WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/PCS/DS/94.85
Original: ENGLISH
Distr.: LIMITED
Date of issue: February 1994
WHO/FAO DATA SHEET ON PESTICIDES No. 85
d-PHENOTHRIN
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
CLASSIFICATION:
Primary use: Insecticide
Secondary use:
Chemical group: Pyrethroid
1.0 GENERAL INFORMATION
1.1 COMMON NAME: phenothrin (BSI, E-ISO); phénothrine (F-ISO).
1.1.1 Identity
d-Phenothrin is a mixture of four stereoisomers. The technical
compound is a 20:80 cis:trans mix of both (1R) - (1S) -
configurations. The (1R) - configurations have a greater
insecticidal activity than the corresponding (1S) - isomers. d-
Phenothrin, a preparation rich in (1R) - isomers, with a cis:trans
ratio 20:80, has been marketed. Data pertaining to this latter
product will be designated d-phenothrin in this data sheet.
IUPAC chemical name: 3-phenoxybenzyl (1RS, 3RS; 1RS, 3SR)-2, 2-
dimethyl-3-(2-methylprop-1-enyl) cyclopropanecarboxylate. The
alternative nomenclature of (1RS)- cis , trans - has also been
used to designate the stereoisomers and will be used in this data
sheet.
CAS chemical name: Cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-
methyl-1-propenyl)-(3-phenoxyphenyl)methyl ester.
CAS registry number: 26002-80-2 (racemic).
RTECS registry number: GZ 1975000 (racemic)
GZ 2002000 (d-phenothrin)
Molecular formula: C23H26O3
Molecular mass: 350.5
Structural formula:
Synonyms and trade names: (1R)-phenothrin; S-2539, Multicide
concentrate F-2271, WellcideR. The (1R)- cis , trans
(d-phenothrin); isomers (20:80) are known as SumithrinR;
S-2539 ForteR; Pesguard-A NS, Pesguard-A NS W, or Pesguard NS.
The (R) - isomers may also be designated (+) or d-;
the (S) - isomers as (-) or 1-.
1.2 SYNOPSIS: d-Phenothrin is a fast acting
insecticide, effective by contact and stomach action. It is rapidly
metabolized and excreted by mammals and has low mammalian toxicity.
Stable to storage in the dark; relatively unstable to sunlight or
ultra violet irradiation, or in alkaline media.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics: d-Phenothrin is a yellow
to yellow-brown liquid, with a density of 1.061 g/cm3 (25 °C) and
a refractive index of 1.5482.
1.3.2 Solubility: Soluble in water (25 °C) 2 mg/L.
Soluble in organic solvents.
1.3.3 Stability: d-Phenothrin is hydrolysed by
alkalis but is stable in neutral or weakly acidic media. Unstable
in most solvents except methanol, ethyl cellosolve, o-cresol and
dimethylsulfoxide. Unstable to ultra violet irradiation and has a
short residual life on pre-harvest application. However,
d-phenothrin applied to wheat after harvest showed only slight
degradation after six months storage at 30 °C. When protected from
light no breakdown of d-phenothrin was observed after one year at
room temperature.
1.3.4 Vapour pressure: d-Phenothrin has a vapour
pressure of 0.16 mPa at 20 °C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations: Water and oil based aerosols,
liquid concentrates, emulsifiable concentrates, powders and dusts.
May be formulated with synergists or with other pyrethroid and non-
pyrethroid insecticides.
1.4.2 Pests controlled: Controls most Lepidoptera,
Hemiptera (bed bugs), Diptera (flies, gnats, and mosquitos),
cockroaches and lice.
1.4.3 Use pattern: d-Phenothrin is a non-systemic
insecticide which is effective by contact and as a stomach poison.
Used for power-spray, mist, thermal fog, aerosol and ULV
applications. The major use of d-phenothrin is in the control of
nuisance insects and insects of importance to public health, and it
is used to control human lice, in which case it is formulated as a
powder, shampoo, or lotion. It is also used to protect grain.
1.4.4 Unintended effects: Toxic to fish and bees.
1.5 PUBLIC HEALTH PROGRAMMES
It is used for the impregnation of bednets and for aircraft
disinsection.
1.5.1 Common formulations: As described in Section 1.4.1,
but also formulated into powders, lotions and shampoos.
1.5.2 Pests mainly controlled: See section 1.4.2.
1.5.3 Use pattern: Should be used according to
manufacturers' instructions on appearance of the pest.
