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    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva, 1990

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    toxicology. Other activities carried out by the IPCS include the
    development of know-how for coping with chemical accidents,
    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of

    WHO Library Cataloguing in Publication Data


        (Environmental health criteria ; 95)

        1.Pyrethrins   I.Series

        ISBN 92 4 154295 0        (NLM Classification: WA 240)
        ISSN 0250-863X

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    1.1. Summary and evaluation 
         1.1.1. Identity, physical and chemical properties, 
                analytical methods  
         1.1.2. Production and use  
         1.1.3. Human exposure  
         1.1.4. Environmental fate  
         1.1.5. Kinetics and metabolism 
         1.1.6. Effects on organisms in the environment 
         1.1.7. Effects on experimental animals and  in vitro test systems   
         1.1.8. Effects on human beings 
    1.2. Conclusions   
         1.2.1. General population  
         1.2.2. Occupational exposure   
         1.2.3. Environment 
    1.3. Recommendations    


    2.1. Identity      
    2.2. Physical and chemical properties   
    2.3. Analytical methods 


    3.1. Industrial production  
    3.2. Use patterns  
    3.3. Residues in food   
    3.4. Residues in the environment    


    4.1. Transport and distribution between media   
    4.2. Photodecomposition 
    4.3. Decomposition in plants    
    4.4. Decomposition in soils 
    4.5. Decomposition in water 


    5.1. Metabolism in mammals  
         5.1.1. Rat    
         5.1.2. Mouse  
         5.1.3. Domestic animals    
    5.2. Enzymatic systems for biotransformation    


    6.1. Aquatic organisms  
         6.1.1. Toxicity to aquatic invertebrates   
         6.1.2. Toxicity to fish    
         6.1.3. Field studies and community effects 
    6.2. Terrestrial organisms  
         6.2.1. Toxicity to soil microorganisms 
         6.2.2. Toxicity to beneficial insects  
         6.2.3. Toxicity to birds   
    6.3. Uptake, loss, and bioaccumulation  


    7.1. Single exposures   
    7.2. Short-term exposures   
         7.2.1. Oral administration     
         7.2.2. Inhalation  
         7.2.3. Dermal application  
    7.3. Skin and eye irritation; sensitization 
         7.3.1. Skin and eye irritation 
         7.3.2. Skin sensitization  
    7.4. Long-term exposures and carcinogenicity    
         7.4.1. Mouse  
         7.4.2. Rat    

    7.5. Mutagenicity  
         7.5.1. Microorganisms and insects  
         7.5.2. Rat    
         7.5.3. Mouse  
         7.5.4. Hamster 
    7.6. Teratogenicity and reproduction studies    
         7.6.1. Teratogenicity  
         7.6.2. Reproduction studies    
    7.7. Neurotoxicity 
    7.8. Behavioural studies    
    7.9. Miscellaneous studies  
    7.10. Mechanism of toxicity - mode of action 


    8.1. Occupational exposure  
    8.2. Clinical studies   







Dr V. Benes,    Toxicology   and   Reference   Laboratory,
   Institute   of   Hygiene   and  Epidemiology,   Prague,

Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood
   Experimental Station, Huntingdon, United Kingdom

Dr Y. Hayashi,  Division of Pathology,  National Institute
   of Hygienic Sciences, Tokyo, Japan

Dr S. Johnson,  Hazard  Evaluation  Division,  Office   of
   Pesticide   Programme,   US  Environmental   Protection
   Agency, Washington DC, USA  (Chairman)

Dr S.K. Kashyap, National Institute of Occupational Health
   (I.C.M.R.) Ahmedabad, India  (Vice Chairman)

Dr Yu. I. Kundiev,  Research Institute of Labour, Hygiene,
   and Occupational Diseases, Kiev, USSR

Dr J.P. Leahey,  ICI Agrochemicals, Jealotts Hill Research
   Station, Bracknell, United Kingdom  (Rapporteur)

Dr J. Miyamoto,   Takarazuka  Research  Centre,   Sumitomo
   Chemical Company, Takarazuka, Hyogo, Japan

Dr J. Sekizawa,  Section of Information and Investigation,
   Division  of  Information on  Chemical Safety, National
   Institute    of   Hygienic   Sciences,   Tokyo,   Japan

Dr Y. Takenaka,   Division  of  Information   on  Chemical
   Safety, Tokyo, Japan


Dr M. Ikeda,   International  Commission  on  Occupational
   Health,  Department  of  Environmental  Health,  Tohoku
   University School of Medicine, Sendai, Japan

Dr H. Naito,  World  Federation of  Poison Control Centres
   and  Clinical  Toxicology, Institute  of Clinical Medi-
   cine,  University  of  Tsukuba,  Tsukuba-Shi,  Ibaraki,

Dr N.  Punja,  Groupement  International des  Associations
   Nationales  de  Fabricants  de  Produits  Agrochimiques
   (GIFAP),  ICI  Plant  Protection  Division,   Fenhurst,
   Haslemere, United Kingdom


Dr M.  Matsuo,  Sumitomo Chemical  Company, Biochemistry &
   Toxicology Laboratory, Osaka, Japan

Dr Y.  Okuno,  Sumitomo  Chemical Company,  Biochemistry &
   Toxicology Laboratory, Osaka, Japan


Dr K.W. Jager, International Programme on Chemical Safety,
   World    Health   Organization,   Geneva,   Switzerland

Dr R.  Plestina, Division of Vector  Control, Delivery and
   Management  of  Vector  Control, World  Health Organiz-
   ation Geneva, Switzerland


    Every effort has been made to present  information  in
the  criteria documents as accurately  as possible without
unduly delaying their publication.  In the interest of all
users  of  the  environmental health  criteria  documents,
readers  are  kindly  requested to  communicate any errors
that may have occurred to the Manager of the International
Programme  on Chemical Safety, World  Health Organization,
Geneva, Switzerland, in order that they may be included in
corrigenda, which will appear in subsequent volumes.

                       *    *    *

    A  detailed  data  profile and  a  legal  file can  be
obtained  from  the International  Register of Potentially
Toxic  Chemicals,  Palais  des Nations,  1211  Geneva  10,
Switzerland (Telephone No. 7988400 - 7985850).

                       *    *    *

    The proprietary information contained in this document
cannot  replace  documentation for  registration purposes,
because the latter has to be closely linked to the source,
the  manufacturing route, and the purity/impurities of the
substance  to be registered.  The data should  be used  in
accordance   with  paragraph  82-84   and  recommendations
paragraph  90  of  the Second  FAO Government Consultation


    A  WHO Task Group on Environmental Health Criteria for
Fenvalerate,  Permethrin,  and  d-Phenothrin met  in Tokyo
from  4 to 8 July 1988. This meeting was convened with the
financial  assistance  of  the  Ministry  of  Health   and
Welfare,  Tokyo,  Japan, and  was  hosted by  the National
Institute of Hygienic Sciences (NIHS) in Tokyo.

    Dr T. Furukawa and Dr K. Shirota opened the meeting on
behalf  of the Ministry of  Health and Welfare, and  Dr A.
Tanimura,  Director-General of the NIHS  welcomed the par-
ticipants to the institute.  Dr M. Mercier, Manager of the
IPCS,  welcomed the participants  on behalf of  the  three
IPCS  cooperating organizations (UNEP/ILO/WHO).  The group
reviewed  and  revised the  draft  monograph and  made  an
evaluation  of the risks for human health and the environ-
ment from exposure to fenvalerate.

    The  first  draft of  this  document was  prepared  by
Dr J. MIYAMOTO   and   Dr   M.  MATSUO   of  the  Sumitomo
Chemical  Company, Japan, with the assistance of the staff
of  the National  Institute  of  Hygienic Sciences, Tokyo,
Japan.  Dr I. Yamamoto of the Tokyo University of Agricul-
ture  and Dr M. Eto of Kyushu University,  Japan, assisted
with the finalization of the draft.

    The second draft was prepared by Dr J. SEKIZAWA, NIHS,
Tokyo,  incorporating  comments received  following circu-
lation of the first draft to the IPCS contact  points  for
Environmental Health Criteria documents. Dr K.W. Jager and
Dr P.G. Jenkins,  both members of  the IPCS Central  Unit,
were   responsible  for  the  technical   development  and
editing, respectively, of this monograph.

    The  assistance  of  the Sumitomo  Chemical Company in
making  available to the IPCS and the Task Group its toxi-
cological proprietary information on fenvalerate is grate-
fully  acknowledged. This allowed  the Task Group  to make
its evaluation on the basis of more complete data.

    The efforts of all who helped in the  preparation  and
finalization of the document are gratefully acknowledged.


ai                  active ingredient

Cl-Vacid (= CPIA)   2-(4-chlorophenyl)isovaleric acid

ECD-GC              gas chromatography with electron capture detector

FID-GC              gas chromatography with flame ionization detector

GLC                 gas-liquid chromatography

HPLC                high-performance liquid chromatography

NOEL                no-observed-effect level

PBacid              3-phenoxybenzoic acid

PBalc               3-phenoxybenzyl alcohol

PBald               3-phenoxybenzaldehyde

PCB                 polychlorinated biphenyl

TOCP                tri- ortho- cresyl phosphate



1.  During  investigations  to modify  the chemical struc-
    tures  of natural pyrethrins, a certain number of syn-
    thetic  pyrethroids were produced with improved physi-
    cal  and  chemical  properties and  greater biological
    activity. Several of the earlier synthetic pyrethroids
    were  successfully commercialized, mainly for the con-
    trol   of   household  insects.    Other  more  recent
    pyrethroids  have been introduced as  agricultural in-
    secticides because of their excellent activity against
    a wide range of insect pests and their non-persistence
    in the environment.

2.  The  pyrethroids constitute another group  of insecti-
    cides in addition to organochlorine, organophosphorus,
    carbamate,  and  other compounds.  Pyrethroids commer-
    cially  available,  to  date include  allethrin,  res-
    methrin,  d-phenothrin, and tetramethrin  (for insects
    of public health importance), and cypermethrin, delta-
    methrin, fenvalerate, and permethrin (mainly for agri-
    cultural  insects). Other pyrethroids are  also avail-
    able,  including furamethrin, kadethrin, and tellalle-
    thrin  (usually for household insects), fenpropathrin,
    tralomethrin,  cyhalothrin, lambda-cyhalothrin, teflu-
    thrin,  cufluthrin,  flucythrinate,  fluvalinate,  and
    biphenate (for agricultural insects).

3.  Toxicological   evaluations   of   several   synthetic
    pyrethroids  have been performed by  the FAO/WHO Joint
    Meeting  on Pesticide Residues (JMPR).  The acceptable
    daily  intake (ADI) has been estimated by the JMPR for
    cypermethrin,  deltamethrin,  fenvalerate, permethrin,
    d-phenothrin,  cyfluthrin, cyhalothrin, and flucythri-

4.  Chemically,  synthetic pyrethroids are esters  of spe-
    cific  acids  (e.g., chrysanthemic  acid, halo-substi-
    tuted chrysanthemic acid, 2-(4-chlorophenyl)-3-methyl-
    butyric  acid)  and  alcohols (e.g.,  allethrolone, 3-
    phenoxybenzyl  alcohol).  For certain pyrethroids, the
    asymmetric  centre(s) exist in the acid and/or alcohol
    moiety,  and the commercial products sometimes consist
    of a mixture of both optical (IR/1S or d/1)  and  geo-
    metric  ( cis/trans )    isomers.  However, most  of the
    insecticidal  activity of such products  may reside in
    only one or two isomers. Some of the  products  (e.g.,
    d-phenothrin,  deltamethrin)  consist  only  of   such
    active isomer(s).

5.  Synthetic  pyrethroids are neuropoisons acting  on the
    axons in the peripheral and central nervous systems by
    interacting  with  sodium  channels in  mammals and/or
    insects.  A single dose produces toxic signs  in  mam-
    mals,  such as tremors, hyperexcitability, salivation,
    choreoathetosis,  and paralysis.  The  signs disappear
    fairly  rapidly,  and  the animals  recover, generally
    within  a week.  At near-lethal dose levels, synthetic
    pyrethroids  cause  transient  changes in  the nervous
    system,  such  as  axonal swelling  and/or  breaks and
    myelin  degeneration in sciatic nerves.   They are not
    considered  to cause delayed neurotoxicity of the kind
    induced by some organophosphorus compounds.  The mech-
    anism  of toxicity of synthetic  pyrethroids and their
    classification  into  two  types are  discussed in the

6.  Some  pyrethroids  (e.g.,  deltamethrin,  fenvalerate,
    flucythrinate, and cypermethrin) may cause a transient
    itching  and/or  burning  sensation in  exposed  human

7.  Synthetic  pyrethroids  are  generally metabolized  in
    mammals  through ester hydrolysis, oxidation, and con-
    jugation,  and there is  no tendency to  accumulate in
    tissues. In the environment, synthetic pyrethroids are
    fairly  rapidly degraded in soil and in plants.  Ester
    hydrolysis  and oxidation at various sites on the mol-
    ecule   are  the  major  degradation  processes.   The
    pyrethroids  are strongly adsorbed  on soil and  sedi-
    ments,  and hardly eluted with water.  There is little
    tendency for bioaccumulation in organisms.

8.  Because of low application rates and rapid degradation
    in  the  environment,  residues in  food are generally

9.  Synthetic  pyrethroids have been shown to be 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  environ-
    ment.   The toxicity of synthetic pyrethroids in birds
    and domestic animals is low.

10. In  addition to the  evaluation documents of  FAO/WHO,
    there  are several good reviews and books on the chem-
    istry,  metabolism, mammalian toxicity,  environmental
    effects,  etc.,  of  synthetic pyrethroids,  including
    those  by  Elliott  [36], Miyamoto  [126],  Miyamoto &
    Kearney [127], and Leahey [101].


1.1  Summary and Evaluation

1.1.1  Identity, physical and chemical properties, 
analytical methods

    Fenvalerate is a potent insecticide that has  been  in
use since 1976.  It is an ester  of  2-(4-chlorophenyl)-3-
methylbutyric acid and alpha-cyano-3-phenoxybenzyl alcohol,
but lacks a cyclopropane ring.  However, in terms  of  its
insecticidal  behaviour,  it  belongs  to  the  pyrethroid
insecticides.   It is a  racemic mixture of  four  optical
isomers with the configurations [2S, alphaS], [2S, alphaR],
[2R, alphaS], and [2R, alphaR]. The [2S, alphaS] isomer is 
the most biologically active, followed by the [2S, alphaR]

    Technical  grade fenvalerate is a yellow or brown vis-
cous liquid having a specific gravity of 1.175  at  25 °C.
The  vapour pressure is 0.037 mPa at 25 °C and it is rela-
tively  non-volatile. It is practically insoluble in water
(approximately  2 µg/litre),   but soluble in organic sol-
vents  such as acetone, xylene, and kerosene. It is stable
to  light, heat, and  moisture, but unstable  in  alkaline
media due to hydrolysis of the ester linkage.

    Residue  and environmental analysis can be carried out
using a gas chromatograph equipped with an  electron  cap-
ture  detector, the minimum detectable concentration being
0.005 mg/kg.   A gas chromatograph with a flame ionization
detector is used for product analysis.

1.1.2  Production and use

    Approximately  1000 tonnes per year of fenvalerate are
used worldwide (1979-1983 figures).  It is mostly employed
in  agriculture but also for  insect control in homes  and
gardens  and on cattle, alone or in combination with other
insecticides.  It  is  formulated as  emulsifiable concen-
trate,  ultra-low-volume  concentrate, dust,  and wettable

1.1.3  Human exposure

    Exposure  of the general population  to fenvalerate is
mainly via dietary residues. Residue levels in crops grown
by  good  agricultural  practice are  generally  low.  The
resulting  exposure of the general  population is expected
to  be very  low, but  data from  total-diet  studies  are

    Analysis  of residues in stored grain showed that over
70%  of the applied dose remained on wheat after 10 months
at 25 °C.  Following milling and baking, white  bread  has
about the same residue level as white flour (approximately
0.06-0.1 mg/kg).

    Information on occupational exposure to fenvalerate is
very limited.

1.1.4  Environmental fate

    In   soil,  degradation  occurs  via  ester  cleavage,
diphenyl  ether cleavage, ring hydroxylation, hydration of
the  cyano group to  amide, and further  oxidation of  the
fragments  formed to yield carbon dioxide as a major final
product.  Studies to investigate the leaching potential of
fenvalerate  and its degradation products showed that very
little downward movement will occur in soils.

    In water and on soil surfaces, fenvalerate  is  photo-
degraded  by sunlight.  Ester cleavage,  hydrolysis of the
cyano group, decarboxylation to yield 2-(3-phenoxyphenyl)-
3-(4-chlorophenyl)-4-methylpentane-nitrile     (decarboxy-
fenvalerate), and other  radical-initiated  reactions have 
been shown to occur.

    On plants, fenvalerate has a half-life of approximate-
ly  14 days.  Ester cleavage is a major reaction, followed
by  oxidation and/or conjugation of  the fragments formed.
Decarboxylation  to  yield decarboxy-fenvalerate  also oc-

    In  general, the degradative processes  which occur in
the environment lead to less toxic products.

    The  degradation of fenvalerate in  the environment is
rather   rapid.  Half-lives are 4-15 days  in river water,
8-14 days on plants, 1-18 days by photodegradation on soil
and 15 days-3 months in soil.

    There is virtually no leaching of fenvalerate in soil.
Thus, it is unlikely that the compound will attain signif-
icant levels in the aquatic environment.

1.1.5  Kinetics and metabolism

    The  fate of  fenvalerate in  rats and  mice has  been
studied using fenvalerate radiolabelled in the acid moiety
or  benzyl  or  cyano groups.   The  administered radioac-
tivity,  except that of  the cyano-labelled compounds,  is
readily excreted (up to 99% in 6 days).  The  major  meta-
bolic  reactions are ester  cleavage and hydroxylation  at
the   4'position.    Various  oxidative   and  conjugation
reactions  that lead to a complex mixture of products have
been shown to occur.  When studies were carried  out  with
fenvalerate  radiolabelled in the cyano group, elimination

of  the radioactive dose  was less rapid  (up to 81%  in 6
days).  The remaining radioactivity was retained mainly in
the  skin, hair, and stomach as thiocyanate.  A minor, but
very  important, metabolic pathway  is the formation  of a
lipophilic conjugate of [2R]-2-(4-chlorophenyl)isovalerate.
This  conjugate, which is  implicated in the  formation of
granuloma,  has been detected  in the adrenals,  liver and
mesenteric  lymph  nodes of  rats,  mice, and  some  other

1.1.6  Effects on organisms in the environment

    In   laboratory   tests,  fenvalerate  is highly toxic
for  aquatic  organisms.   The LC50    values  range  from
0.008 µg/litre     for  newly  hatched  mysid  shrimps  to
2 µg/litre    for a stonefly. The no-observed-effect level
in life-cycle tests using  Daphnia galeata mendotae is less
than  0.005 µg/litre.    Fenvalerate is  also highly toxic
for  fish. The 96-h  LC50 values  range from  0.3 µg/litre
for larval grunion to 200 µg/litre  for adult  Tilapia. The
no-observed-effect  level,  over  28 days, for  early-life
stages of the sheepshead minnow is 0.56 µg/litre.  Fenval-
erate is less toxic for aquatic algae and  molluscs,  with
96-h LC50 values > 1000 µg/litre.

    In  field tests and in  the use of the  compound under
practical  conditions,  the  potentially high  toxicity to
aquatic   organisms  is  not  manifested.    Some  aquatic
invertebrates  are killed when  water is oversprayed,  but
the effect on populations is temporary.  There  have  been
no  reports of fish kills.  This reduced toxicity in field
use is related to the strong adsorption of the compound to

    Fenvalerate is highly toxic to honey bees. The topical
LD50   is 0.41 µg/bee,   but there is a  strong  repellent
effect of fenvalerate to bees, which reduces the effect in
practice.   There is no  evidence of significant  kills of
honey bees under normal use.  Fenvalerate is more toxic to
predator mites than to the target pest species.

    Fenvalerate  has very low toxicity to birds when given
orally  or applied to  the diet.  LD50 values   are > 1500
mg/kg  body weight for acute oral dosage and an LD50 value
for dietary exposure of Bobwhite quail has  been  reported
at > 15 000 mg/kg diet.

    Fenvalerate  is readily taken up by aquatic organisms.
Bioconcentration factors ranged from 120 to 4700 for vari-
ous  organisms (algae, snail,  Daphnia and fish)  in model
ecosystem  studies.  The fenvalerate  taken up by  aquatic
organisms is rapidly lost on transfer to clean water.  The
compound can, therefore, be regarded as having no tendency
to bioaccumulate in practice.

1.1.7  Effects on experimental animals and  in vitro test systems

    Fenvalerate  has moderate to low  acute oral toxicity.
However,  LD50   values differ considerably  (82 to > 3200
mg/kg) according to animal species and vehicle of adminis-
tration.   The  acute  clinical signs  of poisoning appear
rapidly but survivors become asymptomatic within 3-4 days.
The  toxic signs of the racemic mixture, as well as of its
[2S, alphaS] isomer, include restlessness,  tremors, pilo-
erection,  diarrhoea, abnormal gait, choreo-athetosis, and
salivation  (CS-syndrome); it is  classified as a  Type II
pyrethroid.   Electrophysiologically it produces bursts of
spikes  in the cercal motor nerve of the cockroach.  There
is, however, no clear-cut link between electro-physiologi-
cal findings in insects and toxicity to mammals.

    Rats  fed fenvalerate at 2000 mg/kg diet for 8-10 days
showed  typical  signs of  acute intoxication.  Reversible
morphological  changes in the sciatic  nerve were observed
in  rats  administered  fenvalerate  at  3000 mg/kg  diet.
Histopathological  changes  in  sciatic nerves  were  also
observed  in rats and mice treated with a single oral does
of fenvalerate at lethal or sublethal levels.

    Hens administered fenvalerate orally at 1000 mg/kg per
day  for 5 days did not show any clinical or morphological
signs of delayed neurotoxicity.

    The  acute  intraperitoneal  toxicity  of  fenvalerate
metabolites   in  mice  was   no  greater  than   that  of
fenvalerate itself.

