Cypermethrin
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Brand names, Trade names |
| 1.6 Manufacturers, Importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First-aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Colour |
| 3.3.2 State/Form |
| 3.3.3 Description |
| 3.4 Hazardous characteristics |
| 4. USES |
| 4.1 Uses |
| 4.1.1 Uses |
| 4.1.2 Description |
| 4.2 High risk circumstance of poisoning |
| 4.3 Occupationally exposed populations |
| 5. ROUTES OF ENTRY |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Others |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination and excretion |
| 7. TOXICOLOGY |
| 7.1 Mode of Action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.2.4 Workplace standards |
| 7.2.5 Acceptable daily intake (ADI). and other guideline levels |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples & specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified). analyses |
| 8.1.3 Transport of laboratory samples &specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological Analyses and Their Interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple Qualitative Test(s). |
| 8.2.1.2 Advanced Qualitative Confirmation Test(s). |
| 8.2.1.3 Simple Quantitative Method(s). |
| 8.2.1.4 Advanced Quantitative Method(s). |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple Qualitative Test(s). |
| 8.2.2.2 Advanced Qualitative Confirmation Test(s). |
| 8.2.2.3 Simple Quantitative Method(s). |
| 8.2.2.4 Advanced Quantitative Method(s). |
| 8.2.2.5 Other Dedicated Method(s). |
| 8.2.3 Interpretation of toxicological analyses |
| 8.3 Biomedical investigations and their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.3.4 Interpretation of biomedical investigations |
| 8.4 Other biomedical investigations |
| 8.5 Overall Interpretation of all toxicological analyses and toxicological investigations |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central Nervous System (CNS). |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Other |
| 9.4.7 Endocrine & reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ears, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid & electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Others |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures and symptomatic treatment |
| 10.3 Decontamination |
| 10.4 Enhanced Elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. ADDITIONAL INFORMATION |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(S). |
CYPERMETHRIN
International Programme on Chemical Safety
Poisons Information Monograph 163
Chemical
1. NAME
1.1 Substance
Cypermethrin
1.2 Group
Synthetic pyrethroid
1.3 Synonyms
(RS).-alpha-cyano-3-phenoxybenzyl (1RS).-cis -,
trans-3-(2,2-dichlorovinyl).-2,2-dimethylcyclopropane
carboxylate (IUPAC chemical name);
(RS).-cyano-(3-phenoxyphenyl).methyl (1RS).-cis -,
trans-3-(2,2-dichloroethenyl).-2.2-dimethylcyclopropane
carboxylate (CAS chemical name);
1.4 Identification numbers
1.4.1 CAS number
52315-07-8 (formerly 69865-47-0). (WHO 1989).
1.4.2 Other numbers
RTECS registry number GZ1250000 (WHO1989).
1.5 Brand names, Trade names
Ammo, Avicide, Barricade, CCN 52, Cymbush, Folcord,
Imperator, Kafil Super, Polytrin, Ripcord, Stockade (WHO
1989).
1.6 Manufacturers, Importers
To be completed by local centre.
2. SUMMARY
2.1 Main risks and target organs
Cypermethrin is a neurotoxic agent most probably acting
through the central nervous system to cause repetitive nerve
activity. It is readily absorbed from the gastrointestinal
tract, by inhalation of dust and fine spray mist and only
minimally through intact skin. The toxic oral dose in mammals
is greater than 100-1000 mg/kg, and the potentially lethal
acute oral dose is 10-100 g.
2.2 Summary of clinical effects
The onset of symptoms varies depending upon such factors
as the route of absorption and quantity involved. In patients
with occupational poisoning, skin symptoms usually develop
within 4-6h post-exposure, with systemic symptoms occurring
as late as 48h post-exposure. Paraesthesia of the facial skin
can develop approximately 30 min post-exposure and does not
usually last beyond 24h when exposure is terminated.
Following ingestion, the initial symptoms involve the
gastrointestinal tract, developing 10-60 min post-exposure.
