WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/DS/85.62
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 62
CHLOROPHACINONE
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
CLASSIFICATION:
Primary use: Rodenticide
Secondary use:
Chemical group: Indandione derivative
1. GENERAL INFORMATION
1.1 COMMON NAME:
Chlorophacinone (ISO, BSI and JMAF)
1.1.1 Identity;
IUPAC: 2-(2-(4-chlorophenyl)-2-phenylacetyl)indan-1, 3-dione
CAS: 2-(2-(4-chlorophenyl)-phenylacetyl)-1H-indene-1,
3(2H)-dione
CAS Reg. No.: 3691-35-8
Molecular formula: C23H15ClO3
Molecular weight: 374.8
Structural formula:
1.1.2 Synonyms:
AFNORR; CaidR; chlorofacinon; chlorfacinon; chlorophacinone;
DeltaR; DratR; LiphadioneR; LM 91R: MicrozulR; MuriolR;
QuickR; RamucideR; RanacR; RatometR; RaviacR; RozolR;
TopitoxR.
1.2 SYNOPSIS:
Chlorophacinone is a chlorinated, diphenyl indane derivative;
an anti-coagulant and metabolic inhibitor which is highly toxic to
rodents but of only slight toxicity to humans and other non-target
organisms. It is compatible with a wide spectrum of bait carriers
and has no repellent action.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
Chlorophacinone is a white crystalline solid. It has a melting
point of 140°C, it is non-corrosive.
1.3.2 Solubility
Chlorophacinone is sparingly soluble in water, but soluble in
organic solvents.
1.3.3 Stability
Chlorophacinone is described as stable and resistant to
weathering effects.
1.3.4 Vapour pressure
Negligible at 20°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
Chlorophacinone is available as a bait, 50-250 mg a.i./kg and
in oil solution, 2.5 g a.i./L.
1.4.2 Pests controlled
Presently used against mice, moles, muskrats, rats, vampire
bats, and voles - in controlled access areas and under field
conditions.
1.4.3 Use pattern
Chlorophacinone is applied wherever the rodents have access to
the bait. It may be replenished as it is consumed. A tracking powder
is recommended in areas where rodents travel. It does not usually
require more than one feeding for a kill. The oil solution may be
used to impregnate or coat any desirable bait. Prevent food
contamination.
1.4.4 Unintended effects
Chlorophacinone could be hazardous to other small mammals and
birds if used indiscriminately. Persons with bleeding problems and
children should not come in contact.
1.5 PUBLIC HEALTH USE
As in 1.4, for control of nuisance and disease vector rodent
pests.
1.6 HOUSEHOLD USE
As in 1.4, for control of nuisance and disease vector rodent
pests.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
Chlorophacinone is primarily absorbed from the gastrointestinal
tract; dermal absorption may also occur.
2.1.2 Mode of action
Chlorophacinone is an anticoagulant agent; it uncouples
oxidative phosphorylation depressing hepatic synthesis of
prothrombin and clotting factors VII, IX and X and, it causes direct
damage to capillary permeability. The ultimate effect is widespread
internal haemorrhage. In rodents, indandlones also cause neurologic
and cardiopulmonary injuries which often lead to death before
haemorrhage occurs.
2.1.3 Excretion products
No published information available.
2.1.4 Toxicity, single dose
A single dose of a 50 mg/kg bait kills Rattus norvegicus from
the fifth day.
Oral LD50:
Rat 20.5 mg/kg bw; technical material
Rabbit 50.0 mg/kg bw; technical material
Dermal LD50:
Rabbit 200.0 mg/kg bw; technical material
A solution of 5 mg in 2 ml of liquid paraffin applied to 100
cm2 of shaved skin on rabbits caused only a slight reduction of
prothrombin rating.
2.1.5 Toxicity, repeated doses
No published information available.
Cumulation of compound
No published information available.
2.1.6 Dietary studies
No published information available.
2.1.7 Supplementary studies of toxicity
No published information available.
2.1.8 Modification of toxicity
No published information available.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption
Chlorophacinone is primarily absorbed from the gastrointestinal
tract, it may also be absorbed through the intact skin and,
inhalation of residual bait dust may also occur.
2.2.2 Dangerous doses
No published information available. It is assumed that, because
of low bait concentrations and the delayed nature of the toxic
effect, it would require the ingestion of over one kilogram of the
bait to produce toxic effects. Persons with "bleeding problems"
should avoid contact.
2.2.3 Observations of occupationally exposed workers
No published information available.
2.2.4 Observations on exposure of the general population
No published information available.
2.2.5 Observations of volunteers
Human volunteers tolerated a single dose of 20 mg a.i. without
ill-effects.
2.2.6 Reported mishaps
No published information available. In reports of cases
involving similar poisons the compounds were either taken
deliberately, were absorbed chronically out of neglect of basic
hygiene or were ingested when rodent baits were inadvertently used
as food.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish
No published information available.
