The Dictionary of Substances and Their Effects (DOSE): Volume 01 A-B
and their Effects
and their Effects
S Gangolli,Consultant,MRC Toxicology Unit,UK
EDITORIAL ADVISORY BOARD
Dr D Anderson, BIBRA International, UK
Dr J Chadwick, Health and Safety Executive, UK
Professor L Ebdon, University of Plymouth, UK
Dr D Gammon, California €PA,USA
Professor L King, University of Surrey, UK
Dr R McClellan, ChemicalIndustry Institute of Toxicology,USA
Professor I Rowland, Universityof Ulster,UK
Dr J Solbk, Unilever,UK
Dr T Sugimura, National CancerCentre,Japan
Professor P van Bladeren, 7"Nutrition and Food Research Institute, TheNetherlands
RSeCROYAL SOClEN OF CHEMISTRY
Ken Wilkinson (Staff Editor)
The publishers make no representation, express or implied, with regard to the accuracy of the
information contained in this book and cannot accept any legal responsibility or liability for
any errors or omissions that may be made.
Volume 1 ISBN 0-85404-808-1
Seven-volume set ISBN 0-85404-803-0
A catalogue record for this book is available from the British Library.
0The Royal Society of Chemistry 1999
All rights reserved
Apart from any fair dealing for the purpose of research or private study, or criticism or review as
permitted under the terms of the UK Copyright, Designs and Patents Act, 1988, this publication may
not be reproduced, stored or transmitted, in anyformor by any means, without the prior permission in
writing of The Royal Society of Chemistry, or in the case uf reprographic reproduction only in
accordance with the terms of the licences issued by the Copyright Licensing Agency in the UK, or in
accordance with the terms of the licences issued by the appropriate Reproduction Rights Organisation
outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to The
Royal Society of Chemistry at the address printed on this page.
Published by The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton
Road, Cambridge, CB4 OWF, UK
Typeset by Land & Unwin (Data Sciences)Ltd, Bugbrooke, UK
Printed and bound by Bookcraft (Bath)Ltd., UK
Guide to Content
Glossary of Medical and BiologicalTerms
Glossary of Organism Names
Guide to Content
Guide to Content
Guide to Content
Guide to Content
Guide to Content
Guide to Content
Index of ChemicalNames and Synonyms
Index of CASRegistry Numbers
Index of Molecular Formulae
The lifestyle of the modern world can only be sustained by the effective utilisation of
chemicals in the protection of our health, production of our food, manufacture and
commerce. Yet these same chemicalsin the wrong place can have potentially harmful effects.
To understand the quantitative risks to human health and ecosystems,reliable information is
required about the substances and their biological effects.The Dictionary of Substances and their
Efiects (DOSE)seeks to provide such information comprehensively yet in an easily accessible
As our understanding of the complexity of life and the intricate interactions which sustain
ecosystems has grown, so has our requirement for information. The toxicologist,
ecotoxicologist,and users and suppliers of chemicals need to know the properties, chemistry,
biological effects and likely use of substances. Yet too often comprehensive data are difficult
to obtain. The first edition of DOSE was hailed as an important breakthrough for those who
needed a comprehensive and reliable compilation of data on chemicals with environmental
impact. This second edition significantly updates the toxicological data and extends the
number of chemicalsto 4123.
While regulators might argue that the provision of toxicological data should be the
responsibility of chemicalsuppliers, the reality is that often when such data are supplied they
are overly brief or ridiculously over-cautious. I recently received a sample labelled "tap
water" with the warning that it contained "hydrogen, which is a flammable substance". To
have a single compilation of data, collected only from the peer-reviewed literature, and
published under the authoritative imprimatur of the Royal Society of Chemistry, is surely the
most effectiveanswer to this problem.
The editorial team which has brought together this excellent second edition is to be
congratulated on its achievement. DOSE will allow users to identify the hazards pertaining to
given substances readily. Professor Lord Lewis in his introduction to the first edition
emphasised the difference between hazard identification and risk assessment. Lord Lewis
stressed the need for training to evaluate risks quantitatively and, in particular, the risks
posed by combinations of chemicals.He quoted Paracelsus, the father of toxicology, and his
famous dictum often translated as "the dose maketh the poison". In a world reliant on
chemicals, but with an environment seriously threatened by anthropological damage, DOSE
will enable scientists and regulators to ensure that the dose received by the organism will be
far less than poison, indeed below that which has an effect.