    In  subacute  and  subchronic toxicity  studies, mice,
rats, dogs, and rabbits were treated with  fenvalerate  by
oral,  dermal, and inhalational  routes for 3 weeks  to  6
months.  In 4-week mouse and rat inhalation studies, a no-
observed-effect  level (NOEL) of  7 mg/m3 was  established
in  both species.   The NOEL  in a  90-day rat  study  was
125 mg/kg diet, in a 2-year feeding study it was 250 mg/kg
diet  (12.5 mg/kg body weight), and in a 24-28 month study
it  was 150 mg/kg diet, (7.5 mg/kg body weight).  The NOEL
in a 2-year mouse study was 50 mg/kg  diet,  corresponding
to 6.0 mg/kg body weight, and 30 mg/kg diet, corresponding
to  3.5 mg/kg body weight,  in a 20-month  feeding  study.
For dogs the NOEL was 12.5 mg/kg body weight in  a  90-day
feeding  study.  Some fenvalerate formulations have caused
skin  and eye irritation.  However,  technical fenvalerate
is non-irritant and has no sensitizing effects.

    In   long-term  toxicity  studies,  microgranulomatous
changes  were observed in mice,  specifically when treated
with the [2R, alphaS]  isomer  of  fenvalerate  (125 mg/kg 
diet) for 1 to 3 months. These changes were reversed  when
fenvalerate  was eliminated from the  diet.  The causative
agent for this change was the cholesterol ester  of  2-(4-
chlorophenyl)isovaleric  acid, a lipophilic  metabolite of

fenvalerate  from  the [2R, alphaS]  isomer.  The NOEL for 
these microgranulomatous changes in mice was 30 mg fenval-
erate per kg diet.

    In  a  long-term  toxicity  study,  microgranulomatous
changes  were  also observed  in rats at  a dose level  of
500 mg/kg diet, the NOEL for these changes being 150 mg/kg

    Fenvalerate  was not carcinogenic to mice, when fed at
dietary levels up to 3000 mg/kg for 78 weeks or 1250 mg/kg
for  2 years.  It was also  not carcinogenic to rats  when
fed at dietary levels up to 1000 mg/kg for 2 years.

    Fenvalerate  did not show any mutagenic or chromosome-
damaging activity in several  in vitro and  in vivo assays.

    Fenvalerate is not teratogenic to mice or  rabbits  at
dose levels of up to 50 mg/kg body weight per day, nor did
it  show any toxic  effects (at up  to 250 mg/kg diet)  on
reproductive parameters in a 3-generation rat reproduction

1.1.8  Effects on human beings

    Fenvalerate  can  induce numbness,  itching, tingling,
and  burning sensations in exposed  workers, which develop
after  a latent period  of approximately 30 min,  peak  by
8 h,  and disappear within 24 hours.  Some poisoning cases
have  resulted from occupational exposure,  owing to over-
exposure due to neglect of safety precautions.

    There are no indications that fenvalerate will have an
adverse  effect on human  beings, provided it  is used  as

1.2  Conclusions

1.2.1  General population

    The  exposure of the general population to fenvalerate
is expected to be very low.  It is not likely to present a
hazard provided it is used as recommended.

1.2.2  Occupational exposure

    With  reasonable work practices, hygiene measures, and
safety  precautions, fenvalerate is unlikely  to present a
hazard to those occupationally exposed to it.

1.2.3  Environment

    It  is  unlikely  that fenvalerate  or its degradation
products  will attain levels of environmental significance
provided  that  recommended  application rates  are  used.
Under laboratory conditions fenvalerate is highly toxic to

fish, aquatic arthropods, and honey bees. However, lasting
adverse effects are not likely to occur under  field  con-
ditions provided it is used as recommended.

1.3  Recommendations

    Although dietary levels arising from recommended usage
are  considered  to  be  very  low,  confirmation  of this
through  inclusion  of  fenvalerate in  monitoring studies
should be considered.

    Fenvalerate  has been used for  many years and only  a
few  cases of temporary effects from occupational exposure
have  been reported.  Nevertheless,  it would be  wise  to
maintain observations of human exposure.


2.1  Identity

    Fenvalerate is a synthetic pyrethroid having no cyclo-
propane  ring in the molecule.  It is prepared by  the es-
terification  of  (2RS)-2-(4-chlorophenyl)-3-methylbutyric
acid  (also  known  as  (2RS)-2-(4-chlorophenyl)isovaleric
acid,  CPIA, or  Cl-Vacid)  with  (alphaRS)-alpha-cyano-3-
phenoxybenzyl alcohol [137].  It has four stereoisomers as 
a result of the two chiral centres in the acid and alcohol
moieties (Fig. 1).


    The composition of the product is a racemic mixture of
the four isomers in equal proportions (Table 1). Technical
grade fenvalerate contains 90-94% of fenvalerate [41]. The
molecular formula is C25H22ClNO3.

Table 1.  Chemical identity of fenvalerate and its various stereoisomers
Common name/            CAS Index name (9Cl)                    Stereoisomeric    Synonyms and
CAS Registry no./                                               compositionc      trade names
NIOSH Accession no.a    Stereospecific nameb
Fenvalerate             Benzeneacetic acid,                     (1):(2):(3):(4)   Sumicidin, Belmark,
51630-58-1              4-chloro- alpha-(1-methylethyl)-,        = 1:1:1:1
CY1576350               cyano(3-phenoxyphenyl)methyl ester                        Pydrin, S-5602
                                                                                  SD43775, WL43775
                        (RS)- alpha-cyano-3-phenoxybenzyl

 alpha-Fenvalerate       Same as fenvalerate
                        Benzeneacetic acid, 4-chloro- alpha-
                        (1-methylethyl)-, cyano-3-phenylbenzyl
                        ester, [S-(R*,R*)]-

 beta-Fenvalerate        Same as fenvalerate
                        Benzeneacetic acid, 4-chloro- alpha-
                        (1-methylethyl)-, cyano-3-phenoxybenzyl
                        ester, [R-R*, S*)]-

a   Registry of Toxic Effects of Chemical Substances (1981-1982 edition).
b   (2S), d, (+) or (2R), 1, (-) in the acid part of fenvalerate signify the same stereospecific 
    conformation, respectively.
c   Numbers in parantheses identify the structures shown in Fig. 1.

Chemical Structure

2.2  Physical and Chemical Properties

    Some  physical and chemical properties  of fenvalerate
are  given in Table 2. It  is stable to heat  and moisture
and  is  relatively  stable  (compared  with  natural  py-
rethrins)  when exposed to  light.  It is  more stable  in
acidic  than in alkaline media, optimum stability being at
pH 4 [41, 117, 207].

Table 2.  Some physical and chemical properties of fenvalerate
Physical state                   viscous liquid

Colour                           yellow or brown

Odour                            mild "chemical" odour

Relative molecular mass          419.9
Boiling point                    300 °C at 4.93 kPa (37 mmHg)

Water solubility                 2 µg/Litre

Solubility in organic solvents   solublea

Relative density (25 °C)         1.175

Vapour pressure (25 °C)          0.037 mPa

Log octanol-water partition
coefficient (log Pow)            6.2
a Acetone (>1 kg/kg), hexane (155 g/kg), xylene (>1 kg/kg), 
  ethanol, cyclohexanone, ether, kerosene, chloroform.

2.3  Analytical Methods

    Methods for the analysis of fenvalerate are summarized
in Table 3. This table includes the procedures for (a) ex-
traction  with  solvent, (b)  liquid-liquid partition, (c)
chromatographic  separation (clean up), and (d) quantitat-
ive  and qualitative determination by  suitable analytical
instruments,  and also includes minimum detectable concen-
tration (MDC) and percentage recovery data.

    The  separation  of  the  cis  and  trans  isomers  of
fenvalerate  has  been  carried out  using  a commercially
available Pirkle type 1-A chiralphase HPLC with,  as  sol-
vent  system,  0.025%  propen-2-ol  in  hexane  (1 ml/min)

    Fenvalerate  can be determined by gas-liquid chromato-
graphy with a flame ionization detector (FID-GC) (3% OV-17
glass column with temperature programming) [11].

    A  laminar  flow,  microwave-induced plasma  torch has
been evaluated for its use in gas chromatography [19]. The
detection limit of fenvalerate on the carbon  channel  was
0.054 µg/ml.

    To analyse technical grade fenvalerate, the product is
dissolved  in  chloroform together  with 2-(4-biphenyl)-5-
phenyl-1,3,4-oxadiazole  (an  internal standard),  and the
solution is injected into an FID-GC system [79].

    The  Joint  FAO/WHO Codex  Alimentarius Commission has
published  recommendations for methods for the analysis of
fenvalerate residues [48].

Table 3.  Analytical methods for fenvalerate
Sample                        Sample preparation                      Determination               MDCb     % Recovery       Reference
                                                                      GLC or HPLC; detector,               (fortification
            Extraction  Partition           Clean-up                  carrier flow, column,                level)
            solvent                                                   temperature, retention               (mg/kg)c
                                     Column          Elution          time
 Residue analysis

apple        n-hexane    ext.sol.a    silica gel      CH2Cl2           ECD-GC, N2, 50 ml/min,      0.01     89-108           6
pear        acetone     /H2O                                          1 m, 3% OV-7, 235 °C                 (0.1-1.0)
cabbage     (1/1)

grape       acetone     saturated    Florisil        acetone/         ECD-GC, N2, 30 ml/min,      0.005    94-99            67
pepper                  NaCl/                        petroleum        1.1 m, 2% XE-60,                     (0.005-1.0)
                        petroleum                    ether (1/99)     215 °C, 7 min

cabbage     CH3CN       1% NaCl/     Florisil        benzene/ n-       ECD-GC, argon/methane       0.005    88-104           103
lettuce                 petroleum                    hexane (1/1)     (95/5), 45 ml/min, 1.8 m,            (0.012-1.2)
                        ether        silica gel      benzene/         4% SE-30/6% QF-1 or 15%
                                                     acetone (3/1)    OV-101, 225 °C, 25-30 min

beef        CH3CN/       n-hexane/    Florisil        CH3CN/           ECD-GC, N2, 100 ml/min,     0.005    82-94            16
muscle      H20         2% NaCl                      CH2Cl2/          1.8 m, Ultra-Bond 20M,               (0.01-1.0)
egg yolk    (85/15)     solution                      n-hexane         220 °C, 11.5, 14.2 min
milk        or CH3CN                                 (0.35/50/50)

 Environmental analysis

soil        acetone,    2% NaCl/     alumina         ether/           ECD-GC, argon/methane                78-105           74
             n-hexane/   ext.sol.a                     n-hexane         (95/5), 60 ml/min,                   (0.005-1.0)
            acetone                                  (1/9)            0.97 m, 6% OV-210,
            (1/1),                                                    230 °C, 10.6, 11.8 min

 Product analysis

Technical   CHCl3                                                     FID-GC, He, 60 ml/min,                                79
grade                                                                 1.0 m, 2% Apiezon L,
                                                                      245 °C
a   extraction solvent.
b   minimum detectable concentration (mg/kg).
c   fortification level indicates the concentration of fenvalerate added to control samples for the measurement of recovery.


3.1  Industrial Production

    Fenvalerate was first marketed in 1976 and  the  esti-
mated production was 1000 tonnes in 1979 and 889 tonnes in
1982  [203].  Recent  world-wide  production  figures  are
listed in Table 4.

Table 4.  World-wide production of 
Year      Production       Reference
1979      1016             200

1980      1067             201

1981      914              202, 203

1982      903              203

1983      1280             204

1984      919              9

3.2  Use Patterns

    Of  the total world-wide consumption  of 473 tonnes of
fenvalerate  in 1980 [8], 271 tonnes were used in the USA,
103 tonnes  in  Latin  America, 43 tonnes  in  Africa,  28
tonnes  in Western Europe, and 26 tonnes each in Australia
and  Turkey. It was  mostly used on  cotton (90.3% of  the
consumption)  but some  was used  on other  crops such  as
vines, tomatoes, potatoes, pomes, and other fruit.

    Fenvalerate has also been used for homes  and  gardens
and for the control of cattle insect infestation  [8].  It
is   formulated   in  emulsifiable   concentrates  (25-300
g/litre),  ultra-low volume concentrates  (25-75 g/litre),
dusts,  and wettable powder,  and is also  used in  combi-
nation with other pesticides (e.g., fenitrothion).

3.3  Residues in Food

    Supervised  trials  have been  carried  out on  a wide
variety  of crops and  comprehensive summaries of  the re-
sults of residue analysis in these trials are contained in
the  evaluation reports of  the Joint FAO/WHO  Meeting  on
Pesticide  Residues (JMPR) [41, 43, 45, 47, 50]. A compre-
hensive  list of Maximum Residue Limits (MRLs) for a large
number  of  commodities  resulted from  these  evaluations

    In  one study,  apples in  the USA  were treated  four
times  with 30% emulsifiable concentrate at a rate of 0.67
kg active ingredient/ha. The residue levels were 2.2 mg/kg
in  whole  apples, 7.3 mg/kg  in  peel, and  0.03 mg/kg in
peeled fruits 6 weeks after the last application [41].

    When wheat grain treated with fenvalerate at a rate of
1.01 mg/kg  was stored at  25 °C, the residue  levels were
0.86 mg/kg  after  6.5 months  of storage  and  0.74 mg/kg
after 10 monthsa.

    Three  lactating  cows  were  fed 14C-(acid-labelled)-
fenvalerate at a dose level of 0.11 mg/kg diet  daily  for
21 days and sacrificed 12 h after receiving the last dose.
The  recovery of 14C  in the milk was less than 1% and the
levels  ranged from < 0.0006 to  0.0019 µg/litre,   with a
plateau  occurring after 1 week  of feeding.  No 14C   was
detectable in fat (< 0.02 mg/kg) or muscle (< 0.01 mg/kg).
In  another study, fenvalerate  was sprayed on  cows at  a
rate of 0.2, 0.4, or 2 g/animal. The residue level did not
exceed 0.01 mg/kg muscle. Maximum residues were 0.22 mg/kg
in  fat and 0.02 mg/kg in milk at the dose rate of 2 g/cow
[132, 154].

    When  wheat containing 0.6 mg fenvalerate/kg  was sub-
jected  to milling and  baking, white bread  was found  to
have  about the same residue  level as white flour,  i.e.,
about 0.06-0.1 and 0.08-0.09 mg/kg, respectivelyb.

3.4 Residues in the Environment

    Data  on actual levels of fenvalerate residues in air,
water, or soil are not available.  Residues in  air  would
not be expected for a compound with a vapour  pressure  of
0.037 mPa at 25 °C.

a   M.  Bengston (1979), personal communication from final
    report  on  silo-scale  experiments 1977-1978  to  the
    Australian Wheat Board Working Party on grain protect-
    ants.  Queensland  Department  of  Primary  Industries
    (unpublished report cited from FAO/WHO [41].

b   B.W.  Simpson (1979), draft report to be published by
    Queensland  Department of Primary Industries Analyti-
    cal Chemical Branch, Brisbane, Australia (unpublished
    report cited in FAO/WHO [41].



     The  major photodegradation routes for  fenvalerate are de-
 carboxylation to yield 3-(4-chlorophenyl)-4-methyl-2-(3-phenoxy-
 phenyl)-valeronitrile,  ester and ether cleavage, hydrolysis of
 the cyanide group, and other radical-initiated reactions. Ester
 cleavage  and  some  photo-initiated reactions  are  the  major
 routes  of decomposition on plants.  In soils, the formation of
 bound  material and  the evolution  of carbon  dioxide are  the
 major  processes observed under both aerobic and anaerobic con-

    The degradation pathways of fenvalerate are summarized
in Fig. 2.


4.1 Transportation and Distribution Between Media

    Hill [74] investigated the distribution of fenvalerate
residues  in soil under field conditions using a microplot

technique.   The microplots (20 x 20 cm) were treated with
fenvalerate at a rate of 150 g/ha.  After 45 weeks, 11% of
the applied fenvalerate was located in the  0-2.5 cm  soil
layer  and less than  0.5% in the  2.5-5 cm soil  samples.
Less  than 0.1% of the applied fenvalerate was detected in
any  of the soil samples taken after 3 or 4 weeks, despite
a  rainfall of 95.4 mm during the first 4 weeks (including
a  25.9 mm  downpour  15 days after  application).   These
results  indicate that fenvalerate does  not readily leach
downward  and  that  lateral  surface  movement  is   very

    A  similar  conclusion  was obtained  from  laboratory
soil-leaching  studies.   More  than 95%  of  the  applied
fenvalerate  remained  in  the  treated  portion  of  soil
columns  when leaching was started  immediately or 30 days
after  treatment of the  soil [133].  The  possibility  of
fenvalerate  accumulating in orchard soils was assessed by
monitoring  soil and  leaf litter  in an  orchard  in  the
Okanagan  valley,  British  Columbia,  Canada,   following
multiple annual application of the pesticide.  Belmark 300
(30%  fenvalerate EC formulation)  had been sprayed  at  a
rate  of 188-500 ml/ha (one to  three times per year)  for
more  than three years.  To  obtain initial concentration,
organic litter samples were sprayed at a rate of 450 ml/ha
and samples were collected 2 h later.  While  the  initial
concentration  thus obtained in the litter was 0.214 mg/kg
(average   value),   orchard   litter  samples   contained
0.30-0.63 mg/kg  while  samples  from a  non-treated block
contained  < 0.002 mg/kg.  Orchard  soil samples  (0-15 cm
depth)  in two orchards contained  fenvalerate residues of
< 0.0035-0.006 mg/kg and 0.0063-0.024 mg/kg [188].

4.2  Photodecompositiona

    In  studies by Holmstead et al. [78], fenvalerate (5),
at  a concentration of 0.01 mol/litre in methanol, hexane,
or  acetonitrilewater (60:40), underwent rapid photodegra-
dation  under the action of  UV light (290-320 nm) with  a
half-life  of 16-18 min (Fig. 2).  With  90-95% conversion
after   60 min,  2-(3-phenoxyphenyl)-3-(4-chlorophenyl)-4-
methyl-pentanenitrile (31) (decarboxy-fenvalerate) was the
major photoproduct, amounting to 54-57% of the total reac-
tion  mixture. There were smaller amounts of the dechlori-
nated analogue (32) of decarboxy-fenvalerate and the dimer
(8) of 2,2-dimethyl-4-chlorostyrene.  3-Phenoxybenzoyl cy-
anide  (4), 3-phenoxybenzaldehyde (18)  (PBald), 4-chloro-
isobutylbenzene  (6), and 2,2-dimethyl-4-chlorostyrene (7)
were  detected in small amounts in hexane or methanol.  3-
Phenoxybenzyl  cyanide (28), its dimer  (26), and 1,2-bis-
(phenoxyphenyl)ethane  (27) were found only in hexane, and
methyl  3-phenoxybenzoate (12) was detected  only in meth-
anol.   Products found uniquely in acetonitrile-water were
2-(4-chlorophenyl)-3-methylbutyric  acid  (17) (CPIA),  3-
phenoxybenzoic  acid (22) (PBacid) and 1-(4-chlorophenyl)-
2-methylpropanol  (9).  Several unknown compounds were ob-
served in the remaining 5-10%. Fenvalerate, in a thin film

(1 mg/cm2)   on glass, decomposed in sunlight with a half-
life  of approximately 4 days.   About 10% of  the applied
material remained after 43 days. In addition to the photo-
products  formed in solution, small  amounts of 3-phenoxy-
benzyl  alcohol (19) (PBalc) and isopropyl 4-chlorophenyl-
ketone (10) were detected.

    On   exposure  to  autumn  sunlight    in  Japan,  the
[2S, alphaS] isomer  of  fenvalerate  in  distilled  water
decomposed  with a half-life of  approximate 10 days. This
isomer  photodecomposed via pathways that  included decar-
boxylation,  hydration  of the  CN  group to  a  carbamoyl
(CONH2)    group, hydrolysis of the CONH2 group  to a car-
boxyl  (COOH) group, and cleavage of the ester or diphenyl
ether  linkage.  Cleavage of the ester linkage was a major
photochemical reaction and led to the formation  of  2-(4-
chlorophenyl)-3-methylbutyric  acid  (17)  (17.3%  of  the
applied 14C,   10 days after exposure). There  was no sig-
nificant difference between fenvalerate and the [2S, alphaS]
isomer in the rates and routes of photodegradation [179].

    The  photodegradation of fenvalerate  (0.3-0.4 ng/cm2)
on two kinds of soil in natural sunlight was compared with
that of the [2S, alphaS] isomer. Fenvalerate and its isomer
photodecomposed  with half-lives of 1.4-2.4 days  and 1.1-
2.5 days,  respectively.  The pathways  included hydration
of the cyano group to the carbamoyl group  (19.2-48.4%  at
10 days)  with subsequent hydrolysis to the carboxyl group
(0.9-2.0% at 10 days), ester-bond cleavage (3.4-4.5% at 10
days),  and decarboxylation (0.3-0.9% at 10 days).  Little
2S/2R  and  alphaS/alphaR  isomerization (as determined by 
HPLC) occurred  on the  soils.  There  was no  significant 
difference between  the  two  compounds  in the rates  and 
pathways  of photodegradation [89].

    Holmstead  & Fullmer [77] investigated the photodecar-
boxylation  of several cyanohydrin esters  in methanol and
hexane  under  artificial  light as  models for pyrethroid
photodecomposition.   The cyanohydrin esters gave  rise to
decarboxylated  products, to a  greater or lesser  extent,
whereas  the analogous compounds  without the cyano  group
did   not   produce  the   photodecarboxylated  compounds.
alpha-Cyanobenzyl  phenylacetate, which yielded the stable 
benzyl radical,  gave substantially larger amounts  of the 
decarboxylated product  than alpha-cyanobenzyl   benzoate,  
which produced the unstable phenyl radical.