Patients suffering from acute oral poisoning usually develop
prominent digestive symptoms such as epigastric pain, nausea
and vomiting. Severely poisoned patients may have frequent
convulsive attacks, coma, or pulmonary oedema. The prognosis
is good if treated, with usually full recovery even in
severely poisoned patients. (The hospitalisation period is
usually longer than 4 weeks). Death may occur from
respiratory paralysis.
2.3 Diagnosis
Diagnosis should be made on the basis of verified
exposure to cypermethrin,corresponding symptoms and signs,
and reasonable exclusion of other diseases.
It is suggested that the facial skin sensations that may be
experienced by people handling cypermethrin may be considered
as an early warning signal that exposure has occurred.
There are no established practical methods for determining
pyrethroids in body fluids. Urinary levels of
3 - phenoxybenzyl degradation products may be a useful index
of exposure. The monitoring of sensory nerve action potential
and central nervous activity (EEG). may be useful in
diagnosis and in assessment of therapy.
2.4 First-aid measures and management principles
Wash skin with copious amounts of water for
10-15 min.
Irrigate eyes with copious water.
Treatment is essentially symptomatic and supportive following
decontamination procedures to prevent further absorption.
The skin irritation and paraethesia following dermal exposure
is self-limiting and may be alleviated with topical vitamin E
cream.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
A synthetic pyrethroid
3.2 Chemical structure
Molecular formula; C22H19Cl2NO3
Molecular weight
Relative molecular mass 416.3
Structural name
(RS).-alpha-cyano-3-phenoxybenzyl (1RS).-cis -,
trans-3-(2,2-dichlorovinyl).-2,2-dimethylcyclopropane
carboxylate (IUPAC chemical name). (WHO 1989).
The molecule embodies three chiral centres, two in the
cyclopropane ring and one on the alpha cyano carbon.
These isomers are commonly grouped into four cis- and four
trans-isomers, the cis-group being the more powerful
insecticide. The ratio of cis- to trans-isomers varies from
50:50 to 40:60. Cypermethrin is the racemic mixture of all
eight isomers. (WHO 1989).
3.3 Physical properties
3.3.1 Colour
Yellow (WHO 1989).
3.3.2 State/Form
Varies from a viscous yellow liquid to a
semi-solid crystalline mass at ambient temperatures
(WHO 1989).
3.3.3 Description
Solubility:
- solubility in water (20C):
0.009 mg/litre (WHO 1989).
- solubility in organic solvents:
hexane 103 g/litre
xylene Greater than 450 g/litre
- also comparable solubility in cyclohexane, ethanol,
acetone, and chloroform (WHO 1989).
Stability:
- highly stable to light and at temperatures
below 220C
- more resistant to acidic than to alkaline media,
with an optimum stability at pH 4. Dilute aqueous
solutions are subject to photolysis which occurs at a
moderate rate (WHO 1989).
Reactivity
Hydrolysed under alkaline conditions (WHO
1989).
3.4 Hazardous characteristics
Environmental fate/effects cypermethrin is adsorbed very
strongly on soil particles. (Ostiz et al., 1994). The
half-life in fertile soil is between 2 and 4 weeks. It
degrades readily in natural waters with a typical half-life
of about two weeks (WHO, 1989).
Toxic for fish, aquatic arthropods, and honey-bees in
laboratory tests, but, in practical usage, no serious adverse
effects have been noticed because of the low rates of
application and lack of persistence in the environment (WHO,
1989).
Boiling point decomposes at 220oC (WHO, 1989).
Melting point up to 80oC depending on purity and cis:
trans ratio (WHO, 1989).
4. USES
4.1 Uses
4.1.1 Uses
Insecticide
4.1.2 Description
Mainly used in the form of an emulsifiable
concentrate, but ultra low volume concentrates,
wettable powders, and combined forms with other
pesticides are also available. Effective against a
wide range of pests in agriculture, public health, and
animal husbandry (WHO, 1989).
4.2 High risk circumstance of poisoning
Unintentional exposure to spray during field
application. Accidental or intentional ingestion by children
or adults.
4.3 Occupationally exposed populations
Manufacturers, Formulators, Spray workers,
Farmers.
5. ROUTES OF ENTRY
5.1 Oral
Cypermethrin is rapidly absorbed from the
gastrointestinal tract.