Professor Les Ebdon
University of Plymouth
The risk evaluation of the potential adverse effects of a chemical on human health and the
ecosystem, widely recognised by regulatory agencies as being of vital importance for the
protection of man and his environment, requires the assessment of a broad range of
information on the chemistry and biological properties of that chemical. Except for certain
special human and veterinary medicine and some agrochemicals,relevant data for the vast
majority of chemicals traded commercially are either not available or sparsely dispersed in
the scientific literature. Thus, the assessment of the health and environmental risks of a
chemical would be an onerous task without access to a single comprehensive compilation of
In the publication of the first edition of The Dictionary of Substances and their €fiects (DOSE),
the Royal Society of Chemistry addressed the formidable logistical problems faced by
scientists in obtaining the relevant data for the risk assessment of chemicals due to the
paucity of publications containing compilations of appropriate data. The aim of this
acclaimed publication was to collect and collate relevant chemical and biological data from
peer-reviewed scientific literature to provide information for the quantitative risk evaluation
of a chemical at its various levels of usage and conditions of exposure. The chemicals in the
first edition were selected mainly from sources such as the Authorised and Approved List
from the EC’s Classification, Packaging and Labelling Regulations; the EC’s “Black” and
“Grey” lists of dangerous substances; the ”Red” list prepared by the UK Department of the
Environment; and the Priority Pollutant Lists from the USA and Canada, and the German
Pollutant List. Data considered to be of relevance for each of the 4003 chemicals in the first
edition included physico-chemical properties; toxic effects on various species in the
ecosystem; persistence and degradability in the environment; and toxicity data,
encompassing genotoxicity, reproductive effects and toxicokinetic studies in avian and
mammalian species,including man. Relevant legislativeinformation was also included.
The success of the first edition of DOSE as a unique reference source of essential information
for the risk evaluation of chemicals was clearly reflected by sales, encouraging reviews and,
most importantly, the favourable comments received from users. Since the publication of the
first edition there has been a year on year increase in the numbers of research papers on
topics relevant for the risk assessment of chemicals in the literature. These considerations,
together with the burgeoning literature on the toxicology of chemicals subsequent to the
publication of the first edition, were persuasive factors in influencing the Royal Society of
Chemistry to embark on the preparation of the present second edition of DOSE. Relevant
information is reported in DOSE if it has been published in the scientific literature, and it is
interesting to note that toxicity data on many industrial chemicals are still not available. A
recent US Environmental Protection Agency study1 has shown that, of the estimated 3000
high production volume chemicals (i.e. in excess of 1million pounds/annum) produced or
imported in the USA, only 7%had a full set of basic toxicity data, and 43% had no toxicity
data at all.
1.Pesticide and Toxic Chemical News 1998, 26 (28), 7-8.
A number of important additions have been incorporated in this second edition. Apart from
updating the toxicological data for the original compounds in the first edition, the number of
compounds has increased to 4123. Special classes of chemicals have been added, including
several endocrine disrupting chemicals, a number of pesticides, a few of the high production
volume chemicalsfor which data have recently been collected by the OECD, and compounds
tested for carcinogenicityby IARC and/or NTP. Risk and safety phrases have been updated,
and some headings have been changed to conform with current practice and convention. A
new field, Toxicity to other species, has been included, occupational exposure data have been
expanded to include values for France, Germany, Sweden and Japan as well as for the UK
and USA. RTECS and EINECSnumbers have also been included in the entries.
It is my fervent hope that the second edition of DOSE will constitute a scientifically sound
foundation and a paradigm for future publications that will be required to satisfy the need
for accurate and timely data in this important field.
I am grateful to members of the Editorial Advisory Board for their helpful suggestions and
advice. I must also place on record my sincere thanks to the staff members of the Royal
Society of Chemistry for their invaluable support and cooperation in the preparation of this
edition of DOSE.
Guide to Content
The data for each chemicalin DOSE are organised as follows:
CAS Registry No.
Toxicity to other species
Adsorption and retention
Mammalian and avian toxicity
Sub-acuteand sub-chronic data
Carcinogenicityand chronic effects
Teratogenicity and reproductive effects
Metabolism and toxicokinetics
Other adverse effects (human)
Any other adverse effects
These headings only appear in an item when data have been identified for that heading. The
user can, therefore, assume that the absence of a heading means that no relevant data were
retrieved from the sources examined.
xi Guide to Content
Each of the 4123 compounds in DOSE is identified by a unique, sequential alphanumeric
DOSE No. For example, the first compound in DOSE, A-a-C,has DOSE No. A2;the last entry,
zoxazolamine,has DOSE No. 225.
