Table Of ContentRISK ASSESSMENT OF CHEMICALS
RISK ASSESSMENT OF CHEMICALS
An Introduction
Edited by
c.J. van Leeuwen
Ministry of Housing, Spatial Planning and Environment, The Hague & Research Institute of
Toxicology, University of Utrecht, The Netherlands
and
J.L.M. Hermens
Research Institute of Toxicology, University of Utrecht, The Netherlands
Springer-Science+Business Media, B.V.
Library of Congress Cataloging-in-Publication Data
RiSk assessment of chemicals an introduction / edited by C. J. van
Leeuwen and J.L.M. Hermens.
p. cm.
Inc ludes index.
ISBN 978-94-015-8522-4 ISBN 978-94-015-8520-0 (eBook)
DOI 10.1007/978-94-015-8520-0
1. Health rlsk assessment. 2. Pollutlon--Environmental aspects.
3. TOXlcology. I. Leeuwen. C. J. van. II. Hermens. Joop L. M.
RA566.27.R575 1995
615.9·02--dc20 95-33375
06-0104-300 ts
Printed on acid-Iree paper
First published 1995
Reprinted 1996, 1997,2000,2001,2004
AII Rights Reserved
© 1995 Springer Science+Business Media Dordrecht
Originally published by Kluwer Academic Publishers in 1995
Softcover reprint ofthe hardcover Ist edition 1995
No part of the material protected by this copyright notice
may be reproduced Of utilized in any form or by any means,
electronic or mechanical, including photocopying,
recording, or by any information storage and retrieval
system, without written permission from the copyright
owners.
v
This book presents information obtained from various sources. Reprinted material is quoted with permission and the
sources have been indicated. A wide variety of references is given. Every reasonable effort has been made to provide
reliable data and information, but the authors, editors and the publisher cannot assume responsibility for the validity of
all the material or for the consequences of its use.
The publication of this book was made possible with the financial support provided by The Netherlands' Ministry of
Housing, Spatial Planning and Environment (VROM). It was approved by the Directorate for Chemicals, External
Safety and Radiation Protection of VROM. Approval does not necessarily signify that the contents reflect the views
and policies of VROM, nor does the mention of trade names or commercial products constitute endorsement or recom
mendation for their use.
Neither this book nor any part of it may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, microfilming and recording, or any information storage and retrieval system,
without the prior written permission of the publisher.
vii
PREFACE
In recent years many developments have taken place in promote co-operation between governments and other
the field of risk assessment of chemicals. Many reports parties involved in chemical safety and to provide policy
have been published by national authorities, industries guidance with emphasis on regional and subregional co
and scientific researchers as well as by international bod operation. The Inter-Organization Programme for the
ies such as the European Union, the Organization of Sound Management of Chemicals (IOMC) was estab
Economic Cooperation and Development (OECD) and lished in 1995 and provides a mechanism for the six par
the joint International Programme on Chemical Safety ticipating organizations (UNEP, ILO, FAO, UNIDO,WHO
(IPCS) of the World Health Organization (WHO), the and OECD) to better co-ordinate policies and activities in
International Labour Organization (lLO), and the United the field of chemical risk management.
Nations Environment Programme (UNEP).
The present book is an introduction to risk assessment of
The development and international harmonization of risk chemicals. It contains basic background information on
assessment methods is an important challenge. In sources, emissions, distribution and fate processes for
Agenda 21 of the United Nations Conference on exposure estimation. It includes dose-effects estimation
Environment and Development (UNCED), chapter 19 is for both human health related toxicology and ecotoxicol
entirely devoted to the management of chemicals. For ogy as well as information on estimation methodologies.
one of its recommendations, i.e. the expansion and accel It describes the basic principles and methods of risk
eration of the international assessment of chemical risks, assessment in their legislative framework. Most of the
mutual acceptance of hazard and risk assessment is a risk assessment methods described are part of the so
pre-requisite. Another very important recommendation called Uniform System for the Evaluation of Substances
of chapter 19 is that national capabilities and capacities (USES), a computerized risk assessment system which
in the management of chemicals should be strengthened. has been developed in The Netherlands.
UNEP as the Task Manager of Chapter 19 reports for the The book is intended to be used by students in health and
Commission on Sustainable Development (CSD), on environmental sciences and as backgroud material for
progress in the implementation of the recommendations those who are involved in risk assessment. I hope that
of Chapter 19 (by international organizations). Two this book will help to bridge the gaps between science
important arrangements for co-operation and co-ordina and application and, particularly, that it will serve to
tion of national and international activities with regard build capacity in many developed and developing coun
to chemical safety have been established since UNCED. tries in order to increase understanding and thus prevent
The Intergovernmental Forum on Chemical Safety man and the environment being exposed to unacceptable
(IFCS) was established in April 1994 in Stockholm to risks due to toxic chemicals and hazardous waste.