5.2 Inhalation
Human poisoning cases have been reported following
exposure to air from contaminated air-conditoning
ducts.
5.3 Dermal
Dermal absorption has been demonstrated in human
volunteers.
5.4 Eye
No data available but is possible in view of dernal
exposure.
5.5 Parenteral
Animal toxicity studies have been conducted via both
intravenous and intraperitoneal routes
5.6 Others
No data available.
6. KINETICS
6.1 Absorption by route of exposure
Oral
Cypermethrin was administered orally to 6 male volunteers as
a single dose of 3.3mg (cis:trans 1:1). as a soya oil-based
formulation. Based on cis and trans
3-(2,2-dichlorovinyl).-2,2-dimethylcyclopropane carboxylic
acid (DCVA). urinary metabolite measurements, the amount of
cypermethrin absorbed was between 27% and 57% (mean 36%). of
the administered dose. (Woollen et al., 1992).
Dermal
Cypermethrin was administered dermally to 6 male volunteers
as a single dose of 31mg/800 cm2 (cis:trans 1:1). as a soya
oil-based formulation (the application site remained
unoccluded for 8h and was then washed off). Based on the
recovery of the phenoxybenzyl urinary metabolites, it was
0.85-1.8% (mean 1.2%). of the administered cypermethrin was
absorbed. (Woollen et al., 1992).
6.2 Distribution by route of exposure
Consistent with the lipophilic nature of cypermethrin,
the highest mean tissue concentrations are found in body fat,
skin, liver, kidneys, adrenals, and ovaries. Only neligible
concentrations are found in the brain (WHO, 1989).
6.3 Biological half-life by route of exposure
The mean elimination half-life for total metabolites
following oral administration of cypermethrin in volunteers
was 16.5 +- 5.8h (range 11-27h). (Woollen et al., 1992).
The mean elimination half-life for total metabolites
following dermal administration of cypermethrin in volunteers
was 13 +/- 5.1h (range 8-22h). (Woollen et al., 1992).
6.4 Metabolism
Synthetic pyrethroids are generally metabolised in
mammals through ester hydrolysis, oxidation, and conjugation
(WHO, 1989).
The major urinary metabolites of cypermethrin are a variety
of conjugates of cis and trans (DCVA)., 3-phenoxybenzoic acid
(3PBA). and 3-(4'-hydroxyphenoxy). benzoic acid (4OH3PBA).
Marked differences in the urinary metabolite profile by oral
and dermal routes in human volunteer studies suggest that
cypermethrin could be significantly metabolised in the skin
before systemic circulation occurs. (Woollen et al.,
1992).
6.5 Elimination and excretion
Oral
Cypermethrin was administered orally to 6 male volunteers as
a single dose of 3.3mg (cis:trans 1:1). as a soya oil-based
formulation. Approximately equal amounts of (cis + trans
DCVA). and (3PBA + 4OH3PBA). were excreted with peak
excretion rates occurring between 8 and 24h after dosing. The
ratio of trans:cis DCVA was on average 2:1. An average of 93%
of the metabolites recovered were excreted within 72h after
dosing (Woollen et al., 1992).
Dermal
Cypermethrin was administered dermally to 6 male volunteers
as a single dose of 31mg/800 cm2 (cis:trans 1:1). as a soya
oil-based formulation. Peak urinary excretion rates of
metabolites occurred between 12 and 36h after dermal dosing.
The amount of metabolites derived from the phenoxybenzyl
moiety (3PBA + 4OH3PBA). was on average 4 times greater than
the amount of (cis + trans DCVA). recovered in urine. Beyond
96h no metabolites were detected except for trace amounts of
4OH3PBA in two of six volunteers (Woollen et al.,
1992).
7. TOXICOLOGY
7.1 Mode of Action
The major target site of cypermethrin is the sodium
channel of the nerve membrane. A sodium channel exposed to
cypermethrin can remain open much longer, even up to several
seconds (He, 1994).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
No data available
7.2.1.2 Children
No data available
7.2.2 Relevant animal data
The toxic oral dose in mammals is greater than
100-1000mg/kg, and the potentially lethal acute oral
dose is 10-100g (Olsen, 1994).