    The  photodegradation of fenvalerate  in water and  on
soil  was investigated using  compounds labelled with  14C
at  the  following  positions: carbonyl  group (CO-fenval-

a   The numbers in brackets following chemical names refer to the
    numbers given in Fig. 2.

erate), alpha-carbon in the benzyl  group (Calpha-fenvale-
rate), and cyano group (CN-fenvalerate) [118]. On exposure  
to sunlight, fenvalerate in very dilute solution in distil-
led water, in  2%  aqueous  acetone,  in filter-sterilized 
river water, or  in sea  water underwent rapid  photolysis  
with half-lives of approximately 4 days in  summer and 13-
15 days in winter.  The  quantum  yield was  calculated at
6.6 x 10-3 (at  313 nm in water) and the half-life of dis-
appearance  at latitude 40°N was calculated at 4.1 days in
summer and 12.4 days in winter, values which were close to
the  experimental  ones. Photodegradation  of 14CN-fenval-
erate  resulted  in the  formation  of greater  amounts of
14CO2    than 14CN-.   After  6  weeks  irradiation, ap-
proximately  30% (in aqueous  acetone or river  water)  or
approximately  55-60% (in distilled water or sea water) of
the 14C   was recovered as 14CO2,    while the correspond-
ing figures for 14CN-    were 5% and 30%. One of the major
photodegradation  products was decarboxy-fenvalerate (31),
which  increased to approximately 20% (in distilled water)
in  summer after 1 week and decreased thereafter.  In win-
ter, the amount was approximately 20% after 6 weeks. Other
major  products were PBacid  (22) and CPIA  (17),  derived
from  the ester bond cleavage,  amounting to 43% and  58%,
respectively,  of the applied radioactivity  after 6 weeks
in  winter. In addition, small amounts of alpha-carbamoyl-
3-phenoxybenzyl-2-(4-chlorophenyl)-3-methylbutyrate   (33)
(CONH2-fenvalerate), alpha-carboxy-3-phenoxybenzyl-2-(4-
chlorophenyl)-3-methylbutyrate (34) (COOH-fenvalerate), 3-
phenoxybenzyl cyanide (28), 3-phenoxyphenylacetamide (29),
3-phenoxyphenylacetic  acid  (30),  PBalc, and  PBald were

    Fenvalerate,  as a deposit (5.5-5.9 µg/100 cm2)     on
Kodaira  light clay, Azuchi  sandy clay loam,  and  Katano
sandy  loam soil from Japan, was decomposed by autumn sun-
light  with the respective half-lives of 2, 6, and 18 days
[118].   The  major product  was CONH2-fenvalerate   (33),
which  amounted to 7.9-25.7% of  the applied radioactivity
after 10 days; it was formed in greatest amounts  in  sun-
light  but also formed  in the dark.   Smaller amounts  of
decarboxy-fenvalerate  (31),  the  desphenyl  analogue  of
CONH2-fenvalerate    (35), COOH-fenvalerate (34),  PBacid,
and PBalc were also detected.  Of the applied radiocarbon,
3-10% remained unidentified.

4.3  Decomposition in Plants

    Fenvalerate   (2.4%  emulsifiable  concentrate  (EC)),
permethrin  (2%  EC),  and deltamethrin  (25 g/litre) were
sprayed  onto cotton fields in Arizona, USA, at respective
rates  of  0.11,  0.11, and  0.23 kg/ha,  and dislodgeable
residues  of the insecticides on cotton foliage were exam-
ined.  Of  the  original  deposits  of  fenvalerate,   65%
remained  at the end of 96 h (there were two rains between
24 and 48 h), compared with 47% and 32% for permethrin and
deltamethrin, respectively [57].

    Fenvalerate  deposits on cotton  plants (0.8 mg/plant)
disappeared rapidly, with only half the material remaining
after 8 days of exposure. After 23 days, decarboxy-fenval-
erate  and ester-cleavage products such  as PBacid, PBald,
PBalc,  and  CPIA  were detectable,  but not quantifiable.
Decarboxy-fenvalerate  was considerably more stable  to UV
light  than fenvalerate, but  it decomposed at  a somewhat
faster  rate than  p,p'-DDT,  yielding mainly the dechlori-
nated analogue [78].

    The  metabolism of fenvalerate  in kidney bean  plants
has  been studied under laboratory conditions by Ohkawa et
al.  [136].  Fenvalerate labelled  with 14C  at the  cyano
group  and the [2S, alphaRS] isomer labelled separately at
the cyano, carboxy, and benzylic carbon atoms were used to
treat  individual bean leaves of 14-day-old seedlings at a
rate  of 10 µg   per leaf.   After 60 days, 85-86% of  the
applied 14C   was recovered from plants treated  with  the
carboxy  and benzyl labels, whereas 67% was recovered from
plants treated with the cyano label. Only limited translo-
cation was observed and only very low levels  of  radioac-
tive   residues  (2-9 µg/kg)    were  detected  in  seeds.
Fenvalerate and the [2S, alphaRS] isomer disappeared at  a
similar rate from the treated leaves with an initial half-
life of 14 days.

    The  metabolism  of  racemic fenvalerate  and  of  its
[2S, alphaS] isomer was  examined in  cabbage plants grown
under laboratory conditions and treated (20 µg   per leaf)
with [14C]-chlorophenyl- and [phenyl-14C]-benzyl-labelled
preparations  of the two compounds.  Both compounds disap-
peared  from the treated leaves with similar half-lives of
approximately  12-14 days.  They underwent  ester cleavage
to  a significant extent, together with some hydroxylation
at the 2- or 4-position of the phenoxy ring and hydrolysis
of the nitrile group to amide and carboxyl groups. Most of
the carboxylic acids and phenols thus produced occurred as
glycoside conjugates. In a separate experiment, the uptake
and metabolism of CPIA (17) was examined in the laboratory
using abscised leaves of kidney bean, cabbage, cotton, cu-
cumber, and tomato plants. The acid (17) was found  to  be
readily  converted, mainly into glucose or 6-O-malonylglu-
cose  esters in kidney  bean, cabbage, and  cucumber, into
glucosylxylose,  sophorose,  and  gentiobiose  esters   in
cotton,  and into two types of triglucose esters with dif-
fering  isomerism  in  tomato.  One  of the acetyl-derived
glucoside  conjugates  was  identical with  the  authentic
deca-acetyl  derivative  of  the  [1-6]-triglucose   ester

    In  studies by Ohkawa  et al. [136],  fenvalerate  was
metabolized or degraded in bean plants via several routes.
A minor route was hydrolysis of the cyano group leading to
the formation of the amide (33) and carboxylic  acid  (34)
derivatives  of fenvalerate.  The  3-phen-oxybenzyl moiety

underwent  metabolism  to  yield  PBacid,   3-(2'-hydroxy-
phenoxy)benzoic acid (23) and PBalc, which occurred mainly
as  sugar  conjugates.  In  addition, glucoside conjugates
of alpha-carboxy-3-phenoxybenzyl   alcohol (36) were  detected
to a lesser extent. The presence of alpha-cyano-3-phenoxyben-
zyl alcohol (16) conjugates was inferred since  PBald  was
released  upon  treatment with  beta-glucosidase.  A major
metabolite  of the acid  moiety was CPIA (17),  which also
occurred  mainly  as glucoside  conjugates.  The decarboxy
derivative  (31)  of  fenvalerate,  presumably  formed  by
photochemical  reaction on plant foliage as discussed pre-
viously, was detected in leaf extracts.  When  bean  plant
seedlings  were planted and left for 30 days in light clay
and  sandy  loam  soils treated  with 14C-fenvalerate   at
1 mg/kg, the roots retained fairly large amounts of radio-
carbon.   However, only limited  radiocarbon was found  in
the  shoots (0.02 mg/kg), pods and seeds (0.01 mg/kg), and
there was no parent compound in the shoots.

    Additional studies were carried out to investigate the
fate  of 3-phenoxybenzoic acid (an important metabolite of
fenvalerate  and most other pyrethroids) in plants.  Using
abscised  leaves of cabbage, cotton, cucumber, kidney bean
and tomato plants, 14C-3-phenoxybenzoic  acid was shown to
conjugate with a complex range of sugars [120].

4.4 Decomposition in Soils

    The  degradation  of  fenvalerate in  soils  has  been
studied  under  various  conditions (aerobic  or anaerobic
conditions, laboratory or field conditions, using radioac-
tive or non-radioactive material).

    Samples of 14C-fenvalerate  labelled separately in the
carboxy  and cyano groups  were used for  soil studies  by
Ohkawa  et al.  [133].  When  several types  of soil  were
treated  at  a rate  of 1 mg/kg and  stored at 25°C  under
aerobic  conditions, the initial half-life  of fenvalerate
ranged   from   15 days   to  3 months.    As  with  other
pyrethroids, hydrolysis at the ester linkage was  a  major
degradation  route, and ring hydroxylation  in the 4'-pos-
ition (25), together with hydrolysis of the cyano group to
the  amide and carboxyl  groups, occurred to  smaller  ex-
tents.   The degradation route  unique to fenvalerate  was
ether-bond  cleavage yielding alpha-cyano-3-hydroxybenzyl-
1-2-(4-chlorophenyl)-3-methylbutyrate (14), which could be
produced through hydroxylation at the 2'7-position (13) in
the alcohol moiety.  No H14CN   released during ester-bond
cleavage  was detected owing  to its rapid  conversion  to
14CO2.       The amount of 14CO2     was greater with  the
cyano  label than the  carboxy label.  For  example, after
30 days  in Katano sandy loam soil, 47.5% and 38.2% of the
applied  radiolabel was evolved as 14CO2 from    the cyano
and  carboxyl groups, respectively.  In a laboratory soil-
leaching  study, less than  1% of the  applied radiocarbon
appeared  in  the  effluent  when  leaching  was   started

immediately  after treatment of  the soil.  Even   after a
30-day incubation, only a trace amount of CPIA  (17)   was
detected  in the effluent  from soil columns  treated with
14C-carbonyl-fenvalerate.    In a separate experiment, the
degradation  of 14C-fenvalerate   was  studied in  a soil-
nutrient  liquid suspension system.  Separate  cultures of
bacteria and fungi were used for the system. After 2 weeks
of  incubation,  larger amounts  of 14CO2 (35-42%   of the
applied  radiolabel) were formed  from both culture  media
when  the 14CN-labelled  compound was  used than when  the
14CO-labelled    compound  was  used (1.1-2.3%).   In  the
latter  case, the main degradation product was CPIA, which
amounted to 34-69% [133].

    Studies using 14C-fenvalerate,  labelled separately in
the  chlorophenyl and benzyl groups,  confirmed the degra-
dation pathways mentioned above. These studies also showed
that  the labelled aromatic  rings were also  readily  de-
graded  to 14CO2 (up   to 66%).  In addition, it was found
that  any  "bound residues"   formed could be  further de-
graded to 14CO2 by admixture with fresh soils [119].

    The rate of degradation of the individual  isomers  of
fenvalerate has been investigated.  In one soil, the half-
lives of the RR, RS, SR, and SS isomers were shown  to  be
178, 89, 155, and 108 days, respectively [105].  Different
rates for the various isomers were similarly  obtained  in
loam and sandy loam soils [160].

    Under  flooded  conditions  fenvalerate degrades  more
slowly  than under aerobic  conditions.  In sterile  soil,
degradation is minimal, indicating that microbial activity
is the major cause of this degradation [102].   Ohkawa  et
al. [133] reported similar findings.

    Studies in which crops were sown in  soils  containing
aged  residues  of 14C-fenvalerate  (aging  periods of 30,
120,  and 345 days) showed that  residues from fenvalerate
should not carry over into rotated crops [102].

    The  persistence of fenvalerate in Lethbridge (Canada)
soil  has  been studied  under  field and  laboratory con-
ditions  [74].   Formulated fenvalerate  (30% emulsifiable
concentrate)  was applied once  to soil microplots  in the
field  at a dose  rate of 600 µg/plot    (150 g/ha) or  to
soil  in pots at a  dose of 88.7 µg/pot   (10 g/ha).   The
treated pots were maintained at a daily temperature regime
of  20°C for 16 h  and 10°C for  8 h in the  environmental
chamber.  Fenvalerate was found mainly in the  top  2.5 cm
of  the field soil, and 16 weeks later, 15% of the applied
fenvalerate  remained.  The  initial half-lives  were  5.9
weeks for the [2S, alphaR] [2R, alphaS]  enantiomeric pair 
and 6 weeks for the [2R, alphaR] [2S, alphaS]   pair.  The  
spring soil samples, taken 45 weeks after application, con-
tained 11% of the total fenvalerate.  Limited  degradation 
occurred during the winter. The degradation of fenvalerate 

in soil incubated in the environmental chamber was similar 
to the field results. The [2S, alphaR] [2R, alphaS] enant-
iomeric  pair  had  a  half-life of 5 weeks while the [2R, 
alphaR] [2S, alphaS] pair had  a half-life  of  5.3 weeks.  
These results were comparable to the average half-life  of 
7 weeks for fenvalerate incubated in British Columbia soils 

    In studies by Harris et al. [69], the  persistence  of
fenvalerate  in subtropical field soil  (average soil tem-
perature,  20-30°C)  was  investigated after  applying 20%
emulsifiable concentrate at a rate of 1 kg active ingredi-
ent (ai)/ha twice a year (spring and autumn) over  a  2.5-
year period.  Residues in the top 15 cm of soil were moni-
tored  for up  to one  year after  the final  application.
Fenvalerate  levels  declined  rapidly  after  the  spring
application  and relatively slowly after the autumn appli-
cation.  There was no carry  over of the insecticide  from
year to year, and after 2.5 years of application  only  2%
of  the total fenvalerate remained. The rate of disappear-
ance  became slightly slower when  fenvalerate application
ceased [181].  The degradation of fenvalerate (14.9 mg/kg)
in  plainfield sand (5% moisture)  at 25°C was  relatively
slow, with an initial half-life of 2 months,  as  compared
with  initial  half-lives  of  0.5,  1,  and  2 months for
fenpropathrin  (7.1 mg/kg),  permethrin  (8.8 mg/kg),  and
cypermethrin  (7.3 mg/kg), respectively, under  laboratory

    A  2-year field study  on the relative  persistence of
permethrin,  cypermethrin, fenpropathrin, and  fenvalerate
in  soils was carried out  by Chapman & Harris  [25].  The
pyrethroids were applied as emulsifiable concentrates at a
rate of 280 g ai/ha or 140 g ai/ha to duplicate  plots  in
Ontario,  Canada, containing either sand  or organic soil.
For  plots treated at the higher rate, the insecticide was
immediately raked into the soil, while the plots receiving
the  lower rate were left undisturbed and the upper 4-5 cm
of  soil was subjected to  gas-liquid chromatography (GLC)
analyses.   The  concentrations  of the  four  pyrethroids
incorporated  in both soils or remaining on the upper soil
layer  decreased to less  than 50% of  the initial  values
within  one month.  Again,  fenvalerate was slightly  more
persistent,  with 7% of the  initial application remaining
in organic soil 28 months after treatment.

    Reed  et al. [157] demonstrated  that when fenvalerate
was  applied  to  soil, adsorption  prevented  significant
leaching  of  the  pesticide.  Soil  metabolites  produced
either  by  photolytic  or microbial  degradation  did not
accumulate  to a significant level or present a problem in
subsequent  rotation  crops  (lettuce, beets,  and  wheat)
planted  at  30 days,  60 days, 120 days,  or 1 year after
soil  treatment.   Although fenvalerate  has intrinsically

high  toxicity to a  variety of aquatic  organisms,  these
field  studies demonstrated that the toxicant was unavail-
able to non-target organisms.  Therefore, it had little or
no  impact in this  test system following  its use at  the
maximum allowed rate of 2.24 kg/ha per year.

4.5  Decomposition in Water

    The  hydrolysis  of  racemic fenvalerate  in  buffered
aqueous  solutions at pH 5.0, 7.0, and 9.0 was compared by
Katagi et al. [90] with that of  the [2S, alphaS]  isomer.
Both compounds were fairly stable at pH 5.0 and 7.0 (half-
lives  of 130-220 days),  while at pH 9.0  they  underwent
hydrolysis (half-lives of 64.6-67.2 days) mainly via ester
bond cleavage.  The main product was 2-(4-chlorophenyl)-3-
methylbutyric  acid (17), which  amounted to 14.9%  of the
applied 14C after  28 days.   As the  [2S, alphaS]  isomer
underwent alphaS/alphaR epimerization in the alcohol moiety 
at pH 7.0 and 9.0, its rate of  hydrolysis appeared to  be
rather faster than that of fenvalerate. However, the half-
life estimated from the total amounts of [2S, alphaS]  and
[2S, alphaR] epimer was close to that of fenvalerate, which
indicates no significant difference in hydrolysis rate.

    The   persistence  of  fenvalerate has  been evaluated
in   water  and  sediment   contained  in  open   trenches
(3 m x 1 m x 30 cm) lined with alkathene sheet [1]. Insec-
ticide emulsion was sprayed on the surface of the water at
the  normal rate and at twice the recommended dosage.  The
dissipation of the insecticide from water was rapid. About
74-80% of the pesticide was lost within 24 h at  both  ap-
plication rates.  However, residues were found to  be  ad-
sorbed  onto sediment, and these persisted beyond 30 days.

In   soil,   persistence  was   moderate,  lasting  around
30 days.



     The metabolic fate of fenvalerate in rats, mice,  and  cows
 has  been studied using variously  labelled racemic fenvalerate
 (acid moiety or benzyl or cyano groups labelled).
     From oral administration studies, fenvalerate appears to be
 absorbed rapidly through the gastrointestinal wall.

     Following  a single oral administration of labelled fenval-
 erate  to rats, the excretion  of radiocarbon from the  acid or
 benzyl  moieties was fairly  rapid.  However, the  excretion of
 radiocarbon  originating  from  the cyano  group was relatively
 slow, the rest of the radioactivity being retained  in  various
 tissues,  particularly in hair and stomach as thiocyanate.  The
 major  routes of metabolism were  ester cleavage, hydroxylation
 at  the  4'position  of  the  alcohol  moiety,  and thiocyanate
 formation  from the cyano  group. Major metabolites  were 2-(4-
 chlorophenyl)isovaleric  acid (Cl-Vacid) and 3-OH-Cl-Vacid (Cl-
 Vacid hydroxylated at the 3 position) from the acid moiety, and
 the  sulfate conjugate of 3-(4'-hydroxyphenyl)benzoic  acid and
 thiocyanate  from the alcohol moiety.  A lipophilic metabolite,
 cholesteryl-[2R]-2-(4-chlorophenyl)isovalerate, which was related
 to  granuloma formation, was  detected  in the adrenals, liver,
 and  the mesenteric lymph nodes  of rats, mice, and  some other
 species.   The excretion of fenvalerate in the milk from orally
 dosed cows was very low (0.44-0.64% of the total dose).

    The metabolic fate of fenvalerate in mammals  is  sum-
marized in Fig. 3.

5.1  Metabolism in Mammals

5.1.1  Rat

    Following  the  single oral  administration of fenval-
erate,  labelled  with 14C  in  the  carbonyl of  the acid
moiety (14CO) and  the benzylic  carbon (14Calpha),     to
male  rats (7-30 mg/kg body weight),  the radiocarbon from
the acid and alcohol moieties was rapidly  and  completely
excreted  [86, 134].  The  tissue residues were  generally
very low, except for those in the fat.  The total recovery
of 14C   in urine, faeces, and  expired air was 93-99%  in
6 days.  However,  on  dosing with 14CN-labelled   fenval-
erate,  the  radiocarbon derived  from  the CN  group  was
excreted  relatively slowly into the urine and faeces, and
a  considerable amount (10%)  of the radiocarbon  was also
excreted  as  CO2.     Total recovery  of 14C   in  urine,
faeces, and expired air was 75-81% in 6 days in this case.
The tissue residue levels were generally higher than those
from  the  acid and  alcohol  moieties.  Hair,  skin,  and

stomach contents showed high residue levels, due to reten-
tion as 14C-thiocyanate.  These excretion and tissue resi-
due  patterns for the radiocarbon  from the CN group  were
similar to those with 14C  dosed as KCN and KSCN  in  male
rats [134].


    It was shown in the same study that fenvalerate under-
went  oxidation at the  2'and 4'positions of  the  alcohol
moiety,  as  well  as at the 2 and 3 positions of the acid
moiety,  ester cleavage, and the  conjugation of resultant
phenols  and carboxylic acids  with glucuronic acid,  sul-
furic  acid, and glycine.  Cleavage of fenvalerate and its
ester  metabolites appeared to release cyanohydrins, which
were, however, unstable under physiological conditions and
decomposed  easily to cyanide and aldehydes (Fig. 3).  The
cyanide   ion  was  converted mainly  to  thiocyanate  and
CO2,   and 2-iminothiazolidine-4-carboxylic acid, a metab-
olite detected with other pyrethroids containing a cyanide
group, was not positively identified [134]. The major fae-
cal metabolites from 14CO-, 14Calpha-,     and 14CN-fenval-
erate  were unchanged fenvalerate (5) and two ester metab-
olites of 2'-hydroxy-(13) and 4'-hydroxy-fenvalerate (25).
The  major metabolites in 0- to 2-day pooled urine (50-55%
of  the dosed radioactivity) from  the acid-labelling were

2-(4-chlorophenyl)isovaleric  acid (17) (Cl-Vacid),  2-(4-
chlorophenyl)-3-hydroxymethylbutyric  acid  (37) (3-OH-Cl-
Vacid),  and  its  lactone  (38)  (3-OH-Cl-Vacid-lactone).
Other minor metabolites were 2-(4-chlorophenyl)-2-hydroxy-
3-hydroxymethylbutyric  acid (39) (2,3-OH-Cl-Vacid) in the
free,  the lactone (40) (2,3-OH-Cl-Vacid-lactone), and the
conjugated   forms,   2-(4-chlorophenyl)- cis-2-butenedioic
acid  anhydride  (41)  (Cl-BDacid  anhydride),  and  2-(4-
chlorophenyl)-3-methyl-2-butene-4-olide  (42)  (Cl-B-acid-
lactone).   On  the  other hand,  the  predominant urinary
metabolite  from the alcohol moiety was the sulfate conju-
gate  of  3-(4'-hydroxyphenoxy)benzoic  acid (23)  (4'-OH-
PBacid),  accounting  for  approximately 40%  of the dose.
Other  major  metabolites were  3-phenoxybenzoic acid (22)
(PBacid) in the free (6%), the glucuronide (2%),  and  the
glycine  (2%)  conjugated forms, 4'-OH-PBacid  in the free
(5%) and the glucuronide (2%) forms, and the sulfate of 3-
(2'-hydroxyphenoxy)benzoic  acid (24) (2'-OH-PBacid) (3%).
With 14CN-fenvalerate,   the major urinary  metabolite was
thiocyanate (43) [134].

    Pydrin   insecticide   (Y-rich)  is   an  isomerically
enriched form of fenvalerate containing an excess ratio of
the active diastereomers SS and RR (designated Y) over the
less  active diastereomers RS and  SR (designated X) at  a
ratio of approximately 85:15.  Fenvalerate contains Y:X in
a  ratio of 45:55.  Following a single oral dose of the Y-
rich  insecticide (8.4 mg/kg) to male  and female Sprague-
Dawley  rats, more than  90% of the  administered radioac-
tivity  from the acid moiety  (chlorophenyl-14C)   and the
alcohol moiety (phenoxyphenyl-14C)   was eliminated within
the first 24 h.  There was no major difference between the
two different fenvalerate preparations in either the elim-
ination  rate  or  the metabolites  distribution  profile.
Cleavage  of the ester  linkage was the  primary metabolic
pathway. The acid and alcohol portions of the parent mole-
cule  underwent hydroxylation, oxidation, and conjugation.
These metabolic reactions were not dependent on  the  iso-
meric  composition of the  test material.  Tissue  residue
data  showed that 14C  residues  were not retained  in the
various organs [104].