In general, the chemical name is the common name of the substance, for example
nitrobenzene. If it is not possible to allocate a precise chemical name (i.e.if the substance is of
unknown or variable composition,or consistsof biological materials),a short phrase appears
instead, for examplechlorinated parafins (C12, 60%).
This is the elemental composition of the compound. The elements appear alphabetically for
inorganic compounds, i.e. Ag2C03, C12Cr, etc, but for organic compounds, carbon and
hydrogen content are shown first followed by the other elements in alphabetical order, i.e.
This is directly calculated from the molecular formula. No molecular weights are given for
CAS Registry No.
The CAS Registry No. is a number sequence adopted by the Chemical Abstracts Service
(American Chemical Society, Columbus, Ohio, USA) to uniquely identify specific chemical
substances. The number contains no information relating to the chemical structure of a
substance and is, in effect, a catalogue number relating to one of the millions of unique
chemical substances recorded in the CASRegistry.New numbers are assigned sequentiallyto
each new compound identified by Chemical Abstracts Service. This information is also
provided in the full index of CAS Registry Numbers available at the end of Volume 7.
For common chemicals, several chemical names and numerous trade names may be applied
to describe the chemical in question. Many of these names are identified to aid users on the
range of names which have been used to describe each substance.
This number is assigned by the European Commission to each record in the EINECS
(EuropeanInventory of Existing Commercial Chemical Substances)inventory. The numbers
are in the format XXX-XXX-X, for example, 202-726-0 for nitrobenzene.
The RTECS (Registry of Toxic Effectsof Chemical Substances)number is a unique identifier
assigned by NIOSH (NationalInstitute of OccupationalSafetyand Health in the US) to every
substancein the RTECS database. The number is in the format of two alphabetic characters
followed by seven numeric characters,forexample, D A 6475000for nitrobenzene.
Guide to Content xii
Principal uses of the substances are given, with information on other sign
ficant uses n
Natural occurrences, whether in plants, animals or fungi are reported.
These data are derived from various sources.
The flash point is the lowest temperature at which the vapours of a volatile combustible
substance will sustain combustion in air when exposed to a flame. The flash point
information is derived from various sources.Where possible the method of determination of
the flash point is given.
Specific gravity (density)
The specific gravity of each substance has been derived from a variety of sources. Where
possible the data have been standardised.
Partition coefficients, important for structure-activity relationship considerations,
particularly in the aquatic environment, are indicated. Ideally the n-octanollwater partition
coefficient is quoted. The major data source for this measurement is:
Sangster,J J. Phys. Chem.ReF Data 1989,18(3),1111-1229
Where no reference is quoted, it can be assumed that the information was derived from this
The vapour pressure and vapour density are quoted where available. Where possible, the
data have been standardised.
Solubility data derived from several sources are quoted for both water and organic solvents
This field contains the occupational exposure limit values (or threshold limit values) from
France, Germany,Japan, Sweden, UK and USA.
The airborne limits of permitted concentrations of hazardous chemicals represent conditions
under which it is believed that nearly all workers may be repeatedly exposed day after day
without adverse effect. These limits are subject to periodic revision and vary between
differentcountries. The term threshold limit relates primarily to the USA, but equivalent terms
are available in most industrialised countries. The data relates to concentrations of substances
expressed in parts per million (ppm)and milligrams per cubic meter (mgvi3).
French exposure limits are published by the French Ministry in Charge of Labour and
presented in the report Valeurs limites d’exposition professionnelle aux agents chimiques en France
(ND 1945-153-93).The values in DOSE have been taken from the 1998 edition. The FR-VLE
values are short-term limits (15minutes), and FR-VME values are long-term limits (8hours).
German data currently include the national MAK values where available. The MAK value
(Maximale Arbeitsplatz-Konzentration) is defined as the maximum permissible
concentration of a chemical compound present in the air within a working area which,
according to current knowledge, does not impair the health of the employee or cause undue
annoyance. Under those conditions, exposure can be repeated and of long duration over a
daily period of eight hours, constituting an average working week of 40 hours. MAK values
are published by the Geschaftsstelle der Deutschen Forschungsgemeinschaft, Bonn, in
”Maximum Concentrations at the Workplace and Biological Tolerance Values for Working
Materials.” The values in DOSE have been taken from the 1998edition.