2.3.2 Birds
Chlorophacinone is of low toxicity to birds. Administration of
15 daily doses of 2.25 mg to grey partridges produced no ill-
effects.
Oral LD50:
Wild Birds 430 mg/kg bw; technical material
Ducks 100 mg/kg bw; technical material
3. FOR REGULATORY AUTHORITIES - RECOMMENDATION ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories see introduction.) All
formulations, categories 4 and 5.
3.2 TRANSPORT AND STORAGE
Formulations in category 4 - Should be transported in clearly
labelled, rigid and leakproof containers out of reach of children,
away from food and drink. Storage should be under lock and key and
secure from access by children and other unauthorized persons.
Formulations in category 5 - Should be transported and stored
in clearly labelled, leakproof containers out of reach of children,
away from food and drink.
3.3 HANDLING
Formulations in category 4 - Protective clothing should be
used by all handling the compound. Adequate washing facilities
should be available at all times during handling and they should be
close to the site of handling. Eating, drinking and smoking should
be prohibited during handling and before washing of hands and face
after handling. Baits of chlorophacinone should be removed and the
area thoroughly cleaned up after purpose has been fulfilled.
Formulations in category 5 - No facilities other than those
needed for the handling of any chemical are required. Baits of
chlorophacinone should be removed and the area thoroughly cleaned up
after purpose has been fulfilled.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations - Containers should not be decontaminated
and should not be used for any other purpose. Containers should be
burned or should be crushed and buried below topsoil. Care must be
taken to avoid subsequent contamination of water sources.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
Formulations in categories 4 and 5 - A pre-employment
examination is essential to exclude from contact all persons with
blood and vascular disorders predisposing them to haemorrhaging. A
periodic medical examination should include tests of blood clotting
time, prothrombin levels, capillary fragility and a record of
evidence of blood in the excreta.
3.6 ADDITIONAL REGULATIONS IF DISTRIBUTED BY AIRCRAFT
NOT APPLICABLE
3.7 LABELLING
Formulations in category 5 - Minimum cautionary statement -
"CAUTION". This formulation contains chlorophacinone, it may be
poisonous if swallowed. Keep this material out of reach of children
and well away from food, animal feed and food utensils. Avoid skin
contact, wear impermeable gloves when handling and wash immediately
after handling the compound. In case of contact, immediately remove
contaminated clothing and wash the skin thoroughly with soap and
water; for eyes, flush with water for 15 minutes.
If poisoning occurs, call a physician. Vitamin K is a specific
antidote.
3.8 RESIDUES IN FOOD
Maximum residue levels have been recommended by the Joint
FAO/WHO Meeting on Pesticide Residues.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General
Chlorophacinone is a rodenticide; an anticoagulant and a
metabolic inhibitor. It depresses hepatic synthesis of factors
essential to blood clotting and causes increased capillary
permeability which ultimately lead to internal haemorrhage.
Indandiones should be considered more toxic than warfarin though
their health hazard to humans may be considerably diminished by
their low concentration in most formulations and their delayed
action. Chlorophacinone is primarily absorbed from the
gastrointestinal tract; to a limited extent through intact skin;
and, inhalation of bait dust may also occur.
4.1.2 Manufacture and formulation - TLV
No information. Closed systems and forced ventilation may be
required to reduce, as much as possible, the exposure of workers to
the chemical.
4.1.3 Mixers and applicators
When opening a container and when mixing, protective
impermeable boots, clean overalls, impermeable gloves and a
respirator should be worn. Mixing, if not mechanical, should always
be carried out with a paddle of appropriate length. Avoid contact
with mouth and eyes. Before eating, drinking or smoking, hands and
other exposed skin should be thoroughly washed with alkaline soap.
4.1.4 Other associated workers
All persons exposed to the concentrate and associated with its
formulation should observe the precautions described above in 4.1.3.
4.1.5 Other populations likely to be affected
With good agricultural practice, subject to 4.2 below, other
populations are not likely to be exposed to hazardous amounts of the
compound.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Chlorophacinone is relatively persistent, all exposed baits
should be clearly marked and identified as a poison. Under these
conditions, unprotected adult persons may enter the treated area
immediately after application without being exposed to a health
hazard.
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGE
Residues in containers should be emptied in a dilute form into
a deep pit taking care to avoid contamination of ground waters.
Decontamination of containers in order to use them for other
purposes should not be permitted. Spillage should be removed as much
as possible and as soon as possible into a deep dry pit and the
residue washed away with large quantities of water. The residue and
containers may also be burned in a well-ventilated location.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning
The signs and symptoms of acute poisoning from a large dose are
not likely to be immediately apparent. When the body's reserves of
prothrombin have been diminished, after two or three days following
a single large dose or after a few weeks of repeated ingestion of
small doses, bleeding gums, pallor, swelling and tenderness of the
joints, haematomata, blood in the urine and faeces, and abdominal
pains may occur. Paralysis, haemorrhagic shock and death may follow
in cases of severe poisoning. Cardiopulmonary and neurologic
symptoms seen in rats have not been reported in human victims.