The acute toxicity of the cis-isomer in the rat LD50
160-300 mg/kg body weight is much higher than that of
the trans-isomer LD50 > 2000 mg/kg . LD50 values
differ considerably among animal species depending on
the vehicle used and the cis-trans-isomeric ratios
used, although the toxic responses in all species was
found to be similar (WHO, 1989).
Neonatal rats are particularly sensitive to
cypermethrin and this sensitivity is higher, the
younger the animal. This is thought to be connected to
the incomplete development of the enzymes which
catalyse the metabolism of cypermethrin in the liver
of young animals (Cantalamessa, 1993).
7.2.3 Relevant in vitro data
Cypermethrin has been shown to significantly
inhibit adenosine triphosphatase in rat liver tissue
following single and repeated oral dosing
(El-Toukhy,1993).
Cypermethrin at 1/14 LD50 had significant adverse
effects on a number of immunological functions in
rats, but lower doses had no effect on these
activities Tulinska, 1995).
7.2.4 Workplace standards
A TLV has not been established for cypermethrin
7.2.5 Acceptable daily intake (ADI). and other guideline
levels
ADI 0.05 mg/kg bw (IPCS, 1995).
7.3 Carcinogenicity
Cypermethrin was not carcinogenic in rats or mice fed
diets containing up to 1600 ppm (equivalent to about 80
mg/kg/day). for two years (WHO, 1989).
7.4 Teratogenicity
Cypermethrin was not embryotoxic or teratogenic in rats
at doses which were toxic to the mother (35 mg/kg or 70 mg/kg
body weight). on days 6-15 of gestation. No teratogenic
effects were observed in rabbits administered doses up to 30
mg/kg on days 6-18 of gestation (WHO, 1989).
7.5 Mutagenicity
Cypermethrin was not mutagenic in three mammalian
in-vivo test systems (chromosomal aberration test in chinese
hamsters, dominant lethal test in mice, and host-mediated
assay in mice). Negative results were also seen in in-vitro
tests using bacteria, yeast and chinese hamster cells. (WHO
1989). However, cypermethrin was found to be genotoxic
(chromosomal aberrations and sister chromatid exchange). in
mouse spleen and bone marrow as well as in cultured mouse
spleen cells (Amer et al., 1993).
7.6 Interactions
No data available.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples & specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified). analyses
8.1.3 Transport of laboratory samples &specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s).
8.2.1.2 Advanced Qualitative Confirmation Test(s).
8.2.1.3 Simple Quantitative Method(s).
8.2.1.4 Advanced Quantitative Method(s).
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s).
8.2.2.2 Advanced Qualitative Confirmation Test(s).
Detection and assay of compound and
residues. (Chapman and Harris 1978,
Papadopoulou-Mourikidou et al., 1981,
Siltanen and Rosenberg 1980).
8.2.2.3 Simple Quantitative Method(s).
8.2.2.4 Advanced Quantitative Method(s).
8.2.2.5 Other Dedicated Method(s).
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical investigations
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
Sample collection
Biomedical analysis
There are no characteristic laboratory tests that are
specific for identifying cypermethrin. Other useful
laboratory studies include electrolytes, glucose,
arterial blood gases or oximetry. (Olsen 1994).
Toxicological analysis
There are no established practical methods for
determining pyrethroids in body fluids. Urinary levels
of 3 - phenoxybenzyl degradation products may be a
useful index of exposure (WHO/FAO).
Other investigations
The monitoring of sensory nerve action potential and
central nervous activity (EEG). may be useful in
diagnosis and in assessment of therapy
(WHO/FAO).
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Gastrointestinal effects may include abdominal
pain, nausea and vomiting. CNS effects may occur after
large ingestions (200-500 ml of concentrated solution,
exact concentration not reported). including seizures,
coma and respiratory arrest (He, 1994).
9.1.2 Inhalation
Inhalationally exposed patients experienced
shortness of breath, cough and congestion at the time
of exposure (Lessenger 1992). Inhalation or pulmonary
aspiration may cause a hypersensitivity pneumonitis
and pulmonary oedema. May precipitate wheezing in
asthmatics (He, 1994).
