A&M University College Station, TX, USA

A. A. J. J. L. Rutten TN0 Nutrition and Food Research

Institute Zeist, The Netherlands

M. A. Smith University of Texas Health Science Center Houston, TX, USA N. Stacey National Institute of Occupational

Health and Safety Sydney, Australia K. A. Stitzel The Procter & Gamble Company Cincinnati. OH, USA H. Tahti University of Tampere Tampere. Finland R. Ulrich The Upjohn Company Kalamazoo, MI, USA E. Walum University of Stockholm Stockholm, Sweden

A. A. Welder University of Oklahoma Oklahoma City, OK, USA F. Zucco Consiglio Nazionale Delle Ricerche Rome, Italy

Publishing Oflice Elsevier Science Ltd. Bdmpfyide Slreel. Exeter EXI 2AH. UK

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Editorial Announcements

D. E. Amacher and S. J. Schomaker

LIST OF CONTENTS

VOLUME 8 NUMBER I

111

1 Effects of hexachlorophene on myelin marker enzymes in rat oligodendrocytes

K. Cain and J. E. Gurney

M. T. D. Cronin, D. A. Basketter and M. York

13

21

Immunomagnetic purification of rat proximal kidney cells

A quantitative structure-activity relationship (QSAR) investigation of a Draize eye irritation database

J. Davies and J. K. Chipman 29 Relative importance of oxidation and Ca2+ in DNA strand break- age by H,O, in the 2sFou cell line

G. Diogene, A. Dubreuil, J. Ph. Breittmayer and S. Puiseux -Dao

37 Cytotoxic quantification of maitotoxin-like activity from the dinoflagellate Gambierdiscus toxicus

R. Jover, X. Ponsoda, J. V. Caste11 and M. J. Gdmez-Lechon

47 Acute cytotoxicity of ten chemicals in human and rat cultured hepatocytes and in cell lines: correlation between in vitro data and human lethal concentrations

M. Jurima-Romet, K. Crawford and H. S. Huang

S. M. Lawlor and N. M. O’Brien

55 Comparative cytotoxicity of non-steroidal anti-inflammatory drugs in primary cultures of rat hepatocytes

67 Development of an in vitro cell culture model to investigate the induction and quantification of oxidative stress and its inhibition by a-tocopherol

R. W. Lewis, J. C. McCall and P. A. Botham

75 Use of an in vitro test battery as a prescreen in the assessment of ocular irritancy

V. Mandys, R. TureEek, W. H. Gispen and P. R. Bar

81 Organotypic cultures of chick dorsal root ganglia in a semi-solid medium: a model for neurotoxicity testing

M. Marinovich, B. Viviani and C. L. Galli

The predominant role of surfactants in the modulation of toxicity of detergent products: an in vitro analysis of shampoos

K. Miiller, P. Kasper and L. Mtiller

91

99

109

117

125

131

I

11

Species differences in the time-dependent induction of unscheduled DNA synthesis in primary hepatocytes

H. Ninomiya, K. Kishida, Y. Ohno, K. Tsurumi and K. Eto

B. J. Phillips, A. C. Tee, P. A. Carroll, R. Purchase and D. G. Walters

Effects of cytosine arabinoside on rat and rabbit embryos cultured in vitro

Toxicity to Chinese hamster ovary (CHO) cells of the products of reaction of butylated hydroxyanisole with nitrite at low pH

E. Pilatte and D. Lison Effects of sulfur mustard on selected biochemical parameters of murine peritoneal macrophages in culture

L. Robbiano, A. Allavena, C. Bagarolo, A. Martelli and G. Brambilla

Comparison in human and rat hepatocytes of the DNA-damaging activity of five chemicals probably carcinogenic to humans

Announcements

Forthcoming Papers

iv TOXICOLOGY IN VITRO

VOLUME 8 NUMBER 2

S. Z. Abdel-Rahman,

A. M. Nouraldeen,

139 Acrylonitrile-induced reversible inhibition of uridine uptake by isolated rat intestinal epithelial cells

A. A. Abo-Elwafa and A. E. Ahmed

C. Clemedson, L. Romert, L. Odland, 145

I. Varnbo and E. Walum

Biotransformation of carbon tetrachloride in cultured neurons and astrocytes

P. F. T. Cumberland, M. Richold. I53 Further evaluation of a teratogenicity screen using an intravitelline

J. F. Parsons and M. K. Pratten injection technique

D. Decker and R. Harper

R. J. Edwards, C. L. Leslie and

N. H. Stacey

167

173

Evaluation of a three-dimensional human dermal model as a predictor of shampoo ocular irritation

Isolation of sinusoidal and canalicular liver plasma membranes: effects of frozen storage of human material

F. Gogot, B. Nihoul, I81

G. Van Maele-Fabry, F. Goethals

and J. J. Picard

Developmental toxicity of valproic acid assessed in a sequential culture of hepatocytes and embryos

M. H. Grant, C. Nugent and R. Bertrand

I91 Studies on nickel-induced inhibition of fibroblast growth

M. Giilden, H. Seibert and J.-U. Voss 197

H. E. M. G. Haenen, P. Rogmans, 207

J. H. M. Temmink and

P. J. van Bladeren

In vitro toxicity screening using cultured rat skeletal muscle cells. II. Agents affecting excitable membranes

Differential detoxification of two thioether conjugates of mena- dione in confluent monolayers of rat renal proximal tubular cells

T. Hayashi, H. Itagaki, T. Fukuda, 215

LJ. Tamura and S. Kato

Multivariate factorial analysis of data obtained in seven in vitro test systems for predicting eye irritancy

M. F. Hughes, H. L. Fisher,

L. S. Birnbaum and L. L. Hall

221 Effect of age on the in vitro percutaneous absorption of phenols in mice

M. Kotani, Y. Masamoto

and M. Watanabe

229 An alternative study of the skin irritant effect of an homologous series of surfactants

V. Masini, M. S. Noel-Hudson

and J. Wepierre

235 Free-radical damage by UV or hypoxanthine-xanthine oxidase in cultured human skin fibroblasts: protective effects of two human plasma fractions

S.-O. Mikalsen and K. R. Modalsli 243

A. Mint, S. A. M. Hotchkiss and 251

J. Caldwell

A simple fluorescence method for the study of the internalization of particles in cultured cells: application to asbestos and glass fibres

Percutaneous absorption of diethyl phthalate through rat and human skin in vitro

K. A. F. O’Brien, D. A. Basketter. 257

P. Jones and M. Dixit

An in vitro study of the eye irritation potential of new shampoo formulations

L. Odland, L. Romert, C. Clemedson 263

and E. Walum

Glutathione content, glutathione transferase activity and lipid peroxidation in acrylamide-treated neuroblastoma N I E I I5 cells

C. G. Rogers, C. Heroux- MetcaB’ and I. Langlois

269 Evaluation of cytotoxicity and genotoxicity of okadaic acid, a non-phorbol ester type tumour promoter, in V79 Chinese hamster lung cells

