SCOPE 30IPCS JOINT SYMPOSIA 6

SGOMSEC 3

Methods for Assessing the Effects ofMixtures of Chemicals

Executive Committee of SCOPE

President: Professor J. W. M. La Riviere, International Institute for Hydraulicand Environmental Engineering, Oude Delft 95, PO Box 3015, 2601 DA Delft,The Netherlands.

Past-President: Professor R. O. Slatyer, Research School of Biological Sciences,Australian National University, P.O. Box 475, Canberra, ACT 2601,Australia.

Vice-President: Professor C. R. Krishna Murti, Commission for ContinuingStudies on Effects on Life Systems of Toxic Gas Leakage at Bhopal, CabinetSecretariat, Rashtrapati Bhavan, New Delhi 110001, India.

Secretary-Genera/: Professor T. Rosswall, Department of Water in Environ-ment and Society, University of Linkoping, S-581 83 Linkoping, Sweden.

Treasurer: Sir Frederick Warner, FRS, Department of Chemistry, University ofEssex, Wivenhoe Park, Colchester, Essex C04 3SQ, UK.

Members

Professor Paul Crutzen, Max-Planck Institut fUrChemie, Postfach 3060, D-6500Mainz, F.R. Germany.

Professor M. V. Ivanov, Institute of Microbiology, USSR Academy of Sciences,GSP-7 Prospekt 60 letija Oktjabrja 7-2, Moscow, USSR.

Professor H. A. Mooney, Department of Biological Sciences, StanfordUniversity, Stanford, CA 94305, USA.

Dr F. di Castri, CNRS, Centre L. Emberger, Route de Mende, BP 5051,34033Montpellier Cedex, France.

Professor J. Kostrowicki, Institute of Geography, Polish Academy of Sciences,Krakowskie Przedmiescie 30, 00927 Warsaw, Poland.

Editor-in-Chief

Professor R. E. Munn, IIASA, Schlossplatzl, A-2361, Laxenburg, Austria.

SCOPE 30IPCS JOINT SYMPOSIA 6

SGOMSEC 3

Methods for Assessingthe Effects of Mixtures

of ChemicalsEdited by

Velimir B. VoukNational Institute of Environmental Health Sciences,

Research Triangle Park, North Carolina, USA

Gordon C. ButlerNational Research Council of Canada, Ottawa, Canada

Arthur C. UptonInstitute of Environmental Medicine,

New York University Medical Center,New York, New York, USA

Dennis V. ParkeUniversity of Surrey, Guildford, Surrey, UK

and

Susan C. AsherNational Research Council of Canada, Ottawa, Canada

Prepared byScientific Group on Methodologies for the

Safety Evaluation of Chemicals(SGOMSEC)

Published on behalf of theScientific Committee on Problems of the Environment (SCOPE)

of the International Council of Scientific Unions (ICSU),and the International Program on Chemical Safety (IPCS)

of the World Health Organization (WHO),the United Nations Environment Programme (UNEP)

and the International Labour Organization (ILO)by

JOHN WILEY & SONSChichester'NewYork' Brisbane.Toronto' Singapore

Copyright ~ 1987 by theScientific Committee on Problems of the Environment (SCOPE)

All rights reserved.

No part of this book may be reproduced by any means, ortransmitted, or translated into a machine languagewithout the written permission of the copyright holder.

Library of Congress Cataloging-in-Publication Data:

Methods for assessing the effects of mixtures ofchemicals.(SGOMSEC; 3) (SCOPE; 30)(IPCS Joint Symposia 6)Based on a workshop held at the University of Surrey,

Guildford, England, Aug. 15-19, 1983.Includes bibliographies and index.1. Toxicity testing-Congresses. 2. Chemicals-

Environmental aspects-Congresses. 3. Environmentalmonitoring-Congresses. 4. Biological monitoring-Congresses. 5. Mixtures-Congresses. I. Vouk, Velimir.II. Scientific Group on Methodologies for the SafetyEvaluation of Chemicals. III. International Councilof Scientific Unions. Scientific Committee on Problemsof the Environment. IV. Series: SGOMSEC (Series); 3.V. Series: SCOPE (Series) (Chichester, West Sussex); 30.RA1199.M46 1987 615.9'02 86-11006

ISBN 0 471 91123 2

British Library Cataloguing in Publication Data:

Methods for assessing the effects of mixturesof chemicals.-(SCOPE; 30)-(SGOMSEC; 3)(IPCS Joint Symposia 6)1. ToxicologyI. Vouk, Velimir B. II. Scientific Groupon Methodologies for the Safety Evaluationof Chemicals III. International Council ofScientific Unions. Scientific Committeeon Problems of the EnvironmentIV. Series V. Series574.5'222 QH545.C47

ISBN 0471911232

Printed and bound in Great Britain.