9.1.3 Skin exposure
Paraesthesia of the facial skin can develop
approximately 30min post-exposure and does not usually
last beyond 24h when exposure is terminated.
Dizziness, headaches, anorexia and fatigue may occur
following dermal exposure (He, 1994). Exposure to
fumes has resulted in itching of the skin (Lessenger,
1992).
9.1.4 Eye contact
Ocular irritation has been reported (Lessenger,
1992).
9.1.5 Parenteral exposure
Animal toxicity studies have been conducted via
both intravenous and intraperitoneal routes . Signs of
toxicity included ataxia with occasional tremors and
convulsions (WHO, 1989).
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
No data available
9.2.2 Inhalation
No data available.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available
9.2.6 Other
No data available
9.3 Course, prognosis, cause of death
The onset of symptoms varies depending upon such factors
as the route of absorption and quantity involved. In patients
with occupational poisoning, skin symptoms usually develop
within 4-6h post-exposure, with systemic symptoms occurring
as late as 48h post-exposure. Paraesthesia of the facial skin
can develop approximately 30min post-exposure and does not
usually last beyond 24h when exposure is terminated.
Following ingestion, the initial symptoms involve the
gastrointestinal tract, developing 10-60min post-exposure.
Patients suffering from acute oral poisoning usually develop
prominent digestive symptoms such as epigastric pain, nausea
and vomiting. Severely poisoned patients may have frequent
convulsions, coma, or pulmonary oedema. The prognosis has
proved to be good if treated with usually full recovery even
in severely poisoned patients. (Hospitalisation period is
usually longer than 4 weeks). Death may occur from
respiratory paralysis. (He et al., 1989; He, 1994).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
No data available.
9.4.2 Respiratory
Inhalationally exposed patients experienced
shortness of breath, cough, congestion at the time of
exposure. Inhalation or pulmonary aspiration may cause
a hypersensitivity pneumonitis and pulmonary oedema.
May precipitate wheezing in asthmatics. (He et al.,
1989; He, 1994). Coughing and sore throat have been
reported in individuals who were exposured to
cypermethrin which was inadvertently introduced to the
air-conditioning ducts (the formulation in addition to
cypermethrin contained xylene, trimethylbenzene and
paraffinic oils) (Lessenger, 1992).
9.4.3 Neurological
9.4.3.1 Central Nervous System (CNS).
Dizziness, headache, fatigue,
transient changes in EEG, signs of
listlessness, mild disturbance of
consciousness, convulsions and coma have been
reported depending on the degree of exposure
(He et al., 1989; He, 1994).
9.4.3.2 Peripheral nervous system
Cypermethrin after dermal contact
produces skin sensory effects characterised
by transient itching and tingling sensations
typically in the face (WHO 1989). In patients
with occupational poisoning, skin symptoms
usually develop within 4-6h post-exposure,
with systemic symptoms occurring as late as
48h post-exposure. Paraesthesia of the facial
skin can develop approximately 30min
post-exposure and do not usually last beyond
24h when exposure is terminated (He,
1994).
9.4.3.3 Autonomic nervous system
No data available
9.4.3.4 Skeletal and smooth muscle
Muscular fasiculation in limbs has
been described (He, 1994).
9.4.4 Gastrointestinal
Epigastric pain, anorexia, nausea and vomiting
has been reported (He, 1994).
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
No data available
9.4.6.2 Other
No data available
9.4.7 Endocrine & reproductive systems
No human data available. In a multigeneration
study using rats, a dose of 500mg/kg (500ppm). in the
diet caused decreased food intake and reduced body
weight in parents. No effects on reproduction or on
survival of the offspring were found. However,
reductions in litter size and total litter weight were
seen. No effect was found at 100ppm (WHO,
1989).
9.4.8 Dermatological
Transient red papules, congestion and oedema of
skin following dermal contact have been reported (He,
1994).
9.4.9 Eye, ears, nose, throat: local effects
Blurred vision, itching/burning of eyes,
coughing and sore throat have been reported in
individuals who were exposured to cypermethrin which
was inadvertently introduced to the air-conditioning
ducts (the formulation in addition to cypermethrin
contained xylene, trimethylbenzene and paraffinic
oils) (Lessenger, 1992).