A. Rogister, Y. Vandenberghe and J. Roha

R. Roguet, C. Cohen, K. G. Dossou and A. Rougier

A. Sierra-Santoyo, M. L. Lripez, A. Hermindez and T. Mendoza - Figueroa

R. W. West and K. L. Rowland

Announcements

Forthcoming Papers

S. P. Aylward, T. M. Walker and C. K. Atterwill

D. G. Bechtel and L. E. J. Lee 317

G. S. Bondy, C. L. Armstrong, B. A. Dawson, C. H&roux-Metcalf, G. A. Neville and C. G. Rogers

V. G. Brunton, M. H. Grant and H. M. Wallace

D. E. Chapman, S. R. Michener and G. Powis

M. R. Cookson and V. W. Pentreath

E. Corsini, M. Marinovich, L. Marahini, E. Chiesara and C. L. Galli

R. L. Fisher, J. T. Sanuik, H. Nau, A. J. Gandolfi and K. Brendel

P. Gautheron, J. Giroux, M. Cottin, L. Audegond, A. Morilla, L. Mayordomo-Blanco, A. Tortajada, G. Haynes, J. A. Vericat, R. Pirorano, E. Gillio Tos, C. Hagemann, P. Vanparys, G. Deknudt, G. Jacobs, M. Prinsen, S. Kalweit and H. Spielmann

S. Ghatineh and J. A. Timbre11

TOXICOLOGY IN VITRO ”

277 Deoxyuridine suppression test on isolated rat bone marrow cells and the in vitro effect of bidisomide

283 Episkin, a reconstituted human epidermis for assessing in vitro the irritancy of topically applied compounds

293 Urea production in long-term cultures of adult rat hepdtocytes

301 In vitro transformation potential of N-polycyclic aromatic hydrocarbons in rat tracheal epithelial cells

11

VOLUME 8 NUMBER 3

309

329

337

343

351

361

371

381

393

Modulation of thyroxine uptake and efflux in vitro by temelastine and phenobarbital in cultured hepatocytes from different species, in relation to toxicological effects on the thyroid gland

Effects of aflatoxin B, in a liver cell line from rainbow trout (Oncorhynchus mykiss)

Toxicity of structurally related anthraquinones and anthrones to mammalian cells in vitro

Spermine toxicity in BHK-2l/CI 3 cells in the presence of bovine serum: the effect of aminoguanidine

Adenine and pyridine nucleotide concentrations and relationships to 2,6-dinitrotoluene metabolism in cultured rat liver slices

Alterations in the glial fibrillary acidic protein content of primary astrocyte cultures for evaluation of glial cell toxicity

Interleukin-1 production after treatment with non-ionic surfactants in a murine keratinocytes cell line

Comparative toxicity of valproic acid and its metabolites in liver slices from adult rats, weanling rats and humans

Interlaboratory assessment of the bovine cornea1 opacity and permeability (BCOP) assay

The biochemical effects and toxicity of hydrazine in cultured rat hepatocytes

VI

G. Groth, K. Kronauer and K. J. Freundt

F. D. Hayes and K. C. Breen

E. S. Hunter, III, J. A. Tugman, K. K. Sulik and T. W. Sadler

P. Maier, B. Saad and H. P. Schawalder

J. Miiller and S. Janz

M. S. Rahman, L. L. Hall and M. F. Hughes

D. Schiffmann and G. H. Degen

H. M. Schuller, M. Orloff and G. K. Reznik

M. Soijiiizzo and A. Visconti

M. P. Vinardell and M. Macicin

P. Yadav, D. Bhatnagar and S. Sarkar

J. G. Zhang and W. E. Lindup

L. Zolla, G. Lupidi and G. Amiconi

Review Paper P. Skett

Forthcoming Papers

401

407

413

423

431

441

449

455

461

467

471

477

483

491

I

TOXICOLOGY IN VITRO

Effects of NJ-dimethylformamide and its degradation products in zebrafish embryos

Glucocorticoid potentiation of lead neurotoxicity in the mouse HN9 hippocampal cell line

Effects of short-term exposure to ethanol on mouse embryos in vitro

Effect of periportal- and centrilobular-equivalent oxygen tension on liver specific functions in long-term rat hepatocyte cultures

In vitro cytotoxicity of neutrophil-like human HL-60 cells under- going an oxidative burst with Escherichia coli reporter strains

In vitro percutaneous absorption of sodium arsenate in B6C3F, mice

Effect of indanyl analogues of diethylstilboestrol on morphological transformation of Syrian hamster embryo fibroblasts and micro- nuclei in vitro

Effect of the dihydropyridine dexniguldipine on the epidermal growth factor-stimulated proliferation of human lung cancer cell lines

Anticholinesterase activity of the fusarium metabolite visoltricin and its N-methyl derivative

Comparative study of the HET-CAM test and the Draize eye test for assessment of irritancy potential

Effect of glucose on lipid peroxidation and antioxidant enzyme activities in rat liver slices

Effects of procaine and two of its metabolites on cisplatin-induced kidney injury in vitro: mitochondrial aspects

Effect of mercuric ions on human erythrocytes. I. Rate of haemolysis induced by osmotic shock as a function of incubation time

Problems in using isolated and cultured hepatocytes for xenobiotic metabolism/metabolism-based toxicity testing-solutions?

VOLUME 8 NUMBER 4

Third International Conference on Practical in vitro Toxicology

A. R. Boobis 505 Preface

Session l-Toxicological Mechanisms and Biokinetics (Chairman: P. Duffy)

J. B. Houston 507 Relevance of in vitro kinetic parameters to in riro metabolism of xenobiotics

TOXICOLOGY IN VITRO vii

D. T. Sladowski, S. J. Steer, L. Moore, A. Willshaw, R. H. Clothier and M. Balls

A. Delbancut, I. Lagroye and J. Cambar

B. G. Lake, J. A. Beamand, M. E. Cunninghame, S. Davies, H. Mistry and R. J. Price

R. U. Pendlington, D. L. Williams, J. T. Naik and R. K. Sharma

M. Jurima-Romet and H. S. Huang 529

K. Miiller, P. Kasper and L. Miller

A. Cooper, J. Fentem and M. Balls

V. Stone, D. J. Lankester, J. C. Wilton, R. Coleman

and J. K. Chipman

C. W. Seaman, C. D. N. Toseland, P. A. Maile, I. Francis and D. J. White

H. Marshall and C. N. Kind

J. A. Beamand, P. T. Wield, C. A. Morin, H. Mistry, S. Davies, R. J. Price and B. G. Lake

E. W. Scholes, R. (1. Pendlington, R. K. Sharma and D. A. Basketter

M. Moret, J. N. Lawrence and D. J. Benford

H. H. Bohets, E. J. Nouwen, M. E. De Broe and P. J. Dierickx

D. J. Van den Dobbelsteen, C. Toxopeus, C. W. M. van Holsteijn, H. A. Nooy, C. I. Droog,

G. J. M. J. Horbach, J. Noordhoek and B. J. Blaauboer

V. Seabra and J. A. Timbreil

C. J. Waterfield, M. Mesyuita, P. Parnham and J. A. Timbre11

513

517

521

525 Distribution of xenobiotic metabolizing enzymes in skin

Comparison of the cytotoxicity of ACE inhibitors and effects of cytochrome P-450 and glutathione modulation in primary rat hepatocyte cultures

533

535

539

543

545

549

551

555

559

563

569

573

The complement activation assay: the test for immediate phototoxicity

Renal cytotoxicity of cisplatin in cultured glomerular mesangial and proximal and distal tubular cells

Effect of peroxisome proliferators and inducers of xenobiotic metabolism on marker enzyme activities in cultured rat liver slices

