IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Health and Safety Guide No. 93
BRODIFACOUM
HEALTH AND SAFETY GUIDE
UNITED NATIONS ENVIRONMENT PROGRAMME
INTERNATIONAL LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
WORLD HEALTH ORGANIZATION, GENEVA 1995
This is a companion volume to Environmental Health Criteria 175:
Anticoagulant Rodenticides
Published by the World Health Organization for the International
Programme on Chemical Safety (a collaborative programme of the United
Nations Environment Programme, the International Labour Organisation,
and the World Health Organization)
This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization
WHO Library Cataloguing in Publication Data
Health and safety guide for Brodifacoum
(Health and safety guide ; no. 93)
1.Rodenticides 2.Anticoagulants
3.Hydroxycoumarins - toxicity 4.Environmental exposure I.Series
ISBN 92 4 151093 5 (NLM Classification: WA 240)
ISSN 0259-7268
The World Health Organization welcomes requests for permission to
reproduce or translate its publications, in part or in full.
Applications and enquiries should be addressed to the Office of
Publications, World Health Organization, Geneva, Switzerland, which
will be glad to provide the latest information on any changes made to
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already available.
(c) World Health Organization 1995
Publications of the World Health Organization enjoy copyright
protection in accordance with the provisions of Protocol 2 of the
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concerning the legal status of any country, territory, city or area or
of its authorities, or concerning the delimitation of its frontiers or
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The mention of specific companies or of certain manufacturers'
products does not imply that they are endorsed or recommended by the
World Health Organization in preference to others of a similar nature
that are not mentioned. Errors and omissions excepted, the names of
proprietary products are distinguished by initial capital letters.
CONTENTS
INTRODUCTION
1. PRODUCT IDENTITY AND USES
1.1. Identity
1.2. Physical and chemical properties
1.3. Analytical methods
1.4. Production and uses
2. SUMMARY AND EVALUATION
2.1. Identity, physical and chemical properties, and
analytical methods
2.2. Sources of human and environmental exposure
2.3. Environmental transport, distribution, and
transformation
2.4. Environmental levels and human exposure
2.5. Kinetics and metabolism in laboratory animals
and humans
2.6. Effects on laboratory mammals and in vitro test systems
2.7. Effects on humans
2.8. Effects on other organisms in the laboratory and field
2.9. Evaluation of human health risks and effects on the
environment
2.9.1. Evaluation of human health risks
2.9.2. Evaluation of effects on the environment
3. CONCLUSIONS AND RECOMMENDATIONS
3.1. Conclusions
3.2. Recommendations for the protection of human health and the
environment
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1. Human health hazards, prevention and protection, first aid
4.1.1. Advice to physicians
4.1.2. Health surveillance advice
4.2. Explosion and fire hazards
4.3. Storage
4.4. Transport
4.5. Spillage
4.6. Disposal
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
6. SUMMARY OF CHEMICAL SAFETY INFORMATION
7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
7.1. Previous evaluations by international bodies
7.2. Exposure limit values
7.3. Specific restrictions
7.4. Labelling, packaging, and transport
7.5. Waste disposal
BIBLIOGRAPHY
INTRODUCTION
The Environmental Health Criteria (EHC) monographs produced by the
International Programme on Chemical Safety include an assessment of
the effects on the environment and on human health of exposure to a
chemical or combination of chemicals, or physical or biological
agents. They also provide guidelines for setting exposure limits.
The purpose of a Health and Safety Guide is to facilitate the
application of these guidelines in national chemical safety
programmes. The first three sections of a Health and Safety Guide
highlight the relevant technical information in the corresponding EHC.
Section 4 includes advice on preventive and protective measures and
emergency action; health workers should be thoroughly familiar with
the medical information to ensure that they can act efficiently in an
emergency. Within the Guide is a Summary of Chemical Safety
Information which should be readily available, and should be clearly
explained, to all who could come into contact with the chemical. The
section on regulatory information has been extracted from the legal
file of the International Register of Potentially Toxic Chemicals
(IRPTC) and from other United Nations sources.