1.6 HOUSEHOLD USE
1.6.1 Common formulations: See Sections 1.4.1 and 1.5.1
for general formulation details.
1.6.2 Pests mainly controlled: See Section 1.4.2.
1.6.3 Use pattern: See sections 1.4.3 and 1.5.3.
2.0 TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route: Absorbed from the gastrointestinal
tract and from the intact skin. The dermal absorption rate differs
between the (1R)- cis - and the (1R)- trans -isomers. No data are
available for the rate or extent of absorption from the lung.
2.1.2 Mode of action: d-Phenothrin is a neuropoison.
The symptoms of poisoning are typical of those of pyrethroids without
a cyano-substituent. The proposed mechanism of action is due to the
reversible binding of d-phenothrin to the sodium channels of the
neuronal membrane, in this way modifying the permeability of the
membrane to ions.
2.1.3 Excretion products: No published data are
available for the combined isomers of d-phenothrin. The metabolism
of the individual (1R)- cis - and (1R)- trans - isomers has been
investigated in the rat. For both isomers an oral dose of 10 mg/kg
b.w. was metabolized by hydrolysis, oxidation and conjugation and 96%
of the administered dose was recovered in the urine and faeces within
six days.
Following oral administration of the (1R)- trans - isomer, the urine
was the major excretory route. The isomer was extensively
metabolized to oxidative and conjugated derivatives of the hydrolysed
ester. Oxidative and conjugated derivatives of the
(1R)- cis -isomer were also observed but hydrolysis of the ester
linkage was a minor metabolic pathway. With this isomer the faeces
was the major excretory route.
The metabolic profiles were similar following dermal application,
although the rates of excretion for each isomer showed some
differences between the two routes of administration.
2.1.4 Toxicity, single dose:
Oral LD50
Rat >10,000 mg/kg b.w. (without vehicle)
Rat > 5,000 mg/kg b.w.
Mouse > 5,000 mg/kg b.w. (in corn oil)
Dermal LD50
Rat >10,000 mg/kg b.w.
Intraperitoneal LD50
Rat > 5,000 mg/kg b.w.
Mouse > 5,000 mg/kg b.w.
Intravenous LD50
Rat 452-492 mg/kg b.w.
Mouse 354-405 mg/kg b.w.
LD50(1R)-phenothrin
Oral
Rat >10,000 mg/kg b.w.
Dermal
Rat >10,000 mg/kg b.w.
Subcutaneous
Rat >10,000 mg/kg b.w.
Inhalation LC50 - 4 hour exposure (1R)-phenotrin
Rat >3.76 g/m3
Mouse >1.2 g m3 (1-2 µm particulates in kerosene)
No sex difference in the toxicity was reported. Following
intravenous administration symptoms of poisoning included
fibrillation, tremor, slow respiration, salivation, lacrimation,
ataxia and paralysis. The symptoms appeared 0.5 - 1 hour after
administration and diminished spontaneously.
No histopathological findings in the nervous system were observed
following four hour inhalation exposure of rats to 3.76 mg/L (see
Section 2.1.7).
2.1.5 Toxicity, repeated dose:
Inhalation: Sprague Dawley rats or ddY mice exposed to
concentrations of less than 0.21 mg (1R)-phenothrin/L, for 4
hours/day, five days/week for four weeks, showed no adverse effect on
behaviour, growth, clinical chemistry or organ histopathology.
2.1.6 Dietary studies:
Short term: A 24 week dietary administration of up to 2500 mg
(1R)-phenothrin/kg diet to Sprague Dawley rats had no adverse
effect on growth, haematology, biochemical or histopathological
parameters. Doses more than 5000 mg/kg diet produced increased
liver weights which were accompanied by histopathological changes of
an unspecified nature. Rats and dogs receiving (1R)-phenothrin in
the diet for six months showed no adverse effect at 1000 and 300
mg/kg diet, respectively.
Long term: A dose related increased incidence of alveolar
amyloidosis was observed in Swiss mice receiving 300-3000 mg d-
phenothrin/kg diet for 18 months. The increased liver weights (both
sexes) and a decreased growth rate (males) were observed at 3000
mg/kg diet.
No compound-related adverse effects were observed in rats receiving
up to 2000 mg d-phenothrin/kg diet for two years. At 6000 mg/kg
diet, growth was affected in both sexes. Serum glutamate-pyruvate
transferase activity was increased in the males of this dose group.
