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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
    




    See Also:
       Toxicological Abbreviations
       Cypermethrin (EHC 82, 1989)
       Cypermethrin (HSG 22, 1989)
       Cypermethrin (ICSC)
       Cypermethrin (PDS)
       CYPERMETHRIN (JECFA Evaluation)
       Cypermethrin (Pesticide residues in food: 1981 evaluations)
       Cypermethrin (Pesticide residues in food: 1982 evaluations)
       Cypermethrin (Pesticide residues in food: 1983 evaluations)
       Cypermethrin (Pesticide residues in food: 1984 evaluations)