Hans Alders
UNEP Regional Director for Europe
Vlll
EDITORS
Cornelis Johannes (Kees) Van Leeuwen studied biology at Josephus Ludovicus Maria (Joop) Hermens studied chem
the University of Utrecht, where he also obtained his Ph.D. istry at the University of Utrecht. He received his Ph.D. in
in ecotoxicology. He began his career in 1980 as plant ecol 1983 for a thesis on quantitative structure-activity relation
ogist at the University of Groningen and, shortly thereafter, ships. Since then he has lead a research group and is now
became head of the Laboratory of Ecotoxicology at the associate professor at the Research Institute of Toxicology
Ministry of Transport and Public Works. He served in a (RITOX) at the University of Utrecht, working in the field
research and advisory role in the implementation of The of environmental toxicology. His major research interests
Netherlands' Pollution of Surface Waters Act. In 1987 he are the development of structure-activity relationships in
joined the Ministry of Housing, Spatial Planning and environmental toxicology, the study of the environmental
Environment (VROM) as a senior expert and deputy head effects of mixtures of chemicals and the development of
of the Chemicals Division. In 1991 he became head of the group parameters for measuring mixture toxicity. In 1987
Risk Assessment and Environmental Quality Division of he spent six months as a research scientist at the EPA
VROM. In addition to his work at VROM, he holds a part Environmental Research Laboratory in Duluth, Min
time professorship in biological toxicology at the Research nesota, U.S. In 1990, he organized the Fourth International
Institute of Toxicology (RITOX) at the University of Workshop on QSAR in Environmental Toxicology in The
Utrecht. He has been member of various policy and expert Netherlands. He is now actively involved in the develop
groups in the European Union, the International Rhine ment and application of estimation methodologies and
Committee, the Organization for Economic Co-operation monitoring tools for the European Union.
and Development, the European and Mediterranean Plant
Protection Organization and the Council of Europe. He was
chairman of the OECD Hazard Assessment Advisory
Body and is vice-chairman of the OECD Joint Committee
on Chemicals.
ix
CONTRIBUTORS AND REVIEWERS
CONTRIBUTORS Research Institute of Toxicology
University of Utrecht
Dr. M. Van Den Berg Utrecht, The Netherlands
Research Institute of Toxicology
University of Utrecht Dr. Ir. D. Van De Meent
Environmental Toxicology Section National Institute of Public Health and Environmental
Utrecht, The Netherlands Protection
Laboratory for Ecotoxicology
Dr. J.H.M. De Bruijn Bilthoven, The Netherlands
Ministry of Housing, Spatial Planning and Environment
Risk Assessment and Environmental Quality Division Dr. M. Nendza
The Hague, The Netherlands Analytisches Laboratorium fiir Umweltuntersuchungen
und Auftragsforschung
Dr. J.L.M. Hermens Luhnstedt, Germany
Research Institute of Toxicology
University of Utrecht Drs. AC.M. De Nijs
Environmental Toxicology Section National Institute of Public Health and Environmental
Utrecht, The Netherlands Protection
Laboratory for Water and Drinking Water
Drs. D.T. Jager Bilthoven, The Netherlands
National Institute of Public Health and Environmental
Protection Dr. Ir. W. Peijnenburg
Laboratory for Ecotoxicology National Institute of Public Health and Environmental
Bilthoven, The Netherlands Protection
Department of Environmental Chemistry
Prof. Dr. R. Kroes Laboratory for Ecotoxicology
National Institute of Public Health and Environmental Bilthoven, The Netherlands
Protection
Board of Directors Ing. P. Van Der Poel
Bilthoven, The Netherlands National Institute of Public Health and Environmental
& Protection
Research Institute of Toxicology Laboratory for Emission and Waste
University of Utrecht Bilthoven, The Netherlands
Utrecht, The Netherlands
Drs. J.P.M. Ros
Dr. F.AAM. De Leeuw National Institute of Public Health and Environmental
National Institute of Public Health and Environmental Protection
Protection Laboratory for Emission and Waste
Air Research Laboratory Bilthoven, The Netherlands
Bilthoven, The Netherlands
Dr. D.T.H.M. Sijm
Prof. Dr. C.J. Van Leeuwen Research Institute of Toxicology
Ministry of Housing, Spatial Planning and Environment University of Utrecht
Risk Assessment and Environmental Quality Division Environmental Chemistry Group
The Hague, The Netherlands Utrecht, The Netherlands
&
x
Dr. J. Struijs Prof. Dr. H.A.J. Govers