Lack of AFB,-induced mutagenicity in the in vitro hepatocyte micronucleus assay: investigation of possible mechanisms

Inhibition of intercellular communication: an in vitro assay for detecting potential tumour promoters

Toxicological insult of canalicular function in rat hepatocyte couplets: the role of calcium

Study of the cardiotoxic potential of pharmaceutical compounds in chick myocardial myocyte reaggregate cultures

Detection and cellular localization of stress-induced 72 kD heat shock protein in cultured Swiss 3T3 mouse fibroblasts

Induction of mixed function oxidase activities in Cynomolgus monkey hepatocyte cultures

Skin metabolism of contact allergens

Effects of some non-genotoxic chemicals on DNA synthesis in rat hepatocytes

Effects of foetal calf serum on cell viability, cytotoxicity and detoxification in the two kidney-derived cell lines LLC-PKI and MDCK

Effect of alkylating and redox cycling quinones on insulin receptor autophosphorylation

Toxicity of a-naphthylisothiocyanate in isolated hepatocytes: possible role of taurine

Cytoprotective effects of taurine in isolated rat hepatocytes

VII, TOXICOLOGY IN VITRO

L. A. Saint-Pardo, I. Anundii, 577 The effects of silymarin on the attachment and viability of primary M. P. Miguez and K. 0. Lindros cultures of rat hepatocytes

M. P. Miguer, I. Anundi, 581 Comparative study of the hepatoprotective etTect of silymarin and

L. A. Sainr-Pardo and silybin on isolated rat hepatocytes

K. 0. Lindros

J. Heuer, I. M. Graeber, 1. Pohl and 585 An in vitro embryotoxicity assay using the differentiation of

H. Spielmann embryonic mouse stem cells into haematopoietic cells

P. C. Luso, A. S. Jurado, 589 Use of model micro-organism to study cytostatics-membrane L. M. Almeida and interactions V. M. C. Madeira

D. Constantin, A. WaNin, P. Mold&s 593 Stimulant effect of nitrite on the activation of benzo[a]pyrene-7,8- and B. Jernstriim dihydrodiol in human polymorphonuclear leucocytes

M. C. Martin Mateo, P. Aragdn and 597 Inhibitory effect of cysteine and methionine on free radicals induced

M. P. Prieto by mercury in red blood cells of patients undergoing haemodialysis

J. A. Rees, J. G. Er>ans, 601 Use of scanning electron microscopy in the study of nephrotoxin-

M. Blackmore, A. J. Spencer induced renal proximal tubular damage in L’itro

and T. J. B. Gray

J. A. M. Berkers, G. A. M. Hassing, 605 Effects of retinoic acid on the 2,3.7,8-tetrachlorodibenzo-p-dioxin-

A. Brouwer and B. J. Blaauboer induced differentiation of in L’itro cultured human keratinocytes

G. Repetto, P. San: and M. Repetto 609 In vitro effects of thallium on mouse neuroblastoma cells

Session 2-Human Systems (Chairman: A. R. Boobis)

B. K. Park, M. Pirmohamed, M. D. Tingle, S. Madden and N. R. Kitteringham

T. F. Meiller and W. A. Falkler. Jr

W. M. Purcell and C. K. Atterwill

T. Donnelly, D. Decker. M. Stemp, L. Rheins and P. Logemann

R. Roguet, M. RPgnier, C. Cohen, K. G. Dossou and A. Rougier

H. Smola, G. Thiekiitter, M. Baur, H.-J. Stark, D. Breitkreutz and N. E. Fusenig

M. R. 0’ Donocwn, M. R. Freemantle, G. Hull. C. F. Arlett and J. Cole

A. Verma and A. J. Shuw

R. K. Ward. S. Agranwlla und R. H. Clothier

613

623

627

631

635

641

651

655

659

Bioactivation and bioinactivation of drugs and drug metabolites: relevance to adverse drug reactions

A system to maximize the in ritro immunological stability of human Langerhans cells

Rodent and human mast cells as an in vitro model in neuroimmunotoxicity testing

A three-dimensional in vitro model for the study of ocular cytotoxicity and irritancy

The use of in vitro reconstituted human skin in dermotoxicity testing

Organotypic and epidermal-dermal co-cultures of normal human keratinocytes and dermal cells: regulation of transforming growth factor 2, /I I and 82 mRNA levels

Extended-term culture of human T lymphocytes: material potentially useful in genotoxicity testing

Reconstitution of human skin in vitro using readily available sources: novel studies of tumour promotion

Investigation of an in vitro cytotoxicity assay for prediction of skin irritation

TOXICOLOGY IN VITRO ix

F. M. Dickson, J. N. Luwrence and 661 Cytotoxicity of 12 chemicals of known human and animal skin

D. J. Beqfbrd irritation potential in human keratinocyte cultures

K. L. Trehilcock, J. R. Hqr’lings 665 In vitro tape stripping as a model for in riro skin stripping

nnd M. F. Wilks

C. Cohen, K. G. Dossou, A. Rougier 669 Episkin: an in pitro model for the evaluation of phototoxicity and

and R. Roguet sunscreen photoprotective properties

C. E. Green, G. R. Gordon, 673 Influence of prior freezing on arylamine acetylation by human liver

J. H. Peters and C. A. rwon preparations

Session S-Hazard and Risk Assessment (Chairman: M. Chamberlain)

0. P. Flint

M. Cumberbatch and 1. Kimber

A. W. Hubbard, L. J. Moore, R. H. Clothier, H. Sulley and

K. A. Rollin

C. S. Hoy and D. Sesardic

D. R. Newall and K. E. Beedles

A. A. J. J. L. Rutten and J. J. M. uan de Sandt

E. Eder, C. Hoffman, C. Deininger and S. Scheckenbach

J. Hilton, R. J. Dearman, R. J. Debicki, L. S. P. Ramdin

and I. Kimber

S. A. Martin, T. A. Ro)‘, K. A. Saladdin, B. A. Fleming and C. R. Mackerer

S. Steer, M. Balls, R. H. Clothier and V. Gordon

A. Willshaw, L. J. Moore and M. Balls

M. Berry, D. L. Easty and E. DeClercy

P. F. T. Cumberland, M. Richold, J. Parsons and M. K. Pratten

A. Kuper-Smith, J. N. Law,rence and D. J. Bertfi,rd

D. .%dowski, S. Steer, R. Clothier and M. Bulls

F. Steckel. W. Pap and I/. Hoppe

677 In vitro studies of the toxicity of nucleoside analogues used in the treatment of HIV infection

685

689

Epidermal cytokines and skin sensitization hazard

Use of in vitro methodology to predict the irritancy potential of

surfactants

693

697

703

fn L’itro assays for detection of diphtheria toxin

The stem-cell test-a novel in oitro assay for teratogenic potential

In Gtro dermal toxicology using skin organ cultures

707

711

Risk assessment for mutagenic and carcinogenic activities of z$- unsaturated carbonyl compounds by a screening strategy based on structure-activity relationships Interleukin 6 production in vitro: an alternative read-out for the

local lymph node assay

715 Safety evaluation of petroleum products using an in vitro eye irritation test battery

719 The development and evaluation of in Gtro tests for photoirritancy

723 In vitro alternatives for the detection of photoirritant chemicals: the EECjCOLIPA trial

727 Effect of antivirals on human cornea1 cells in vitro

731

735

739

743

Intravitelline injection of rodent conceptuses: an improved in vitro developmental toxicity screen