The target readership includes occupational health services, those in
ministries, governmental agencies, industry, and trade unions who are
involved in the safe use of chemicals and the avoidance of
environmental health hazards, and those wanting more information on
this topic. An attempt has been made to use only terms that will be
familiar to the intended user. However, sections 1 and 2 inevitably
contain some technical terms. A bibliography has been included for
readers who require further background information.
Revision of the information in this Guide will take place in due
course, and the eventual aim is to use standardized terminology.
Comments on any difficulties encountered in using the Guide would be
very helpful and should be addressed to:
The Director
International Programme on Chemical Safety
World Health Organization
1211 Geneva 27
Switzerland
THE INFORMATION IN THIS GUIDE SHOULD BE CONSIDERED AS A STARTING POINT
TO A COMPREHENSIVE HEALTH AND SAFETY PROGRAMME
1. PRODUCT IDENTITY AND USES
1.1 Identity
Common name: brodifacoum
Chemical formula: C31H23BrO3
Chemical structure:
Common synonyms: Super-warfarin, bromfenacoum, BFC, PP-581,
WBA 8119, ICI-581
Trade names: Finale, Folgorat, Havoc, Klerat, Matikus,
Mouser, Ratak +, Rodend, Talon, Volak, Volid
CAS chemical name: 3-[3-(4'-bromo-[1,1'-biphenyl]-4-yl)-1,2,3,4-
tetrahydro-1-naphthalenyl]-4-hydroxy-2H-1-
benzopyran-2-one
IUPAC chemical name: 3-[3-(4'-bromobiphenyl 4-yl)- 1,2,3,4-
tetrahydro-1-naphtyl]-4-hydroxycoumarin
CAS registry number: 56073-10-0
RTECS registry number: GN4934750
1.2 Physical and Chemical Properties
Brodifacoum is an off-white powder, which is stable in the solid form.
Its solubility in water is very low (less than 10 mg/litre at 20°C and
pH 7); it is slightly soluble in benzene and soluble in acetone.
Further physical and chemical properties of brodifacoum are given in
the "Summary of Chemical Safety Information" (section 6).
1.3 Analytical Methods
Analytical methods for the determination of brodifacoum include liquid
chromatography with fluorescence detection and high-performance liquid
chromatography, with detection limits of 0.001 mg/litre and
0.002 mg/kg, respectively.
1.4 Production and Uses
The rodenticidal properties of brodifacoum were described in 1976. It
is an anticoagulant that is effective against rats and mice, including
warfarin-resistant strains. It is used in agriculture and urban
rodent control as ready-to-use baits of low concentration (usually
0.005% brodifacoum).
2. SUMMARY AND EVALUATION
2.1 Identity, Physical and Chemical Properties, and Analytical
Methods
Brodifacoum is an off-white to fawn powder, which is stable at room
temperature in the solid form and has a melting point of 228-232°C.
Its solubility in water is very low; it is slightly soluble in benzene
and chloroform and soluble in acetone. Determination of brodifacoum
is based on high-performance liquid chromatography.
2.2 Sources of Human and Environmental Exposure
Brodifacoum does not occur naturally. It is used as a rodenticide
against pest rodents and acts by preventing the production of
essential blood-clotting factors.
2.3 Environmental Transport, Distribution, and Transformation
Brodifacoum does not enter the atmosphere, because of its low
volatility. It is practically insoluble in water. Brodifacoum is
strongly bound on soil particles and is not taken up by plants. The
rate of degradation is relatively slow and depends on soil type.
Residues in crops have never been detected in field studies.
2.4 Environmental Levels and Human Exposure
Brodifacoum is not intended for direct application to growing crops or
for use as a food additive.
No information is available on concentrations in air, water, and soil.
Residues of brodifacoum were detected in dead barn owls in the United
Kingdom at levels of 0.019-0.515 mg/kg. Brodifacoum residues were
also found in the liver, muscle, and fatty tissues of rabbits,
intentionally poisoned during field trials with baits containing
0.005% active ingredient, at concentrations of 4.4, 0.26, and
0.86 mg/kg, respectively.