9.4.10 Haematological
No human data available. Decreases in
haemoglobin concentrations and the red blood cell
count in female rats and decreases in packed cell
volume in male rats fed dietary levels of cypermethrin
has been reported. An increase in plasma alkaline
phosphatase activity in rats fed dietary levels of
cypermethrin (1600 mg cypermethrin/kg feed for three
months). has also been reported (WHO, 1989).
9.4.11 Immunological
Animal experiments showed the possibility of
immunosuppression by cypermethrin but the relevance in
the extrapolation of these data to humans is unclear
(WHO, 1989).
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
No data available
9.4.12.2 Fluid & electrolyte disturbances
No data available
9.4.12.3 Others
No data available
9.4.13 Allergic reactions
Allergic syndromes associated with pyrethrin
insecticides include dermatitis, allergic rhinitis,
asthma, hypersensitivity pneumonitis, and
anaphylactoid reactions including bronchospasm,
oropharyngeal oedema, and shock (Wax, 1994).
9.4.14 Other clinical effects
No data available
9.4.15 Special risks
Neonatal rats are particularly sensitive to
cypermethrin. The younger the animal the higher the
sensitivity. This is thought to be connected to the
incomplete development of the enzymes which catalyse
the metabolism of cypermethrin in the liver of young
animals (Cantalamessa, 1993). In view of this finding
infants exposed to cypermethrin may be more at
risk.
9.5 Others
No data available
9.6 Summary
10. MANAGEMENT
10.1 General principles
Treatment is essentially symptomatic and supportive
following decontamination procedures to prevent further
absorption.
10.2 Life supportive procedures and symptomatic treatment
Make proper assessment of airway, breathing,
circulation and neurological status of the patient. Treat
bronchospasm or anaphylaxis if they occur. Control
convulsions with appropriate drug regimen.
10.3 Decontamination
Consider gastric lavage. Administer activated charcoal
within two hours of significant oral ingestions. The toxic
oral dose in mammals is greater than 100-1000mg/kg, and the
potentially lethal acute oral dose is 10-100g.
Wash skin with copious amounts of water for 10-15min. The
skin irritation and paraethesia following dermal exposure is
self-limiting and may be alleviated with topical vitamin E
cream.
Irrigate eyes with copious water.
10.4 Enhanced Elimination
Cypermethrin is fairly rapidly metabolised by the body
(93% of metabolites excreted within 72h after oral dosing;
see section 6.1)., and extracorporeal methods of elimination
would not be expected to enhance elimination (Olsen,
1994).
10.5 Antidote treatment
10.5.1 Adults
There is no specific antidote
10.5.2 Children
There is no specific antidote
10.6 Management discussion
The toxic dose in humans has not been determined
adequately.
Human studies with cypermethrin have shown that vitamin E
acetate (dl-alpha tocopheryl acetate ). reduced or eliminated
the sensations from skin contact (Flannigan, 1985).
Certain muscle relaxants, including mephenesin, diazepam and
methocarbamol, have been used successfully in treating
experimental pyrethroid poisoning in rodents (Valentine,
1990).
It has been demonstrated experimentally in rodent studies
that MK-801 an N-methyl-D-aspartate antagonist significantly
attenuated the convulsant action of cypermethrin (Chugh,
1992).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Five cases of cypermethrin poisoning were described
following exposure to the chemical which was inadvertently
introduced to the air-conditioning ducts (the formulation in
addition to cypermethrin contained xylene, trimethylbenzene
and paraffinic oils). Exposed patients experienced shortness
of breath, cough, congestion, burning of the eyes, and
itchness of their skin at the time of exposure. The exposure
was compounded by repeated entry into the contaminated area
(Lessenger, 1992).
In Greece a man died 3 hours after eating a meal cooked in a
10% cypermethrin concentrate used in error instead of oil.
Nausea, prolonged vomiting with colicky pain, tenesmus, and
diarrhoea began a few minutes after eating the meal and
progressed to convulsions, unconsciousness, and coma. Death
due to respiratory failure occurred despite intensive
emergency treatment. Other family members developed less
severe symptoms and survived after intensive hospital
treatment (Poulos, 1982). There is some doubt whether this
was a cypermethrin intoxication (WHO, 1989).