In Pitt-o cytotoxicity studies of particulate samples in cultures of hamster tracheal epithelial (HTE) cells

Use of a filtration plate in the MTT assay

Differentiation of monocytes in vitro: influence of different types of substances

x

J. Degwert, W. Pape and U. Hoppe 141

C. Meredith and M. P. Scott 751

W. J. W. Pape, M. Brandt and U. Pfirnnenbecker

755

M. B. Dhit. M. West, L. K. Earl and W. W. Love/l

759

W. Fiillmann and C. Guhe 763

C. E. M. Jones and J. R. Fry 767

M. Blackmore, J. C. Richardson, S. Costello, E. S. Harpur and T. J. B. Gra.y

771

H.-P. K&king, Cr. Schlegelmilch and R. K&king

775

M. Ciilden, H. Seibert and J.-U. Voss

779

M. cervinka, V. P&a, M. Hroch and Z. cervinkovci

783

TOXICOLOGY IN VITRO

In vitro analysis of immunoprotective effects of topical sunscreens

Altered gene expression in immunotoxicology screening in vitro: comparison with e.y rive analysis

Combined in vitro assay for photohaemolysis and haemoglobin oxidation as part of a phototoxicity test system assessed with various phototoxic substances

A screen for photoirritants in cultured cells

A cell culture model of isolated porcine urinary bladder epithelial cells for genotoxicity studies

Characterization of fresh mechanically isolated rat proximal tubule suspensions during prolonged incubation

In vitro toxicity of cephalosporin and aminoglycoside antibiotics to LLC-PK, cells assessed by changes in glucose uptake

Assessment of membrane toxicity using [“Hlarachidonic acid release in U937 cells

The use of cultured skeletal muscle cells in testing for acute systemic toxicity

In vitro cytotoxicity testing of metal alloys used in medicine: comparison of different approaches

Session 4-Validation (Chairman: B. Phillips)

J. M. Frazier 787 The role of mechanistic toxicology in test method validation

H. Spielmann, M. Balls, M. Brand, 793 EECjCOLIPA project on in vitro phototoxicity testing: first results

B. DGring, H. G. Holzhiitter, obtained with a Balb/c 3T3 cell phototoxicity assay

S. Kalweit, G. Klecak, H. L. Eplattenier, M. Liebsch, W. W. Love& T. Maurer, F. Moldenhauer, L. Moore, W. J. W. Pape, CT. efhnenbecker, J. Potthast, 0. De. Silva, W. Steiling and A. Willshaw

T. A. Roy, K. A. Saladdin and 797 Evaluation of the EYTEX system as a screen for eye irritancy of C. R. Mackerer petroleum products

S. P. Williams, J. Davenport -Jones, 799 Phase I of an in vitro neurotoxicological pre-validation trial C. Egan, S. O’Hare, M. Cookson, R. McClean, M. J. Garle, V. Pentreath and C. K. Atterwill

E. Margfficnte, T. Smyrniotis and M. Balls

E. Walum, C. Clemedson and B. EkwaN

803 ECVAM: the European Centre for the Validation of Alternative Methods

807 Principles for the validation of in c-itro toxicology test methods

S. Y. Brendler-S~ll,l,arrh. H. Mager, 813 Definition of a new intrdlaboratory limit value for a positive UDS H. Lehn and B. Herbold assay in vitro

TOXICOLOGY IN VITRO xi

M. R. Cookson, R. McClean, 817

S. P. Williams, J. Dat~enport-Jones, C. Egan, S. O’Hare, C. K. Atterwill and V. W. Pentreath

S. P. Fricker

M. D. Barratt, D. A. Basketter and D. W. Roberts

H. M. Clowes, R. C. Scott and J, R. Heylings

M. C. Lopes, L. Guilhermino, A. Donato, L. Siheira, A. M. V. M. Soares and A. P. Caroalho

P. L. Casterton, L. F. Potts and

B. D. Klein

M. D. Barratt, D. A. Basketter, M. Chamberlain, M. P. Payne, G. D. Admans and J. J. Langowski

821

823

827

831

835

837

Use of astrocytes for in vitro neurotoxicity testing

The application of sulforhodamine B as a calorimetric endpoint in a cytotoxicity assay

Skin sensitization structure-activity relationships for phenyl benzoates

Skin absorption: flow-through or static diffusion cells

Quantitative concentration-toxicity relationship for the injury of rat thymocytes by chemical compounds used in inter-laboratory toxicity ring-tests

Use of in oitro methods to rank surfactants for irritation potential in support of new product development

Development of an expert system rulebase for identifying contact allergens

Session 5-Hierarchical Testing Strategies (Chairman: P. Botham)

D. W. Straughan 841 The UK Animals (Scientific Procedures) Act-implications for the future of alternative toxicity tests

B. J. Blaauboer, M. Balls, V. Bianchi, G. Bolcsfoldi, A. Guillouzo, G. A. Moore, L. Odland, C. A. Reinhardt, H. Spielmann and E. Walum

H. Seibert, M. Giilden and J.-U. Voss

D. Howes

D. A. Basketter

E. Whittle and D. A. Basketter

R. W. Lewis, J. C. McCall und P. A. Botham

R. W. Lewis, J. C. McCall, P. A. Botham and R. Trebilcock

B. M. Elliott

845 The ECITTS integrated toxicity testing scheme: the application of in tritro test systems to the hazard assessment of chemicals

847 An in oitro toxicity testing strategy for the classification and labelling of chemicals according to their potential acute lethal potency

851 A strategy for the assessment of percutaneous absorption

855 Strategic hierarchical approaches to acute toxicity testing

861 In tritro skin corrosivity test using human skin

865 Development of an in llitro test battery for use within a stepwise approach to the assessment of ocular irritancy in L,iw

867 A comparison of two cytotoxicity tests for predicting the ocular irritancy of surfactants

871 Genotoxicity testing strategies

Session Q-Product Design and Selection (Chairman: T. J. B. Gray)

D. J. Lhingstone 873 Computational techniques for the prediction of toxicity

S. P. Fricker 879 A role for in vitro cytotoxicity testing in the selection and development of metal-based pharmaceutical and materials products

Xii TOXICOLOGY IN VITRO

R. H. Clothier. S. J. Morgan, K. A. Atkinson, M. J. Garlc

rind M. Balls

883 Development of a fixed-dose approach for the fluorescein leakage test

M. D. Barraft 885 A quantitative structure-activity relationship (QSAR) for prediction of z,,,-globulin nephropathy

C. L. Cannon, P. J. Neal, J. A. Southee, J. Kubilus and M. Klausner

889 New epidermal model for dermal irritancy testing

A. Rougier. M. Cottin, 0. de Silva, 893 The use of in vitro methods in the ocular irritation assessment of

P. Catrou.\-, R. Roguet and cosmetic products

K. G. Dossou

Session 7-Regulatory Acceptance (Chairman: M. Balls)

D. G. Clark 907 Barriers to the acceptance of in c.itm alternatives

R. J. Fielder 91 I Acceptance of in vitro studies by regulatory authorities

I. C. Shaw 917 The use of in vitro methods for studying drug metabolism to replace animal studies as part of veterinary medicines product licence applications

