SA Cage MSc M Inst Inf Sci
    SM Bradberry BSc MB MRCP
    S Meacham BSc

    National Poisons Information Service
    (Birmingham Centre),
    West Midlands Poisons Unit,
    City Hospital NHS Trust,
    Dudley Road,
    B18 7QH

    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information


    Toxbase summary

    Type of product



    Dermal and inhalational exposures are associated usually with no or
    only mild adverse effects. Following substantial ingestion, patients
    may develop coma, convulsions and severe muscle fasciculations and may
    take several days, occasionally weeks, to recover.

    Fatalities have occurred rarely after pyrethroid exposure, usually
    following ingestion (He et al, 1989). No fatalities have been reported
    after cyhalothrin exposure.


    Dermal exposure

         -    Tingling and pruritus with blotchy erythema on the face or
              other exposed areas, exacerbated by sweating or touching.
              Systemic toxicity may ensue following substantial exposure
              (see below).

    Ocular exposure

         -    Lacrimation and transient conjunctivitis may occur.


    Brief exposure:

         -    Respiratory tract irritation with cough, mild dyspnoea,
              sneezing and rhinorrhea.

    Substantial and prolonged exposure:

         -    Systemic toxicity may ensue - see below.


         -    May cause nausea, vomiting and abdominal pain. Systemic
              toxicity may ensue following substantial ingestion (see

    Systemic toxicity

         -    Systemic symptoms may develop after widespread dermal
              exposure, prolonged inhalation or ingestion. Features
              include headache, dizziness, anorexia and hypersalivation.
         -    Severe poisoning is uncommon. It usually follows substantial
              ingestion and causes impaired consciousness, muscle
              fasciculations, convulsions and, rarely, non-cardiogenic
              pulmonary oedema.

    Chronic exposure

         -    Long-term exposure is no more hazardous than short-term



    1.   Remove soiled clothing and wash contaminated skin with soap and
    2.   Institute symptomatic and supportive measures as required.
    3.   Topical vitamin E (tocopherol acetate) has been shown to reduce
         skin irritation if applied soon after exposure (Flannigan et al,
         1985), but it is not available as a pharmaceutical product in the
    4.   Symptoms usually resolve within 24 hours without specific


    1.   Irrigate with lukewarm water or 0.9 per cent saline for at least
         ten minutes.
    2.   A topical anaesthetic may be required for pain relief or to
         overcome blepharospasm.
    3.   Ensure no particles remain in the conjunctival recesses.
    4.   Use fluorescein stain if corneal damage is suspected.
    5.   If symptoms do not resolve following decontamination or if a
         significant abnormality is detected during examination, seek an
         ophthalmological opinion.


    1.   Remove to fresh air.
    2.   Institute symptomatic and supportive measures as required.


    1.   Do not undertake gastric lavage because solvents are present in
         some formulations and lavage may increase risk of aspiration
    2.   Institute symptomatic and supportive measures as required.

    3.   Atropine may be of value if hypersalivation is troublesome,
         0.6-1.2 mg for an adult, 0.02 mg/kg for a child.
    4.   Mechanical ventilation should be instituted if non-cardiogenic
         pulmonary oedema develops.
    5.   Isolated brief convulsions do not require treatment but
         intravenous diazepam should be given if seizures are prolonged or
         recur frequently. Rarely, it may be necessary to give intravenous
         phenytoin or to paralyze and ventilate the patient.


    Box SA, Lee MR.
    A systemic reaction following exposure to a pyrethroid insecticide.
    Hum Exp Toxicol 1996; 15: 389-90.

    Flannigan SA, Tucker SB, Key MM, Ross CE, Fairchild EJ, Grimes BA,
    Harrist RB.
    Synthetic pyrethroid insecticides: a dermatological evaluation.
    Br J Ind Med 1985; 42: 363-72.

    He F, Wang S, Liu L, Chen S, Zhang Z, Sun J.
    Clinical manifestations and diagnosis of acute pyrethroid poisoning.
    Arch Toxicol 1989; 63: 54-8.

    Lessenger JE.
    Five office workers inadvertently exposed to cypermethrin.
    J Toxicol Environ Health 1992; 35: 261-7.

    O'Malley M.
    Clinical evaluation of pesticide exposure and poisonings.
    Lancet 1997; 349: 1161-6.

    Substance name


    Origin of substance

         Cyhalothrin was developed in 1977. It consists of a mixture of
         four stereoisomers                      (IPCS, 1990d).