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Workers suffering from asthma, allergies and other
respiratory disorders should be excluded from contact.
Persons under medication with neuroactive medicines should
avoid contact. Special account should be taken of workers'
ability to comprehend and follow instructions. Training of
workers in techniques to avoid contact is essential
(WHO/FAO).
12.2 Other
13. REFERENCES
Amer SM, Ibrahim AA-ElS & El-Sherbeny KM (1993). Induction of
chromosomal aberrations and sister chromatid exchange in vivo and
in vitro by the insecticide cypermethrin. J App Toxicol,
13(5):341-345
Cantalamessa F (1993). Acute toxicity of two pyrethroids,
permethrin, and cypermethrin in neonatal and adult rats. Arch
Toxicol, 67:510-513
Chapman RA & Harris CR (1978). J Chromatography, 166(2): 513-516
Chugh Y, Sankaranarayanan A & Sharma PL (1992). MK-801 antagonizes
the lethal action of centrally and peripherally administered
cypermethrin in mice and rats. J Pharm Pharmacol, 44:521-523
Flannigan SA (1985). Variation in cutaneous sensation between
synthetic pyrethroid insecticides. Contact Dermatitis,
13(3):140-147
He F, Wang S, Liu L, Chen S, Zhang Z & Sun J (1989). Clinical
manifestations and diagnosis of acute pyrthroid poisoning. Arch
Toxicol 63:58-59
He F (1994). Chapter 6 Synthetic pyrethroids. Toxicology 91:43-49
IPCS (1995). Summary of toxicological evaluations performed by the
Joint Meeting on Pesticide Residues (JMPR).
Lessenger JE (1992). Five office workers inadvertently exposed to
cypermethrin. J Tox Environ Health, 35:261-267
Olsen KR (1994). Poisoning and Drug Overdose, 2nd edition,
Appleton & Lange, Norwalk, Connecticut
Ostiz SB & Khan SU (1994). Nonextractable (bound). residues of
cypermethrin in soils. Bull Environ Contam Toxicol, 53:907-912
Papadopoulou-Mourikidou E, Iwata Y & Gunther FA (1981). J Agric
Food Chem, 29(6): 1105-1111
Poulos L, Athanaselis S, & Coutsellnis A (1982). Acute
intoxication with cypermethrin (NDRC 149). J Toxicol Clin Toxicol
19(5):519-520
Siltanen H & Rosenberg C (1980). Publ State Inst Agric Chem
(Finland). 17: 61pp
Tulinska J, Kubova J, Janota S & Nyulassy S (1995). Investigation
of immunotoxicity of supercypermethrin forte in the wistar rat.
Human Exp Toxicol, 14:399-403
Valentine VM (1990). Pyrethrin and pyrethroid insecticides.
Veterinary Clinics of North America. Small Animal Practice
20(2):375-382
Wax PM & Hoffman RS (1994). Fatality associated with inhalation of
a pyrethrin shampoo. Clin Tox 32(4):457-460
WHO (1989). Cypermethrin Environmental Health Criteria 82
WHO/FAO Pesticide Data Sheets No. 58 Cypermethrin
Woollen BH, Marsh JR, Laird WJD & Lesser JE (1992). The metabolism
of cypermethrin in man: differences in urinary metabolite profiles
following oral and dermal administration. Xenobiotica,
22(8):983-991
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(S).
Authors: Dr Wayne A Temple
National Toxicology Group
Dunedin School of Medicine
University of Otago
Box 913
Dunedin
New Zealand
Phone: 64-3-4797239
Fax: 64-3-4770509
e-mail wtemple@gandalf.otago.ac.nz
Dr Nerida A. Smith
School of Pharmacy
University of Otago
Box 913
Dunedin
New Zealand
Phone 64-3-4797244
Fax: 64-3-4770509
e-mail nerida.smith@stonebow.otago.ac.nz
Date: July 1996
Reviewer: Ms Rita Fitzpatrick
London Poisons Unit
Date: August 1996