Japanese exposure limits are those recommended by the Japanese Society of Occupational
Health. Unless otherwise indicated, these values are long-term exposure limits (the mean
exposure concentration at or below which adverse health effects caused by the substance do
not appear in most workers, working 8 hours a day, 40 hours a week under a moderate
workload). The values in DOSE were published in 1997.
Swedish data can include short-term exposure limit, a level limit, or a ceiling limit. The
values in DOSE were adopted in 1996.
In the UK occupational limits relating to airborne substances hazardous to health are
published by the Health and Safety Executive annually in Guidance Note EH40. The values
in the DOSE items have been taken from the 1999edition.
There are Maximum Exposure Limits (MEL)in the UK which are subject to regulation and
which should not normally be exceeded. They derive from Regulations, Approved Codes of
Practice, European Community Directives, or from the Health and Safety Commission. In
addition, there are Occupational Exposure Standards (OES) which are considered to
represent good practice and realistic criteria for the control of exposure. In an analogous
fashion to the USA Threshold Limits, there are long-term limits, expressed as time-weighted
average concentrations over an 8-hour working day, designed to protect workers against the
effects of long-term exposure. The short-term exposure limit is for a time-weighted average
of 15minutes. For those substances for which no short-term limit is listed, it is recommended
that a figure of three times the long-term exposure limit averaged over a 15-minute period be
used as a guideline for controlling exposure to short-term excursions.
Guide to Content xiv
The threshold limit values for the USA have been taken from the Threshold Limit Values and
Biological Exposure Indices, 1999 produced by the American Conference of Governmelital
Industrial Hygienists, Cincinnati, USA. The limits relate to Threshold Limit - Time Weighted
Average, Threshold Limit - Short Term Exposure Limit and Threshold Limit - Ceiling Limit. The
Threshold Limit Value -Time Weighted Average (TLV-TWA)allows a time-weighted average
concentration for a normal %hour working day and a 40-hour working week, to which nearly
all workers may be repeatedly exposed day after day, without adverse effect. The Threshold
Limit Value - Short Term Exposure Limit (TLV-STEL) is defined as a 15-minute, time-
weighted average which should not be exceeded at any time during a work day, even if the
&hour time-weighted average is within the TLV. It is designed to protect workers from
chemicals which may cause irritancy, chronic or irreversible tissue damage, or narcosis of
sufficient degree to cause the likelihood of accidental injury. Many STELs have been deleted
pending further toxicological assessment. With Threshold Limit - Ceiling Values (TLV-C)the
concentration should not be exceeded during any part of the working day.
The United Nations Number is a four-figure code used to identify hazardous Chemicals and
is used for identification of chemicals transported internationally by road, rail, sea and air. In
the UK this number is also called the ”SubstanceIdentificationNumber” or “SI Number”.
The Hazchem Code is used to instruct United Kingdom emergency services on equipment,
evacuation and other methods of dealing with transportation incidents. It is administered by
the Chemical Industries Association.
The information presented for the transportation of substances dangerous for conveyance by
road is derived from the UK’s Approved Carriage List, Health and Safety Commission, UK.
The information presented for the supply of substances is derived from the UK’s Approved
Supply List: information approved for the classification and labelling of substances and
preparations dangerous for supply [Chemicals (Hazard Information and Packaging)
Regulations 1999(CHIP99)*]Health and Safety Commission,UK.
Risk and safety phrases
Risk and safety phrases used in connection with DOSE items are approved phrases for
describing the risks involved in the use of hazardous chemicals and have validity in the
United Kingdom and throughout the countries of the European Community. The approved
texts have designated R (Risk) and S (Safety) numbers from which it is possible to provide
translations for all approved languages adopted by the European Community. The risk and
safety phrases quoted in DOSE relate to the UK’s Approved Supply List: information
*At the time of going to press the Health and Safety Commission, UK announced that an amendment (Amendment No. 2) to the
CHIP 99 regulations is intended to come into force on 1January 2000. The supply classificationsand the risk and safety phrases
reported in this edition of DOSE do not include any changes which are proposed in Amendment No. 2 to CHIP99. Thesechanges are
incorporated in the updates to the electronicversions of DOSE released after 1January2000.
xv Guideto Content
approved for the classification and labelling of substances and preparations dangerous for
supply [Chemicals(Hazard Information and Packaging) Regulations, 1999(CHIP99)] Health
and Safety Commission, UK. The risk and safety phrases should be used to describe the
hazards of chemicals on data sheets for use and supply; for labelling of containers, storage
drums, tanks etc., and for labelling of articles specified as dangerous for conveyanceby road.