National Institute of Public Health and Environmental University of Amsterdam
Protection Laboratory of Environmental and Toxicological
Department of Environmental Chemistry Chemistry
Laboratory for Ecotoxicology Amsterdam, The Netherlands
Bilthoven, The Netherlands
Dr. K. Grein
Dr. W. Tas Commission of the European Communities
National Institute of Public Health and Environmental DG XI/C/6
Protection Brussels, Belgium
Advisory Centre for Toxicology
Bilthoven, The Netherlands Prof. Dr. M. Matthies
University of Osnabrock
Drs. T.G. Vermeire Institute of Environmental Systems Research
National Institute of Public Health and Environmental Osnabrock, Germany
Protection
Advisory Centre for Toxicology Dr. A. Opperhuizen
Bilthoven, The Netherlands Ministry of Transport, Public Works and Water
Management
Ir. P.T.J. Van Der Zandt Tidal Waters Division
Ministry of Housing, Spatial Planning and Environment The Hague, The Netherlands
Risk Assessment and Environmental Quality Division
The Hague, The Netherlands Prof. Dr. W. Seinen
Research Institute of Toxicology
REVIEWERS University of Utrecht
Utrecht, The Netherlands
Dr. B.J. Blaauboer
Research Institute of Toxicology Dr. W. Slooff
University of Utrecht National Institute of Public Health and Environmental
Biochemical Toxicology Protection
Utrecht, The Netherlands Environmental Forecasting Bureau
Bilthoven, The Netherlands
Drs. P.F.H. Bont
Resources Planning Consultants B.Y. Prof. Dr. N.M. Van Straalen
Delft, The Netherlands Vrije Universiteit
Faculty of Biology
Prof. Dr. F. Bro-Rasmussen Amsterdam, The Netherlands
Danish Technical University
Faculty of Environmental Science and Ecology Prof. Dr. H.A. Udo De Haes
Lyngby, Denmark University of Leiden
Centre of Environmental Science
Dr. Ir. T.C.J. Fey tel Leiden, The Netherlands
Procter & Gamble
Strombeek-Bever, Belgium
Dr. Ir. C.A.M. Van Gestel
Vrije Universiteit
Department of Ecology & Ecotoxicology
Amsterdam, The Netherlands
xi
ACKNOWLEDGEMENTS
This book is the result of a joint effort between the Special thanks are due to those who reviewed one or
Ministry of Housing, Spatial Planning and Environment more chapters of this book. For the correction of English
(VROM), RPC Resources Planning Consultants B.V and we would like to thank Mrs. A. Oostenbrink and Mrs. S.
various experts in the field of risk assessment and the Hunt. We would also like to thank Prof. Dr. VI. Feron
management of chemicals at the National Institute of for his contribution to Section 5.5.3, Prof. Dr. P. W.l.
Public Health and Environmental Protection (RIVM), the Peters, Prof. Dr. G. R. Mohn, Drs. 1. Bol and Ms. 1.
Research Institute of Toxicology (RITOX), and various Smink and the secretary of the Research Institute of
other organizations. The editors would like to thank RPC Toxicology for their contributions.
Resources Planning Consultants B.V for their technical
assistance and VROM for its financial support for this
project.
xii
EXPLANATORY NOTES
Prefixes to the names of units Other abbreviations
M mega (106) a.i. active ingredient
k kilo (103) b.p. boiling point
d deci (101) bw body weight
c centi (10-2) c.v. coefficient of variation
m milli (10-3) Cyt cytochrome
J1 micro (10-6) Eh electrode potential
n nano (10-9) F variance ratio
p pico (10-12) GC-MS gas chromatography-mass spectrometry
f femto (10-15) GLC gas-liquid chromatography
HPLC high performance liquid chromatography
Chemical prefixes k rate constant
0 ortho K equilibrium constant
m meta log logarithm (common, base 10)
p para In logarithm (natural, base e)
n normal mol.wt. molecular weight
sec secondary m.p. melting point
tert tertiary MS mass spectrometry
norN total number of individuals or variates
Units No. number (in tables and parentheses)
A Angstrom (0.1 mm) p level of significance (probability of
atm atmosphere wrongfully rejecting the null hypothesis)
°C degree Ce1cius or centigrade ppb parts per billion
cal calorie ppm parts per million
d day r coefficient of correlation
g gram R coefficient of multiple correlation
h hour s2 sample variance
ha hectare (J standard deviation of population
J Joule SD standard deviation of series
K degree absolute (Kelvin) SE standard error of mean
kg kilogram sp. species (when part of a bionomial)
L litre t1l2 half-life
m metre TLC thin layer chromatography
M molar (moillitre) UV ultraviolet
mIll minute m mean of population
Pa pascal (unit of pressure; 100kPa = 1 bar) v/v volume/volume (concentration)
s second w/v weight/volume (concentration)
V Volt
W Watt
y year