P. F. Evans 921 Updated toxicology text methods for new industrial chemicals: implications for regulatory acceptance of in rYtro alternatives now and in the future

J. H. Fentem and M. Balls 923 Why, when and how in citra tests should be accepted into regulatory toxicology

H. B. W. M. Kadter 925 Principles for a pragmatic approach to the regulatory acceptance of alternative tests

Forthcoming Papers I

VCILUME 8 NUMBER 5

Proceedings of the Fourth CFN Symposium “Immunotoxicology and In Vitro Possih:”

Erik Walum, Ian Kinzber and Lena Odland

iii Preface

Mats Denninger 931 Opening Address

J. H. Dean 933 Immunotoxicology: an overview

J. H. Dean, J. B. Cornacofl; P. J. Haley and J. R. Hincks

939 The integration of immunotoxicology in drug discovery and development: investigative and in rritro possibilities

M. I. Luster, C. Portier. D. G. Pait 945 The use of animal tests in risk assessment for immunotoxicology and D. R. Germolel

J. G. Vas and H. Van Lweren 951 Developments of immunotoxicology methods in the rat and applications to the study of environmental pollutants

K. L. WllitcJ, Jr, C. Cennings, M. J. Murray and J. H. Dean

957 Summary of an international methods validation study, carried out in nine laboratories, on the immunological assessment of cyclosporin A in the Fischer 344 rat

TOXICOLOGY IN VITRO Xl,,

J. Descotes and Th. Vial 963

A.-T. Karlberg. J. L. G. Nilsson

and J. E. Wahlberg

967

Th. Maurer, A. Arthur and P. Bentley 911

I. L. Bernstein 915

J. Pauluhn 981

I. Kimber 987

V. D. M. Stejskal, K. Cederbrant, A. LindvaN and M. Forsbeck

991

C. Meredith and K. Miller

L. A. Rheins, S. M. Edwards, 0. Miao and T. A. Donnelly

1001

1007

I. K. Grundt and H. Nyland 1015

R. W. R. Crevel, P. Buckley and J. A. Robinson

1021

R. Fautz and H. G. Miltenburger 1027

H. J. Dahlman, P. I. Gaarder, 1033 PCB congeners and the murine immune system: the capacity of M. Lsvik, J. Alexander, G. Becher isolated congeners to decrease spleen specific antibody forming cell

and A. Bergman numbers varies with the toxic equivalence factors of the congeners

P. F. A. Wright, L. M. Schlichting 1037 and N. H. Stacey

Effects of chlorinated solvents on the natural lymphocytotoxic activities of human liver immune cells

V. A. J. Mariu und R. M. M. Victorino

1041 Lymphocyte proliferative response to drugs: analysis of the value of a 24-well lymphocyte culture system

I. Chuzal, F. Verdier, M. Virut and J. Descotes

1045 Prediction of drug-induced immediate hypersensitivity in guinea

pigs

T. E. Steinsoik, 1. S. Aaberge, D. Belsnes, P. I. Guarder und M. Lsvik

1049 Specific human IgE response after immunization with birch pollen in scid mice transplanted with human peripheral blood mono- nuclear cells-a model for human allergy?

M. D. Burratt, D. A. Basketter, 1053 M. Chamberluin, G. D. Admans und J. J. Lungowski

An expert system rulebase for identifying contact allergens

M. Schlumpf; E. E. Biitikofer, A. A. Schreiber. R. Parmar. H. R. Rumseier and W. Lichtensteiger

1061 Delayed developmental immunotoxicity of prenatal benzo- diazepines

lmmunotoxic effects of xenobiotics in humans: a review of current evidence

Structure-activity relationship as a tool in contact allergy risk assessment

Contact hypersensitivity: animal tests

Respiratory allergy: clinical aspects

Assessment of chemicals for their potential to induce respiratory allergy in guinea pigs: a comparison of different routes of induction and confounding effects due to pulmonary hyperreactivity

Chemical allergy: cellular and molecular mechanisms and novel approaches to predictive testing

MELISA-an in vitro tool for the study of metal allergy

Molecular immunotoxicology testing in vitro

SkinZTM: an in vitro model to assess cutaneous immunotoxicity

Activation of cultured glial cells by amitriptyline and platelet activating factor

The value of in vitro immune function tests in the detection of potential immunotoxicants

Influence of organophosphorus compounds on different cellular immune functions in vitro

XiV TOXICOLOGY IN VITRO

A. Sundwall, B. Andersson, 1067 M. Balls, J. Dean, J. Descotes, S. Hammarstriim, P. H&man, I. Kimber, M. Lorentz, M. Luster, P. Mold&us, L. Odland, H. 0. SjGgren, V. Stejskal, E. Walum, B. Veronesi, K. White and J. Vos

General Papers H. Babich, D. F. Markenson,

L. Blau and A. Stern

C. T. Cramer and R. G. Ulrich

H. Dutertre-Catella, C. Martin, M. F. Olivier, M. Theuenin, J.-M. Warnet, B. Vannier, J.-R. Claude and R. A. Podevin

C. Graillet and J.-P. Girard

H. Saito, J. Koyasu, T. Shigeoka and 1. Tomita

T. Sasaki and T. Ohno

I. W. Smoak

M. J. M. Toussaint, M. M. L. de Wit, B. J. Blaauboer and H. Nederbragt

C. Westmoreland, D. J. Benford, L. J. Eales and P. Grass0

Forthcoming Papers

R. C. Bowes, 111 and K. S. Ramos

B. Diener, M. Traiser, M. Arand, J. Leissner, U. Witsch, R. Hoheqf~llner, F. FSindrich. I. Vogel, D. Utesch and F. Oesch

M. E. Herrero and J. V. Caste11

G. H. Holland

1075

1083

1091

1097

1107

1113

1121

1129

1139

I

Workshop: immunotoxicology and in oitro possibilities

In vitro cytotoxicity of the chlorinated naphthoquinone dichlone to human endothelial ECV304 cells

Cytotoxicity and lamellar body induction potential of a racemic benzamide antiarrhythmic compound and enantiomers in cultured rat hepatocytes

I!% uivo study on ATPase activities of rabbit renal proximal tubules as a predictive model for nephrotoxicity: comparison with an in oitro study on a new cephalosporin (cefpirome)

Embryotoxic potency of 2,4,Strichlorophenoxyacetic acid on sea urchin eggs: association with calcium homoeostasis

Cytotoxicity of chlorophenols to goldfish GFS cells with the MTT and LDH assays

Cytotoxicity tests on eye drop preparations by LDH release assay in human cultured cell lines

Embryopathic effects of diazoxide and the reduction of sulfonylurea-induced dysmorphogenesis in vitro

Phenobarbital pretreatment in uivo and in vitro and the effect of hepatotoxicity of D-galactosamine in rat hepatocytes in culture

Investigations into the mechanisms of carcinogen-induced nuclear enlargement in HeLa S3 cells in tlitro

VOLUME 8 NUMBER 6

I 151 Assessment of cell-specific cytotoxic responses of the kidney to selected aromatic hydrocarbons

1161 Xenobiotic metabolizing enzyme activities in isolated and cryo- preserved human liver parenchymal cells

II67 Quantification of CYPIAI and 2B1/2 in rat hepatocytes cultured in microwells by immunological methods

II77 Verification of a mathematical method for the estimation of the acute ingestion hazard of detergent preparations