    The fate of sugar conjugates, which may be  formed  as
plant  metabolites, has been investigated by Mikami et al.
[122].   Upon single oral administration  to male Sprague-
Dawley  rats at a  concentration of 3.8 mg/kg,  the mono-,
di-,  and tri-glucose conjugates  of [14C]-3-phenoxybenzyl
alcohol  (19) and the  mono-glucose conjugate of  [14C]-3-
phenoxybenzoic  acid  (22)  were  rapidly  hydrolysed  and
extensively eliminated in the urine, mostly as the sulfate
conjugate   of   3-(4-hydroxyphenoxy)benzoic  acid   (24).
Faecal  elimination  was  a minor  route,  whereas biliary
excretion was responsible for about 42% of the  dose,  and
the glucuronide conjugates of (19), (22), and  (24)   were
common  major metabolites.  The biliary  glucuronides were
metabolized  in  the  small intestine  to  the  respective

aglycones, which were reabsorbed, metabolized further, and
excreted  in the urine as  the sulfate conjugate of  (24).
Although small amounts of the mono-, di-,  and  tri-gluco-
sides  were found in  the 30-min blood  and liver  samples
following  oral  administration  of the  tri-glucoside  of
(19), they were not detected in the urine, bile,  or  fae-
ces. Similarly, the sulfate conjugate was one of the major
urinary  metabolites  in  germ-free male  rats, when dosed
with  the 14C-glucosides  at a rate of 9 µmol/kg   via the
oral  or  intraperitoneal route,  although certain amounts
were excreted unchanged in the urine and faeces.  The glu-
cose  conjugates  were metabolized  in  vitro by intestinal
microflora  and  in  various rat  tissues including blood,
liver,  small intestine, and small  intestinal mucosa. The
tissue enzymes showed a different substrate specificity in
hydrolysing the glucosides.  However, they were not metab-
olized  in  gastric  juice,  bile,  pancreatic  juice,  or

5.1.2  Mouse

    In mice, fenvalerate is metabolized in a  similar  way
to  that in rats,  but the following  significant  species
differences  were found  by Kaneko  et al.  [86]: (a)  the
taurine conjugate of PBacid was found in mice but  not  in
rats;  (b)  4'-OH-PBacid  sulfate occurred  to  a  greater
extent in rats than in mice; and (c) a greater  amount  of
thiocyanate  was excreted in  mice than in  rats. No  sig-
nificant sex differences were observed in rats  and  mice.
The   metabolism  of  the  stereoisomers  of  fenvalerate,
([2S, alphaRS] and [2S, alphaS]) was apparently  similar to
that of racemic fenvalerate.

    Following  a  single  oral administration  of the four
chiral   isomers  of  [14C-chlorophenyl]-fenvalerate    to
Sprague-Dawley  rats and ddY mice (2.5 mg/kg body weight),
the [2R, alphaS] isomer showed, in both rats and mice, rel-
atively greater residues in  the analyzed tissues  (except
fat),  particularly in adrenal  glands, compared with  the
other   three  isomers.   Similarly,  this  isomer  showed
higher  tissue concentrations than the  other isomers when
mice  were  fed  a  diet  containing  500 mg/kg   of   the
[2S, alphaS],  [2R, alphaS],  or  [2R, alphaR] isomers for 
two weeks. The greater amount of radioactive residues from
the  administration of [2R, alphaS]  isomer,  as  compared 
with  those   of  other  isomers,  was  explained  by  the  
preferential formation of a lipophilic metabolite from the
[2R, alphaS]  isomer found  in all examined tissues, which 
was  not  easily excreted.  The  amounts of the lipophilic 
metabolite differed among tissues, being higher in adrenal,
liver,  and mesenteric lymph  nodes.  This metabolite  was
identified  as  cholesteryl [2R]-2-(4-chlorophenyl)isoval-
erate.  The presence of the same metabolite was also indi-
cated in rat tissues [87].

5.1.3  Domestic animals

    Two  3-month-old  lambs  were fed  a  diet  containing
45 mg/kg fenvalerate for 10 days and then killed to deter-
mine  the  concentrations  of fenvalerate  in  the kidney,
liver, leg muscle, and renal fat [210]. Among the analyzed
tissues, fat showed the highest fenvalerate level (3.6-4.4
mg/kg  dry weight) while other tissues contained less than
0.3 mg/kg.  Fenvalerate gave two gas chromatographic peaks
and each peak contained a pair of its enantiomers.  In all
cases,  the ratio  of the  areas of  these  peaks  (peak 1
(RS,SR)/peak 2 (SS,RR)) was 1.08 both for  fenvalerate  in
the  diet and for fenvalerate recovered from the fortified
control  fat.  In contrast, the  fenvalerate isolated from
lamb fat had a peak area ratio of 0.76-0.78.  Thus, one or
both  of  the first  eluting  enantiomers appeared  to  be
metabolized more rapidly than the other enantiomers.

    In  a study by Wszolek et al. [209], two Holstein cows
were fed fenvalerate at 5 and 15 mg/kg diet for 4 days and
were  then given a clean diet for 6 days.  Total excretion
of fenvalerate in milk amounted to 0.44 and 0.64%  of  the
total  dose for the  5 and 15 mg/kg  levels, respectively,
whereas  about  25%  of the  dose  was  eliminated in  the

    A  lactating Holstein cow was fed grain fortified with
227 mg fenvalerate daily for 4 days and the urine was ana-
lysed.  Intact fenvalerate was not detected in any samples
of the urine excreted by the cow during the 10-day feeding
study,  nor was the acid metabolite (Cl-Vacid) (17) ident-
ified.   The  in vitro study on fenvalerate  degradation in
rumen  fluid indicated that no  significant degradation of
fenvalerate was observed during the 6-h incubation [211].

    Saleh  et al. [161] gave a single oral dose of fenval-
erate (10 mg/kg body weight) to chickens and monitored the
persistence  and distribution of  the insecticide over  15
days.  A concentration of 4.7 mg/litre in blood after 24 h
fell to 0.05 mg/litre after 7 days. Levels in  other  tis-
sues reached maxima of less than 1.0 mg/kg and  fell  rap-
idly. However, brain residues rose to a level of 4.0 mg/kg
over  7 days and persisted for  the 15 days of the  exper-
iment.  Concentrations  in  eggs  reached  a  maximum   of
0.3 mg/kg  yolk  after  4 to  5 days,  and  a  maximum  of
0.24 mg/kg egg white. By day 6, levels had returned to the
pre-dosing level.

5.2  Enzymatic Systems for Biotransformation

    The  [2R, alphaRS]   isomer of fenvalerate  has been found
to be more rapidly hydrolysed by mouse liver esterase than
the  [2S, alphaRS]   isomer, but less rapidly metabolised than
the  [2R, alphaRS]   isomer with an oxidase system.  A similar
correlation was observed with the [2S] and [2R] isomers of
S-5439 (3-phenoxybenzyl-2-(4-chlorophenyl)isovalerate) [165].

    In  an  in vitro study on  the metabolism of  the  four
chiral isomers of fenvalerate using homogenates from vari-
ous  tissues of mice,  rats, dogs, and  monkeys, only  the
[2R, alphaS] isomer yielded  cholesteryl-[2R]-2-(4-chloro-
phenyl)isovalerate  (CPIA-cholesterol  ester)  as a  major
metabolite. Mouse tissues exhibited a higher rate of CPIA-
cholesterol  ester formation than those  of other animals.
Of the mouse tissues tested, the kidney, brain, and spleen
showed the greatest ability to form this ester,  the  rel-
evant  enzyme  activity  being  mainly  localized  in  the
microsomal  fractions.  Carboxyesterases for  mouse kidney
microsomes hydrolyzed the  [2R, alphaS]   isomer  only  of
fenvalerate  to  give  CPIA and  yielded the corresponding
cholesterol  ester in the presence of artificial liposomes
containing   cholesterol.   It  appears   that  the  CPIA-
cholesterol   ester  resulted  from   the  stereoselective
([2R, alphaS]    only)  formation of  the CPIA-carboxyesterase
complex,  which  subsequently reacted  with cholesterol to
yield the CPIA-cholesterol ester [128].

    Hydrolysis  of the four chiral  isomers of fenvalerate
by microsomes of various mouse tissues has  been  investi-
gated by Takamatsu et al. [180].  The kidney,  spleen  and
brain hydrolyzed only the [2R, alphaS] isomer. Liver hydro-
lyzed the [2R, alphaS] and [2R, alphaR] isomers to a great-
er extent than the [2S, alphaR] and [2S, alphaS]   isomers, 
while plasma hydrolysed the [2S, alphaR]   and [2R, alphaR]   
isomers more rapidly than the [2S, alphaS] and [2R, alphaS]   
isomers.  The  stereoselectivity  of hydrolysis of the four 
isomers by mouse liver microsomes was  found to be  same as  
that  in vivo. Of the four isomers, the [2R, alphaS]  isomer 
alone was transformed to cholesteryl-[2R]-2-(4-chlorophenyl)
isovalerate (CPIA-cholesterol ester)  by microsomes  of the
brain,  kidney, spleen, or liver  but not by plasma.   The
rate  of CPIA-cholesterol ester formation was lower in the
liver than in other tissues.  The optimum pH (7.4-9.0) for
the  formation of this ester  was nearly the same  as that
for  hydrolysis of the [2R, alphaS] isomer to form CPIA in
mouse kidney microsomes.

    The  substrate specificity of microsomal carboxyester-
ase(s)  responsible for the formation of cholesteryl-[2R]-
2-(4-chlorophenyl)isovalerate  from fenvalerate was inves-
tigated  by incubating mouse kidney  microsomes with 14C-
cholesterol and fenvalerate or its analogues.  Of the four
isomers of fenvalerate, only the [2R, alphaS]   isomer yielded
a cholesterol ester. This specificity of cholesterol ester
formation was the same as that in the  in vivo study.  Some
of the fenvalerate analogues also produced similar choles-
terol  esters.  Steroids other than  cholesterol were also
investigated  as  acceptors  of  the  acid  moiety  of the
[2R, alphaS]    isomer by incubating egg  lecithin and several
steroids  with the [2R, alphaS]    isomer in the  presence  of
solubilized carboxyesterase(s). Dehydroisoandrosterone and
pregnenolone reacted with the [2R, alphaS]  isomer to give the
corresponding ester conjugates [88].

    One  or more carboxyesterases  located in the  soluble
fraction  of  mouse  brain homogenates  hydrolyzed several
pyrethroid  esters with a substrate  specificity different
from  that  of  the  hepatic  esterases.   In  particular,
fenvalerate  and  fluvalinate  were  hydrolyzed  by  brain
esterases  at rates equal to or greater than that measured
for  trans-permethrin.  The results suggest that hydrolysis
in  the brain may contribute  to the detoxication of  some
pyrethroids in mammals [64].


    The  acute toxicity data of fenvalerate to aquatic and
terrestrial  non-target organisms are summarized in Tables
5, 6, and 7.

6.1  Aquatic Organisms

6.1.1  Toxicity to aquatic invertebrates

    Non-target  invertebrates,  except molluscs,  are more
susceptible   to  the  insecticide  than   fish,  the  LC50
ranging from 0.08 to 2 µg/litre.

    Fenvalerate  is  relatively  non-toxic to  oysters and
algae (LC50 >1000 µg/litre)   over short exposure periods.
Snails  (Heliosoma  trivolvis) exposed for 28 days  to 0.79
µg/litre,   the  highest  concentration tested,  showed no
change in behaviour or survival [4].

    Day  &  Kaushik  [32] conducted   short-term  toxicity
tests  on three species of  cladoceran and one species  of
calanoid  (Diaptomus  oregonensis). The 48-h LC50   values
for daphnids were: 2.52 µg/litre  for adult  Daphnia magna,
0.83 µg/litre     for  D.   magna aged   48 h  (or   less);
0.29 µg/litre     for   adult  Daphnia  galeata   mendotae;
0.21 µg/litre     for  adult  Ceriodaphnia  lacustris; 0.16
µg/litre   for  D.  galeata  mendotae aged 48 h  (or less).
 Diaptomus  oregonensis was the most sensitive species with
a 48-h LC50 of  0.12 µg/litre.  No toxicity was found with
the  emulsifiable  concentrate from  which fenvalerate was
omitted  (EC control). Rates  of filtration of  algae were
reduced  at  sub-lethal  concentrations  of   fenvalerate.
 Ceriodaphnia   lacustris was  the most  sensitive species,
with   rates  of  filtration  significantly  decreased  at
fenvalerate  concentrations of 0.01 µg/litre.     Rates of
assimilation  of algae were decreased  at fenvalerate con-
centrations of 0.05 µg/litre or more.

    Day & Kaushik [33] conducted life-cycle studies on the
toxicity  of  fenvalerate  to  Daphnia  galeata   mendotae.
Lifetable   methods  were  used  to  generate  statistical
comparisons  between  treatments.   At a  concentration of
0.005 µg/litre,    fenvalerate increased the  longevity of
the  daphnids significantly from  37.6 to 51.6 days.  How-
ever, at the same concentration, production of  young  was
decreased.   Higher  concentrations of  fenvalerate caused
reduced  survival of the  adults.  The intrinsic  rate  of
natural increase in the population was reduced at  a  con-
centration  of 0.5 µg/litre.   At 0.01 µg/litre,  the  net
reproductive  rate decreased from 126  to 73 offspring per
female and the generation time from 20.3 to 17.3 days.

Table 5.  Acute toxicity of fenvalerate to non-target freshwater organisms
Species                         Sizea           Parameter     Toxicity    Formu-   Systemc  Temperature   pH       Hardnessd   Reference
                                                              (µg/litre)  lationb           (° C)
   Gammarus pseudolimnaeus       adult-juv       96-h LC50     0.03        T         F       15            7.6-7.8  46-48       4
   Gammarus pseudolimnaeus       1-3 mm, juv     96-h LC50     0.05        T         R       17            7.6-7.8  46-48       4
  Waterflea                     1st instar      96-h LC50     0.032       T         S       17            7.4      44          115
   (Daphnia magna)
  Midge                         3rd instar      48-h LC50     0.43        T         S       22            7.4      44          115
   (Chironomus pulmosus)
  Mayfly                        larva           9-day LC50    0.08        T         F       15            7.6      46-48       4
   (Ephemerella sp.)
  Rhagionid fly                 larva           28-day LC50   0.03        T         F       15            7.6-7.8  46-48       4
  Stonefly                      naiad           72-h EC50     0.13        T         F       15            7.6-7.8  46-48       4
   (Pteronarcys dorsata)
  Stonefly                      3-6 weeks old   96-h LC50     1.9         EC        S       20-22         7.8      7%          107
   (Nitocra spinipes)

  Atlantic salmon               6.2 cm, 5.3 g   96-h LC50     1.2         T         R       10                                 110
   (Salmo salar)
  Rainbow trout                 5-6 cm          48-h LC50     3.0         EC        S       12-25.5                            129
   (Salmo gairdneri)
  Rainbow trout                 6 cm, 3 g       24-h LC50     76          T         S       10            7.5      110         28
   (Salmo gairdneri)
  Rainbow trout                 6 cm, 3 g       24-h LC50     21          EC        S       10            7.5      110         28
   (Salmo gairdneri)
  Mosquitofish                  4-5 cm          48-h LC50     15.0        EC        S       8.8-16                             129
   (Gambusia affinis)
  Mosquitofish                  3-days old      72-h LC50     2.6         T         S       24-27                              124
   (Gambusia affinis)
  Desert pupfish                4-5 cm          48-h LC50     25.0        EC        S       11-16.6                            129
   (Cyprinodon macularis)
   Tilapia mossambica            5-6 cm          48-h LC50     200.0       EC        S       15-21.4                            129
  Bluegill sunfish              adult           96-h LC50     0.76        T         S       22            7.4      40          115
   (Lepomis macrochirus)
  Fathead minnow                adult           96-h LC50     2.35        T         S       22            7.1      49          115
   (Pimephales promelas)
a   juv = juvenile.
b   T = Technical, EC = Emulsifiable concentrate.
c   R = Renewal, S = Static, F = Flow-through.
d   expressed as mg CaCO3 per litre.

Table 6.  Acute toxicity of fenvalerate to non-target estuarine & marine organisms
Species                            Sizea           Parameter    Toxicity    Formul-   Systemc  Temper-  pH   Salinity  Reference
                                                                (µg/litre)  ationb             ature         o/oo
                                                                                               (° C)
   Skeletonema costatum                             96-h EC50    > 1000      T                  20            30        212
   Isochrysis galbana                               96-h EC50    > 1000      T                  20            30        212
   Thalassiosira pseudonana                         96-h EC50    > 1000      T                  20            30        212
   Nitzschia angularum                              96-h EC50    > 1000      T                  20            30        212

  Eastern oyster                   2-h larva       48-h EC50    > 
1000      T         S         25            20        212
   (Crassostrea virginica)

  Lobster  (Homarus americanus)     450 g           96-h LC50    0.14        T         R        10            30        110
  Shrimp  (Crangon septemspinosa)   1.3 g           96-h LC50    0.04        T         R        10                      110
  Shrimp  (Mysidopsis bahia)        1-day juv       96-h LC50    0.021       T         S        25            20        212
  Shrimp  (Mysidopsis bahia)        newly hatched   96-h LC50    0.008       T         F        25.4          25.3      163
  Shrimp  (Penalus duorarum)        adult           96-h LC50    0.84        T         F        24.8          24.9      163
  California grunion               3-day larva     96-h LC50    0.29        T         F        26            25        114
   (Leuresthes tenuis)
  California grunion               juv             96-h LC50    0.60        T         F        25            22        114
   (Leuresthes tenuis)
  Inland silverside                26-day larva    96-h LC50    1.00        T         F        24            20        114
   (Nenidia beryllina)
  Tidewater silverside             juv             96-h LC50    1.00        T         F        25            20        114
   (Menidia peninsulae)

  Sheepshead minnow                28-day fry      96-h LC50    121         T         S        25            20        212
   (Cyprinodon variegatus)
  Sheepshead minnow                adult           96-h LC50    5           T         F        30            26.5      163
   (Cyprinodon variegatus)                                                                                   
  Bleak  (Alburnus alburnus)        8 cm            96-h LC50    2-3         EC        S        10       7.8  7         107
  Atlantic silverside              adult           96-h LC50    0.31        T         F        24.1          25        163
   (Menidia menidia)
  Striped mullet                   adult           96-h LC50    0.58        T         F        25.9          25.8      163
   (Mugil cephalus)
  Gulf toadfish                    adult           96-h LC50    5.4         T         F        30            24.8      163
   (Opsanus beta)                   
a   juv = juvenile.
b   T = Technical, EC = Emulsifiable concentrate.
c   R = Renewal, S = Static, F = Flow-through.

Table 7.  Acute toxicity of fenvalerate to non-target terrestrial organisms
Species                          Size              Application         Parameter   Toxicity          Temper-  Reference
 Broiler chicks                  8-12 weeks old,   oral                LD50        12 590 (mg/kg)    31-32    155
                                 0.99-2.2 kg
 Hen                                               oral                LD50        > 1500 (mg/kg)             123

 Insect parasite
  Ichneumoid                     adult male        film                24-h LC50   1760 (ng/vial)             152
    (Campoletis sonorensis)
 Insect predators
  Lacewing                       adult 2.74 mg     topical             LD50        4.3 (mg/kg)       15       176
    (Austromicromus tasmaniae)    larva 2.52 mg     topical             LD50        67 (mg/kg)        20       176
  Lacewing  (Chrysopa carnea)     3rd instar,       topical             72-h ED50   > 25 (mg/g)       28       164
                                 larva 9.9-10 mg   topical             ED50        ~ 1 (mg/g)        28       164
                                 one generation
  Lacewing  (Chrysopa carnea)     larva             film                LC50        0.073 (mg/vial)   25       151
                                 5-6 days old

  Beetle                         11.2 mg           topical             LD50        0.38 (mg/kg)      15       164
   (Coccinella undecimpunctata)
  Earwig  (Labidura riparia)      mature            soil 0.11 kg ai/ha  mortality   6%                         205
                                                   0.22 kg ai/ha       mortality   25%                        205
                                                   0.44 kg ai/ha       mortality   50%                        205
  Honey bee  (Apis mellifera)     adult             topical             LD50        410 ng/bee        -        5

Predaceous mite species
    Amblyseius fallacis           adult female      slide dip method    LC50        2.6 (mg ai/litre) 27       158
    Amblyseius fallacis           adult female      slide dip method    LC50        7.0 (mg ai/litre) 26       199
    Typhlodromus pyri             adult female      slide dip method    LC50        8.1 (mg ai/litre) 26       199
    Typhlodromus occidentalis     adult female      slide dip method    LC50        2.1 (mg ai/litre) 26       199
    McKenney  & Hamaker [109] exposed  the estuarine grass
shrimp  Palaemonetes  pugio to  fenvalerate,  in  a   flow-
through  system to maintain constant  exposure, throughout
20 days  of larval development.   The study was  conducted
under  optimal  salinity conditions  (20 o/oo).  A nominal
concentration  of  3.2 ng/litre significantly  reduced the
percentage  of  larvae  successfully  completing  metamor-
phosis. Exposure to 1.6 ng/litre prolonged larval develop-
ment.   Larvae  were  also found  to  be  less capable  of
responding  successfully to osmotic stress  after exposure
to fenvalerate at 0.1 or 0.2 ng/litre.

6.1.2   Toxicity to fish

    Fenvalerate   is  toxic  to fish,  LC50 values   being
0.29-200 µg/litre   (Tables 5 and 6).  The LC50 value  for
rainbow  trout  obtained with  an emulsifiable concentrate
was  3.6 times lower than  that for the  technical product
[28]. The toxicity of fenvalerate to adult  bluegill  sun-
fish  (Lepomis  macrochirus) was  unaffected by  changes in
water hardness and pH [115].

    The  acute toxicities (96-h LC50)   of  fenvalerate to
juvenile   steelhead   trout  were   172 ng/litre  and  88
ng/litre,  respectively, under continuous and intermittent
exposure   (approximate   peak   concentration:   460 ± 40
ng/litre  for  4.5 h).  Prolonged  intermittent   exposure
(70 days)  of  the  early life-stage  resulted  in  marked
lethality (32%) and reduced terminal weight (50%  of  con-
trol)  (mean  concentration:  80 ng/litre,  peak   concen-
tration:  461 ng/litre).  However, continuous  exposure to
80 ng/litre  for 70 days did  not effect these  parameters

    Fenvalerate   has  narrow  safety  margins   for  fish
(LC50 of   fish : LC50 of  mosquito larvae is in the ratio
of 1:24) when the insecticide is used  against  mosquitoes

    Four  rainbow  trout  (Salmo gairdneri) died  within 11
hours  when exposed to 412 µg fenvalerate/litre.   Visible
signs  of poisoning included elevated cough rate, tremors,
and  seizures.   Ventilatory and  cardiac activity stopped
during  the  seizures.   Histopathological examination  of
gill  tissue showed damage consistent with irritation, and
Na+ and   K+ excretion  rates were  elevated.  Fenvalerate
concentrations  in brain, liver, and carcass at death were
0.16,  3.62,  and  0.25 mg/kg,  respectively.   The  study
suggested  that, apart from effects on the nervous system,
effects  on respiratory surfaces and  renal ion regulation
may be associated with fenvalerate toxicity in fish [15].