    Synonyms/Proprietary names

         ICI 146814
         ICI PP563
         Saber                    (RTECS, 1997; Pesticide Manual, 1997)

    Chemical group

         Type II synthetic pyrethroid

    Reference numbers

         CAS            68085-85-8               (Pesticide Manual, 1997)
         RTECS          GZ1227770                (RTECS, 1997)
         UN             NIF

    Physicochemical properties

    Chemical structure
         IUPAC name:  (RS)-alpha-cyano-3-phenoxybenzyl
         (Z)-(1RS)- cis-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-


         C23H19ClF3NO3                           (Pesticide Manual, 1997)

    Molecular weight
         449.9                                   (Pesticide Manual, 1997)

    Physical state at room temperature
         Technical grade is a viscous oil.       (Pesticide Manual, 1997)

         Yellow to brown                         (Pesticide Manual, 1997)

         Mild                                    (HSDB, 1997)



         Low solubility in water: 3 x 10 -6 g/L at 20°C
         Acetone > 500 g/L at 20°C
         Dichloromethane > 500 g/L at 20°C
         Methanol > 500 g/L at 20°C
         Diethyl ether > 500 g/L at 20°C
         Ethyl acetate > 500 g/L at 20°C
         Hexane > 500 g/L at 20°C
         Toluene > 500 g/L at 20°C
                                  (HSDB, 1997; Pesticide Manual, 1997)

    Autoignition temperature

    Chemical interactions

    Major products of combustion
         Combustion and/or pyrolysis of cyhalothrin can lead potentially
         to the production of compounds such as formaldehyde, acrolein,
         hydrogen cyanide, hydrogen chloride and hydrogen fluoride
                                                 (Hartzell, 1996).

    Explosive limits

         Burns with difficulty.                  (HSDB, 1997)

    Boiling point
         187-190°C at 0.2 mm Hg (26.7 Pa)        (Pesticide Manual, 1997)

         1.25 at 25°C                            (Pesticide Manual, 1997)

    Vapour pressure
         Approx. 1 x 10 -6 Pa at 20°C            (Pesticide Manual,1997)

    Relative vapour density

    Flash point
         > 100°C                                 (Pesticide Manual, 1997)



         Cyhalothrin is used for control of animal ectoparasites; it is
         applied as a dip or spray around animal housing
                                                 (Pesticide Manual, 1997).

    Hazard/risk classification



    Pyrethrins were developed as pesticides from extracts of dried and
    powdered flower heads of  Chrysanthemum cinerariaefolium. The active
    principles of these (see Fig. 1) are esters of chrysanthemumic acid
    (R1 = CH3) or pyrethric acid (R1 = CH3O2C) (both cyclopropane
    (three membered ring) carboxylic acids), with one of three
    cyclopentanone alcohols (cinerolone, R2 = CH3; jasomolone, R2 =
    CH2CH3; or pyrethrolone, R2 = CHCH2), giving six possible
    structures. These natural pyrethrins have the disadvantage that they
    are rapidly decomposed by light.

    FIGURE 1

    Once the basic structure of the pyrethrins had been discovered,
    synthetic analogues, pyrethroids, were developed and tested. Initially
    esters were produced using the same cyclopropane carboxylic acids,
    with variations in the alcohol portion of the compounds.

    The first commercial synthetic pyrethroid, allethrin, was produced in
    1949, followed in the 1960s by others including dimethrin,
    tetramethrin and resmethrin. 3-Phenoxybenzyl esters were also found to
    be active as pesticides (e.g phenothrin, permethrin). Synthetic
    pyrethroids with the basic cyclopropane carboxylic ester structure
    (and no cyano group substitution) are known as type I pyrethroids. In
    animal studies type I pyrethroids have been shown generally to produce
    a typical toxic syndrome (see below).

    The insecticidal activity of synthetic pyrethroids was enhanced
    further by the addition of a cyano group at the benzylic carbon atom
    to give alpha-cyano (type II) pyrethroids including cyhalothrin. In
    animal studies type II pyrethroids have been shown generally to
    produce a typical toxic syndrome (see below).

    Despite the lack of the cyclopropane ring, similar insecticidal
    activity was found in a group of phenylacetic 3-phenoxybenzyl esters.
    This led to the development of fenvalerate, an
    alpha-cyano-3-phenoxy-benzyl ester, and other related compounds such
    as fluvalinate. These all contain the alpha-cyano group and hence are
    type II pyrethroids.

    Animal studies suggest that the two structural types of pyrethroids
    give rise generally to distinct patterns of systemic toxic effects.
    Type I pyrethroids produce in animals the so-called "T (tremor)
    syndrome", characterized by tremors, prostration and altered "startle"
    reflexes. Type II (alpha-cyano) pyrethroids produce the so-called "CS
    (choreoathetosis/salivation) syndrome" with ataxia, convulsions,
    hyperactivity, choreoathetosis and profuse salivation being observed
    in experimental studies.

    These observations are consistent with some differences in the
    mechanisms of toxicity between type I and type II pyrethroids (see
    below) but the division of reactions by chemical structure is not
    exclusive. Some compounds produce a combination of the two syndromes,
    and different stereoisomeric forms can produce different syndromes
    (Dorman and Beasley, 1991). The classification into "T" and "CS"
    syndromes is not used clinically.

    All pyrethroids have at least four stereoisomers, with different
    orientation of the substituents on the cyclopropane ring (or the
    equivalent part of the phenylacetate). The isomers have different
    biological activities, as discussed below (see Mechanisms of
    toxicity). Different isomers may have separate common names,
    reflecting their commercial importance (Aldridge et al, 1978).
    Cyhalothrin is a mixture of four stereoisomers of which two are
    produced separately as lambda-cyhalothrin.

    Further details are given in the pyrethroid generic monograph.


    In 1989-1990, world-wide annual production of pyrethroids was at least
    2000 tonnes (IPCS, 1989a; IPCS, 1989b; IPCS, 1989c; IPCS, 1990a; IPCS,
    1990b; IPCS, 1990c; IPCS, 1990d; IPCS, 1990e; IPCS, 1990f).