2.5 Kinetics and Metabolism in Laboratory Animals and Humans
Brodifacoum is absorbed through the gastrointestinal tract, skin, and
respiratory system. The major route of elimination in different
species after oral administration is through the faeces. The liver is
the main organ of accumulation and storage. Brodifacoum has mainly
been found as an unchanged compound. After a single oral dose to
rats, liver concentrations remained high and relatively constant for
96 h. Elimination from the liver is slow and biphasic with an initial
rapid phase lasting from 2 to 8 days after dosing and a slower
terminal phase with an elimination half-life of 130 days. In
accidentally poisoned patients, the plasma half-life was found to be
approximately 16-36 days.
2.6 Effects on Laboratory Mammals and in vitro Test Systems
Brodifacoum has a high acute oral toxicity (LD50 less than 1 mg/kg)
for various species, including rodents and non-rodents. The dermal
and inhalation toxicities are also high. Signs of poisoning are
similar for all routes of administration and are those associated with
an increased tendency to bleeding.
Brodifacoum is a slight irritant for the skin and a mild eye irritant.
In feeding studies on rats, the only effect was that associated with
anticoagulant action. No long-term studies have been reported.
Mutagenicity and teratogenicity studies did not show any mutagenic,
embryotoxic, or teratogenic effects.
2.7 Effects on Humans
Symptoms of acute intoxication by brodifacoum vary from an increased
tendency to bleed in less severe poisonings to massive haemorrhage in
more severe cases. The signs of poisoning develop with a delay of one
to several days after ingestion.
Both intentional and unintentional poisoning incidents have been
reported.
2.8 Effects on Other Organisms in the Laboratory and Field
Brodifacoum was highly toxic for fish when tested as a technical
material.
Bird species varied in their susceptibility to brodifacoum, oral
LD50s ranging from less than 1 mg/kg body weight to more than
20 mg/kg body weight.
The possible effects of brodifacoum on non-target organisms can be
considered in two categories, i.e., primary (direct poisoning) and
secondary (through consumption of poisoned rodents).
Cases of abortion and haemorrhage in sheep and goats caused by the
misuse of brodifacoum have been reported.
Secondary poisoning through the consumption of rats and mice killed
with brodifacoum may occur in dogs and cats in urban situations, but
are more likely in farm situations.
2.9 Evaluation of Human Health Risks and Effects on the Environment
2.9.1 Evaluation of human health risks
Brodifacoum is widely used in urban rodent control and against rodent
pests in agriculture. As it is used as low-concentration baits,
increased levels in air are unlikely. Being slightly soluble in
water, its use cannot be a significant source of water contamination.
Brodifacoum is not intended for direct application to growing crops
and no residues are expected in plant foodstuffs. Occupational
exposure may occur during manufacture, formulation, and bait
application, but data indicating the levels of exposure are not
available.
Brodifacoum may be absorbed through the gastrointestinal tract, skin,
and respiratory system. The major route of elimination in different
species, after oral administration, is through the faeces. The urine
is a very minor route of elimination. The liver is the major organ
for the accumulation and storage of brodifacoum, which has mainly been
found as the unchanged parent compound. Its elimination from the
liver is slow.
As a technical material, brodifacoum is extremely toxic for mammalian
species. Signs of poisoning in all species, including humans, are
associated with an increased bleeding tendency.
Both intentional and unintentional poisoning incidents have been
reported.
Prothrombin time is a satisfactory guide to the severity of acute
intoxication, and also for the effectiveness and duration of the
therapy.
Vitamin K1 is a specific antidote for both animals and humans (see
section 4.1.1).
2.9.2 Evaluation of effects on the environment
Brodifacoum is applied to discrete sites in the form of
low-concentration baits and is stable under normal conditions. The
solubility of brodifacoum in water is low and, in bait formulation,
its use is unlikely to be a source of water pollution. As a technical
material, it is highly toxic for fish.
Brodifacoum appears to bind rapidly in the soil with very slow
desorption and without leaching.
Non-target organisms are potentially at risk in two ways: from direct
consumption of baits (primary hazard) and through eating poisoned
rodents (secondary hazard).
Small pellets and whole grain baits are highly attractive to birds.
Wax-block formulations appear to decrease the attractiveness to the
birds and this reduces the possibility of poisoning incidents. Bird
species vary in their susceptibility to brodifacoum.