    When  sheepshead minnows  (Cyprinodon variegatus)  were
studied  during  28 days  for  early-life-stage  toxicity,
3.9 µg fenvalerate/litre    significantly reduced the sur-
vival  of  hatched  fish and  2.2 µg/litre    reduced both
length  and  weight,  but  no  effects  were  detected  at
0.56 µg/litre [68].

6.1.3   Field studies and community effects

    Caplan  et  al.  [23] applied  fenvalerate  at concen-
trations of 0.2 and 1.0 mg/kg to sediment in a tidal marsh
sediment model ecosystem.  No adverse effects were seen on
the  heterotrophic microorganisms in the  sediment after a
7-day  exposure to either concentration.   Plate counts to
assess  numbers of organisms and measurements of substrate
degradation were not different from those of controls. The
half-life of fenvalerate was 6.3 days for the treatment at
0.2 mg/kg and 8.9 days at 1.0 mg/kg.

    In  the  field, fenvalerate  was  applied to  ponds at
rates  of  28-112 g ai/ha  as a  mosquito larvicide [124].
Populations  of  plankton, crustaceans,  and mayfly nymphs
decreased  but recovered quickly.   Corixids, notonectids,
and  aquatic beetle populations decreased slightly and the
effects  remained throughout the study.  Chironomid larval
populations  were suppressed and emergence  was inhibited.
However,  no deleterious effects were  observed on rotifer

    When  fenvalerate  was applied  to  ponds at  rates of
11.2-56 g ai/ha  for  mosquito  control,  the  insecticide
produced  complete  mortality  of mayfly  naiads [130].  A
single  treatment  by  fenvalerate at  28 g/ha  controlled
mosquito larvae for more than 7 days, and it also affected
populations of mayfly naiads, dragonfly naiads, and diving
beetle  larva,  but  not  ostracods  or  damselfly  naiads

    Studies  into the effects of  fenvalerate on estuarine
benthic  communities  were  conducted  in  a  flow-through
system for 8 weeks and 1 week for laboratory-  and  field-
colonized   communities,  respectively.   Technical  grade
fenvalerate  (100%),  dissolved  in a  stock solution con-
sisting  of  15% acetone  and 85% triethylene  glycol, was
metered  by syringe  pump into,  and mixed  with, the  sea
water entering the centre of the constant-head box of each
apparatus  receiving  fenvalerate.   The  same  amount  of
carrier  solvent (10 ml/day, 5 mg/litre) was  metered into
the  control apparatus.  Nominal concentrations of fenval-
erate  in sea water  were 0.01, 0.1,  and  1.0 µg/litre.
Samples of water were taken from the  constant-head  boxes
once  a week for chemical analyses for fenvalerate concen-
tration.  Community structure was altered significantly in
both  cases by fenvalerate at 0.1 or 1 µg/litre,   but not

by  0.01 µg/litre.    The  groups most  sensitive  to  the
insecticide  were chordates  (Branchiostoma caribaeum)  and
amphipods,  while annelids and molluscs  tolerated concen-
trations up to 10 µg/litre [177].

    Tagatz  et  al.  [178] placed  boxes  containing sand,
either  uncontaminated  or  contaminated (nominal  concen-
tration  of fenvalerate of 0.1,  1.0, or 10 mg/kg), in  an
estuary  for  8 weeks,  and  the  community  structure  of
benthic  organisms colonising the boxes was assessed.  The
average  number  of species  colonising  the sand  at  the
highest  treatment level was  significantly less than  for
the controls (35.6 compared to 47.8); lower concentrations
had  no  effect  on species  diversity.   Colonisation  by
annelids,  molluscs, and arthropods was unaffected even at
the  highest  dose.  The  only  organisms deterred  by the
fenvalerate were chordates (primarily lanceolets).

6.2  Terrestrial Organisms

6.2.1  Toxicity to soil microorganisms

    In  laboratory  trials  for  effects  on  soil  algae,
Megharaj  et  al. [116]  applied  fenvalerate to  a  black
cotton soil, taken from a fallow cotton field. Fenvalerate
applied  once at a dose equivalent to 0.5 or 1.0 kg/ha had
no inhibitory effect on soil algae, but  two  applications
of  fenvalerate, at concentrations  of 0.75 or  5.0 kg/ha,
resulted in increased algal populations.

6.2.2  Toxicity to beneficial insects

    Fenvalerate  is  highly  toxic to  honey  bees    (Apis
 mellifera) with a topical LD50 of  0.41 µg/bee.   However,
in field tests at a normal application rate of 0.22 kg/ha,
the  hazard is  low because  the residue  repels bees  for
about  10 h  following  application and  decreases to non-
toxic levels within one day. During the first 5 days after
application,  fenvalerate caused only light bee mortality.
At  higher  application rates  (0.44 kg/ha), however, mor-
tality remained high 8 hours after application [5, 63, 84,

    Fenvalerate is toxic to the tobacco budworm  (Heliothis
 virescens) and  to its predator green  lacewing   (Chrysopa
 carnea) as well as to the parasite  (Campoletis sonorensis)
of  the tobacco budworm. But, it is more toxic to the pest
than to either the predator or the parasite. Comparison of
the LC50 value  for the parasite  (C. sonorensis) with that
for  the  host  (H. virescens) indicated  similar toxicity,
the  value for the host being 1.5 times that for the para-
site  [152]. However,  in the  case of  the predator    (C.
 carnea), the  insecticide was much less toxic to the pred-
ator than to the pest, the selectivity ratio  being  0.037

    When  third instar larvae of  C.  carnea were topically
dosed  with 250 µg/insect,   they exhibited  marked toler-
ance  during a 72-h  period.  The ED50 value   (paralysis,
failure  to pupate, knockdown, and mortality)  for fenval-
erate through one generation (larva to larva) was approxi-
mately 1000 µg/g [164].

    Syrett   &  Penman  [176]  compared  LC50 values   for
fenvalerate  when  applied topically  to lucerne-infesting
aphids  (Acyrthosipho   kondoi and  A. pisum) and to  their
predators,  namely  the  brown  lacewing   ( Austromicromus
 tasmaniae, adult  and larva) and the ladybird   (Coccinella
 undecimpunctata).   The values were 0.071, 0.033, 4.3, 67,
and  0.38 mg/kg, respectively.  From these data, the lady-
bird  was  slightly  (5-10 times) more  tolerant  than the
aphid  species, but lacewing  adults were 60-120 times  as
tolerant  as the aphids.  Furthermore, the larvae  were 15
times more tolerant than the adults.  There was a negative
temperature  coefficient  for  A. tasmaniae,   with greater
toxicity  (approximately 3 times) at  10 °C than at  25 °C

    When  fenvalerate was applied  to loamy sand  and then
striped  earwigs  (Labidura  riparia),   a predator of  the
cabbage looper  (Trichoplusia ni),  were added to the soil,
fenvalerate  was  of low  toxicity  at rates  giving  good
looper control [205].

    Laboratory  studies of the activity  of fenvalerate on
spider  mites and their  predators showed that  the spider
mite  (Tetranychus urticae) was considerably more  (67-548
times)  resistant to fenvalerate  than were its  predators
 (Amblyseius  fallacis, Typhlodromus pyri, and  Typhlodromus
 occidentalis) [199].  The LC50 value  for  T.  urticae  was
approximately  25 times greater than that for the predator
 (A. fallacis) [158].

    In the field, the predatory mite  (T. pyri) disappeared
during  the first 4-6 weeks after  fenvalerate was sprayed
at  25 mg/litre to drip-off,  and then small  numbers were
found  7 weeks  after  spraying.  The  insecticide  had no
appreciable  toxicity for spider  mites  (Panonychus ulmi).
The   virtual elimination of the  predatory mite led to  a
marked  population  increase of  P. ulmi later  in the same
season [3].

    In  apple and pear orchards, dramatic increases in the
populations  of  spider  mites  (T.  urticae,   Tetranychus
 mcdanieli, or  P. ulmi)  were seen after the application of
fenvalerate  at rates of 7.5 and 15 mg ai/litre.  This was
due  to a reduction in  the numbers of the  predatory mite
 (Mataseiulus occidentalis) to zero or near zero [80].

    From  these results, it  was suggested that  the  rec-
ommended application rates for fenvalerate would sometimes
be  detrimental to integrated mite control programs in or-
chards, and these would require careful reconsideration.

6.2.3   Toxicity to birds

    The toxicity of fenvalerate to birds is very low.  The
acute   LD50 for   the  chicken   is  more  than   12 g/kg
(Table 7).  The toxicity to  the bobwhite quail    (Colinus
 virginianus) and American kestrel is similarly low.

    Bradbury  &  Coats  [13]  measured  the  toxicity   of
fenvalerate  for  the  bobwhite quail.   Acute oral dosing
yielded an LC50 in  excess of 4 g/kg body weight for adult
birds and 1.785 g/kg body weight for 5-week-old juveniles.
Dietary  dosing of 2-week-old  chicks for 5 days  (with  a
further  3 days  of  observation) indicated  an  LC50   of
> 15 g/kg diet.

    Rattner  & Franson [156] dosed  American kestrels with
fenvalerate  (1-4 g/kg body weight) and examined the birds
for toxic effects over 10 h after dosing.  Some birds were
kept at temperatures of 22 °C and others under cold stress
at -5 °C. Fenvalerate, at exposures far greater than could
be  expected in the environment,  caused mild intoxication
and  elevated  plasma  alanine aminotransferase  activity.
Cold did not increase the toxicity of the pyrethroid.

6.3 Uptake, Loss, and Bioaccumulation

    Fenvalerate  is taken up readily  by aquatic organisms
and  rapidly reaches, within the organism, a plateau level
related to the water concentration of the pyrethroid. Loss
of  fenvalerate  from organisms  is  rapid when  they  are
transferred  to uncontaminated water.  There is no sugges-
tion of biomagnification in food chains.

    Under  laboratory conditions, the half-life of fenval-
erate in sea water containing 100 g sediment per litre sea
water  was 34 (27-42) days  in foil-covered samples  and 8
8 days   in   sunlight-exposed   ones.   Eastern   oysters
 (Crassostrea   virginica) kept  for  28 days in  sea water
containing  24 µg fenvalerate/litre   gave a  steady state
bioconcentration  factor of 4700.  After treatment ceased,
fenvalerate was depurated by the oysters to non-detectable
concentrations within a week [163].

    Snails  exposed  for  28 days to  fenvalerate (0.79 µg
per  litre)  did  not show  any  changes  in behaviour  or
survival.   The bioaccumulation ratios ranged  from 356 to
1167 [4].

    In  a study by Spehar et al. [166], embryonic, larval,
and  early juvenile stages of  fathead minnows  (Pimephales
 promelas) were exposed to fenvalerate in a continuous-flow

system for 30 days. At 0.33 µg/litre   the only effect was
a temporary initial impairment of swimming in some larvae.
This  was more marked  at 0.43 µg/litre   at  which  level
survival of the larvae was also reduced. The  30-day  bio-
concentration  factor  was 3000 ± 1500,  but 25 days after
transfer  to clean water  the fenvalerate had  again  been

    Rainbow  trout  (Salmo gairdneri) were used to evaluate
the  gill  uptake and  toxicokinetics of [3H]-fenvalerate.
Fish (weight between 0.64 and 0.97 kg) were exposed  in  a
respirometer-metabolism   chamber   to   technical   grade
fenvalerate  (0.28  or  23 ng/litre) or  an  emulsifiable-
concentrate  formulation (16 ng/litre) at 11.0-11.5 °C for
36  to  48 h.  No  significant  effects of  emulsifiers or
fenvalerate  concentration  on uptake  were observed.  The
overall mean gill uptake efficiency was 28.6 ± 4.4%. After
8-  to 48-h depuration periods, carcass and bile contained
80-90%  and 10-20% of the gill-absorbed material, respect-
ively.   Urine, faeces, and blood each contained less than
2% of the dose.  Significant excretion and blood transport
of  fenvalerate  equivalents were  completed within 8-12 h
after exposure ceased. Specific tissues from trout exposed
to  0.28 ng/litre  were analyzed  for fenvalerate equival-
ents.   After a 48-h depuration period, bile contained the
highest concentration of fenvalerate equivalents (7 ng/g),
followed  by fat (0.2 ng/g).  Remaining  tissues contained
0.015-0.045 ng/g.  Analysis  of biliary  metabolites indi-
cated  that the glucuronide  of 4 -OH-fenvalerate was  the
only  significant  degradation product.   Results from the
present  study suggest that efficient gill uptake does not
explain  the sensitivity of fish to fenvalerate.  Instead,
a low rate of biotransformation and excretion may  play  a
significant  role in the  susceptibility of rainbow  trout

    When  juvenile Atlantic salmon were  exposed to static
water containing 0.8-9.3 µg fenvalerate/litre for 16-96 h,
the  concentration of fenvalerate in dead fish ranged from
0.16  to 0.43 mg/kg. The insecticide was not detected (de-
tection limit: 5 µg/kg)  either in dead lobster hepatopan-
creas or in dead shrimps [110].

    When  carp  (Cyprinus carpio) was exposed to [14C-CN]-
[2S, alphaRS]-fenvalerate (0.8 µg/litre) under semi-static
conditions for 7 days, the radioactivity in fish increased
to a level of 922 µg/kg.    Once the fish were transferred
to  fresh water, the levels  of radioactivity in the  fish
decreased with an initial half-life of 5 days [135].

    In  studies  by Ohkawa  et  al. [135],  carp,  snails,
 Daphnia,    and algae were  exposed to fenvalerate  in  an
aquatic model ecosystem  where 14C-[2S, alphaRS] fenval-
erate  (0.3 mg/kg) was applied  to the bottom  sandy  loam

soil.   During  a  30-day run,  concentrations  of fenval-
erate in  the  water  were  0.35-0.63 µg/litre   and 0.14-
0.21 µg/litre    on days 7 and 30, respectively.  The bio-
concentration  factors for fenvalerate were 122, 617, 683,
and 477 on day 7 (162-300, 993-1110, 629-829, and 714-1180
on  day 30) in carp, snails,  Daphnia,  and algae, respect-
ively.  In  carp,  large  amounts  of  CP-Vacid  (17)  and
3-phenoxybenzoic  acid  (22) were  detected, together with
small amounts of alpha-cyano-3-(4'-hydroxyphenoxy)benzyl-2-
(4-chlorophenyl)-3-methylbutyrate  (4'-OH-Fen) (25). Small
amounts of alpha-carbamoyl-3-phenoxybenzyl-2-(4-chlorophe-
nyl)-3-methylbutyrate  (CONH2-Fen)  (33), alpha-carboxy-3-
phenoxybenzyl-2-(4-chlorophenyl)-3-methylbutyrate   (COOH-
Fen) (34), and  4 -OH-Fen  (25) were  detected  in snails.   
CPIA was specifically present in both Daphnia  (prey)  and  
carp (predator). CONH2-Fen (33) and alpha-carboxy-3-phenoxy-
benzyl  alcohol (36) were common to algae (prey)  and carp
(predator).  Based on the products identified, degradation
pathways  were proposed for  this aquatic model  ecosystem
(Fig. 4).

    In  a  28-day  early-life  stage  study  (see  section
6.1.2), the mean bioconcentration factor in whole fish was
570 [68].



7.1  Single Exposures

    Table 8 shows the results of acute toxicity tests with
technical grade fenvalerate in various animal species.

    The  acute  toxic  signs in  rats  were  restlessness,
tremors, piloerection, occasional diarrhoea, and an abnor-
mal  gait.  Following oral administration,  surviving rats
recovered  rapidly from acute clinical  signs of poisoning
and were asymptomatic within 3-4 days [20].

    Table 9  shows the results of an acute intraperitoneal
toxicity  study of fenvalerate  metabolites in mice  [96].
All  the  compounds  were  dissolved  in  corn  oil except
3-phenoxybenzoic  acid, which was dissolved  in DMSO.  The
acute  intraperitoneal  toxicity  in mice  of the proposed
decarboxylated  photo-products was found to be similar to,
or greater than, that of fenvalerate [78].

    In  a study by Blair and Roderick [12], groups of four
male and four female rats were exposed by inhalation (head
only)  to  an aerosol  formulation (77-µm particle   size)
generated from an aqueous suspension containing 3 g/litre.
Following  a  single  administration (4 h)  of  this  non-
inhalable particulate, acute signs of poisoning were noted
for  a short period, presumably from oral ingestion of the
large particles.  There was no mortality and  all  animals
appeared normal within 3 days following exposure.

7.2  Short-Term Exposures

7.2.1  Oral administration

    Groups  of Carworth Farm E  rats (12 of each  sex  per
group)  were fed fenvalerate in the diet at dose levels of
0, 125, 500, 1000, and 2000 mg/kg for 90 days  [72].  Mor-
tality  (11/12 male,  9/12 female)  was  observed  at  the
highest  concentration. Body weight gain and food consump-
tion were decreased and blood urea nitrogen concentrations
were  increased  at 1000  and  2000 mg/kg.  There  were no
treatment-related  changes in any  groups of rats  in  the
haematological parameters examined.  Increases in liver to
body weight ratios and kidney to body weight  ratios  were
observed  at  500 mg/kg  or more.   Gross  and microscopic
examinations  revealed no compound-related changes  in any
groups.  The NOEL was 125 mg/kg diet.

Table 8.  Acute toxicity of fenvalerate (technical grade) administered to various species
Species     Route               Sex      Vehiclea          LD50 (mg/kg)            Reference
Rat         oral                         DMSO              451                     195
            oral                         PEG:water         > 3200                  168
            dermal                                         5000 (24 h)             140
            inhalation          M, F     water             > 101 mg/m3 (3 h)       94
            intraperitoneal                                340                     162

Mouse       oral                M        DMSO              200-300                 195
                                F                          100-200                 
            oral                         PEG:water         1202                    169
            intraperitoneal     M, F     corn oil          85-89                   96
            intraperitoneal                                132                     162
            intravenous                  glycerolformol    65                      2
            inhalation          M, F     water             > 101 mg/m3 (3 h)       94

Chinese     oral                M        DMSO              98                      195
hamster                         F                          82                      

Rabbit      percutaneous                 undiluted         1000-3200               75

Hen         oral                                           > 1500                  123
a  PEG = polyethylene glycol; DMSO = dimethylsulfoxide.

Table 9.  Acute intraperitoneal toxicity of fenvalerate metabolites in mice
Chemical                                No.a       LD50 (mg/kg body weight)

                                                   Male           Female
Fenvalerate                             (5)        88.5           85
2-(4-Chlorophenyl)isovaleric acid       (17)       351            350
3-Phenoxybenzyl alcohol                 (19)       371            424
3-(4'-Hydroxyphenoxyl) benzyl alcohol   (21)       750-1000       750-1000
3-(2'-Hydroxyphenoxyl) benzyl alcohol   (20)       876            778
3-Phenoxybenzoic acid                   (22)       154            169
3-(4'-Hydroxyphenoxy) benzoic acid      (24)       783            745
3-(2'-Hydroxyphenoxy) benzoic acid      (23)       859            912
3-Phenoxybenzaldehyde                   (18)       415            416
NaSCN                                              604            578
a Refers to chemical identification no. in Fig. 3 and in text.
    In  a study by Parker  et al. [150], Fischer 344  rats
(30 of  each sex per group)  were fed decarboxyfenvalerate
(one  of the major  photodegradation products) at  concen-
trations of 0, 30, 100, 300, 3000 or 10 000 mg/kg diet for
up to 13 weeks. Body weight was decreased in male rats fed
10 000 mg/kg, but no treatment-related mortality or clini-
cal  signs  were  observed.  Absolute  and  relative liver
weight  of male and female  rats fed 300, 3000,  or 10 000
mg/kg were all higher than those of the controls. Signifi-
cant increases in absolute or relative kidney weights were
observed in male and female rats fed 3000 or 10 000 mg/kg.
Significant  treatment-related  microscopic  effects  were
limited  to glomerulonephrosis in male and female rats fed
10 000 mg/kg  and  hepatocellular  hypertrophy  with  pale
eosinophilic  cytoplasm and hepatocellular  focal necrosis
in  male and female rats fed 3000 or 10 000 mg/kg.  A NOEL
of 300 mg/kg diet was established in this study.

    Groups  of young adult beagle  dogs (four of each  sex
per group) were fed fenvalerate in the diet at dose levels
of  0, 0.25, 0.5, 1.25,  or 12.5 mg/kg body weight  for 90
days [70]. There were no treatment-related changes in body
weight,  food  consumption,  clinical signs,  and clinical
laboratory  data.   Gross  and  microscopic   examinations
revealed  no  effects  of the  fenvalerate.   Thus,  daily
administration  at a level of 12.5 mg/kg body weight for a
period of 90 days produced no detectable evidence of toxi-
cological effect.

    In  a study by  Parker et al.  [148], male and  female
beagle  dogs (six of  each sex per  group) were fed  diets
containing 0, 250, 500, or 1000 mg fenvalerate/kg diet for
a period of 6 months.  Prominent clinical signs related to
treatment  were emesis, head  shaking, biting of  the  ex-
tremities, and tremors.  The mean body weights  of  female
dogs  fed  fenvalerate  at 1000 mg/kg  were  significantly
lower than those of controls.  Red blood cell  counts  and
haematocrit and haemoglobin values in both male and female
dogs fed the highest dose were significantly lower.  Serum
cholesterol  and  alkaline  phosphatase levels  were  also
increased,  mostly in the  group fed 1000 mg/kg.   Hepatic
multifocal  microgranulomas  observed  during  microscopic
examination increased in incidence and severity in a dose-
dependent  way and were considered to be related to treat-
ment. Histiocytic cell infiltrates in the mesenteric lymph
nodes  of some female  dogs fed 500  or 1000 mg/kg and  of
male  dogs fed 1000 mg/kg  were the only  other treatment-
related effects observed microscopically.

