WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/DS/84.47
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 47
METHOPRENE
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: Insect growth regulator
Secondary use:
Chemical group: Juvenile hormone analogue
1. GENERAL INFORMATION
1.1 COMMON NAME:
Methoprene (ISO, BSI, ANSI)
1.1.1 Identity:
IUPAC and CAS No. 1: Isopropyl (2E, 4E)-11-methoxy-3,7,11
trimethyl-2-1,4-dodecadienoate
CAS Reg. No.: 40596-69-8
Molecular formula: C19H34O3
Molecular weight: 310.0
Structural formula:
1.1.2 Synonyms:
Altosid(R); Kabat(R); Apex(R); Diacon(R); Minex(R);
Pharorid(R); Precor(R); Manta(R); Altosand(R); ZR-515
1.2 SYNOPSIS:
Methoprene is a selective, stable and potent larvicide; an ether and
diunsaturated fatty acid ester; a juvenile hormone analogue, its
toxicity to insects is manifest through interference with
metamorphosis, a process without parallel in mammals. Methoprene is
non-persistent and non-toxic to mammals and presents no long-term
hazard to other species at recommended application rates.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
Methoprene technical material is an amber liquid boiling at 100°C
(0.05 mmHg) and having a specific gravity of 0.261 at 20°C.
1.3.2 Solubility
In water, 1.39 mg/l; soluble in organic solvents.
1.3.3 Stability
It is described as a stable compound though non-persistent due to
rapid biodegradation mainly to CO2. The soil half-life is 10 days;
in water, less than one day in sunlight and over four weeks in dark
and, on plants, 1-2 days.
1.3.4 Vapour pressure
3.15 x 10-6 kPa (2.37 x 10-5 mmHg) at 20°C.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
Methoprene is available as an emulsifiable concentrate; in granules
and briquettes; and, premixed in ant baits and cattle feed
supplements at concentrations up to 10% a.i.
1.4.2 Pests controlled
These include fleas., flies, moths, pharaoh's ants, bollweevil,
lice, mosquitos, leaf hoppers, plant hoppers, cucumber beetles,
cigarette beetle, tobacco moth and others.
1.4.3 Use pattern
Methoprene may be sprayed on flooded pasture and crops at a rate of
40-100 g/ha for control of mosquitos, etc. It may also be fed to
livestock in a premix food supplement for control of hornfly. When
used in structures (e.g. tobacco curing sheds), use as directed. It
should not be mixed with oil or other pesticides.
1.4.4 Unintended effects
Methoprene is not phytotoxic, it may be toxic to some beneficial
aquatic invertebrates when used at excessive rates. Used in Japan to
treat silkworms making them extend the time period in which they
produce silk.
1.5 PUBLIC HEALTH USE
As in 1.4, for control of nuisance and disease vector pests, the
most important being the control of flood water mosquitos.
1.6 HOUSEHOLD USE
For control of fleas at approximately 0.15 µg/1000 cm2. Also used
in houseplant sprays.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
Methoprene may be absorbed from the gastrointestinal tract; through
the intact skin; and, by inhalation of spray mist.
2.1.2 Mode of action
Methoprene is an invertebrate metabolic inhibitor which does not
seem to cause direct toxic effects in mammals. In in vitro studies
of mouse L929 cells, methoprene inhibited macromolecular synthesis
including DNA and RNA, at concentrations exceeding its maximum water
solubility level. Degeneration of cells and uncoupling of oxidative
phosphorylation has also been reported in mouse hepatocyte cultures
at very high dose levels.
2.1.3 Excretion products
Methoprene metabolism and excretion have been studied in several
vertebrate organisms - cattle, rodents and hens. Methoprene is
metabolized primarily by hepatocyte microsomal esterases, mainly to
methoprene acid, which after alpha oxidation is susceptible to beta
oxidation to acetate then, via the Krebs' cycle to carbon dioxide or
intermediary metabolites. In 14C-labelled methoprene studies at
low doses, most of the radioactivity was respired from the body as
CO2. The remainder, was found to be associated with complex and
simple secondary metabolites in body tissues and fluids and also as
primary breakdown products in urine and faeces. A significant amount
of radioactivity was also found in the milk of lactating cows and in
eggs of laying hens. Less than 1% of this excreted radioactivity was
found as methoprene and the rest was associated with natural
products; no primary metabolites were found. The finding of large
quantities of unmetabolized methropene in faeces but not in urine or
blood suggests poor intestinal absorption at higher doses and rapid
metabolism of the absorbed material. The primary products of urinary
excretion are the hydroxyepter (isopropyl
11-hydroxy-3,7,11-trimethyl - 2,4-dodecadienoate), the hydroxyacid
(11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid), and several
lesser metabolites including 7-methoxycitronellic acid,
7-hydroxycitronellic acid and 7-methoxycitronellal. These are
excreted as free compounds and as conjugates.
2.1.4 Toxicity, single dose
Oral LD50:
Rat: + 34 600 mg/kg b.w. Technical material
Dog: 5000-10 000 mg/kg b.w. Technical material
Dermal LD50:
Rabbit: 3000-10 000 mg/kg b.w. Technical material
Rat: + 5000 mg/kg b.w. Technical material
Inhalation LC50:
Rat and guinea pig: + 210 mg/l (highest dose tested) Technical
material
2.1.5 Toxicity, repeated doses
Oral: See 2.1.6, Dietary studies and 2.1.7, Teratogenicity.
Dermal: No signs of toxicity were observed in a 21-day dermal
toxicity test in rabbits given 400 (mg/kg b.w.)/day.
Inhalation: No toxic effects were observed in a 21-day inhalation
test in rats at a 20 mg/l dose level.
Cumulation of compound: There was no evidence of the accumulation
of methoprene or its primary metabolites in body tissues and fluid
in 14C-labelled methoprene tracer studies.