TOXICOLOGY IN VITRO xv

C. Kiyohara and T. Hirohata 1185

W. W. Ku and R. E. Chapin 1191

S. J. McGuinness and M. P. Ryan 1203

R. P. Moody and B. Nadeau 1213

R. P. Moody, B. Nadeau and I. Chu

1219

R. P. Moody, B. Nadeau and I. Chu

1225

A. R. Parrish, R. T. Dorr, A. J. Gandoifi and K. Brendel

1233

S. Sarkar, D. Bhatnagar and Poonam Yadao

1239

H. V. Sheevers, K. Brendel, S. H. Wright, R. B. NagIe and A. J. Gandolfi

1243

T. Tsutsui, Y. Matsudo, Y. Tanaka, A. Rokukawa, H. Sato, N. Omori and J. C. Barrett

1253

P. Yadav, D. Bhatnagar and S. Sarkar

1259

M. York, A. P. Wilson and C. S. Newsome

1265

N. Zanesi, P. Ferraro, S. Pavanello, D. Furlan and L. Celotti

1269

Brief Communication C. Del Casino, A. Tiezzi, M. Scali, 1277

G. Neri and A. Moscatelli

Review Papers S. Y. Brendler-Schwaab, 1285

P. Schmezer, U. Liegibel, S. Weber, K. Michalek. A. Tompa and B. L. Pool-Zobel

Effects of vitamin C and PCB metabolites on the inhibition of aryl hydrocarbon hydroxylase and suppression of mutagenicity of benzo[a]pyrene

Spermatocyte toxicity of 2-methoxyethanol in viva and in vitro: requirement for an intact seminiferous tubule structure for germ cell degeneration

Mechanism of cisplatin nephrotoxicity in rat renal proximal tubule suspensions

In vitro dermal absorption of pesticides: IV. In viva and in vitro comparison with the organophosphorus insecticide diazinon in rat. guinea pig, pig, human and tissue-cultured skin

In vitro dermal absorption of pesticides: V. In viva and in vitro comparison of the herbicide 2,4-dichlorophenoxyacetic acid in rat, guinea pig, pig, human and tissue-cultured skin

In vitro dermal absorption of pesticides: VI. In oivo and in vitro comparison of the organochlorine insecticide DDT in rat, guinea pig, pig, human and tissue-cultured skin

Adult rat myocardial slices: a tool for studies of comparative cardiotoxicity

Cadmium-induced lipid peroxidation in rat liver slices: a possible involvement of hydroxyl radicals

Nephrotoxicity and uptake of I-benzyl quinolinium in precision-cut rabbit renal cortical slices

Quantitative comparison of cytotoxicity of dental antiseptics to normal human oral keratinocytes in vitro

Counteraction by glutathione and selenium of the prooxidant effect of alloxan in erythrocytes in vitro

The classification of soluble silicates for eye hazard using the enucleated rabbit eye test

Cytotoxic and mutagenic effects of anti- and syn-benzo[a]pyrene diol epoxide in human lymphocytes

The influence of vinyl-4-cyclohexene dioxide on the vimentin- containing intermediate filaments and the microtubular cyto- skeleton of cultured mouse fibroblasts: immunofluorescence investi- gations

Cells of different tissues for in citro and in rho studies in toxicology: compilation of isolation methods

xvi TOXICOLOGY IN VITRO

M. J. Garlc, J. H. Fentem and J. R. Fr.,

I303 In vitro cytotoxicity tests for the prediction of acute toxicity in ko

Erratum 1313

Forthcoming Papers I

Index of Authors

Aaberge 1. S., 1049 Abdel-Rahman S. Z., 139 Abo-Elwafa A. A.. 139 Admans G. D.. 837. 1053 Agrawalla S., 659 Ahmed A. E., 139 Alexander J., 1033 Allavena A., 131 Almeida L. M.. 589 Amacher D. E., I Amiconi G., 483 Andersson B., 1067 Anundi 1.. 577, 581 Aragon P., 597 Arand M., 1161 Arlett C. F., 651 Armstrong C. L., 329 Arthur A., 971 Atkinson K. A., 883 Atterwill C. K., 309, 627. 799, 817 Audegond L., 381 Aylward S. P., 309

Babich H., 1075 Bagarolo C., 131 Balls M., 513. 535, 719, 723, 739, 793,

803, 845, 883, 923, 1067 Bar P. R.. 81 Barratt M. D., 823. 837, 885. 1053 Barrett J. C., 1253 Basketter D. A.. 21.257. 551. 823. 837.

855, 861. 1053 Baur M.. 641 Beamand J. A., 521. 549 Becher G., 1033 Bechtel D. G.. 317 Beedles K. E., 697 Belsnes D., 1049 Benford D. J., 555. 661, 735. 1139 Bentley P., 971 Bergman A.. 1033 Berlkers J. A. M., 605 Bernstein I. L., 975 Berry M., 727 Bertrand R., I91 Bhatnaear D.. 471. 1239. 1259 BianchrV., 845 Birnbaum L. S., 221 Blaauboer B. J.. 563, 605, 845, 1129 Blackmore M., 601. 771 van Bladeren P. J.. 207 Blau L., 1075 Bohets H. H.. 559 Bolcsfoldi G., 845 Bondy G. S.. 329 Boobis A. R.. 505 Botham P. A., 75, 865. 867 Bowes 111 R. C., II51 Brambilla G., 131 Brand M., 793 Brandt M.. 755 Breen K. C., 407 Breitkreutz D., 641 Breittmayer J. Ph., 37 Brendel K.. 371. 1233, 1243 Brendler-Schwaab S. Y.. 813, 1285 Brouwer A., 605 Brunton V. G.. 337 Buckley P., 1021 Biitikofer E. E.. 1061

Cain K.. I3 Caldwell J.. 251 Cambar J.. 517 Cannon C. L.. 889 Carroll P. A.. II7 Carvalho A. P.. 831 Castell J. V., 47, II67 Casterton P. L., 835 Catroux P.. 893 Cederbrant K., 991 Celotti L.. 1269 Chamberlain M.. 837, 1053 Chapin R. E., II91 Chapman D. E., 343 Chazal I., 1045 Chiesara E.. 361 Chipman J. K., 29, 539 Chu I., 1219, 1225 Clark D. G., 907 Claude J.-R., 1091 Clemedson C., 145, 263, 807 Clothier R. H., 513,659, 689, 719, 883 Clothier R.. 739 Clowes H. M., 827 Cohen C., 283, 635, 669 Cole J.. 651 Coleman R., 539 Constantin D., 593 Cookson M. R.. 351. 817 Cookson M., 799 Cooper A., 535 Cornacoff J. B.. 939 Corsini E.. 361 Costello S., 771 Cottin M., 381, 893 Cramer C. T.. 1083 Crawford K.. 55 Crevel R. W. R., 1021 Cronin M. T. D., 21 Cumberbatch M., 685 Cumberland P. F. T., 153, 731 Cunninghame M. E.. 521 Cervinka M., 783 Cervinkova Z., 783