7.2.2  Inhalation

    Groups of Sprague-Dawley rats and ICR mice (10 of each
sex per group) were exposed to fenvalerate  by  inhalation
for 3 h daily for 4 weeks at concentration levels of 0, 2,
7, or 20 mg/m3 (fully  respirable particle size). Although
animals  showed acute signs  of poisoning at  the  highest

dose level, no mortality was observed in any group.  There
were  no treatment-related effects in  body weight, haema-
tology,  or  clinical  biochemistry parameters,  nor  were
there  any  gross  or microscopic  abnormal  findings [82,

7.2.3  Dermal application

    In a study by Hine [75], groups of  rabbits  (7-8 male
rabbits  per group) were administered fenvalerate dermally
at  dose levels  of 0,  100, or  400 mg/kg daily  for  6 h
(14 exposures   were  performed  over  a  22-day  period).
Severe weight loss, clinical signs of poisoning, and gross
dermal effects were observed at 400 mg/kg, where mortality
was also observed.

7.3  Skin and Eye Irritation; Sensitization

7.3.1  Skin and eye irritation

    Two  formulated products (an  emulsifiable concentrate
and  an  ultra-low-volume  formulation) were  found  to be
severe  eye and skin  irritants in rabbits.   Dermal irri-
tation was evident for 7 days after a 24-h  exposure,  and
severe  conjunctivitis,  corneal opacity,  and iritis were
observed  within 30 min of an application of 0.2 ml of the
formulation to the conjunctival sac. Irrigation of the eye
after treatment reduced the irritation [29, 30].  However,
when  experiments were carried out  using pure (non-formu-
lated) fenvalerate, there was no irritation [138].

7.3.2  Skin sensitization

    Skin  sensitization by pure fenvalerate (95%) has been
evaluated  using the Landsteiner-Draize method  on guinea-
pigs.   No  sensitization was  detected  by Okuno  et  al.

7.4  Long-Term Exposures and Carcinogenicity

7.4.1  Mouse

    When  groups of ddY mice (35-47 of each sex per group)
were  administered fenvalerate in the diet for 78 weeks at
levels  of  0, 100,  300,  1000, or  3000 mg/kg, mortality
occurred at the highest dose level.  Hyperexcitability was
observed  at  1000 mg/kg  or  more,  and  body  weight was
depressed  at 3000 mg/kg over  the 18-month period  and at
1000 and 3000 mg/kg over the first 3 months.  A variety of
haematological  parameters were affected at 3 months, pre-
dominantly  at the highest  dose level, but  no  haematol-
ogical  changes were  observed at  the end  of the  study.
Several  biochemical changes suggestive  of hepatotoxicity
were  observed at 3 months and at termination of the study
in the 300, 1000, and 3000 mg/kg groups.  There were gross
changes  in  several  organ weights  and  in organ-to-body

weight  ratios,  predominantly in  the liver.  Microscopic
examination  revealed  changes  in the  liver,  mesenteric
lymph  nodes,  and  kidney.  Dose-dependent  granulomatous
changes were observed in the liver and/or mesenteric lymph
nodes  in all treatment  groups.  At the  3-month  interim
sacrifice, multiple small necrotic foci in the  liver  and
changes in the epithelial cells of the proximal convoluted
tubules  were noted at the two highest dose levels.  There
were  no indications in  this study of  tumorigenicity  or
carcinogenicity  as a result of fenvalerate administration
[81, 83, 173, 175].

    In studies by Okuno et al. [144], male ddY  mice  were
fed diets containing the [2S, alphaS], [2S, alphaRS], [2R, 
alphaS], and [2R, alphaR] isomers of fenvalerate  at diet-
ary dose levels of 0,  500, or  1000  mg/kg, 500, 1000, or 
2000 mg/kg, 0, 125,  or 1000 mg/kg, and 125, or 1000 mg/kg 
for 52, 52, 13, and 13 weeks, respectively.  Microgranulo-
matous changes were observed in the mice treated with  the 
[2R, alphaS] isomer after 1, 2, or 3 months.  In contrast, 
the changes did not occur  in  mice  treated with the [2R, 
alphaR] isomer under  the  same  conditions.  Neither [2S, 
alphaS] nor [2S, alphaRS] isomers caused microgranulomatous  
changes at 500 or 1000 mg/kg after 1 year. To  clarify the 
causative agent  of  granuloma  formation, the cholesterol 
ester  of  2-(4-chlorophenyl)isovaleric  acid  (CPIA),   a 
lipophilic conjugate from the [2R, alphaS] isomer of fenva-
lerate, was injected intravenously  into ddY mice.  Micro-
granulomatous  changes were observed in the liver of  mice 
treated with the  [2R]-, [2S]-, or  [2RS]-CPIA-cholesterol  
esters 1 week after a  single  treatment of 1, 10,  or 100 
mg/kg body weight, as well as in the liver of mice treated 
with a single dose of  10  or 30 mg/kg body  weight of the  
[2R]-CPIA-cholesterol ester and kept up to 26 weeks after-
wards. Histochemical examination and microscopic autoradio-
graphy of the liver demonstrated the  presence  of tritium,  
derived from 3H-labelled [2R]-CPIA and cholesterol in giant  
cells and Kuppfer cells. Another histochemical examination 
showed  the presence of cholesterol ester  in the liver of 
mice treated with the [2R, alphaS]  isomer.  These results 
support the hypothesis that the CPIA-cholesterol  ester is 
the causative agent of the microgranulomatous changes ind-
uced by fenvalerate.

    In  further studies by  Okuno et al.  [145], male  and
female  ddY  mice  were  fed  diets  containing  technical
fenvalerate  (either 0, 10, 30, 100, or 300 mg/kg diet for
20 months or 0, 100, 300, 1000, or 3000 for 17-18 months).
Microgranulomatous  changes  were  observed in  the  lymph
nodes,  liver, and spleen, the NOEL for such changes being
30 mg/kg.   To examine the reversibility of these changes,
ddY  mice (male and  female)  were fed  a diet  containing
technical  fenvalerate  at dose  levels  of 1000  and 3000
mg/kg  for 6 weeks, followed by  a control diet for  up to
12 months.   The size and number of the microgranulomatous
changes were reduced with time. These changes were typical

of foreign body granulomas and did not have the appearance
of  granulomas  formed  in response  to  an  immunological

    When  B6C3F1 mice  (50 of each sex per group) were fed
fenvalerate at dietary concentrations of 0, 10,  50,  250,
or  1250 mg/kg  for  2 years, mortality  was increased and
body  weight  significantly  decreased in  male and female
mice  fed 1250 mg/kg.  The mean body weight of female mice
fed 250 mg/kg was also generally lower than that  of  con-
trols after the 60th week of feeding.  The only treatment-
related non-neoplastic pathological effect observed in the
study  was multifocal microgranulomata in the lymph nodes,
liver,  and spleen  of male  mice fed  1250 mg/kg  and  of
female  mice fed 250 or 1250 mg/kg.  No statistically sig-
nificant differences were observed in either the number or
type  of neoplasms in  mice fed fenvalerate  (compared  to
concurrent  controls).  Thus, fenvalerate was found not to
be carcinogenic in B6C3F1   mice under the  conditions  of
the test [146].

7.4.2   Rat

    When  groups of Wistar rats (15 of each sex per group)
were fed fenvalerate at concentrations of 0, 50, 150, 500,
or 1500 mg/kg diet for 15 months, there was  no  mortality
attributable  to  fenvalerate.  The hyperexcitability  ob-
served  during the early  stages of the  study disappeared
within  3 months.  Body weight was significantly depressed
in  both sexes at  the highest dose  level.  No  compound-
related changes were detected in the urine or in the eyes,
but  the haemoglobin concentration was  depressed in males
at  the highest dose level and the females at 150 mg/kg or
more.  Several blood biochemistry parameters were signifi-
cantly  altered  at the  highest  dose level  (blood  urea
nitrogen  was increased in both sexes; protein content and
plasma  cholinesterase were decreased in  females).  Gross
and  microscopic  examination  revealed  no   dose-related
effects [174].

    In a study by Gordon & Weir [66], groups  of  Sprague-
Dawley  rats (93 males and  93 females per treated  group;
183 of  each  sex  used as  the  control  group) were  fed
fenvalerate  in the diet  at dose levels  of 0, 1,  5, 25,
250,  or  500 mg/kg.  There was  no  compound-related mor-
tality,  although body weight  was reduced at  the highest
dose level. The group fed 500 mg/kg and a separate control
group  were sacrificed at 26 weeks while the other animals
were maintained for 2 years. There were no significant ef-
fects  on food consumption, growth, behavior, haematology,
blood biochemical composition or urine consumption. At the
conclusion  of the study,  organ weight and  organ-to-body
weight ratios were normal.  Gross and microscopic findings
in  the treated groups  did not differ  significantly from
those  of the controls.  A  specific pathology examination

of  the sciatic nerve of animals fed 250 mg/kg revealed no
treatment-related  changes.  Thus, the  no-observed-effect
level in this study was 250 mg/kg diet.

    Parker  et al. [147]  fed Sprague-Dawley rats  (93  of
each sex per group) diets containing 0.1, 5, 25, or 250 mg
fenvalerate/kg  for up to 2 years.  The control group con-
sisted of 183 males and 183 females.  Ten treated  and  20
control  rats of each sex  from each group were  killed at
intervals of 3, 6, 12, and 18 months.  When  body  weight,
organ  weight, food consumption, haematology, and clinical
chemical  analysis measurements did not  reveal any effect
resulting  from  the  treatment, two  additional groups of
rats  (50 of  each sex  per group) were  fed 0 or  1000 mg
fenvalerate/kg diet for 2 years. Body weight was decreased
and  organ-to-body weight ratios were  increased in brain,
liver,  spleen, testes, kidneys (females  only), and heart
(females  only), in the treated animals. Mammary and pitu-
itary tumours were commonly observed, along with a variety
of  other tumours that occurred randomly among all control
and treatment groups. No statistically significant differ-
ences in the number and type of neoplasms  were  observed,
except for mammary tumours in females in the  main  study.
These effects were judged not to be  toxicologically  sig-
nificant,  since mammary tumour incidences  did not exceed
expected  incidences  in aged  female Sprague-Dawley rats.
In  addition, the time taken for tumours to appear was un-
changed, and no change in the ratio of benign to malignant
tumours occurred.  Sarcomas identified in the subcutis and
dermis  in 5  out of  51 males fed  1000 mg/kg  were  also
identified  in 2% (1/50), 2% (2/102), and  0-6% of concur-
rent,  original,  and  historical controls,  respectively.
The no-observed-effect level was 250 mg/kg.

    When  male and  female Wistar  rates were  fed a  diet
containing  technical fenvalerate at  0, 50, 150,  500, or
1500 mg/diet  for 24-28 months, microgranulomatous changes
were observed in lymph nodes, liver, spleen,  and  adrenal
glands. The no-observed-effect level for these microgranu-
lomatous changes was 150 mg/kg [145].

7.5  Mutagenicity

7.5.1  Microorganism and insects

    The  DNA-damaging  capacity  of fenvalerate  has  been
examined in  a  Rec-assay  with   Bacillus subtilis M45  rec-
and   H17 wild  type strains  at concentrations  up to  10
mg/disk per plate. Fenvalerate had no inhibitory effect on
the growth of indicator strains, and was judged to be non-
mutagenic [170].

    Fenvalerate  has also been examined  for its mutagenic
potency  with  the  Ames test  in  Salmonella  typhimurium
(TA 1535,  TA 1538, TA 98, and TA 100),  using dose levels
of  up to  1 mg/plate both  with and  without a  metabolic

enzyme  system.   Fenvalerate  was non-mutagenic  in these
tests [170].  It was also tested using  hepatic  metabolic
enzyme  systems prepared from various  PCB-treated animals
(three strains of rats, six strains of mice and the Syrian
golden  hamster).   At dose  levels  of up  to 1 mg/plate,
Fenvalerate was non-mutagenic [171, 172].

    In further studies by Suzuki & Miyamoto [170], fenval-
erate  was given orally  at doses of  60 and 125 mg/kg  to
groups  of mice, and indicator  cells (S. typhimurium G46)
were  injected  intraperitoneally.  Fenvalerate  did   not
induce any significant level of mutation among  the  indi-
cator cells recovered from the abdominal cavity.   On  the
other  hand,  the  positive control,  dimethylnitrosamine,
significantly  increased  the  mutation frequency  of  the
indicator organism.

    Another host-mediated assay of fenvalerate in mice was
conducted   using  Saccharomyces   cerevisiae as  indicator
microorganism.   Groups of mice were  administered fenval-
erate  orally at doses  of 25 and  50 mg/kg, and were  in-
jected  with a suspension of  indicator cells intraperito-
neally.   No mutagenic effect  on the indicator  cells was
detected [17].

    Fenvalerate  was  not  found  to  be  mutagenic  in S.
typhimurium  strains TA 100 or  TA 98 in the  presence  or
absence  of a rat  liver activation system  by fluctuation
tests  at a concentration  of up to  10 µg/ml   or in  V79
Chinese  hamster  cells  in  the  presence  or  absence of
hepatocytes at a concentration of up to 40 µg/ml [153].

    Fenvalerate   did  not  induce   sex-linked  recessive
lethals,  sex-chromosome  losses,  or  non-disjunction  in
 Drosophila   melanogaster when it was given  to adults (up
to 20 mg/litre in the diet) or larvae (up  to  50 mg/litre
in  the diet), or was injected into adults (at 20 µg/ml)

7.5.2  Rat

    In a study by Chatterjee et al. [26], groups  of  rats
(21  per group)  were  administered fenvalerate orally  at
doses  of 50, 75, or  100 mg/kg per day for  3 weeks.  The
rats  were killed 24 h after  the last treatment and  bone
marrow  cells  were examined  for chromosomal aberrations.
Although an increase in the frequency of chromosomal aber-
rations  was  observed in  fenvalerate-treated animals, it
was not possible to draw any definite  conclusion  because
it was not dose related and may have been non-specific.

    Fenvalerate  has also been studied for the enhancement
of  gamma-glutamyl  transpeptidase-positive enzyme-altered
focus  incidence  in partially  hepatectomized, nitrosodi-
ethylamine-initiated male Sprague-Dawley rats. Fenvalerate
administered  peritoneally (75 mg/kg body weight  per day,

5 days  a  week  for 10 weeks)  induced significantly more
foci  per  cm3 and  a  larger  percentage of  liver tissue
occupied  by focus tissue, compared with a vehicle-control
group.   Analysis  of the  size  distribution of  foci  in
fenvalerate-  and  vehicle-treated  rats  showed  elevated
focus  incidences in fenvalerate-treated rats at all focus
sizes.   Fenvalerate  induced  no hepatotoxic  effects, as
judged  by  serum transaminase  activities and histopatho-
logical analysis [58].

7.5.3  Mouse

    In a dominant lethal assay, groups of male mice (10-11
per  group) were administered fenvalerate  orally at doses
of  25, 50, or 100 mg/kg body weight.  Each male was mated
with three virgin females for 7 days.  The  procedure  was
repeated weekly as a standard dominant lethal  test.   The
females   were   sacrificed  and   examined  for  dominant
lethality at the 13th day of gestation.  Fetal implants in
females,  mated to males  that had been  treated with  100
mg/kg  for  2 weeks,  showed a  significant  reduction  in
viability.   A significant increase  in early fetal  death
was  observed in females  mated with males  that had  been
treated for 4 weeks with the highest dose [34].

    The significance of the above data was further studied
as follows:

    (1) By using a two-way analysis of variance,  it  was
judged  that the reduction  in fetal implants  in  females
mated to males the second week after dosing  at  100 mg/kg
and  the increase in  early fetal deaths  in the  4th week
were  statistically  significant.  But  these increases or
decreases appeared to be random and were not considered to
be biologically significant.

    (2) Using  a t-test and  the Mann-Whitney U-test,  no
significance  was shown in  any mean proportions  for  the
above parameters.

    From these findings, it was concluded that fenvalerate
did not cause dominant lethal effects in micea.

a   Personal communication, J. Miyamoto, 1981, Comments on
    "Further  work information"   required by 1979 JMPR on
    fenvalerate, Laboratory of Biochemistry and Toxicology
    (Unpublished  report  submitted  to  WHO  by  Sumitomo
    Chemical Co. Ltd).

7.5.4  Hamster

    In  a study  by Dean  & Senner  [35], fenvalerate  was
administered orally to groups of hamsters (six  males  and
six  females per group) at  two successive daily doses  of
12.5 and 25 mg/kg.  The chromosomal preparations were made
8 or 24 h after administration. Fenvalerate did not induce
any  chromosomal  damage in  the  bone marrow  cells  from
treated  animals,  whereas  the positive  control,  methyl
methanesulfonate  (50 mg/kg),  had  induced a  substantial
number of chromatid gaps within 8 h of dosing.

    Fenvalerate,  and  the  fenvalerate  metabolite  2-(4-
chlorophenyl)isovaleric  acid,  were investigated  for the
inhibition  of gap-junctional intercellular  communication
 in   vitro in  the  Chinese hamster  lung fibroblast (V79)
metabolic  cooperation assay [58].  This study showed that
both  fenvalerate  and  2-(4-chlorophenyl)isovaleric  acid
were  inhibitors  of  intercellular communication  at non-
cytotoxic concentrations.

7.6  Teratogenicity and Reproduction Studies

7.6.1  Teratogenicity

    In  studies by Kohda et  al. [93], groups of  pregnant
ICR   mice  (32-33 per  group)  were  orally  administered
fenvalerate  at dose levels of  0, 5, 15, or  50 mg/kg per
day  on days 6 to 15 of gestation.  Groups of 20 mice were
sacrificed  on day 18, and  the fetuses were  removed  and
examined  for  visceral  and skeletal  abnormalities.  The
remaining dams were allowed to deliver naturally  and  the
young  were maintained until weaning to evaluate postnatal
deficits.   Additionally two male and two female weanlings
from  each dam were  maintained for 8 weeks  and mated  to
investigate  their reproductive potential.  Although toxic
signs  were noted in the  dams at the highest  dose level,
there  was no significant  mortality.  Examination of  the
fetuses revealed no external, visceral, or skeletal abnor-
malities.   Treatment of the dams with fenvalerate did not
affect the reproductive performance of the offspring.

    Van  Der Pauw et  al. [187] dosed  groups of  pregnant
Dutch rabbits (20 to 31 per group) orally with fenvalerate
(0,  12.5, 25, or 50 mg/kg body weight per day) from day 6
to  day 18 of gestation. The dams were sacrificed  on  day
28  and  standard  teratogenic assessments  made. The body
weights of the dams given the highest dose  were  reduced.
There were no significant differences from controls in any
of  the  other  parameters examined.   Fenvalerate was not
found to be teratogenic in this study.

7.6.2  Reproduction studies

    In  studies by Stein  [167] and Beliles  et al.  [10],
groups of Sprague-Dawley rats (11 males and 22 females per
group) were fed fenvalerate in the diet at levels of 0, 1,
5, 25, or 250 mg/kg.  The animals were dosed  for  9 weeks
prior  to mating and the  initiation of a standard  three-
generation  (two  litters  per  generation)   reproduction
study.  Fertility, viability, gestation, and lactation in-
dices were calculated for each group of rats and were com-
pared  to control values.  Ten of the female weanlings and
all of the males from the F3b litters   were examined his-
tologically at the conclusion of the study.  The mean body
weight of the F2b adults   was decreased at 250 mg/kg, but
no  pathological changes were  noted to account  for  this
weight loss.  No effects on reproductive parameters in any
of  the  three  generations were  observed.   Histological
examination  revealed no treatment-related changes  in any

    Groups  of pregnant ICR  mice (32-33 mice  per  group)
were  orally administered fenvalerate at dose levels of 0,
5,  15, or 50 mg/kg body weight per day on days 6 to 15 of
gestation in a standard teratogenicity bioassay.  Two male
and two female weanlings from each dam were maintained for
8 weeks and mated to investigate their reproductive poten-
tial.   Toxic signs  were noted  in maternal  mice at  the
highest  dose  level.  There was  no significant mortality
over the course of the study, and no effects were noted on
any  of the other animals as a result of continuous admin-
istration  of fenvalerate.  The animals  maintained in the
abbreviated  reproduction study showed no differences from
the  control value in  their ability to  reproduce.  There
were  no  changes in  the  reproduction indices  with  any
animals examined [93].

7.7  Neurotoxicity

    In a study by Butterworth & Carter  [20],  histopatho-
logical examination was performed on the sciatic nerve and
posterior  tibial nerve of rats  that had been exposed  to
acutely toxic levels of fenvalerate.  After poisoning, and
for 9 days during the course of recovery,  axonal  breaks,
swelling,  and vacuolisation, accompanied  by phagocytosis
of myelin, were seen.  The degree to which myelin was dis-
rupted  was dose dependent and was closely associated with
the acute signs of toxicity.

    Acute  oral  administration  of  fenvalerate,   cyper-
methrin,  resmethrin, permethrin, and natural pyrethrum to
rats  at very high dose levels resulted in severe clinical
signs  of poisoning and mortality within 24 h. Histopatho-
logical  lesions were observed  in the sciatic  nerve with

all compounds tested. Fenvalerate did not cause the clini-
cal  signs or histopathological  lesions at a  lower  dose
level  (200 mg/kg),  nor  did the  other  compounds  [141,

    When groups of six male and six female rats  were  fed
fenvalerate in the diet at a concentration  of  2000 mg/kg
for  8 to 10 days, all the animals showed typical signs of
acute  intoxication, such as ataxia, tremors, and hyperex-
citability.  Histopathological examinations did not reveal
any  adverse effects of  fenvalerate on the  sciatic nerve

    In  order to evaluate the reversibility of the lesions
induced  in  the  sciatic nerve,  rats  were  administered
fenvalerate  in the diet at dose levels of 0 or 3000 mg/kg
diet for 10 days.  This was followed by a control diet for
12 weeks.   During the treatment period, mortality was 60%
in  the  animals treated  with  fenvalerate.  Rats  on the
recovery  control diets, sacrificed at  3 weeks, continued
to  show  swelling  and  disintegration  of  axons  of the
sciatic  nerves.  However, there were no histopathological
lesions  after 6, 9, or  12 weeks of the recovery  period.
These  results  showed  the reversibility  of  the sciatic
nerve lesions caused by fenvalerate [143].

    In studies by Butterworth & Hend [21], fenvalerate was
administered  orally to Wistar  or Carworth Farm  E  (CFE)
rats either as single doses or in the diet.  When given in
large  quantities by a  single dose of  250, 500, 800,  or
1000 mg/kg body weight, which were sufficient to kill some
of  the  treated  animals, fenvalerate  produced  sporadic
Wallerian  degeneration in the  sciatic nerve. The  neuro-
pathy was never severe and was not seen in  animals  given
the compound in sub-lethal doses.  In feeding studies (for
5 weeks  at 1000 mg/kg diet and for 3 months at 2000 mg/kg
diet),  no  lesions were  seen  in the  peripheral  nerve,
brain,  or spinal cord, and there was no evidence of cumu-
lative neurotoxicity.