    In spite of their long history of use, there are relatively few
    reports of pyrethroid, and specifically cyhalothrin, toxicity. Less
    than ten deaths have been reported from ingestion or occupational
    (primarily dermal/inhalational) pyrethroid exposure (He et al, 1989;
    Peter et al, 1996) with no deaths from cyhalothrin exposure.


    In neuronal cells the generation of an action potential by membrane
    depolarization involves the opening of cell membrane sodium channels
    and a rapid increase in sodium influx. The closure of sodium channels
    begins the process of action potential inactivation. Delayed sodium
    channel closure thus increases cell membrane excitability.

    Pyrethroids modify the gating characteristics of voltage-sensitive
    sodium channels in mammalian and invertebrate neuronal membranes
    (Eells et al, 1992; Narahashi, 1989) to delay their closure. They are
    dissolved in the lipid phase of the membrane (Narahashi, 1996) and
    bind to a receptor site on the alpha sub-unit of the sodium channel

    (Trainer et al, 1997). This binding is to a different site from local
    anaesthetics, batrachotoxin, grayanotoxin, and tetrodotoxin
    (Narahashi, 1996).

    The interaction of pyrethroids with sodium channels is highly
    stereospecific (Soderlund and Bloomquist, 1989), with the 1R and 1S
     cis isomers binding competitively to one site and the 1R and 1S
     trans isomers binding non-competitively to another. The 1S forms do
    not modify channel function but do block the effect of the 1R isomers
    (Ray, 1991).

    The prolonged opening of sodium channels by the neurotoxic isomers of
    pyrethroids produces a protracted sodium influx which is referred to
    as a sodium "tail current" (Miyamoto et al, 1995; Soderlund and
    Bloomquist, 1989; Vijverberg and van den Bercken, 1982). This lowers
    the threshold of sensory nerve fibres for the activation of further
    action potentials, leading to repetitive firing of sensory nerve
    endings (Vijverberg and van den Bercken, 1990) which may progress to
    hyperexcitation of the entire nervous system (Narahashi et al, 1995).
    At high pyrethroid concentrations, the sodium "tail current" may be
    sufficiently great to depolarize the nerve membrane completely,
    generating more open sodium channels (Eells et al, 1992) and
    eventually causing conduction block.

    Only low pyrethroid concentrations are necessary to modify sensory
    neurone function. For example, when tetramethrin was added to a
    preparation of rat cerebellar Purkinje neurons, only about 0.6-1 per
    cent of sodium channels needed to be modified to produce:

    (i)    Repetitive discharges in nerve fibres and nerve terminals;

    (ii)   An increase in discharges from sensory neurons (due to membrane
           depolarization); and

    (iii)  Severe disturbances of synaptic transmission (Narahashi, 1989;
           Narahashi et al, 1995; Song and Narahashi, 1996).

    These effects on sodium channels are common to all pyrethroids
    although specific effects of type II pyrethroids such as cyhalothrin
    have been clarified in experimental studies. These show that type II

    (i)    Cause depolarization of myelinated nerve membranes without
           repetitive discharges (Dorman and Beasley, 1991; Vijverberg and
           van den Bercken, 1982);

    (ii)   Are associated with a decrease in action potential amplitude
           (Dorman and Beasley, 1991);

    (iii)  Stabilize a variety of sodium channel states by reducing
           transition rates between them (Dorman and Beasley, 1991; Eells
           et al, 1992; Narahashi, 1989), causing a greatly prolonged open
           time (Vijverberg and van den Bercken, 1982), and producing
           stimulus-dependent nerve depolarization and block (Soderlund
           and Bloomquist, 1989);

    (iv)   May act post-synaptically by interacting with nicotinic
           acetylcholine and GABA receptors (Dorman and Beasley, 1991;
           Eells et al, 1992); and

    (v)    Produce effects on cultured neurons that are largely
           irreversible after washing cells with a pyrethroid-free
           solution (Song et al, 1996).

    In addition, type II pyrethroids, such as deltamethrin, enhance
    noradrenaline (norepinephrine) release (Clark and Brooks, 1989).

    In human investigations, maximal conduction velocity in sensory nerve
    fibres of the sural nerve showed some increase in subjects exposed to
    pyrethroids, but there were no abnormal neurological signs, and other
    electrophysiological studies were normal in the arms and legs (Le
    Quesne et al, 1980). He et al (1991) assessed nerve excitability using
    an electromyograph and pairs of stimuli at variable intervals. They
    showed a prolongation of the "supernormal period" in the median nerve
    in individuals who had been exposed to pyrethroids occupationally for
    three days. The "supernormal period" was even more prolonged two days
    after cessation of exposure. (Note: the "supernormal period" is the
    period for which the action potential induced by a second stimulus is
    greater than the action potential produced by an initial stimulus).

    Pyrethroids are some 2250 times more toxic to insects than mammals.
    This can be explained in terms of differences in their potency as
    neuronal toxins and differences in rates of detoxification between
    invertebrates and vertebrates (Narahashi, 1996; Narahashi et al, 1995;
    Song and Narahashi, 1996).