The main reason for the poisoning of domestic animals is direct
consumption of brodifacoum baits.
Brodifacoum shows a similar range of acute toxicity for non-target and
target mammals. The primary hazard is usually expressed by the amount
of finished bait that must be consumed to approach the lethal dose.
To reach the toxic or lethal dose, the non-target animals must consume
comparatively large amounts of bait with a concentration of 0.005%
active ingredient.
Some secondary toxicity laboratory studies on wildlife have shown that
captive predators could be intoxicated by the no-choice feeding of
brodifacoum-poisoned or dosed prey. The significance of these results
in terms of hazard under field conditions is difficult to assess,
because the predators would not be expected to eat only poisoned
animals. However, predators may take poisoned, but not dead, small
mammals preferentially. In areas close to baiting, poisoned rodents
may represent a high proportion of the diet for individual birds.
However, only few individuals will be affected, unless there has been
very widespread and constant use of the baits.
3. CONCLUSIONS AND RECOMMENDATIONS
3.1 Conclusions
Exposure of the general population to brodifacoum through air,
drinking-water, or food is unlikely and does not constitute a
significant health hazard. Poisoning incidents may occur in cases of
massive intentional or unintentional ingestion or prolonged skin
contact during manufacture and formulation.
Brodifacoum is relatively persistent in the environment, but its
specific use in the form of low-concentration bait formulations cannot
be a significant source of air, water, soil or food contamination.
Direct and secondary poisoning of birds, domestic and farm animals,
and wildlife has been observed.
3.2 Recommendations for the Protection of Human Health and the
Environment
Potentially exposed workers should receive appropriate biomonitoring
and health evaluation.
To prevent primary poisonings, baits should be placed where they
cannot be readily available to non-target species, e.g., in bait
stations.
Killed rodents should be burned or buried to prevent secondary
poisoning in predators.
4. HUMAN HEALTH HAZARDS, PREVENTION AND PROTECTION, EMERGENCY ACTION
4.1 Human Health Hazards, Prevention and Protection, First Aid
The oral, dermal, and inhalation toxicities of brodifacoum for mammals
are extremely high (rat oral LD50 0.3 mg/kg; rat inhalation LC50
0.005 mg/litre). The ingestion of 1 mg of brodifacoum by an adult
person was reported to produce bleeding that persisted for more than
two months. The average fatal dose for an adult man (60 kg) is
estimated to be approximately 15 mg brodifacoum or 300 g of 0.005%
bait.
The main features in less severe cases of brodifacoum poisoning are
excessive bruising, nose and gum bleeding, and blood in the urine and
faeces. Bleeding from several organs within the body leading to shock
and possibly death is seen in more severe cases. The onset of the
signs of poisoning may not be evident until a few days after
absorption.
Brodifacoum is a mild eye irritant and a slight skin irritant, but it
is not a skin sensitizer.
It is slowly metabolized by mammals and, following prolonged exposure,
may accumulate in the liver reaching toxic levels.
Full air-fed protection and an impervious suit, suitable for
wash-down, are necessary when handling technical material or powder
concentrates. In operations involving liquid concentrates, it is
necessary to wear PVC or nitrile-rubber gloves, armlets, and an apron,
together with a face shield and rubber boots.
All persons who are bleeding must obtain medical attention.
4.1.1 Advice to physicians
If poisoning following ingestion has occurred recently (within a few
hours), treatment involving gastric lavage and the administration of
charcoal in repeated doses is recommended.
A venous blood sample should be taken for measurement of the
haemoglobin level, prothrombin time, blood grouping, and
cross-matching.
If a patient is bleeding severely, give 25 mg of vitamin K1
(phytomenadione) by slow intravenous injection. Transfuse patient
with whole blood or plasma. Fresh, frozen plasma may be given. Check
prothrombin time at 3-h intervals and repeat injections of vitamin
K1 if no improvement occurs. Administration of factor concentrate
may be considered to avoid volume overload.
In less severe cases of poisoning, vitamin K1 may be given in lower
doses and also fresh, frozen plasma to rapidly restore the blood
clotting factors. Check prothrombin time after 8-10 h and repeat
vitamin K1 administration, if necessary.