4.4.2 Treatment before a person is seen by a physician
Due to the delayed appearance of symptoms, it is unlikely that
specific symptoms will be seen directly following exposure. If the
compound has been swallowed, vomiting should be induced immediately
if the person is conscious; call a physician immediately and
transport the victim to hospital as soon as possible.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1. General information
Chlorophacinone is a rodenticide; an anticoagulant and a
metabolic inhibitor; and, it may specifically inhibit Vitamin
K1-epoxidase activity. It depresses hepatic synthesis of factors
essential to normal blood clotting and causes increased fragility
and permeability of capillaries leading to widespread internal
haemorrhage. Chlorophacinone is absorbed primarily from the
gastrointestinal tract and to a limited extent through the intact
skin. It is highly toxic to rodents but it is considered to be
slightly toxic to humans, in most formulations.
5.1.2 Symptoms and signs
The victims of small ingested doses and even those of
substantial, hypoprothrombinemia inducing doses are usually
asymptomatic,. The onset of clinical signs of poisoning may be
delayed several days after exposure to a single large dose or after
a few weeks of repeated ingestion of small doses. The signs of
poisoning are epistascis and bleeding gums; pallor and sometimes
petechial rash; massive ecchymoses and/or haematomata (especially of
the articulating joints); blood in urine and faeces; occasionally
paralysis due to cerebral haemorrhage; and, haemorrhagic shock and
death. Cardiopulmonary and neurologic signs and symptoms, common in
rat poisonings, have not been reported in human cases.
5.1.3 Laboratory
The principle diagnostic test in a demonstration of markedly
reduced prothrombin activity in blood plasma, as measured by the
method of Quick or one of its modifications. The test should be
repeated at least twice daily until a normal prothrombin time is
established. Also, the blood clotting time and the bleeding time
should be obtained. Blood is often demonstrable in the excreta.
Secondary anaemia (hypochromic and microcytic) may be marked.
5.1.4 Treatment
If small amounts of the compound have been ingested by either
an adult or a child and the victim is asymptomatic, treatment is
probably unnecessary. If there is uncertainty about the dose or the
general health of the victim, Vitamin K1 may be given orally as a
prophylactic treatment. Observe the patient for 4-5 days.
If the dose is known to be large or the victim is showing signs
of poisoning, induce vomiting with Syrup of Ipecac or perform a
gastric lavage within 2-3 hours of ingestion. Follow with activated
charcoal treatment to limit absorption of any toxicant remaining in
the gastrointestinal tract. Vitamin K1 is a specific antidote, 5-
10 mg by subcutaneous or intramuscular injection may be repeated if
necessary. Only if the victim is bleeding severely or otherwise in
serious distress should the drug be given intravenously at a rate no
more than 1 mg/min. On subsequent days Vitamin K1 treatment may be
continued, if necessary. The usual precautions in Vitamin K1
therapy should be followed. Small transfusions of fresh whole blood
may be necessary or an immediate and temporary source of prothrombin
and erythrocytes. Vitamin C may be a useful adjunct to Vitamin K1
therapy, at 100 mg several times a day as necessary. Neither
Vitamins K3 nor K4 are effective antidotes in cases of
Indandione poisoning.
Following the establishment of control of haemorrhage and the
repair of the coagulation defect, iron replacement therapy should be
initiated to correct the secondary anaemia. In severe incidences it
may also be necessary to aspirate the haematomas after normal blood
clotting has been restored.
5.1.5 Prognosis
If the acute toxic effect is survived, the chances of complete
recovery are very good provided that subdural haemorrhages or
vascular lesions in other tissues do not: produce secondary effects.
5.1.6 References of previously reported cases
No information available.
5.2 SURVEILLANCE TESTS
Blood clotting time and bleeding time could be monitored in
chronically exposed individuals. Also, vigilance for blood in the
excreta and peripheral signs of capillary fragility is appropriate.
The blood levels of active Vitamin K1 relative to Vitamin
K1-expoxide or the level of Vitamin K1 epoxidase would also
prove useful to assess overexposure or the progress of therapy.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
Bullard, R. W. et al. (1975) J. Agric. Food Chem., 23(1), 72.
Davis, R. S. (1977), Bull. OEPP, 7(2), 477. Grant, R. G. & Pike,
R. K. (1979), J. Assoc. Off. Anal. Chem, 62(5), 1001. Kawano, Y. &
Chang, W. (1980), J. Assoc. Off. Anal. Chem, 63(5), 996. Reynolds,
R. (1980), Proc. Annu. Meet. Am. Assoc. Vet. Lab.; 23, 187. Vigh,
G. et al. (1981), J. Chromatogr., 214(3), 335.