    The sensitivity of invertebrate neuronal sodium channels to
    pyrethroids is ten times greater than in mammals (Song and Narahashi,
    1996). Furthermore, invertebrates typically have body temperatures
    some 10°C lower than mammals and  in vitro studies show tetramethrin
    to be more potent at evoking repetitive neuronal discharges at lower
    temperatures (Song and Narahashi, 1996). In these experiments it was
    noted that the recovery of sodium channels from tetramethrin
    intoxication after washing was some five times faster in mammals than
    invertebrates. In addition pyrethroid hepatic metabolism
    (detoxification) is faster in mammals. Finally small insect size
    increases the likelihood of end-organ (neuronal) toxicity prior to
    detoxification (Song and Narahashi, 1996).


    In addition to the important differences between invertebrates and
    vertebrates outlined above, the low toxicity of pyrethroid
    insecticides in mammals is due to poor dermal absorption (the main
    route of exposure) and metabolism to non-toxic metabolites (Bradbury
    and Coats, 1989).



    Based on excretion studies involving cyhalothrin and other pyrethroids
    (Nassif, et al, 1980; Chester et al, 1987; Eadsforth et al, 1988;
    IPCS, 1989c; Woollen et al, 1991; Woollen et al, 1992; Chester et al,
    1992) dermal absorption of cyhalothrin is likely to be low (less than
    1.5 per cent).

    Only about 0.0001 per cent (54 µg) of lambda-cyhalothrin handled and
    sprayed each day by spraymen was absorbed, based on estimation of
    metabolites in urine and serum (Chester et al, 1992). After handling
    (with gloves) more than six litres 2.5 per cent lambda-cyhalothrin
    while impregnating 512 mosquito nets during six consecutive days, two
    operators had extremely low blood concentrations (0.009-0.011 ng/µL)
    of one of the metabolites of lambda-cyhalothrin with undetectable
    urine concentrations (Baskaran et al, 1992).


    Between 19 and 57 per cent of orally administered cypermethrin
    (another type II pyrethroid) was absorbed in human studies (Woollen et
    al, 1991; Woollen et al, 1992). There are no human data specific to


    Pyrethroids are hydrolyzed rapidly in the liver to their inactive acid
    and alcohol components (Hutson, 1979; Ray, 1991), probably by
    microsomal carboxylesterase (Hutson, 1979). Further degradation and
    hydroxylation of the alcohol at the 4' position then occurs, and
    oxidation produces a wide range of metabolites (Hutson, 1979; Leahey,

    There is some stereospecificity in metabolism, with  trans-isomers
    being hydrolyzed more rapidly than the  cis-isomers, for which
    oxidation is the more important metabolic pathway (Soderlund and
    Casida, 1977). Although the alpha-cyano group reduces the
    susceptibility of the molecule to hydrolytic and oxidative metabolism
    (Hutson, 1979; Soderlund and Casida, 1977), the cyano group is
    converted to the corresponding aldehyde (with release of the cyanide
    ion), followed by oxidation to the carboxylic acid, sufficiently
    rapidly for efficient excretion by mammals (Leahey, 1985). Other

    differences in the chemical structure of pyrethroids have less effect
    on rates of metabolism (Soderlund and Casida, 1977).

    The pattern of metabolites varies between oral and dermal dosing in
    humans (Wilkes et al, 1993). For example, following dermal dosing with
    cypermethrin (another type II pyrethroid) the ratio of  trans/cis 
    cyclopropane acids excreted was approximately 1:1, compared to 2:1
    after oral administration. Such measurements might be useful in
    determining the route of exposure (Woollen, 1993; Woollen et al, 1991;
    Woollen et al, 1992).

    Animal studies have shown that pyrethroid hydrolysis is inhibited by
    dialkylphosphorylating agents such as organophosphorus insecticides
    (Abou-Donia et al, 1996; He et al, 1990; Hutson, 1979), and urinary
    excretion of unchanged pyrethroid was higher in sprayers using a
    methamidophos/ deltamethrin or methamidophos/fenvalerate mixture than
    from those using the pyrethroid alone (Zhang et al, 1991).

    Experiments with chickens (Abou-Donia et al, 1996) showed that
    pyrethroid (permethrin) toxicity was also enhanced by pyridostigmine
    bromide and by the insect repellent N,N-diethyl-m-toluamide (DEET).
    The authors hypothesized that competition for hepatic and plasma
    esterases by these compounds led to decreased pyrethroid breakdown and
    increased transport of the pyrethroid to neural tissues.


    Pyrethroids are excreted mainly as metabolites in urine but a
    proportion is excreted unchanged in faeces. An overview of human
    pyrethroid elimination data is included in the generic pyrethroid
    monograph though there are no human data specific to cyhalothrin.


    Occupationally, the main route of pyrethroid absorption is through the
    skin; inhalation is much less important (Adamis et al, 1985; Chen et
    al, 1991; Zhang et al, 1991). Inhalation is more likely when
    pyrethroids are used in confined spaces (Llewellyn et al, 1996). The
    use of protective clothing can reduce dermal exposure (Chester et al,
    1987). The physical formulation also affects exposure, with inhalation
    being more important for dust and powder formulations, and dermal
    exposure more important for liquids (Llewellyn et al, 1996).