(Seealso footnote on page xv.)
Information is presented on the effectsof chemicals on various ecosystems. Results of studies
carried out on aquatic species, primarily fish and invertebrates, but also fresh water and
marine microorganisms and plants are reported. Persistence and potential for accumulation
in the environment and any available information on the harmful effects to non-target
species, i.e. the unintentional exposure of terrestrial and/or aquatic species to a toxic
substance is given. Ecotoxicologycan be defined as that science involved in the study of the
production of harmful effects by substances entering the natural environment, especially
effects on populations, communities and ecosystems; or as the study of the effects of
chemicals on ecosystems and their non-human components. An essential part of the
ecotoxicology is the assessment of movement of potentially toxic imbalance through
environmental compartments and through food webs.
Ecotoxicology, unlike human toxicology, is more concerned with the effects to populations
than to individuals. Human toxicology is based on the extrapolation of data from many
species to one species man, whereas ecotoxicology necessitates the extrapolation from a few
species to many, or from limited field data to entire ecosystems.
Ecotoxicologymust not be confused with environmental toxicology which is the direct effects
of environmental chemicals to humans. The term environmental toxicology should only be
applied to the study of direct effects of environmental chemicals on human beings. Although
the main thrust of preventative toxicology is in the area of human health, it is becoming
increasinglyevident that human health is intimately connected with conditions in the natural
environment. Chemicals released into the environment far from human habitation may
become a health hazard for humans through food chain accumulation. Other chemicals may
adversely affectcrop growth or kill economically important fish stocks or bird life.
LC50 values, with duration of exposure, are quoted for two species of freshwater and one
marine species if available. Any additional information on bioassay type (static or flow
through) and water condition (pH, temperature, hardness or oxygen content) is reported.
LC50values with duration of exposure, are quoted for molluscs and crustaceans. EC50 values,
i.e. concentrations which will immobilise 50% of an exposed population, are given for
microbes, algae and bacteria. Values which will inhibit microbial or algal growth are
reported. Duration of exposure is given when available.
Guideto Content xvi
Toxicityto other species
Toxicity to species other than mammals, birds, invertebrates and fish (e.g. reptiles,
amphibians, plants, seaweeds), is reported here. LD50, LC50 and EC50 values are given with
duration of exposure, concentration and as much supplementary information as possible.
Bioaccumulation, biomagnification and bioconcentration data are quoted primarily for fish,
invertebrates, bacteria and algae. Bioaccumulation is the progressive increase in the amount
of a chemical in an organism or part of an organism which occurs because the rate of intake
exceeds the organism’s ability to remove the substance from its body. Bioconcentration is a
process leading to a higher concentration of a chemical in an organism than in its
environment. Lastly, biomagnification is a sequence of processes in an ecosystem by which
higher concentrations are attained in organisms at higher trophic levels, i.e. at higher levels in
the food chain.
Degradation data are used to assess the persistence of a chemical substance in the
environment, in water, soil and air. If the substance does not persist, information on the
degradation products is also desirable. Intermediates may be either harmless or toxic
substances which will themselves persist. Degradation occursvia two major routes, microbial
degradation utilising microorganisms from a variety of habitats and decomposition by
chemical methods. Microbial degradation is associated with the production of elemental
carbon, nitrogen and sulfur from complex molecules. Standard biodegradation tests estimate
the importance of microbial biodegradation as a persistence factor. Most tests use relatively
dense microbial populations adapted to the compound being studied. Rapid degradation
results in these tests implies that the compound will degrade under most environmental
conditions, although specialised environments where degradation would not occur can exist.
Compounds which are not readily degradable are likely to persist over a wide range of
Chemical degradation processes include photolysis, hydrolysis, oxidation and removal by
reversible/irreversible binding to sediment. Factors which influence degradation rates, such
as duration of exposure, temperature, pH, salinity,concentrations of test substance, microbial
populations, and other nutrients, must also be taken into account.
Due care must also be given when metabolism results in th