2.1.7 Supplementary studies of toxicity:
Carcinogenicity: No tumours attributable to d-phenothrin exposure
were observed in Swiss mice following 18 months administration of up
to 3000 mg/kg diet, or in rats receiving less than 6000 mg/kg diet in
the long-term feeding studied described above.
Teratogenicity: No teratogenic effects were observed. The NOELs for
New Zealand white rabbits and mice were 30 and 3000 mg/kg b.w./day
respectively.
Mutagenicity: Two oral doses of 1500 mg/kg b.w./day to male mice
did not induce mutation in a host-mediated assay with Salmonella
typhimurium -G46. Similar investigations with (1R)- trans
-phenothrin (250 mg/kg b.w./day) or (1R)- cis -phenothrin (90 mg/kg
b.w./day) were also negative.
No mutagenic potential was observed with or without metabolic
activation of d-phenothrin, or the individual isomers, in several
strains of S. typhimurium or Escherichia coli . d-Phenothrin
did not induce mutations in Bacillus subtilis . In vivo and
in vitro chromosomal aberration tests showed negative results.
Reproduction: No significant changes in reproductive potential were
observed in a three generation reproduction study on Charles River
rats. The NOEL was 2000 mg/kg diet.
Neurotoxicity: d-Phenothrin at high doses, in common with
pyrethroids of similar chemical structure, may induce ataxia.
Rats receiving oral doses of 5000 mg (1R)-phenothrin/kg b.w./day (as
SumithrinR) for five days showed evidence of poisoning, such as leg
weakness or ataxia, and some died. In survivors three days after
cessation of exposure no clinical signs of poisoning were apparent.
No significant morphological changes were observed.
Other: (1R) - phenothrin had no effect on a variety of in vitro
and in vivo pharmacological parameters. These tests included
hexabarbital sleeping times in mice, body temperature in rats, blood
pressure and heart rate in dogs, and the contractile activity of
various muscle preparation in vitro .
2.1.8 Modifications of toxicity: The geometric
isomers undergo different metabolic pathways (see Section 2.1.3).
The rapid hydrolysis of the trans -isomers and the slower
oxidation of the cis - isomers are similar to that observed with
other pyrethroids. Inhibition of the oxidative enzymes may increase
the toxicity of the cis isomers.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption route: No published data available but
d-phenothrin may be absorbed from the skin, gastrointestinal tract or
from the lungs.
2.2.2 Dangerous doses:
Single: No published information available.
Repeated: No published information available.
2.2.3 Observations on occupationally exposed workers:
No published information available.
2.2.4 Observations on exposure of the general population:
No published information available. Manufacturers' instructions
should be carefully followed to ensure that the general population
is not exposed to undue amounts of d-phenothrin during agricultural,
public health or domestic usage.
2.2.5 Observations on volunteers: In a special study,
d-phenothrin in a talc powder formulation with Span 80 as a
stabilizer was applied to the head and pubic hair of eight male
volunteers three times at intervals of 3 days, at a dose of 32
mg/man per administration (0.44 to 0.67 mg/kg body weight per day).
The powder was washed off 1 hour after application. There were no
significant abnormalities due to d-phenothrin in terms of dermal
irritation, clinical signs, or blood biochemical and haematological
parameters. The blood levels of d-phenothrin were below the
detection limit of 0.0006 mg/kg.
2.2.6 Reported mishaps:
No published information available.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish: Toxic to fish.
LC50 - 48 hour
Goldfish 0.25 - 0.5 mg/L
Killifish 0.2 mg/L
LC50 - 96 hour
Bluegill 0.018 mg/L (1R)-phenothrin
Rainbow trout 0.017 mg/L (1R)-phenothrin
2.3.2 Birds:
LD50 - Oral
Bobwhite quail > 2510 mg/kg b.w.
(1R)-phenothrin
2.3.3 Other species:
Toxic to bees but no quantitative data are available.
LC50 3 hour
Daphonia pulex > 50 mg/L
3.0 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON
REGULATION OF COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
[For definition of categories see the 'Introduction to data sheets'].
Liquid formulations > 25% - Category 4*
All other formulations - Category 5*
Based on WHO documented oral LD50 of >5000 mg/kg b.w.
3.2 TRANSPORTATION AND STORAGE
Formulations in category 4: Should be transported and stored in
clearly labelled, leak-proof containers well away from food or drink.
The containers should be kept under lock and key, secure from access
by children and unauthorized personnel.
Formulations in category 5: Should be transported and stored in
clearly labelled, leak-proof containers, well away from food and
drink and secure from access by children.