    Dermal exposure

    This is the most common route of pyrethroid exposure. Adverse effects
    manifest primarily as peripheral neurotoxicity with reversible
    hyperactivity of sensory nerve fibres (paraesthesiae), though erythema
    and pruritus are also described (see below).

    Peripheral neurotoxicity

    Paraesthesiae have been reported frequently, particularly after the
    inappropriate handling of pyrethroids including cyhalothrin (IPCS,
    1990a, IPCS 1990g). Paraesthesiae occur most commonly on the face (He
    et al, 1991). It seems probable that paraesthesiae are related to the
    repetitive firing of sensory nerve endings in contaminated skin
    (Aldridge, 1990) and not to inflammation as there is little effect on
    neurogenic vasodilatation (Flannigan and Tucker, 1985b). The symptoms
    are exacerbated by sensory stimulation (heat, sun, scratching
    (Aldridge, 1990), sweating or application of water and may prevent
    sleep (Tucker and Flannigan, 1983).

    Paraesthesiae generally start 30 minutes to two hours after exposure
    and peak after about six hours. Recovery is usually complete within 24
    hours (Aldridge, 1990; He et al, 1989; Knox and Tucker, 1982; Knox et
    al, 1984; Tucker and Flannigan, 1983).

    Dermal toxicity

    When used at recommended doses in the treatment of scabies and lice,
    pyrethroids only rarely produce adverse effects. Pruritus is the
    side-effect reported most frequently (Brandenburg et al, 1986;
    DiNapoli et al, 1988), although this may also be caused by the skin
    infestation being treated.

    Skin irritation during occupational pyrethroid exposure may occur in
    up to ten per cent of workers (Kolmodin-Hedman et al, 1982) and may be
    influenced by the ratio of stereoisomers used in the pyrethroid
    formulation, being more severe with a higher proportion of the 
     trans isomer. In addition to pruritus, erythema, burning and
    blisters have been reported (Brandenburg et al, 1986; Kalter et al,
    1987; IPCS, 1990b; Kolmodin-Hedman et al, 1995).

    There are no reports of dermal toxicity specific to cyhalothrin

    Ocular exposure

    Symptoms of mild eye irritation have been reported following
    occupational pyrethroid exposure (Kolmodin-Hedman et al, 1982; IPCS,
    1990d; Lessenger, 1992).

    Villagers handling mosquito nets pre-treated with lambda-cyhalothrin
    complained of mild burning of the eyes and lacrimation (Baskaran et
    al, 1992).


    Inhalational pyrethroid exposure typically is occupational and
    produces symptoms and signs of pulmonary tract irritation. The
    frequency and severity of symptoms may vary with the ratio of
    different stereoisomers in a formulation, being more prevalent with a

    higher proportion of the  trans isomer. Systemic effects may occur
    following more substantial exposure (He et al, 1989) and are described

    There are no reports of inhalational toxicity following cyhalothrin


    Pyrethroid ingestion typically gives rise to nausea, vomiting and
    abdominal pain within minutes. In one series (He et al, 1989)
    involving some 344 cases, vomiting was a prominent feature in 56.8 per
    cent. The Chinese literature includes a case of erosive gastritis with
    haematemesis following ingestion of 900 mL deltamethrin solution
    (concentration not given) (Poisindex, 1996). In another case,
    permethrin/pyrethrins accidentally sprayed directly into the mouth
    resulted in a burning sensation which commenced several hours after
    exposure, and only gradually improved over five months, with
    persistent disordered taste sensation (Grant, 1993).

    Substantial pyrethroid ingestion may give rise to neurological
    features and other systemic effects as discussed below.

    Systemic effects

    Systemic effects generally have occurred after inappropriate
    occupational handling of pyrethroids. This may involve using too
    concentrated solutions, prolonged exposure, spraying against the wind
    or using unprotected hands or mouth to unblock congested sprayers (He
    et al, 1989). Most reported cases have involved dermal, inhalational
    and sometimes also oral exposure to fenveralate, deltamethrin or
    cypermethrin with systemic features occurring between four and 48
    hours after spraying (He et al, 1989). Intentional ingestion may also
    produce systemic effects (He et al, 1989; Peter et al, 1996). Most
    patients recover over two to four days with only seven fatalities
    among 573 cases in one review (He et al, 1989). Four of the seven
    fatalities developed convulsions, one patient died from
    non-cardiogenic pulmonary oedema, one from "atropine intoxication" and
    one death followed exposure to a pyrethroid/organophosphorus pesticide

    A further death has been reported recently in a patient who became
    comatose within ten hours of 30 mL deltamethrin ingestion and died
    from aspiration pneumonia complicated by renal failure (Peter et al,

    Gastrointestinal toxicity

    As discussed above gastrointestinal irritation is common following
    pyrethroid ingestion. Vomiting was a prominent symptom also in 16 per
    cent of  occupational cases (He et al, 1989) in whom ingestion was
    not suspected, but where exposure involved deltamethrin, cypermethrin
    or fenvalerate. In this review, which included occupational exposures,

    anorexia occurred in 45 per cent of 573 cases of acute pyrethroid
    poisoning (He et al, 1989).