    B6C3F1 mice    and  Sprague-Dawley  rats   showed  the
characteristic signs of intoxication following single oral
doses  of fenvalerate ranging  from 56 to  320 and 133  to
1000 mg/kg body weight, respectively.  Neurological signs,
such  as  splayed gait,  tremors,  ataxia, and  hind  limb
incoordination,  were  observed  at doses  of 100 mg/kg or
more  (mice)  and 133 mg/kg  or  more (rats)  within 1-8 h
after dosing.  These signs had disappeared in most animals
within  72 h.   Slight  peripheral nerve  fibre damage was
detected  in  surviving  mice and  rats sacrificed 10 days
after dosing. The incidence and severity were dose related
at  doses > 56 and > 180 mg/kg; however, even  at  lethal
doses,  there was  no evidence  of nerve  lesions in  some
animals.   Thus,  two  distinct neurological  effects were

observed,  i.e., (a) a reversible ataxia and (b) incoordi-
nation  plus  a  neuropathological  effect  manifested  as
sparse axonal damage in peripheral nerves [149].

    In  a study by Milner  & Butterworth [123], groups  of
six  hens  were  administered fenvalerate  orally  at dose
levels  of 0 or 1000 mg/kg per day for 5 days.  A positive
control of tri- ortho-cresyl   phosphate (0.5 ml/kg) (TOCP)
was  also included in the  study.  The fenvalerate-treated
birds were retreated, using the same dose  regimen,  after
3 weeks.   The TOCP-treated hens  showed signs of  delayed
neurotoxicity  and  histopathological  lesions  in   their
sciatic nerve and spinal cord.  As would be expected for a
non-organophosphorus  insecticide,  there were  no typical
clinical  signs  and histopathological  lesions related to

7.8  Behavioural Studies

    Guinea-pigs   responded  to  dermal   applications  of
fenvalerate by scratching the treated sites of  the  skin.
This  characteristic response was essentially  over within
3-4 h.  When the powerful skin irritant oil of mustard was
applied  to fenvalerate-treated sites of skin 4-72 h after
the  fenvalerate  treatment, the  behavioural skin sensory
response  was re-stimulated.  Oil of mustard alone did not
produce  skin sensory stimulation.  These results indicate
that  pyrethroid treatment causes a  transient sensitivity
to stimulation produced by chemical irritants [111].

    To develop an animal model for studying  skin  sensory
stimulation,  Duncan-Hartley guinea-pigs were treated with
pyrethroid solutions on one side and control substances on
the other side of their shaved back. The animals responded
by  licking,  scratching, or  biting  the test  sites, and
activity  was quantified by  counting the number  of times
the  animals responded.  This behavioural activity reached
a maximum 1-4 h after treatment.  A chemical irritant (oil
of  mustard) was able  to restimulate the  behavioural ac-
tivity  when applied within  24 h after pyrethroid  appli-
cation.   Skin  sensory  stimulation  produced  by  cyano-
containing   pyrethroids,   including   fenvalerate,   was
significantly  greater  than  that produced  by non-cyano-
containing pyrethroids.  This behavioural model provides a
quantitative  means of evaluating pyrethroid non-erythema-
tous skin sensory stimulation [22].

7.9  Miscellaneous Studies

    In  an antidotal study,  phenobarbital, pentobarbital,
and  diphenylhydantoin  were  found  to  be  effective  in
relieving  the  acute signs  of  intoxication in  the rat.
Intraperitoneal   injection  of  phenobarbital  (50 mg/kg)
prevented  tremor,  diphenylhydantoin  (100 mg/kg) by  the
same  route reduced the toxic  reaction, and pentobarbital
(35 mg/kg  intraperitoneally) removed the  tremor reaction

completely  within  30 min.  The  combination of diphenyl-
hydantoin with either of the barbiturates was effective in
reducing the onset and severity of tremors whereas various
other   agents   d-tubocurarine,  atropine,   meprobamate,
diazepam,  biperiden, and trimethadione)  were ineffective

    The  therapeutic  potency of  intraperitoneally admin-
istered  methocarbamol was examined as an antidote against
the  acute oral intoxication of  rats by a lethal  dose of
fenvalerate.   Methocarbamol was initially administered at
a  dose  of 400 mg/kg  body  weight, followed  by repeated
doses of 200 mg/kg body weight when tremors or hyperexcit-
ability  to  sound were  observed.  Methocarbamol markedly
decreased the mortality from 80%, which would be caused by
an administration of 850 mg fenvalerate/kg, to 0%, and was
effective  in alleviating motor  symptoms such as  fibril-
lation,  tremors, hyperexcitability, clonic  seizures, and
choreoathetotic  movements.  A subcutaneous administration
of atropine sulfate (25 mg/kg body weight) was also effec-
tive  in reducing the  salivation produced by  fenvalerate

    Effective  treatments against fenvalerate-mediated ef-
fects  have  been investigated  by quantifying behavioural
skin  sensory  responses  such as  licking, scratching, or
biting of the treated sites by fenvalerate-treated guinea-
pigs.  Preparations containing vitamin E, corn oil, or the
local anesthetic benzocaine were most effective [111].

    Intraperitoneal  administration of  O-ethyl- O-(4-nitro-
phenyl)phenylphosphonothioate  (EPN) or  S,S,S-tributylphos-
phorotrithioate  (DEF) to mice  at 25 mg/kg increased  the
intraperitoneal  toxicity of fenvalerate (administered 1 h
later)  by  more  than 25-fold;  the  LD50 decreased  from
> 1000 mg/kg to 37 or 42 mg/kg.  This suggests  that  mam-
malian esterases highly sensitive to inhibition by certain
organophosphorus  compounds  may  play a  critical role in
fenvalerate  detoxication.   This kind  of synergism among
pesticides would be detrimental in increasing the toxicity
of certain pyrethroids to mammals [62].

    Fenvalerate, administered to dogs at a dose sufficient
to induce toxic signs, showed no consistent cardiovascular
effects. Respiratory stimulation was noted at high levels,
and  this  was  not  reduced  by  anaesthetic  supplements
(urethane, chloralose, and pentobarbital)  [91].

7.10  Mechanism of Toxicity - Mode of Action

    The intravenous toxicity of fenvalerate (50-100 mg/kg)
to  rats  was examined  by  Verschoyle &  Aldridge  [189].
[2S, alphaS]-Fenvalerate induced choreoathetosis with sali-
vation  (CS-syndrome),  and  was classified  as  a Type II
pyrethroid.   For  the mode  of  action of  pyrethroids in
general see Appendix 1.

    The  intracerebral injection of [2S, alphaS]-fenvaler-
ate (0.01 mg/kg)   to mice produced the Type II syndrome, 
consisting  of  choreoathetosis,  convulsion, and  saliv-
ation [98].  The Type II syndrome is produced  character-
istically by pyrethroids with an alpha-cyano   group  and 
the  site  of  action in  mammals is considered to be the 
central nervous system.

    In  intact  locusts and  neuromuscular preparations of
locusts,  fenvalerate caused (a)  prolonged firing in  the
crural  nerve without associated muscle  contractions; (b)
sustained muscle contractions; and (c) a block of neurally
evoked muscle contractions at low concentration (10-8   to
10-5 mol/litre).     However,  fenvalerate  did not  cause
repetitive  firing  and  after-discharges with  associated
muscle  contractions [27].  The  fenvalerate stereoisomers
with an (S) configuration in the alcohol moiety  are  more
active  pharmacologically  and toxicologically  than those
with  the (R) configuration or the  racemate (R,S).  It is
also  apparent  that stereoisomers  with the (S) configur-
ation in the acid moiety are more active than  those  with
the (R) configuration or the racemate (R,S) [27].

    [S,S]-Fenvalerate does not induce repetitive firing in
the  cockroach cercal sensory nerves either  in vivo or   in
 vitro.  It does, however, cause different signs, including
bursts of spikes in the cercal motor nerve [60].

    There  are  no clear-cut  links between electrophysio-
logical findings in insects and toxicity to mammals.


8.1  Occupational Exposure


     Fenvalerate  has been found  to induce skin  sensations  in
 some  of  the workers  who  handle this  insecticide.  Clinical
 studies showed that the skin sensations develop with  a  latent
 period  of approximately 30 min,  peak by 8 h  and  deteriorate
 after 24 h.  Numbness, itching, tingling, and burning are symp-
 toms  frequently  reported.  Alpha-tocopheryl acetate  has been
 found to inhibit the occurrence of these skin sensations.

    In a study by Kolmodin-Hedman et al.  [97],  personnel
(52 people)  at  various  plant nurseries  who had handled
conifer  seedlings treated with fenvalerate were examined.
The  symptoms  were  mainly irritative,  such  as itching,
paraesthesia  and  burning of  the  skin, and  itching and
irritation  of the eyes.  The  frequency (% of people  who
reported  these  signs)  was about  10%.   Increased nasal
secretion was reported by 19% of the personnel.

    No  clinical  case  of pyrethroid  poisoning  had been
reported until outbreaks of acute deltamethrin and fenval-
erate  poisoning occurred among cotton growers in China in
1982.   Having been told (in error)  that pyrethroids were
non-toxic, the farmers handled the pyrethroid insecticides
without  taking any precautions.  After  repeated spraying
in  the  cotton fields,  the  mild cases  presented severe
headaches,  dizziness, fatigue, nausea, and anorexia, with
transient changes in the electroencephalogram (EEG), while
a severe case developed muscular fasciculation, repetitive
discharges  in the electromyogram (EMG), and frequent con-
vulsions.  However, all were found by follow-up studies to
have  completely  recovered  and the  prognosis  of  acute
pyrethroid poisoning proved to be correct [71]a.

a   More recently, the same author reviewed 573  cases  of
    acute  pyrethroid  poisoning  reported in  the Chinese
    medical literature during 1983-1988 [213]. Among these
    there  were 196 cases of  acute fenvalerate poisoning,
    63  of which were  occupational, due to  inappropriate
    handling  and 133 accidental, mostly due to ingestion.
    Two  died of convulsions.   All others recovered  with
    symptomatic  and supportive treatment within 1-6 days.
    A  comprehensive review of clinical  manifestations is

    Among  23 workers  exposed  to synthetic  pyrethroids,
including fenvalerate, 19 experienced one or more episodes
of  abnormal  facial sensation,  developing between 30 min
and  3 h after exposure and  persisting for 30 min to  8 h
[106]. However, there were no abnormal neurological signs,
and  electrophysiological studies showed  normal responses
in the arms and legs.  The symptoms were most  likely  due
to  transient lowering of  the threshold of  sensory nerve
fibres  or sensory nerve endings following exposure of the
facial skin to pyrethroids.

    In  a  study by  Tucker  & Flannigan  [182],  selected
individuals who had worked extensively with fenvalerate in
the delta region of the Mississippi and Alabama, USA, were
interviewed  and examined.  They  had, on some  occasions,
noted paraesthesia associated with exposure to this insec-
ticide.  The cutaneous sensation was described as a sting-
ing or burning, which progressed to numbness  in  approxi-
mately  one-third of the  exposed workers.  The  sensation
typically began a number of hours after contact, peaked in
the evening, and rarely was present the following morning.
The  intensity of the  sensation varied according  to  the
type  and extent of  exposure. Clinical signs  of  inflam-
mation such as oedema or vesiculation were  not  apparent.
Erythema  was present in  a few individuals  but this  was
difficult  to distinguish from sunburn.   Several environ-
mental  factors were found  to affect the  cutaneous  sen-
sation associated with fenvalerate exposure.

8.2  Clinical Studies

    A  double-blind  study  with  29 male  volunteers  was
performed  to test the skin reaction to formulated fenval-
erate.   The  emulsifiable  concentrate  formulation   was
diluted with water and applied to one side of the face, on
the  cheek,  with a  control  formulation on  the opposite
cheek. There were no signs of dermatitis 24 h after appli-
cation,  nor did the  fenvalerate formulation produce  any
abnormal  skin sensations.  There were no indications that
any  of the symptoms such as tingling, itching, or burning
were associated with fenvalerate [18].

    A  double-blind study was  performed to compare  human
discrimination  of  technical fenvalerate,  the heavy-ends
fraction  of  distilled  fenvalerate,  and  ethyl  alcohol
(vehicle)  applied to the lower edge of each earlobe of 36
adult  (both male and female) volunteers on three separate
occasions.   Both forms of fenvalerate  caused a statisti-
cally  significant increase in paraesthesia, compared with
the  vehicle alone.  The onset of the cutaneous sensations
occurred  1 h  after  application, peaked  at  3-6 h,  and
lasted  approximately  24 h.  Numbness, itching,  burning,

tingling,  and  warmth  were the  most frequently reported
sensations.  The difference between the effects of the two
fractions of fenvalerate was not statistically significant

    Flannigan  & Tucker [55],  Flannigan et al.  [56, 57],
and  Malley et  al. [112]  studied the  difference in  the
degree of paraesthesia induced by a number of pyrethroids.
Applications  of  0.05 ml fenvalerate  formulated to field
strength  (0.13 mg/cm2)    were  made to  a 4 cm2 area  of
earlobe  on five occasions, the opposite earlobe receiving
distilled  water. Participant evaluation after each appli-
cation  continued for 48 h and involved description of the
cutaneous  sensations.  Each participant was treated after
each  application  with  one of  the  remaining compounds.
Fenvalerate (like the other pyrethroids) induced skin sen-
sations.   The paraesthesia developed with a latent period
of  approximately 30 min, peaked by  8 h, and deteriorated
as  early  as 24 h.   The  local application  of  dl-alpha
tocopheryl  acetate  markedly inhibited  the occurrence of
skin sensations.


    The Joint FAO/WHO Meeting on Pesticide Residues (JMPR)
has discussed and evaluated fenvalerate at its meetings in
1979, 1981, 1982, 1984, 1986, and 1987 [40-47, 49, 50, 52-

    Since 1986, an acceptable daily intake (ADI) of 0-0.02
mg/kg body weight has been established.

    In the WHO Recommended Classification of Pesticides by
Hazard,  technical  fenvalerate is  classified as  "moder-
ately hazardous"  (Class II) [197].


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    On the basis of electrophysiological studies with per-
ipheral  nerve preparations of frogs  (Xenopus laevis; Rana
 temporaria, and  Rana  esculenta), it  is possible  to dis-
tinguish  between  2 classes  of pyrethroid  insecticides:
(Type I and Type II).  A similar distinction between these
2 classes of pyrethroids has been made on the basis of the
symptoms  of toxicity in mammals and insects [65, 98, 186,
189, 196].  The same distinction was found in  studies  on
cockroaches [60].

    Based  on the binding assay  on the gamma-aminobutyric
acid    (GABA)   receptor-ionophore   complex,   synthetic
pyrethroids   can  also  be  classified  into  two  types:
the alpha-cyano-3-phenoxybenzyl  pyrethroids  and the non-
cyano pyrethroids [59, 61, 99, 100].

Pyrethroids  that  do  not contain  an alpha-cyano   group
(allethrin,  d-phenothrin,  permethrin,  tetramethrin,
cismethrin, and bioresmethrin) (Type I: T-syndrome)

    The  pyrethroids that do not contain an alpha-cyano  group
give  rise  to  pronounced repetitive  activity  in  sense
organs and in sensory nerve fibres [185]. At room tempera-
ture,  this repetitive activity usually consists of trains
of 3-10 impulses and occasionally up to 25 impulses. Train
duration is between 10 and 5 milliseconds.

    These  compounds  also  induce  pronounced  repetitive
firing  of  the presynaptic  motor  nerve terminal  in the
neuromuscular  junction  [183].  There  was no significant
effect  of the insecticide on  neurotransmitter release or
on the sensitivity of the subsynaptic membrane, nor on the
muscle  fibre membrane.  Presynaptic repetitive firing was
also  observed  in  the sympathetic  ganglion treated with
these pyrethroids.

    In the lateral-line sense organ and in the motor nerve
terminal,  but not in the  cutaneous touch receptor or  in
sensory  nerve  fibres, the  pyrethroid-induced repetitive
activity  increases  dramatically  as the  temperature  is
lowered, and a decrease of 5 °C in temperature may cause a
more  than 3-fold increase in the number of repetitive im-
pulses per train.  This effect is easily reversed by rais-
ing the temperature.  The origin of this   "negative  tem-
perature coefficient"  is not clear [194].

    Synthetic pyrethroids act directly on the axon through
interference with the sodium channel gating mechanism that
underlies  the generation and conduction of each nerve im-
pulse.   The transitional state  of the sodium  channel is
controlled  by  2 separately  acting  gating   mechanisms,
referred  to as the  activation gate and  the inactivation
gate.   Since pyrethroids only appear to affect the sodium
current  during depolarization, the  rapid opening of  the

activation gate and the slow closing of  the  inactivation
gate proceed normally. However, once the sodium channel is
open, the activation gate is restrained in the  open  pos-
ition  by the pyrethroid molecule.   While all pyrethroids
have  essentially the same basic mechanism of action, how-
ever, the rate of relaxation differs substantially for the
various pyrethroids [55].

    In the isolated node of Ranvier, allethrin causes pro-
longation of the transient increase in sodium permeability
of the nerve membrane during excitation [184]. Evidence so
far  available indicates that allethrin  selectively slows
down the closing of the activation gate of a  fraction  of
the sodium channels that open during depolarization of the
membrane.   The time constant of closing of the activation
gate  in  the  allethrin-affected channels  is  about  100
milliseconds  compared with less than  100 microseconds in
the  normal sodium channel, i.e.,  it is slowed down  by a
factor  of more than 100.   This results in a  marked pro-
longation  of the sodium current across the nerve membrane
during  excitation, and this  prolonged sodium current  is
directly  responsible for the repetitive  activity induced
by allethrin [194].

    The  effects of cismethrin on synaptic transmission in
the  frog  neuromuscular  junction, as  reported  by Evans
[38],  are almost identical  to those of  allethrin, i.e.,
presynaptic  repetitive firing, and no significant effects
on transmitter release or on the subsynaptic membrane.

    Interestingly, the action of these pyrethroids closely
resembles  that of the  insecticide DDT in  the peripheral
nervous  system of the  frog. DDT also  causes  pronounced
repetitive  activity  in  sense organs,  in  sensory nerve
fibres,  and  in  motor nerve  terminals,  due  to a  pro-
longation of the transient increase in sodium permeability
of the nerve membrane during excitation.  Recently, it was
demonstrated  that allethrin and DDT  have essentially the
same  effect on sodium  channels in frog  myelinated nerve
membrane.  Both compounds slow down the rate of closing of
a  fraction of the sodium channels that open on depolariz-
ation of the membrane [185, 186, 193].

    In  the  electrophysiological experiments  using giant
axons  of crayfish, the  type I pyrethroids and  DDT  ana-
logues  retain sodium channels  in a modified  open  state
only intermittently, cause large depolarizing after-poten-
tials,  and evoke repetitive firing with minimal effect on
the resting potential [108].

    These  results  strongly  suggest that  permethrin and
cismethrin,  like  allethrin, primarily  affect the sodium
channels in the nerve membrane and cause a prolongation of
the  transient increase in sodium permeability of the mem-
brane during excitation.

    The  effects  of  pyrethroids on  end-plate and muscle
action  potentials were studied  in the pectoralis  nerve-
muscle  preparation  of the  clawed frog  (Xenopus laevis).
Type I  pyrethroids (allethrin, cismethrin, bioresmethrin,
and  1R,  cis-phenothrin)  caused moderate  presynaptic re-
petitive activity, resulting in the occurrence of multiple
end-plate potentials [159].

Pyrethroids with an alpha-cyano group on the 3-phenoxy-
benzyl  alcohol  (deltamethrin, cypermethrin,  fenval-
erate, and fenpropanate) (Type II: CS-syndrome)

    The pyrethroids with an alpha-cyano group cause an in-
tense repetitive activity in the lateral line organ in the
form  of long-lasting trains  of impulses [192].   Such  a
train may last for up to 1 min and contains  thousands  of
impulses. The duration of the trains and the number of im-
pulses  per train increase  markedly on lowering  the tem-
perature.  Cypermethrin does not cause repetitive activity
in  myelinated  nerve  fibres.  Instead,  this  pyrethroid
causes  a  frequency-dependent  depression of  the nervous
impulse,  brought about by a progressive depolarization of
the  nerve membrane as  a result of  the summation of  de-
polarizing after-potentials during train stimulation [190,

    In  the isolated node  of Ranvier, cypermethrin,  like
allethrin, specifically affects the sodium channels of the
nerve  membrane and causes a  long-lasting prolongation of
the  transient  increase  in  sodium  permeability  during
excitation,  presumably by slowing down the closing of the
activation  gate of the  sodium channel [190,  194].   The
time  constant of closing  of the activation  gate in  the
cypermethrin-affected  channels is prolonged to  more than
100 milliseconds.   Apparently, the amplitude of  the pro-
longed sodium current after cypermethrin is too  small  to
induce  repetitive activity in  nerve fibres, but  is suf-
ficient to cause the long-lasting repetitive firing in the
lateral-line sense organ.

    These results suggest that alpha-cyano pyrethroids pri-
marily  affect the sodium  channels in the  nerve membrane
and  cause  a  long-lasting prolongation  of the transient
increase  in  sodium  permeability of  the membrane during

    In  the  electrophysiological experiments  using giant
axons  of crayfish, the Type II  pyrethroids retain sodium
channels in a modified continuous open state persistently,
depolarize  the membrane, and  block the action  potential
without causing repetitive firing [108].

    Diazepam, which facilitates GABA reaction, delayed the
onset of action of deltamethrin and fenvalerate,  but  not
permethrin and allethrin, in both the mouse and cockroach.

Possible  mechanisms  of  the Type II  pyrethroid syndrome
include action at the GABA receptor complex or  a  closely
linked class of neuroreceptor [61].

    The  Type II syndrome of  intracerebrally administered
pyrethroids  closely  approximates that  of the convulsant
picrotoxin  (PTX).   Deltamethrin inhibits  the binding of
[3H]-dihydropicrotoxin    to rat brain synaptic membranes,
whereas  the non-toxic R  epimer of deltamethrin  is inac-
tive.   These findings suggest a possible relation between
the Type II pyrethroid action and the GABA  receptor  com-
plex.   The  stereospecific  correlation between  the tox-
icity  of Type II pyrethroids and their potency to inhibit
the  [35S]-TBPS   binding was  established using a  radio-
ligand, [35S]- t-butyl-bicyclophosphoro-thionate [35S]-TBPS.
Studies  with  37 pyrethroids revealed  an absolute corre-
lation,  without any false  positive or negative,  between
mouse intracerebral toxicity and  in vitro inhibition:  all
toxic  cyano  compounds  including  deltamethrin,  1R, cis-
cypermethrin,  1R, trans-cypermethrin,  and  [2S,  alphaS]-
fenvalerate were inhibitors, but their  non-toxic  stereo-
isomers were not; non-cyano  pyrethroids  were  much  less  
potent or were inactive [99].