3.3 HANDLING
Formulations in category 4: Protective clothing (see section 4)
should be worn when handling these formulations. Adequate washing
facilities should be available in the immediate area. Eating,
drinking and smoking should be prohibited during handling. Hands and
face should be washed immediately after handling the formulation.
Formulations in category 5: Facilities as required for the
handling of any chemical should be provided. Hands and face should
be washed before eating, drinking or smoking and immediately after
handling the compound.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
Technical d-phenothrin and its formulations (other than pressurized
products): Empty containers should be decontaminated (See Section
4.3), but decontaminated containers must not be used for
transportation or storage of food or feed stuffs. Containers which
are not decontaminated should be burned or crushed and buried below
topsoil. Extreme care must be taken to ensure that the disposal site
will not cause subsequent contamination of water sources.
Pressurized products must be disposed of according to manufacturers'
instructions and the containers must never be heated or punctured.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
Formulations in category 4: Persons under medication with
neuroactive drugs should avoid contact with d-phenothrin.
Consideration should be given to the workers' ability to comprehend
and follow instructions. Workers should be trained in techniques to
avoid contact with the formulations.
Formulations in category 5: A warning to workers to avoid contact
is essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations: Pilots and loaders should have specialized
training in application methods and in the recognition of early
symptoms of pesticide poisoning. A suitable respirator should be
worn in addition to overalls and impermeable gloves. Flagmen should
wear impermeable gloves and boots, overalls and a broad brimmed hat
and should be located well away from the dropping zone.
3.7 LABELLING
Formulations in category 4 - Minimum cautionary statement: d-
Phenothrin is a synthetic pyrethroid insecticide which may be
poisonous following ingestion, skin contact or inhalation of fogs,
dusts or mists. These formulations may be irritating to the skin and
eyes. Avoid skin contact; wear protective overalls, impermeable
gloves and eye protection while handling concentrate. Keep the
material out of reach of children and well away from food and feed
stuffs. If poisoning occurs call a physician.
Formulations in category 5 - Minimum cautionary statement: This
formulation contains phenothrin and is poisonous if swallowed. It
may be absorbed from the skin or following inhalation of dusts, mists
or fogs. Keep this product out of the reach of children and well
away from food and feed stuffs. Wash thoroughly after use.
3.8 RESIDUES IN FOOD
Maximum residue limits have been established by the FAO/WHO Joint
Meeting on Pesticide Residues. There are eight Codex Committees
MRLs. The Joint FAO/WHO Meeting on Pesticide Residues has estimated
the Acceptable Daily Intake (ADI) to be 0.07 mg/kg body weight.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General: d-Phenothrin is a synthetic pyrethroid
which may elicit an effect on nerve function when administered at
high doses to animals. It may be absorbed from the gastrointestinal
tract or from intact skin. Absorption from the lungs may occur
following exposure to dusts, aerosol, mists or fogs formulations.
4.1.2 Manufacture and formulation - TLV:
No published information available. Closed systems and forced
ventilation should be used to reduce the exposure of workers to
d-phenothrin. Protective clothing (see Section 4.1.3) should be worn.
4.1.3 Mixers and applicators: Workers should wear
impermeable gloves and boots, clean overalls and eye protection. A
respirator should additionally be worn during mixing operations and
when applying aerosol, mist, dust or fog formulations. Mixing, if
not mechanical, should always be carried out with a paddle of
appropriate length. Avoid contact with the mouth, skin and eyes.
Before eating, drinking, or smoking, the face, hands and exposed skin
should be thoroughly washed.
4.1.4 Other associated workers: Persons associated
with the application of d-phenothrin should observe the precautions
described above (see sections 3.6 and 4.1.3).
4.1.5 Other populations likely to be affected:
The domestic and public health usage of d-phenothrin will expose
persons other than those associated with agricultural practices.
Careful attention to the manufacturers' instructions and the low
concentrations of d-phenothrin in many formulations should ensure
that this usage dose not expose the public to hazardous amounts of
d-phenothrin.
Good agricultural practices should ensure that the general public are
not exposed to hazardous amounts of d-phenothrin following commercial
applications.
4.2 ENTRY OF PERSONS INTO TREATMENT AREA
Entry of unprotected persons into enclosed areas treated with
aerosol, mist or fog formulations should be prevented until the area
has been thoroughly ventilated.