    He et al (1989) described dizziness in 60.6 per cent, headache in 44.5
    per cent, fatigue in 26 per cent, increased salivation in 20 per cent
    and blurred vision in seven per cent of 573 cases of acute pyrethroid
    poisoning (229 occupational and 344 accidental exposures to
    fenvalerate, deltamethrin or cypermethrin).

    Limb muscle fasciculations, coma and convulsions may complicate severe
    acute pyrethroid poisoning, and have occurred as soon as 20 minutes
    after ingestion (He et al, 1989). "Convulsions" was the stated cause
    of death in four of seven fatalities among 573 cases of acute
    pyrethroid poisoning (He et al, 1989) but further details were not

    An electromyelogram (EMG) in one case of acute pyrethroid poisoning
    (not specified) showed repetitive muscle discharges without
    denervation potentials (He et al, 1989).

    Cardiovascular toxicity

    Palpitation was reported in 13.1 per cent of 573 cases of acute
    pyrethroid poisoning involving oral, inhalational and dermal exposure
    to fenvalerate, deltamethrin or cypermethrin (He et al, 1989). An
    electrocardiogram (ECG) showed ST and T wave changes in eight of 71
    patients. Other ECG abnormalities included sinus tachycardia,
    ventricular ectopics and (rarely) sinus bradycardia (He et al, 1989).
    All ECG changes resolved over 2-14 days.

    Pulmonary toxicity

    Chest tightness was described in patients following accidental or
    deliberate ingestion of deltamethrin, fenvalerate or cypermethrin (He
    et al, 1989).

    Non-cardiogenic pulmonary oedema has been reported rarely following
    substantial pyrethroid ingestion, usually in association with severe
    neurological complications and may contribute to a fatal outcome (He
    et al, 1989).

    Musculoskeletal toxicity

    A case of acute polyarthralgia after skin exposure to flumethrin
    (another type II pyrethroid) has been reported recently (Box and Lee,


    Among 235 cases of occupational or accidental acute pyrethroid
    poisoning in whom a full blood count was performed, 15 per cent showed
    a leucocytosis (He et al, 1989); this was probably a non-specific


    Urinalysis among 124 patients with acute pyrethroid poisoning
    (involving oral, dermal and inhalational exposure) showed three
    patients with haematuria (He et al, 1989).


    Dermal exposure

    Few long-term adverse effects from pyrethroids have been reported
    (IPCS, 1990d; Chen et al, 1991, He, 1994). There is no confirmed
    evidence that repeated exposure to pyrethroids leads to permanent
    damage to sensory nerve endings (Vijverberg and van den Bercken,

    One hundred and ninety-nine workers employed in a pyrethroid packaging
    plant over four to five months on two occasions (winter and summer
    sessions) were observed for cutaneous effects (He et al, 1988). Work
    involved transferring pyrethroid emulsions (deltamethrin 2.5 per cent,
    fenvalerate 20 per cent and (to a lesser extent) cypermethrin 10 per
    cent, all other type II pyrethroids) in xylene, from large containers
    to fill some 50,000 100 mL bottles daily. Gloves (and gauze masks)
    were used in winter only with no protective measures in summer. One
    hundred and forty of 199 (70 per cent) workers complained of "abnormal
    facial sensation" with burning, tingling, itching, tightness or
    numbness. Symptoms were more prevalent (p<0.05) in summer, occurring
    in 92 per cent of summer workers (n=87) compared to only 54 per cent
    of winter workers (n=112). Red miliary, mildly pruritic papules were
    found in 14 per cent of all workers, mainly on the face and chest and
    again were more prevalent (p<0.05) in summer. This was probably due
    to increased sweating during summer months (which tends to exacerbate
    cutaneous symptoms), but may also have been contributed to by the
    absence of protective measures during summer (He et al, 1988). The
    symptoms described in this study are identical to those following
    acute pyrethroid exposure and did not last more than 24 hours once
    subjects were away from the work environment. This suggests there are
    no true  chronic effects from repeated pyrethroid exposure.


    The 199 workers described above were exposed to estimated fenvalerate
    and deltamethrin ambient air concentrations of 0.012-0.055 mg/m3 and
    0.005-0.012 mg/m3 respectively. Sixty-four (32 per cent) complained
    of sneezing and increased nasal secretions but these symptoms were
    only present at work, again suggesting no difference in effect between

    chronic or acute pyrethroid exposure. Systemic symptoms of dizziness,
    fatigue and nausea were mild and reported by only 14, nine and ten per
    cent of workers respectively.


    Dermal exposure


    Clothes contaminated with cyhalothrin should be removed, and
    contaminated skin washed with soap and water (He, 1994).

    Specific measures

    Topical alpha tocopherol (vitamin E) to treat paraesthesiae

    As paraesthesiae usually resolve in 12-24 hours, specific treatment is
    not generally administered or required. However, the topical
    application of  dl-alpha tocopherol acetate (vitamin E) has been
    shown to reduce the severity of skin reactions to other pyrethroids
    including fenvalerate (IPCS, 1990c; Tucker et al, 1984; Tucker et al,
    1983), flucythrinate, permethrin and cypermethrin (Flannigan and
    Tucker, 1985a). The reaction to cypermethrin was completely inhibited
    by vitamin E (Flannigan et al, 1985). Vitamin E appears to be useful
    both prophylactically and therapeutically (Flannigan and Tucker,
    1985a). In a controlled human volunteer study, a commercial vitamin E
    oil preparation produced 98 per cent inhibition of the cutaneous
    symptoms from fenvalerate when applied immediately (Flannigan et al,
    1985). At four hours the inhibition was only 50 per cent (Advisory
    Committee on Pesticides, 1992). The mechanism of the effect of topical
    vitamin E has not been clarified, although some  in vitro studies
    suggest vitamin E may block the pyrethroid-induced sodium "tail
    current" in neuronal membranes (Song and Narahashi, 1995).