Once the prothrombin time has stabilized, continue treatment with oral
vitamin K1, giving 10 mg four times daily.
Oral treatment may be sufficient in mild cases.
Keep the patient in hospital until the prothrombin time has remained
normal for three days.
Discharge the patient from hospital with the following treatment:
vitamin K1, 10 mg to be taken orally, twice daily, for up to 60
days, with close monitoring of the prothrombin time. It may be
possible to reduce the length of treatment.
4.1.2 Health surveillance advice
Workers handling concentrates must have periodic determination of the
potential disturbances of the clotting mechanisms by the most
appropriate method, such as, circulating descarboxyprothrombin,
prothrombin concentration, or prothrombin time.
4.2 Explosion and Fire Hazards
Brodifacoum is a combustible solid. Most industrial operations
involve the solution concentrates with flash point of solvents higher
than 90°C.
Heating of containers will cause a pressure rise, with the risk of
bursting and subsequent ignition. Fire-exposed containers should be
kept cool by spraying with water.
High temperature decomposition or burning in air will lead to the
formation of toxic gases, which may include carbon monoxide as well as
fumes of unchanged rodenticide; breathing apparatus must be worn in
fire-fighting.
Carbon dioxide or dry powders are recommended for extinguishing small
fires, and foam or water fog for larger fires. A water jet should not
be used.
Run-off water from the fire should be prevented from entering
surface-water drains or water sources.
4.3 Storage
Technical brodifacoum and formulations should be stored in sealed
containers in locked, well-ventilated, dry areas away from frost,
direct sunlight, and sources of heat and ignition. Keep products out
of reach of children and unauthorized personnel. Do not store near
food and animal feed.
4.4 Transport
Comply with any local regulations regarding the movement of hazardous
goods. Before despatch, ensure that the containers are sound and that
labels are securely fixed and undamaged.
4.5 Spillage
During decontamination, the operator must wear protective clothing,
PVC gloves, face shield, and rubber boots.
Dry spillages should be collected at once, by suction, and disposed of
as toxic waste, according to local legislation.
Liquid spillages should be adsorbed onto vermiculite or other inert
adsorbent and treated similarly.
Contaminated areas should be washed down with cold water containing
surfactant; the washings must be prevented from entering surface-water
drains.
4.6 Disposal
Disposal should be carried out according to national regulations.
Brodifacoum is stable, but is rapidly bound to the soil, with very
slow desorption and without leaching. It is only slightly soluble in
water and, in the form of bait formulations, it is unlikely to be a
source of water contamination.
Do not place baits where domestic or farm animals and birds can reach
them. Burn or bury any uneaten bait. Do not dump it in water. Look
for dead rats and mice and burn or bury them.
5. HAZARDS FOR THE ENVIRONMENT AND THEIR PREVENTION
Brodifacoum is stable, but is rapidly bound to the soil, with very
slow desorption and without leaching. It is only slightly soluble in
water and, in the form of bit formulations, it is unlikely to be a
source of water contamination.
Do not place baits where domestic or farm animals and birds can reach
them. Burn or bury any uneaten bait. Do not dump it in water. Look
for dead rats and mice and bury them.
6. SUMMARY OF CHEMICAL SAFETY INFORMATION
This summary should be easily available to all health workers
concerned with, and users of, brodifacoum. It should be displayed at,
or near, entrances to areas where there is potential exposure to
brodifacoum, and on processing equipment and containers. The summary
should be translated into the appropriate language(s). All persons
potentially exposed to the chemical should also have the instructions
in the summary clearly explained.
Space is available for insertion of the National Occupational Exposure
Limit, the address and telephone number of the National Poison Control
Centre, and local trade names.