Dahlman A. J., 1033 Davenport-Jones J., 799. 817 Davies J., 29 Davies S., 521, 549 Dawson B. A., 329 De Broe M. E.. 559 De Silva 0.. 793 DeClercq E., 727 Dean J. H., 933, 939, 957 Dean J.. 1067 Dearman R. J.. 71 I Debicki R. J.. 711 Decker D., 167, 631 Deaen G. H.. 449 Degwert J., 747 Deinineer C.. 707 Deknudt G.. 381 Del Casino C., 1277 Delbancut A.. 517 Denninger M., 931 Descotes J.. 963, 1045. 1067 Dickson F. M.. 661 Diener B.. II61 Dierickx P. J.. 559 Diogene G.. 37

xvii

Dixit M. B.. 759 Dixit M.. 257 Donato A.. 831 Donnelly T. A., 1007 Donnelly T.. 631 Ddring B.. 793 Dorr R. T.. 1233 Dossou K. G.. 283, 635. 669, 893 Droog C. I., 563 Dubreuil A., 37 Dutertre-Catella H., 1091

Eales L. J., II39 Earl L. K., 759 Easty D. L.. 727 Eder E., 707 Edwards R. J., 173 Edwards S. M.. 1007 Egan C., 799, 817 Ekwall B.. 807 Elliott B. M., 871 Enlattenier H. L.. 793 Eio K., 109 Evans J. G., 601 Evans P. F.. 921

Falkler W. A. Jr, 623 Flndrich F., II61 Fautz R., 1027 Fentem J. H., 923, 1303 Fentem J.. 535 Ferraro P., 1269 Fielder R. J., 911 Fisher H. L., 221 Fisher R. L., 371 Fleming B. A., 715 Flint 6 P., 677 Fiillmann W., 763 Forsbeck M., 991 Francis I.. 543 Frazier J. M.. 787 Freemantle M. R., 651 Freundt K. J.. 401 Fricker S. P., 821, 879 Fry J. R., 767. 1303 Fukuda T.. 215 Furlan D., 1269 Fusenig N. E.. 641

Gaarder P. I., 1033, 1049 Galli C. L.. 91. 361 Gandolfi A. J.. 371, 1233. 1243 Garle M. J.. 799, 883. 1303 Gautheron P.. 381 Genninas C.. 957 Germol& D. R.. 945 Ghatineh S.. 393 Gillio Tos E., 381 Girdrd J.-P.. 1097 Giroux J., 381 Gispen W. H.. 81 Goethals F.. I81 Gofflot F., I81 Gordon G. R., 673 Gordon V.. 719 Gbmez-Lechon M. J.. 47 Graeber I. M.. 585 Grdillet C., 1097 Grant M. H.. 191. 337

xv,,, Index of Authors

Grass0 P.. II39 Gray T. J. B.. 601. 771 Green C. E.. 673 Groth G., 401 Grundt 1. K.. 1015 Guhe C.. 763 Guilhermino L., 831 Guillouzo A.. 845 Giilden M., 197, 779. 847 Gurney J. E.. I3

Haenen H. E. M. G., 207 Hagemann C., 381 Haley P. J., 939 Hall L. L.. 221. 441 Hammarstrom S., 1067 Harper R., 167 Harpur E. S., 771 Hassing G. A. M., 605 Hayashi T.. 215 Hayes F. D.. 407 Haynes G., 381 Herbold B.. 813 Hernandez A.. 293 Heroux-Metcalf C., 269. 329 Herrero M. E.. II67 Heuer J., 585 Heylings J. R.. 665. 827 Hilton J., 71 1 Hincks J. R., 939 Hirohata T.. II85 Hoffman C.. 707 Hohenfellner R., I I61 Holland G. H.. II77 van Holsteijn C. W. M., 563 Holzhiitter H. G., 793 Hoppe U.. 743, 747 Horbach G. J. M. J.. 563 Hotchkiss S. A. M.. 251 Houston J. B., 507 Howes D., 851 Hoy C. S., 693 Hroch M., 783 Huang H. S.. 55. 529 Hubbard A. W., 689 Hughes M. F., 221. 441 Hull G., 651 Hultman P.. 1067 Hunter. III E. S., 413

ltagaki H., 215

Jacobs G.. 381 Janz S.. 437 Jernstrdm B., 593 Jones C. E. M., 767 Jones P., 257 Jover R.. 47 Jurddo A. S., 589 Jurima-Romet M., 55. 529

Kalweit S., 381. 793 Karlberg A.-T.. 967 Kasper P., 99. 533 Kato S.. 215 Kimber I.. iii, 685. 711. 987. 1067 Kind C. N., 545 Kishida K.. 109 Kitteringham N. R.. 613 Kiyohara C., I I85 Klausner M., 889 Klecdk G.. 793 Klein B. D.. 835

Klocking H.-P.. 775 Kliicking R.. 775 Koeter H. B. W. M.. 925 Kotani M., 229 Koyasu J.. II07 Kronauer K.. 401 Ku W. W., II91 Kubilus J.. 889 Kuper-Smith A.. 735

Lagroye 1.. 517 Lake B. G., 521, 549 Langlois 1.. 269 Langowski J. J.. 837, 1053 Lankester D. J.. 539 Lawlor S. M.. 67 Lawrence J. N., 555. 661, 735 Lee L. E. J., 317 Lehn H.. 813 Leissner J., II61 Leslie C. L., 173 Lewis R. W.. 75. 865, 867 Lichtensteiger W.. 1061 Liebsch M.. 793 Liegibel U.. 1285 Lindros K. 0.. 577. 581 Lindup W. E., 477 Lindvall A., 991 Lison D.. 125 Livingstone D. J.. 873 Logemann P.. 631 Lopes M. C., 831 Lopez M. L., 293 Lorentz M.. 1067 Love11 W. W.. 759. 793 Lsvik M., 1033, 1049 Lupidi G., 483 Luster M. 1.. 945 Luster M.. 1067 Luxo P. C.. 589

Macian M.. 467 Mackerer C. R.. 715, 797 Madden S.. 613 Madeira V. M. C., 589 Mager H., 813 Maier P., 423 Maile P. A., 543 Mandys V.. 81 Marabini L., 361 Marafante E.. 803 Maria V. A. J., 1041 Marinovich M., 91, 361 Markesnon D. F.. 1075 Marshall H.. 545 Martelli A., 131 Martin C., 1091 Martin S. A.. 715 Masamoto Y., 229 Masini V., 235 Mateo M. C. M.. 597 Matsudo Y.. 1253 Maurer T., 793 Maurer Th., 971 Mayordomo-Blanc0 L.. 38 I McCall J. C.. 75, 865, 867 McClean R., 799. 817 McGuinness S. J.. 1203 Meiller T. F., 623 Mendoza-Figueroa T., 293 Meredith C.. 751. 1001 Mesquita M.. 573 Miao 0.. 1007

Michalek K., 1285 Michener S. R., 343 Miguez M. P., 577. 581 Mikalsen S.-O.. 243 Miller K.. 1001 Miltenburger H. G.. 1027 Mint A.. 551 Mistrv H.. 521. 549 Modalsli K. R.. 243 Moldenhauer F.. 793 Mold&us P.. 593, 1067 Moody R. P.. 1213. 1219. 1225 Moore G. A., 845 Moore L. J.. 689. 723 Moore L.. 513, 793 Moret M.. 555 Morgan S. J.. 883 Morilla A., 38 I Morin C. A., 549 Moscatelli A., 1277 Miiller J.. 437 Miiller K., 99, 533 Miiller L., 99. L., 533 Murray M. J., 957