    Vitamin E is not included in the British National Formulary but is
    available from health food or alternative medicine sources.

    Other agents to treat paraesthesiae

    Various other topical therapies have been tested for treatment of
    pyrethroid-induced paraesthesiae: in human trials mineral oil, corn
    oil and "A&D ointment" (Tucker et al, 1984; Tucker et al, 1983) were
    almost as effective as Vitamin E cream (but the oils may lead to
    defatting of skin). Butylated hydroxyanisole and an industrial barrier
    cream (Tucker et al, 1984) and topical indomethacin (Flannigan and
    Tucker, 1984), were of little therapeutic benefit and in two studies
    zinc oxide paste exacerbated paraesthesiae (Tucker et al, 1984; Tucker
    et al, 1983) .

    Ocular exposure

    Irrigate the affected eye with lukewarm water or 0.9 per cent saline
    for at least ten minutes. A topical anaesthetic may be required for
    pain relief or to overcome blepharospasm. Ensure no particles remain
    in the conjunctival recesses. Use fluorescein if corneal damage is
    suspected. If symptoms do not resolve following decontamination or if
    a significant abnormality is detected during examination, seek an
    ophthalmological opinion.


    Removal from exposure is the priority. Mild symptoms of rhinitis
    respond to oral antihistamines. Other symptomatic and supportive
    measures should be dictated by the patient's condition.


    Gut decontamination

    Gastric lavage should be avoided since solvents may be present in
    cyhalothrin formulations and may increase the risk of aspiration

    Systemic toxicity

    Most patients exposed to pyrethroids require only simple supportive
    care. Systemic toxicity is rare but in such patients the presence of
    excess salivation, muscle fasciculations and pulmonary oedema may
    present diagnostic difficulty since similar features are typical also
    of severe organophosphorus pesticide poisoning. Measurement of the red
    cell cholinesterase activity (which is reduced in acute
    organophosphorus poisoning but not in pyrethroid intoxication) allows
    clarification but may not be available rapidly.

    Isolated brief convulsions do not require treatment but intravenous
    diazepam 5-10 mg should be given if seizures are prolonged. Rarely it
    may be necessary to give intravenous phenytoin, or to paralyze and
    ventilate the patient. Diazepam is useful also in the treatment of
    muscle fasciculations. The role of atropine is discussed below.

    Several experimental studies have investigated the role of
    pharmaceuticals in the management of the neurological complications of
    severe pyrethroid poisoning. However, these should be interpreted with
    caution, not only because they usually have involved high-dose
    parenteral pyrethroid administration, but also because there is
    considerable interspecies variation with regard to therapeutic
    efficacy (Casida et al, 1983; Vijverberg and van den Bercken, 1990).

    Atropine for hypersalivation and pulmonary oedema

    In experimental studies atropine sulphate (25 mg/kg subcutaneously)
    reduced hypersalivation produced by oral fenvalerate or cypermethrin
    (each at a dose exceeding the LD50), but did not increase survival
    (Hiromori et al, 1986).

    Intravenous atropine (0.6-1.2 mg in an adult) may be useful to control
    excess salivation but care should be taken to avoid excess
    administration. In a review of pyrethroid poisoning cases reported
    from China (He et al, 1989), 189 of 573 patients were treated with
    atropine which led to an improvement in salivation and pulmonary
    oedema in a few severe cases, but eight patients developed atropine
    intoxication following intravenous administration of 12-75 mg. One
    patient, probably misdiagnosed as having acute organophosphorus
    insecticide poisoning, died of atropine intoxication after a total
    dose of 510 mg, and one patient acutely intoxicated with a
    fenvalerate/dimethoate mixture could not be revived despite a total
    atropine dose of 170 mg.

    Atropine and ethylcarbamate

    In a French study a combination of intravenous atropine 3 mg/kg and
    ethylcarbamate 1000 mg/kg effectively protected rodents against the
    lethal effects of intravenous deltamethrin, increasing the LD50 by a
    factor of 3.48 (Leclercq et al, 1986).

    Diazepam and phenobarbital for convulsions

    In mice (n=10) pre-treatment with intraperitoneal diazepam (1 mg/kg),
    but not phenobarbital (10-30 mg/kg), significantly increased the time
    to onset of convulsions caused by the intracerebroventricular
    administration of deltamethrin (p<0.005) and fenvalerate (p<0.05)
    (Gammon et al, 1982). Under the same conditions diazepam was not
    effective in preventing permethrin- or allethrin-induced seizures.

    Propranolol and procainamide for tremor

    Pre-treatment with intravenous propranolol or procainamide (each 15
    µmol/kg) reduced the severity of tremor or writhing induced in rats by
    the intravenous administration of deltamethrin (10 µmol/kg) (Bradbury
    et al, 1983).