    In the [35S]-TBPS   and [3H]-Ro   5-4864 (a convulsant
benzodiazepine  radioligand) binding assay, the inhibitory
potencies  of  pyrethroids  were closely  related to their
mammalian  toxicities.  The most toxic pyrethroids of Type
II  were the most  potent inhibitors of  [3H]-Ro    5-4864
specific  binding  to  rat brain  membranes.  The [3H]-di-
hydropicrotoxin  and  [35S]-TBPS    binding  studies  with
pyrethroids  strongly  indicated  that Type II  effects of
pyrethroids are mediated, at least in part, through an in-
teraction with a GABA-regulated chloride ionophore-associ-
ated binding site. Moreover, studies with [3H]-Ro   5-4864
support  this hypothesis and,  in addition, indicate  that
the pyrethroid-binding site may be very closely related to
the convulsant benzodiazepine site of action [100].

    The  Type II pyrethroids (deltamethrin, 1R,  cis-cyper-
methrin and [2S, alphaS]-fenvalerate) increased  the input
resistance of crayfish claw opener muscle fibres bathed in
GABA.  In contrast, two non-insecticidal stereoisomers and
Type I  pyrethroids  (permethrin,  resmethrin,  allethrin)
were  inactive.  Therefore, cyanophenoxybenzyl pyrethroids
appear  to  act  on the  GABA  receptor-ionophore  complex

    The  effects  of  pyrethroids on  end-plate and muscle
action  potentials were studied  in the pectoralis  nerve-
muscle  preparation  of the  clawed frog  (Xenopus laevis).
Type II   pyrethroids (cypermethrin and  deltamethrin) in-
duced  trains of repetitive muscle action potentials with-
out  presynaptic repetitive activity.  However,  an inter-
mediate group of pyrethroids (1R-permethrin, cyphenothrin,
and  fenvalerate) caused both  types of effect.   Thus, in

muscle or nerve membrane the pyrethroid induced repetitive
activities  due to a  prolongation of the  sodium current.
But  no clear distinction  was observed between  non-cyano
and alpha-cyano pyrethroids [159].


    In  summary,  the  results strongly  suggest  that the
primary  target  site  of pyrethroid  insecticides  in the
vertebrate  nervous system is  the sodium channel  in  the
nerve  membrane. Pyrethroids without an alpha-cyano  group
(allethrin,   d-phenothrin,  permethrin,  and  cismethrin)
cause a moderate prolongation of the transient increase in
sodium  permeability  of  the nerve  membrane during exci-
tation. This results in relatively short trains of repeti-
tive  nerve impulses in  sense organs, sensory  (afferent)
nerve  fibres, and, in  effect, nerve terminals.   On  the
other  hand, the alpha-cyano  pyrethroids  cause  a  long-
lasting prolongation of the transient increase  in  sodium 
permeability  of  the  nerve  membrane  during excitation.  
This results in long-lasting trains of repetitive impulses 
in sense organs and a frequency-dependent depression of the
nerve  impulse in nerve fibres.  The difference in effects
between  permethrin and cypermethrin, which have identical
molecular structures except for the  presence of an alpha-
cyano  group on the phenoxybenzyl  alcohol, indicates that
it is  this alpha-cyano  group that is responsible for the
long-lasting prolongation of the sodium permeability.

    Since  the  mechanisms  responsible for  nerve impulse
generation  and conduction are basically the same through-
out   the  entire  nervous system,  pyrethroids  may  also
induce  repetitive activity in various parts of the brain.
The difference in  symptoms  of  poisoning  by alpha-cyano
pyrethroids,  compared with the classical  pyrethroids, is
not  necessarily  due  to  an  exclusive  central  site of
action.   It may be related to the long-lasting repetitive
activity  in sense organs and  possibly in other parts  of
the  nervous system,  which, in  a more  advance state  of
poisoning,  may  be  accompanied by  a frequency-dependent
depression of the nervous impulse.

    Pyrethroids  also cause pronounced repetitive activity
and  a prolongation of  the transient increase  in  sodium
permeability  of the nerve  membrane in insects  and other
invertebrates.   Available information indicates  that the
sodium  channel in  the nerve  membrane is  also the  most
important  target site of pyrethroids  in the invertebrate
nervous system [196, 208].

    Because  of the universal  character of the  processes
underlying  nerve excitability, the action  of pyrethroids
should  not be considered restricted  to particular animal
species,  or to a  certain region of  the nervous  system.
Although  it has been  established that sense  organs  and
nerve  endings are the  most vulnerable to  the action  of
pyrethroids,  the ultimate lesion  that causes death  will
depend  on  the animal  species, environmental conditions,
and on the chemical structure and physical characteristics
of the pyrethroid molecule [191].


1.  Résumé et évaluation

1.1 Identité, propriétés physiques et chimiques, méthodes

    La  fenvalérate  est  un insecticide  puissant utilisé
depuis 1976. C'est un ester de l'acide (chloro-4 phényle)-
2 méthyl-3 butyrique et de  l'alcool  alpha-cyano-phénoxy-
benzylique.   Malgré l'absence du cycle  cyclopropane, ses
propriétés   insecticides  le  rattachent  au  groupe  des
pyréthroïdes.   Il s'agit d'un mélange racémique de quatre
isomères optiques dont les configurations sont [2S, alphaS],
[2S, alphaR], [2R, alphaS] et [2R, alphaR].  L'isomère [2S, 
alphaS]  est  le  plus  actif biologiquement; vient ensuite 
l'isomère [2S, alphaR].

    Le  fenvalérate de qualité technique  se présente sous
la  forme d'un  liquide visqueux  jaune ou  brun  dont  la
densité  est de 1,175  à 25 °C.  Il  est relativement  non
volatil,  sa tension de vapeur étant de 0,037 mPa à 25 °C.
Pratiquement  insoluble  dans l'eau  (environ 2 µg/litre),
il   est  soluble  dans  les   solvants  organiques  comme
l'acétone, le xylène et le kérosène.  Il est stable  à  la
lumière,  à la chaleur et  à l'humidité, mais instable  en
milieu  alcalin  par  suite de  l'hydrolyse  du groupement

    Le  dosage  des  résidus et  les  analyses  écotoxico-
logiques  peuvent s'effectuer par chromatographie en phase
gazeuse   avec  détection  par  capture   d'électrons,  la
concentration  minimale  décelable  étant de  0,005 mg/kg.
Pour  l'analyse des produits techniques on utilise la même
méthode mais avec un détecteur à ionisation de flamme.

1.2 Production et usage

    On  utilise  dans  le  monde  environ  1000 tonnes  de
fenvalérate  par an (chiffres de  1979-1983), essentielle-
ment  en  agriculture  mais également  pour la désinsecti-
sation des habitations et des jardins et  le  déparasitage
des bestiaux, soit seul, soit en association avec d'autres
insecticides.   Il  est  présenté sous  forme de concentré
émulsionnable,  de  concentré  pour épandage  à  très  bas
volume, de poudre pour poudrage et de poudre mouillable.

1.3 Exposition humaine

    C'est  essentiellement  du  fait  de  la  présence  de
résidus  dans  les aliments  que  la population  dans  son
ensemble  est exposée à  cet insecticide.  Le  respect des
règles  de bonne pratique  permet en général  de maintenir

les résidus dans les récoltes à un faible niveau.  L'expo-
sition  qui en découle pour la population générale devrait
a  priori  être  très faible  mais  on  ne dispose  pas de
données tirées d'études de la ration totale.

    L'analyse  des  résidus  présents  dans  les  céréales
ensilées  a montré que  plus de 70%  de la dose  appliquée
subsistent  sur le blé au bout de dix mois à 25 °C.  Après
mouture  et  panification, la  teneur  en résidus  du pain
blanc  et  de  la farine de froment est à peu près la même
(environ 0,06-0,1 mg/kg).

    Les  informations relatives à l'exposition profession-
nelle au fenvalérate sont très fragmentaires.

1.4 Destinée dans l'environnement

    Dans  le  sol, il  y a dégradation  par coupure de  la
liaison  ester et du groupement  diphényl-éther, hydroxyl-
ation  du  cycle  benzénique, hydratation  du  nitrile  en
amide,  l'oxydation  des fragments  se poursuivant jusqu'à
l'obtention   d'anhydride  carbonique  qui   constitue  le
principal  produit final.  L'étude du potentiel de lixivi-
ation du fenvalérate et de ses produits de  dégradation  a
montré qu'il n'y avait guère de pénétration au  niveau  du

    Dans  l'eau et  à la  surface du  sol, la  fenvalérate
subit une photodégradation par la lumière solaire.   On  a
montré  qu'il  se  produisait une  coupure  du  groupement
ester,  une hydrolyse du groupement  cyano, une décarboxy-
lation  conduisant  au  (phénoxy-3)-2 (chloro-4 phényle)-3
méthyl-4 pentane-nitrile (décarboxy-fenvalérate), ainsi que
d'autres réactions à initiation radicalaire.

    Sur  les  végétaux,  la  fenvalérate  a  une  demi-vie
d'environ  14 jours.  La principale réaction consiste dans
la  rupture  de la  liaison  ester suivie  d'une oxydation
et/ou  d'une  conjugaison  des fragments.   Il  se produit
également une décarboxylation en décarboxy-fenvalérate.

    En   général,  la  dégradation   dans  l'environnement
conduit à des produits moins toxiques.

    Dans   l'environnement,   le  fenvalérate   est  assez
rapidement  dégradé.  La demi-vie est de 4 à 15 jours dans
les  rivières, 8 à 14 jours sur les végétaux, 1 à 18 jours
par  photodégradation à la  surface du sol  et 15 jours  à
3 mois dans le sol.

    Il  n'y  a  pratiquement aucune  lixiviation du fenva-
lérate présent dans le sol.  Il est donc improbable que ce
composé  puisse  s'accumuler  de façon  importante dans le
milieu aquatique.

1.5 Cinétique et métabolisme

    On  a étudié la destinée du fenvalérate chez le rat et
la souris au moyen de fenvalérate radio-marqué  au  niveau
du  groupement carboxylate, ou des  groupements benzyle ou
cyano.  Sauf dans le cas des composés marqués au niveau du
groupement   cyano,   la  radioactivité   administrée  est
rapidement  excrétée  (jusqu'à  99% en  six  jours).   Les
principales  réactions  métaboliques  consistent  en   une
rupture  du  groupement  ester  et  une  hydroxylation  en
position 4.   On  a  également observé  diverses réactions
d'oxydation  et  de  conjugaison conduisant  à  un mélange
complexe.   Lorsque  le  fenvalérate est  radio-marqué  au
niveau  du groupement cyano, la dose radioactive s'élimine
moins   rapidement  (jusqu'à  81%   en  six  jours).    La
radioactivité restante est principalement confinée dans la
peau,  les poils et  l'estomac sous forme  de thiocyanate.
Il  existe aussi une voie  métabolique secondaire, quoique
très  importante,  qui  consiste dans  la  formation  d'un
conjugué  lipophile  de  (chloro-4  phényle)-2-[2R]   iso-
valérate.  Ce conjugué qui intervient dans la formation de
granulomes  a été décelé dans  les surrénales, le foie  et
les  ganglions mésentériques des  rats, des souris  et  de
certaines autres espèces.

1.6  Effets sur les êtres vivant dans leur milieu naturel

    Au  laboratoire,  le  fenvalérate se  révèle extrêment
toxique  pour les organismes aquatiques. La CL50 varie  de
0,008 µg/litre    pour des mysidacées nouvellement écloses
à  2 µg/litre    pour  une  espèce  d'éphéméroptère.   Les
épreuves  portant sur le cycle évolutif de  Daphnia galeata
 mendotae ont  révélé  que  la dose  sans  effet observable
était  de 0,005 µg/litre.    Le fenvalérate  est également
extrêment  toxique pour les  poissons.  Les valeurs  de la
CL50 à  96 heures vont de 0,03 µg/litre   pour la larve de
 Leuresthes   tenuis à  200 µg/litre    pour  le     Tilapia
adulte.   La  dose  sans  effet  observable  sur  28 jours
s'établit  à 0,56 µg/litre   pour  les premiers stades  de
certains  vairons.  Le fenvalérate est  moins toxique pour
les  algues et les mollusques  aquatiques, la CL50   à  96
heures étant supérieure à 1000 µg/litre.

    La  forte toxicité potentielle du fenvalérate pour les
organismes  aquatiques ne se manifeste pas dans les essais
sur  le  terrain  ni  dans  les  conditions  d'utilisation
pratique.   Certains invertébrés aquatiques  sont détruits
par un épandage à la surface des eaux mais l'effet sur les
populations   est  temporaire.  On  n'a   pas  signalé  de
mortalité chez les poissons.  La toxicité moindre observée
lors des épandages de plein champ s'explique par une forte
adsorption du composé par les sédiments.

    Le  fenvalérate est très  toxique pour l'abeille.   En
applications  topiques la DL50   est  de  0,41 µg/abeille,
toutefois  l'effet  répulsif  intense qu'exerce  le fenva-
lérate  sur  ces  insectes  en  réduit  l'action  dans  la
pratique.   Rien n'indique qu'il y ait eu des destructions
importantes   d'abeilles  dans  les   conditions  normales
d'utilisation.   Le fenvalérate est plus  toxique pour les
acariens  prédateurs  que  pour  les  espèces  cibles   de

    Administré  par voie orale ou mêlé à la nourriture, le
fenvalérate  est très peu  toxique pour les  oiseaux.   La
DL50    est supérieure à  1500 mg/kg de poids  corporel en
administration  orale  directe et  dépasse 15 000 mg/kg de
nourriture  en  administration dans  la ration alimentaire
pour le colin de Virginie.

Les  organismes  aquatiques  fixent rapidement  le  fenva-
lérate.   Le facteur de  bioconcentration varie de  120  à
4700 selon  l'organisme  en  cause  (algues,   mollusques,
daphnies  et poissons) selon les études effectuées sur des
modèles d'écosystèmes. Toutefois, ce fenvalérate s'élimine
rapidement  lorsque  les  organismes sont  replacés en eau
propre. On peut donc considérer qu'en pratique, ce composé
ne présente aucune tendance à la bioaccumulation.

1.7  Effets  sur  les  animaux d'expérience  et  les systèmes
d'épreuve  in vitro

    La  toxicité aiguë par  voie orale du  fenvalérate est
modérée  à faible.  Toutefois,  les valeurs de  la  DL50
peuvent  varier  considérablement (de  82  à plus  de 3200
mg/kg)  selon  l'espèce animale  en  cause et  le véhicule
d'administration.   Les  signes  cliniques  d'intoxication
aiguë   apparaissent   rapidement   mais  les   survivants
redeviennent  asymptomatiques  au  bout de  trois à quatre
jours.   Parmi les signes  d'intoxication produits par  le
mélange racémique, ainsi que par l'isomère [2S, alphaS], on
note  de l'agitation, des tremblements, une horripilation,
de la diarrhée, une démarche anormale, une choréo-athétose
et  une  salivation (syndrome  CS);  il est  classé  comme
pyréthroïde  du  type II.  Du point  de vue électrophysio-
logique,  il produit des bouffées de pointes au niveau des
nerfs moteurs des cerques de la blatte.  Toutefois, il n'y
a pas de relation bien définie entre les  effets  électro-
physiologiques  chez  l'insecte  et la  toxicité  pour les

    Des  rats ayant  reçu du  fenvalérate pendant  8 à  10
jours  à raison de  2000 mg/kg de nourriture  ont présenté
des  signes typiques d'intoxication  aiguë.  A la  dose de
3000 mg/kg  de nourriture, on observait  des modifications
morphologiques  réversibles  au niveau  du nerf sciatique.

On  a  également  observé  des  modifications  histopatho-
logiques  au niveau  du même  nerf chez  des rats  et  des
souris  ayant reçu en  une seule fois  du fenvalérate  par
voie orale à des doses létales ou sublétales.

    Des poulets ayant reçu par voie orale  du  fenvalérate
pendant cinq jours à raison de 1000 mg/kg par  jour  n'ont
pas  présenté  de  signes cliniques  ou  morphologiques de
neurotoxicité retardée.

    Chez  la  souris, la  toxicité  aiguë par  voie intra-
péritonéale  des  métabolites  du  fenvalérate  n'est  pas
supérieure à celle du fenvalérate lui-même.

    Lors  d'études  de toxicité  subaiguë et subchronique,
des  souris, des rats, des  chiens et des lapins  ont reçu
pendant trois semaines à six mois, du fenvalérate par voie
orale,  percutanée  et respiratoire.   Chez  le rat  et la
souris,  des  études  d'inhalation de  quatre semaines ont
permis de fixer la dose sans effet observable  à  7 mg/m3.
Chez   le  rat,  lors   d'une  étude  de   90 jours,  elle
s'établissait à 125 mg/kg de nourriture, et sur deux ans à
250 mg/kg   de   nourriture  (soit   12,5 mg/kg  de  poids
corporel).  Dans une  étude de  24 à  28 mois, elle  s'est
établie à 150 mg/kg de nourriture, soit 7,5 mg/kg de poids
corporel.  Une étude de deux ans sur la souris a permis de
fixer  la dose à 50 mg/kg  de nourriture, soit 6 mg/kg  de
poids  corporel et  une étude  de 20 mois,  à 30 mg/kg  de
nourriture,  soit  3,5 mg/kg  de poids  corporel.  Chez le
chien  cette dose  a été  établie à  12,5 mg/kg  de  poids
corporel,  lors d'une étude de 90 jours.  Certaines formu-
lations de fenvalérate ont provoqué une irritation cutanée
et  oculaire.   Toutefois, le  fenvalérate technique n'est
pas irritant et n'a pas d'effet sensibilisateur.

    Lors  d'études de  toxicité à  long terme,  on a  noté
l'apparition   de  microgranulomes  chez  des  souris  qui
avaient été traitées avec l'isomère [2R, alphaS] (125 mg/kg
de  nourriture) sur une période  de un à trois  mois.  Ces
anomalies  disparaissaient lorsqu'on supprimait le fenval-
érate.   L'agent causal en était  l'ester cholestérique de
l'acide  (chloro-4 phényl)-2 isovalérique,  un  métabolite
lipophile de  l'isomère  [2R, alphaS] du  fenvalérate.  La 
dose sans  effet  observable  relative  à la formation  de 
microgranulomes  chez  la souris  s'établit  à  30 mg   de 
fenvalérate par kg de nourriture.

    Lors  d'une autre étude de toxicité à long terme, on a
également  observé ces anomalies microgranulomateuses chez
des  rats à la  dose de 500 mg/kg  de nourriture, la  dose
sans effet observable étant dans ce cas de 150 mg  par  kg
de nourriture.

    Administré  à des souris dans  leur nourriture pendant
78 semaines  en doses allant jusqu'à 3000 mg/kg ou pendant
deux ans à raison de 1250 mg/kg, le fenvalérate  ne  s'est

pas révélé cancérogène.  Il ne l'a pas été non  plus  chez
des  rats qui avaient  reçu pendant deux  ans une  alimen-
tation contenant jusqu'à 1000 mg d'insecticide par kg.

    Le fenvalérate n'est ni mutagène, ni délétère pour les
chromosomes   ainsi  qu'il  ressort  d'un  certain  nombre
d'épreuves  in vitro et  in vivo.

    Il  n'est pas non plus tératogène pour la souris et le
lapin à des doses quotidiennes allant jusqu'à 50 mg par kg
de  poids corporel et,  lors d'une étude  de  reproduction
portant  sur  trois générations  de  rats où  les  animaux
recevaient   des   doses   allant  jusqu'à   250 mg/kg  de
nourriture,  il  n'a affecté  aucun  des paramètres  de la
fonction de reproduction.

1.8 Effets sur l'être humain

    Le   fenvalérate   peut   provoquer   des   sensations
d'engourdissement,  de  démangeaison, de  picotement et de
brûlure  chez  les  travailleurs exposés;   les  symptômes
apparaissent   après  une  période  de  latence  d'environ
30 minutes,  atteignent leur acmé  au bout de  8 heures et
disparaissent  dans les 24 heures suivantes.  Certains cas
d'intoxication  se sont produits  à la suite  d'une  expo-
sition professionnelle due au non respect des  mesures  de

    Rien  n'indique  que  le fenvalérate  soit  nocif pour
l'être humain dans la mesure où il est  utilisé  conformé-
ment aux recommandations.

2.  Conclusions

2.1  Population générale

    L'exposition  de la population générale au fenvalérate
est probablement très faible.  Il n'y a sans  doute  aucun
risque si on l'emploie conformément aux recommandations.

2.2 Exposition professionnelle

    Utilisé de manière raisonnable, et moyennant certaines
mesures  d'hygiène  et  de  sécurité,  le  fenvalérate  ne
devrait pas être dangereux pour les personnes qui lui sont
exposées de par leur profession.

2.3 Environnement

    Il est improbable que le fenvalérate ou  ses  produits
de  dégradation puissent s'accumuler  dans l'environnement
en quantité suffisante pour créer des problèmes,  dans  la
mesure  où l'on respecte les  doses d'emploi recommandées.
Au  laboratoire,  le  fenvalérate  se  révèle  extrêmement
toxique  pour les poissons, les  arthropodes aquatiques et

les  abeilles.  Toutefois, il ne semble pas que des effets
nocifs  durables puissent se  produire sur le  terrain  si
l'insecticide  est  utilisé  conformément  aux   recomman-

3.  Recommandations

    Les  concentrations  alimentaires qui  résultent d'une
utilisation  conforme aux recommandations sont considérées
comme très faibles; toutefois il conviendrait de confirmer
ce  point de vue en étendant les études de surveillance au

    Le fenvalérate est utilisé depuis de nombreuses années
et seuls quelques effets temporaires ont été  observés  ça
et  là  à  la suite  d'expositions professionnelles. Néan-
moins,  il serait bon  de poursuivre les  observations sur
l'exposition humaine.

    See Also:
       Toxicological Abbreviations
       Fenvalerate (HSG 34, 1989)
       Fenvalerate (PDS)
       Fenvalerate (Pesticide residues in food: 1979 evaluations)
       Fenvalerate (Pesticide residues in food: 1981 evaluations)
       Fenvalerate (Pesticide residues in food: 1984 evaluations)
       Fenvalerate (Pesticide residues in food: 1984 evaluations)
       Fenvalerate (UKPID)
       Fenvalerate (IARC Summary & Evaluation, Volume 53, 1991)