SCOPE 1:

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SCOPE 4:

Global Environmental Monitoring 1971, 68 pp (out of print)

Man-Made Lakes as Modified Ecosystems, 1972, 76pp (out ofprint)

Global Environmental Monitoring Systems (GEMS): Action Planfor Phase 1, 1973, 132pp (out of print)

Environmental Sciencesin Developing Countries, 1974,72pp (outof print)

Environment and Development, proceedings of SCOPEjUNEP Symposium onEnvironmental Sciences in Developing Countries, Nairobi, February 11-23,1974,418pp.

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Environmental Impact Assessment: Principles and Procedures,Second Edition, 1979, 208pp

Environmental Pollutants: Selected Analytical Methods, 1975,277 pp (available from Butterworth & Co. (Publishers) Ltd,Sevenoaks, Kent, UK). (out of print)

Nitrogen, Phosphorus, and Sulphur: Global Cycles, 1975, 192pp(available from Dr Thomas Rosswall, Swedish Natural ScienceResearch Council, Stockholm, Sweden) (out of print)

Risk Assessment of Environmental Hazard, 1978, 132pp

Simulation Modelling of Environmental Problems, 1978, 128pp(out of print)

Environmental Issues, 1977, 242 pp

Shelter Provision in Developing Countries, 1978, 112pp

Principles of Ecotoxicology, 1978, 372pp

The Global Carbon Cycle, 1979,491 pp

Saharan Dust: Mobilization, Transport, Deposition, 1979,320 pp

Environmental Risk Assessment, 1980, 176pp

Carbon Cycle Modelling, 1981, 404 pp

Some Perspectives of the Major Biogeochemical Cycles, 1981175pp

The Role of Fire in Northern Circumpolar Ecosystems, 1983,344 pp

The Global Biogeochemical Sulphur Cycle, 1983, 495 pp

Methods for Assessing the Effects of Chemicals on ReproductiveFunctions, 1983, 568pp

VI

SCOPE 21: The Major BiogeochemicalCycles and Their Interactions, 1983,554 pp

SCOPE 22:

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SCOPE 25:

Effects of Pollutants at the Ecosystem Level, 1984, 443 pp

The Role of Terrestrial Vegetation in the Global Carbon Cycle:Measurement by Remote Sensing, 1984, 272 pp

Noise Pollution, 1986

Appraisal of Tests to Predict the Environmental Behaviour ofChemicals, 1985, 400pp

Methods for Estimating Risks of Chemical Injury: Human andNon-human Biota, 1985, 712pp

Climate Impact Assessment: Studies of the Interaction of Climateand Society, 1985, 649 pp

SCOPE 28: Environmental Consequences of Nuclear WarVolume I Physical, 1985, 342ppVolume II Ecological and Agricultural Effects, 1985, 523pp

SCOPE 29: The Greenhouse Effect, Climatic Change and Ecosystems

SCOPE 30: Methods for Assessing the Effects of Mixtures of Chemicals

Funds to meet SCOPE expenses are provided by contributions from SCOPENational Committees, an annual subvention from ICSU (and through ICSU,from UNESCO), an annual subvention from the French Ministere del'Environnement et du Cadre de Vie, contracts with UN Bodies, particularlyUNEP, and grants from Foundations and industrial enterprises.

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SCOPE 27:

International Council of Scientific Unions (ICSU)Scientific Committee on Problems of the Environment(SCOPE)

SCOPE is one of a number of committees established by a non-governmentalgroup of scientific organizations, the International Council of Scientific Unions(ICSU). The membership of ICSU includes representatives from 68 NationalAcademies of Science, 18 International Unions, and 12 other bodies calledScientific Associates. To cover multidisciplinary activities which include theinterests of several unions, ICSU has established 10 scientific committees, ofwhich SCOPE is one. Currently, representatives of 34 member countries and 15Unions and Scientific Committees participate in the work of SCOPE, whichdirects particular attention to the needs of developing countries. SCOPE wasestablished in 1969in response to the environmental concerns emerging at thattime; ICSU recognized that many of these concerns required scientific inputsspanning several disciplines and ICSU Unions. SCOPE's first task was toprepare a report on Global Environmental Monitoring (SCOPE 1, 1971)for theUN Stockholm Conference on the Human Environment.

The mandate of SCOPE is to assemble, review, and assess the informationavailable on human-induced environmental changes and the effects of thesechanges on humans; to assess and evaluate the methodologies of measurement ofenvironmental parameters; to provide an intelligence service on current research;and by the recruitment of the best available scientific information andconstructive thinking to establish itself as a corpus of informed advice for thebenefit of centres of fundamental research and of organizations and agenciesoperationally engaged in studies of the environment.

SCOPE is governed by a General Assembly, which meets every three years.Between such meetings its activities are directed by the Executive Committee.

R. E. MunnEditor-in-ChiefSCOPE Publications

Executive Secretary: V. Plocq

Secretariat: 51 BId de Montmorency75016 PARIS

VB