    Ivermectin and pentobarbital for choreoathetosis

    In rodents administered 2 mg/kg intravenous deltamethrin,
    pre-treatment with 4 mg/kg intravenous ivermectin reduced
    choreoathetosis from 3.9 to 3.2 (as graded on a scale of 1-4) 
    (p = 0.023), and reduced salivation by 72 per cent. Pentobarbital 
    (15 mg/kg i.p.) reduced choreoathetosis produced by 1.5 mg/kg
    intravenous deltamethrin from 3.0 to 1.3 (p = 0.004). An equi-sedative
    dose of phenobarbital produced a non-significant fall to 2.4 
    (p = 0.11) (Forshaw and Ray, 1997).

    Mephenesin and methocarbamol

    The skeletal muscle relaxant mephenesin 22 µmol/kg prevented all motor
    symptoms induced in rats by the intravenous administration of
    deltamethrin (10 µmol/kg) (n=4-20 in different treatment groups)
    (Bradbury et al, 1983).

    Mephenesin has a short half-life in vivo, but intraperitoneal
    methocarbamol (a mephenesin derivative) (400 mg/kg intraperitoneally
    followed by 200 mg/kg whenever tremor was observed) significantly
    (p<0.01) reduced mortality in rats administered more than the oral
    LD50 of fenvalerate, fenpropathrin, cypermethrin or permethrin (n=10
    in each treatment group) (Hiromori et al, 1986).

    There are insufficient data to advocate a clinical role for
    methocarbamol in systemic pyrethroid toxicity.

    Sodium-channel blockers (local anaesthetics)

     In vitro studies suggest local anaesthetics may be useful as
    antagonists of the effect of deltamethrin on sodium channels
    (Oortgiesen et al, 1990). The relevance to human poisoning is not


    Avoiding dermal and inhalational exposure via adequate self-protection
    and sensible use is the most important requirement to reduce adverse
    effects from occupational use.


    Maximum exposure limit

    International Standards Organization (ISO) limits for natural
    pyrethrins are: long-term exposure limit (8 hour TWA reference period)
    5 mg/m3; short-term exposure limit (15 min reference period) 10
    mg/m3 (Health and Safety Executive, 1995).


    Endocrine toxicity

     In vitro studies show that several pyrethroids interact
    competitively with human skin fibroblast androgen receptors and with
    sex hormone binding globulin (Eil and Nisula, 1990). A possible
    anti-androgenic effect of pyrethroids in humans was suggested
    following an outbreak of gynaecomastia in refugees exposed to
    fenothrin, but there was insufficient evidence to confirm this (Eil
    and Nisula, 1990).

    Animal studies evaluating other endocrine effects of pyrethroids have
    produced conflicting results (Akhtar et al, 1996; Kaul et al, 1996).


    In oral dosing studies in rodents, several pyrethroids suppressed the
    cellular immune response (Blaylock et al, 1995; Tulinská et al, 1995)
    or produced thymus atrophy (Madsen et al, 1996).

    The significance of these immunological studies to man is not known.


    There is no evidence that cyhalothrin is carcinogenic (IPCS, 1990a).


    In a variety of animal studies there was no evidence that cyhalothrin
    was teratogenic, embryotoxic or fetotoxic (IPCS, 1990a). Dermal
    application (1 mL of a 0.02 per cent [w/v] solution) to pregnant rats,
    however, has been shown to produce a delay in testicular descent in
    male offspring and delayed ear and eye opening. Animal studies also
    have shown that cyhalothrin is present in breast milk of
    cyhalothrin-fed lactating rodents (Reprotox, 1997). There are no human
    reprotoxicity data.


    Data regarding the potential genotoxicity of pyrethroids provide
    conflicting results (Puig et al, 1989; Barrueco et al, 1992; Herrera
    et al, 1992; Dolara et al, 1992; Barrueco et al, 1994; Surrallés et
    al, 1995), though a toxicity review of  in vitro and  in vivo data
    for cyhalothrin (IPCS, 1990a) has concluded there is insufficient
    evidence for cyhalothrin to be considered genotoxic or mutagenic.

    Fish toxicity

    Cyhalothrin is toxic to fish. It is more toxic at cooler temperatures,
    and thus more toxic to cold than warm water fish, but the toxicity of
    pyrethroids is little affected by pH or water hardness (Mauck et al,

    LC50 (96 hr) for rainbow trout is 0.54 µg/L cyhalothrin (DOSE,

    EC Directive on Drinking Water Quality 80/778/EEC

    Maximum admissible concentration (any pesticide) 0.1 µg/L (EC
    Directive, 1980).


    SA Cage MSc M Inst Inf Sci
    SM Bradberry BSc MB MRCP
    S Meacham BSc

    National Poisons Information Service (Birmingham Centre),
    West Midlands Poisons Unit,
    City Hospital NHS Trust,
    Dudley Road,
    B18 7QH

    This monograph was produced by the staff of the Birmingham Centre of
    the National Poisons Information Service in the United Kingdom. The
    work was commissioned and funded by the UK Departments of Health, and
    was designed as a source of detailed information for use by poisons
    information centres.

    Date of last revision


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