BRODIFACOUM
Chemical formula: C31H23BrO3
CAS chemical name: 3-[3-(4'-bromo-[1,1'-biphenyl]-4-yl)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-hydroxy-2H-1-benzopyran-2-one
IUPAC chemical name: 3-[3-(4'-bromobiphenyl 4-yl)-1,2,3,4-tetrahydro-1-naphtyl]-4-hydroxycoumarin
CAS registry number: 56073-10-0
RTECS number: GN4934750
PHYSICAL PROPERTIES OTHER CHARACTERISTICS
Physical state powder Brodifacoum is an anticoagulant rodenticide; it is formulated as
Colour off-white low-concentration baits (usually 0.005% active ingredient)
Relative molecular mass 523.4
Melting point (°C) 228-232
Vapour pressure (25°C) less than 0.13 mPa
Solubility in water less than 0.01 g/litre
at 20°C, pH 7
Solubility
in acetone 6-20 g/litre
in benzene <0.6 mg/litre
in chloroform 3 g/litre
HAZARDS/SYMPTOMS PREVENTION AND PROTECTION FIRST AID
GENERAL: Readily absorbed Avoid exposure Obtain medical attention; antidote - vitamin K1
following ingestion, inhalation or
through the skin; if absorbed, may
cause increased bleeding tendency
to massive haemorrhage
SKIN: Slight irritant; significant Wear gloves when handling Wash with soap and water; seek medical
skin absorption occurs with liquid concentrate advice
concentrates; the baits are not
irritant
EYES: Mild irritant Use face shield when handling Flush eyes with water for at least 15 min
concentrates
INHALATION: Significant Avoid inhaling concentrate aerosols Obtain immediate medical attention
vapour exposure unlikely or bait dust
INGESTION: Nausea/vomiting Wash hands before eating, drinking, Rinse out the mouth with water; transfer
acute anticoagulant poisoning in or smoking to hospital immediately
several hours or days may occur
SPILLAGE STORAGE FIRE/EXPLOSION
Wear protective clothing during Store in sealed containers in a dry, Combustible solid; burning in air will lead
decontamination; dry spillage - ventilated, and locked storeroom, to the formation of toxic gases; for small fires
collect by suction and dispose of as away from children, unauthorized use carbon dioxide, halons, or dry powder;
toxic waste; liquid spillage - absorb persons, domestic animals, food, and for larger fires, use foam or water fog;
onto vermiculite or other inert animal feed keep containers cool by spraying with water
absorbent and treat similarly; do
not contaminate surface-water
drains
WASTE DISPOSAL NATIONAL INFORMATION
Proper incineration is the
method of choice
7. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
7.1 Previous Evaluations by International Bodies
Technical brodifacoum has been classified by WHO in Class Ia -
Extremely Hazardous, based on acute oral LD50 of 0.3 mg/kg for rats.
A Poisons Information Monograph for brodifacoum has been issued by
IPCS.
7.2 Exposure Limit Values
No information is available.
7.3 Specific Restrictions
Brodifacoum has been officially approved for use as a rodenticide in
many countries. In some countries, specific uses are defined, as well
as limitations and precautions.
7.4 Labelling, Packaging, and Transport
The European Community legislation requires labelling of technical
brodifacoum as very toxic with a hazard symbol T+ and the following
pictogram:
The United Nations in its Recommendations on the Transport of
Dangerous Goods classified brodifacoum in category 6.1, as a poisonous
substance (No. 3027).
7.5 Waste Disposal
No specific information is available.
BIBLIOGRAPHY
Hayes WJ Jr, & Laws ER Jr (1991) Handbook of pesticide toxicology,
Vol. 3, New York, Academic Press.
IPCS (1992) Poisons information monograph - brodifacoum, IPCS/
INTOX/Project, Geneva, World Health Organization (unpublished document
IPCS/INTOX/PIM.77).
IPCS (1995) Environmental Health Criteria 175: Anticoagulant
rodenticides, Geneva, World Health Organization.
WHO (1994) The WHO recommended classification of pesticides by hazard
and guidelines to classification 1994-1995, Geneva, World Health
Organization (unpublished document WHO/PCS/94.2).
Widdershoven J, van Munster P, De Abreu R, Bosman H, van Lith Th, van
der Putten-van Meyel M, Motohara K, & Matsuda I (1987) Four methods
compared for measuring des-carboxy-prothrombin (PIVKA-II), Clin Chem
33(11): 2074-2078.
Worthing CR & Hance RJ, ed. (1991) The pesticide manual, 9th edition,
Surrey, United Kingdom, British Crop Protection Council.