Nadeau B.. 1213, 1219. 1225 Naele R. B., 1243 Naik J. T., 525 Nau H., 371 Neal P. J., 889 Nederbragt H., II29 Neri G., 1277 Neville G. A., 329 Newall D. R., 697 Newsome C. S., 1265 Nihoul B., I81 Nilsson J. L. G., 967 Ninomiya H.. 109 Noel-Hudson M. S.. 235 Noordhoek J., 563 Nooy H. A.. 563 Nouraldeen A. M., 139 Nouwen E. J.. 559 Nugent C.. I91 Nyland H., 1015

O’Brien K. A. F., 257 O’Brien N. M.. 67 O’Donovan M. R., 651 O’Hare S., 799, 817 Odland L., iii, 145, 263. 845, 1067 Oesch F.. I I61 Ohno T.. III3 Ohno Y.. 109 Olivier M. F., 1091 Omori N.. 1253 Orloff M.. 455

Pait D. G., 945 Pape W. J. W., 755. 793 Pape W.. 743. 747 Park B. K.. 613 Parmar R.. 1061 Parnham P., 573 Parrish A. R.. 1233 Parsons J. F., 153 Parsons J.. 731 Pauluhn J., 981 Pavane110 S.. 1269 Payne M. P., 837 Pendlington R. U.. 525. 551 Pentreath V. W.. 351. 817 Pentreath V.. 799

Index of Authors

SchitTmann D.. 449 Schlegelmilch U.. 775 Schlichting L. M., 1037 Schlumpf M.. 1061 Schmezer P.. 1285 Scholes E. W.. 551 Schomaker S. J., I Schreiber A. A.. 1061 Schuller H. M., 455 Scott M. P.. 751 Scott R. C.. 827 Seabra V., 569 Seaman C. W.. 543 Seibert H., 197. 779. 847 Sesardic D.. 693 Sharma R. K.. 525, 551 Shaw A. J.. 655 Shaw 1. C.. 917 Sheevers H. V.. 1243 Shigeoka T.. II07 Sierra-Santoyo A., 293 de Silva O., 893 Silveira L.. 831 Siogren H. 0.. 1067 Skeit P.. 491 Smoak I. W., II21 Smola H., 641 Smyrniotis T.. 803 Soares A. M. V. M., 831 Solfrizzo M.. 461 Southee J. A.. 889 Spencer A. J., 601 Spielmann H.. 381, 585. 793, 845 Stacey N. H., 173. 1037 Stark H.-J., 641 Steckel F.. 743 Steer S. J.. 513 Steer S., 719. 739 Steiling W., 793 Steinsvik T. E.. 1049 Stejskal V. D. M.. 991 Steiskal V., 1067 Stemp M., 631 Stern A., 1075 Stone V.. 539 Straughan D. W., 841 Sulik K. K.. 413 Sulley H., 689 Sundwall A.. 1067 Sladowski D. T., 513 Sladowski D.. 739

Peters J. H.. 673 Pfanenbecker U , 793 Pfannenbecker U., 755 Phillips B. J.. II7 Picard J. J.. I81 Pilatte E., 125 Pirmohamed M.. 613 Pirovano R., 381 Podevin R. A.. 1091 Pohl I., 585 Ponsoda X.. 47 Pool-Zobel B. L., 1285 Portier C., 945 Potthast J.. 793 Potts L. F.. 835 Powis G.. 343 Pratten M. K.. 153, 731 Price R. J.. 521, 549 Prieto M. P., 597 Prinsen M.. 381 Puiseux-Dao S., 37 Purcell W. M., 627 Purchase R.. II7 Pdia V.. 783

Rahman M. S., 441 Ramdin L. S. P., 711 Ramos K. S.. II51 Ramseier H. R., 1061 Rees J. A., 601 Reinhardt C. A., 845 Rtgnier M., 635 Repetto G., 609 Repetto M., 609 Reznik G. K.. 455 Rheins L. A., 1007 Rheins L., 631 Richardson J. C., 771 Richold M., 153. 731 Roba J., 277 Robbiano L.. I31 Roberts D. W.. 823 Robinson J. A., 1021 Rogers C. G., 269. 329 Rogister A.. 277 Rogmans P., 207 Roguet R., 283, 635, 669, 893 Rokukawa A.. 1253 Rollin K. A., 689 Romert L., 145, 263 Rougier A.. 283. 635, 669, 893 Rowland K. L., 301 Roy T. A.. 715, 797 Rutten A. A. J. J. L., 703 Ryan M. P.. 1203

Saad B., 423 Sadler T. W., 413 Sainz-Pardo L. A.. 577, 581 Saito H., II07 Saladdin K. A., 715, 797 van de Sandt J. J. M.. 703 Sanuik J. T.. 371 Sanz P., 609 Sarkar S., 471. 1239, 1259 Sasaki T.. I I I3 Sato H.. 1253 Scali M., 1277 Schawalder H. P.. 423 Scheckenbach S., 707

Tamura U.. 215 Tanaka Y.. 1253 Tee A. C.. II7 Temmink J. H. M.. 207 Thevenin M.. 1091 Thiekotter G., 641 Tiezzi A.. 1277 Timbre11 J. A.. 393. 569, 573 Tingle M. D.. 613 Tomita 1.. II07 Tompa A., 1285 Tortajada A.. 381 Toseland C. D. N.. 543 Toussaint M. J. M.. II29

Toxopeus C.. 563 Traiser M., I I61 Trebilcock K. L.. 665 Trebilcock R.. 867

Tsurumi K.. 109 Tsutsui T.. 1253 Tugman J. A., 413 Turei-ek R.. 81 Tyson C. A., 673

Ulrich R. G.. 1083 Utesch D.. II61

Van Loveren H.. 951 Van Maele-Fabry G.. I81 Van den Dobbelsteen D. J.. 563 Vandenberghe Y., 277 Vannier B.. 1091 Vanparys P.. 381 Varnbo I., 145 Verdier F.. 1045 Vericat J. A.. 381 Verma A., 655 Veronesi B.. 1067 Vial Th.. 963 Victorino R. M. M., 1041 Vinardell M. P.. 467 Virat M.. 1045 Visconti A.. 461 Viviani B.. 91 Vogel I., II61 Vos J. G., 951 Vos J., 1067 Voss J.-U., 197. 779, 847

Wahlberg J. E.. 967 Walker T. M.. 309 Wallace H. M., 337 Wallin A.. 593 Walters D. G., I17 Walum E.. iii, 145, 263, 807. 845, 1067 Ward R. K., 659 Warnet J.-M.. 1091 Watanabe M.. 229 Waterfield C. J., 573 Weber S., 1285 Wepierre J., 235 West M.. 759 West R. W.. 301 Westmoreland C.. II39 White D. J., 543 White K. L. Jr. 957 White K.. 1067 Whittle E., 861 Wield P. T., 549 Wilks M. F., 665 Williams D. L., 525 Williams S. P., 799, 817 Willshaw A., 513. 723. 793 Wilson A. P., 1265 Wilton J. C., 539 de Wit M. M. L.. II29 Witsch U.. II61 Wright P. F. A., 1037 Wright S. H., 1243

Yadav P.. 471. 1239. 1259 York M.. 21. 1265

Zanesi N.. 1269 Zhang J. G.. 477 Zolla L.. 483