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
Care must be taken during decontamination procedures to ensure that
water sources are not contaminated. Impermeable gloves and eye
protection should be worn. Residues in containers should be emptied
in a diluted form into a dry pit deeper than 0.5 m. Dispose of
pressurized products according to manufacturers' recommendations.
These containers should not be punctured, heated or burned. For
other products, the empty container may be decontaminated by
scrubbing with water and detergent followed by soaking overnight with
5% sodium hydroxide solution. Decontaminated containers must not be
used for the transportation or storage of food or drink. Containers
which are not decontaminated should be burned or crushed and buried
below topsoil.
Spillage of liquid formulations should be covered with absorbent
material. This material, or spillage of dry formulations, should be
collected and burned or buried in a deep dry pit. Residual
contamination should be removed from the spillage site by washing
with water and detergent.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning: No reported
incidences. Unless exposure to d-phenothrin has been exceptionally
high, the symptoms of over-exposure may be due to the accompanying
chemicals in the formulation. Symptoms may include headache, nausea
and vomiting.
4.4.2 Treatment before person is seen by physician, if these
symptoms appear following exposure:
The person should stop work immediately, remove contaminated clothing
and wash the affected skin area. If the formulation has entered the
eyes they should be flushed with clean water. The majority of
formulations contain hydrocarbon solvents or oils. Vomiting should
not be induced unless it can be definitely determined that all of the
following apply: that the formulation was free of solvents and oil;
that large amounts of the formulation have been ingested; that the
patient is fully conscious. In all cases, keep the patient calm and
obtain immediate medical help.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information: d-Phenothrin is a synthetic
pyrethroid insecticide of low mammalian toxicity. It may be absorbed
from the gastrointestinal tract; by inhalation of dusts, mists or
fogs or through intact skin. d-Phenothrin is rapidly metabolized to
hydrolysis and oxidation products, which are rapidly excreted in the
urine and faeces.
5.1.2 Symptoms and signs: No published information
available on the acute toxic effects of d-phenothrin in humans.
Accompanying chemicals in the formulation may elicit symptoms before
those observed from d-phenothrin exposure. Early symptoms may
include headache, nausea and vomiting.
5.1.3 Laboratory: There are no simple methods for
determining d-phenothrin in body fluids. The metabolism is rapid and
there are numerous excretory products. The proportion of each
metabolite may not be constant in all types of exposure and cannot
therefore be used as a quantitative measure of exposure. Some
urinary metabolites may not be specific to d-phenothrin.
5.1.4 Treatment: Treatment is symptomatic. Wash
contaminated skin with soap and water. Wash contaminated eyes with
copious amounts of water. Ingestion of a small amount
(< 5 mg/kg b.w.) of d-phenothrin should be treated with a large dose
of activated charcoal followed by sodium or magnesium sulfate
(0.25 g/kg b.w.) in water.
Following ingestion of larger quantities of d-phenothrin, vomiting
should be induced if the patient is fully conscious. Care must be
taken however to avoid pulmonary complications from the accompanying
solvents or oils. Subsequent administration of activated charcoal
may limit absorption of remaining d-phenothrin.
5.1.5 Prognosis: There are no published data
available. Based on animal experiments it is expected that any
effects should be reversible.
5.1.6 References to previously reported cases:
No published information available.
5.2 SURVEILLANCE TESTS - None.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound and residues:
Papadopoulou-Mourkidou E, Iwata Y, Gunther FA (1984), J Agric Food
Chem 32: 800-805.
Sakaue S, Kitajima M, Horiba M, Yamamoto S (1981), Agric Biol Chem
45(5): 1135-1140.
5.3.2 Other tests in case of poisoning: None.
REFERENCES
1. WHO (1990), Environmental Health Criteria 96; d-Phenothrin; Geneva,
World Health Organization, 64 pp.
2. WHO (1989), Health and Safety Guide 32; d-Phenothrin; Geneva, World
Health Organization, 28 pp.
3. FAO/WHO (1980) Pesticide Residues in Food 1988, Evaluations 1988,
Part II - Toxicology, FAO Plant Production and Protection Paper 93/2,
Rome, 1989.
4. The Pesticide Manual, A World Compendium (9th edition 1991),
Worthing, C.R. and Hance, eds., British Crop Protection Council, 20
Bridport Road, Thornton Heath, CR4 7QG, United Kingdom.
5. WHO (1991), Fourteenth Report of the WHO Expert Committee on Vector
Biology and Control, WHO Technical Report Series No. 813, Safe Use of
Pesticides; Geneva, World Health Organization, 27 pp.
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