2.1.6 Dietary studies
Short-term: In 90-day studies, dogs and rats showed no toxic
effects at the 500 mg/kg diet level and there were no irreversible
ill-effects at the 5000 mg/kg diet level. No deaths occurred in any
of the diet groups. In a 6-month study, male and female rats were
fed 0, 80, 400, 2000 or 10 000 mg/kg of diet. One female on the
2000 mg/kg diet died. At 10 000 mg/kg, mild degenerative changes,
which would be expected to be reversible, were observed in hepatic
parenchyma cells. The maximum no-effect-level for rats was estimated
to be 20 (mg/kg b.w.)/day in a 90-day study.
Long-term: In two-year studies rats were fed diets containing 250,
1000 or 5000 mg/kg of methoprene. The no observed adverse effect
level was determined to be 5000 mg/kg (diet), equivalent to 250
(mg/kg b.w.)/day.
Mice were fed dietary levels of 250, 1000 or 2500 mg/kg for 18
months. There was no treatment related mortality. Amyloidosis was
more prevalent in the high dose group than others and hepatic
pigmentation was also observed at this dose level and to a lesser
extent at 1000 mg/kg (diet). The no observed effect level was
determined to be 250 mg/kg (diet), equivalent to 37.5 (mg/kg
b.w.)/day.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: No evidence of carcinogenic potential was
obtained in the long-term dietary studies with mice and rats nor in
the several studies of mutagenicity described below.
Mutagenicity: Methoprene was not mutagenically active in a
microbial assay with S. typhimurium strains sensitive to base pair
substitutions and frame shift mutations. It was also not active in a
mouse cell culture assay or in a (rat) dominant lethal mutagenicity
study at 2000 mg/kg b.w. (single dose).
Teratogenicity: No evidence of teratogenic activity was observed
in sheep (dose unknown), in rabbits at 500 (mg/kg b.w.)/day, in rats
at 1000 (mg/kg b.w.)/day or in mice at 600 (mg/kg b.w.)/day.
Reproduction: In a three-generation study, rats continuously fed
2500 mg/kg diets showed no toxic or reproductive adverse effects.
Mortality, pregnancy and fertility rates, food consumption, duration
of gestation, foetal viability, neonatal survival, litter size and
sex ratios were normal. No reproductive or embryotoxic effects were
seen in quail or ducks at 30 ppm continuous feeding.
Neurotoxicity: No adverse clinical or pathological findings were
noted in the acute, subchronic or chronic studies.
Endocrine effects: Methoprene was found to have no estrogenic,
androgenic, anabolic or glucocorticoid activity in mice and rats.
Primary irritation and skin sensitization: No eye irritation was
observed in rabbits up to 72 hours after applications of 0.1 ml of
69.8% solution. No dermal irritation was observed in rabbits exposed
to 0.5 ml of a 69.8% solution for 24 hours on either intact or
abraded skin under occlusive wraps. Methoprene showed no
sensitization potential in two standard guinea-pig sensitization
tests.
2.1.8 Modification of toxicity
No information available.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption routes
Methoprene may be absorbed from the gastrointestinal tract; through
the intact skin; or by inhalation of spray mist.
2.2.2 Dangerous doses
Not known.
2.2.3 Observations on occupationally exposed workers
No reports of adverse effects.
2.2.4 Observations on exposure of the general population
No information available.
2.2.5 Observations on volunteers
Following a standard Draize method skin sensitization study on 231
volunteers it was concluded that the test substance, a domestic use
formulation, was not a human skin sensitizer.
2.2.6 Reported mishaps
No information available.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish
Methoprene is only slightly toxic to fish, 10 weekly treatments of
wild populations of mosquito fish in ponds at 56-560 g/ha caused no
mortalities or long-lasting ill effects.
LD50 static tests:
Bluefill 4.62 ppm Technical material
Channel catfish + 100.0 ppm Technical material
Coho salmon 32.0 ppm Technical material
Trout 4.39 ppm Technical material
Trout 106.0 ppm Technical material
2.3.2 Birds
Methoprene is relatively non-toxic to birds. No adverse effects were
found in adult birds in reproductive studies of Bobwhite quail and
Mallard ducks at a dose level of 30 ppm (continuous feeding), no
reproductive nor embryotoxic adverse effects were observed in these
studies.
Dietary studies LC50:
Mallard duck 10 000 ppm Technical material
Bobwhite quail 10 000 ppm Technical material
Chicken 4 640 ppm Technical material
2.3.3 Other species
Methoprene has shown no clear adverse effects in most aquatic
invertebrate organisms. Mayfly naiads and diving beetle populations
declined temporarily at an application rate of 80 g/ha but rapidly
recovered after treatment stopped. Crustaceans have shown the
greatest sensitivity.
LC50 (5-day exposures):
Crayfish 100 ppm Technical material
Fresh water shrimp 100 ppm Technical material
White and pink shrimp 100 ppm Technical material
Methoprene was well tolerated by juvenile Bufo boreas
3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION
OF COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories see Introduction to data sheets).
All formulations, Category 5
3.2 TRANSPORTATION AND STORAGE
Formulations in Category 5 - Should be transported and stored in
clearly labelled, leakproof containers out of reach of children,
away from food and drink. Avoid contact with metals other than
aluminium and tin.
3.3 HANDLING
Formulations in Category 5 - No facilities other than those needed
for the handling of any chemical are required.
3.4 AND/OR DECONTAMINATION OF CONTAINERS
All formulations - Containers need not be decontaminated.
Containers should not be used for other purposes, they should be
burned or should be crushed and buried below topsoil. Care must be
taken to avoid subsequent contamination of water sources.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
Formulations in Category 5 - Warning of workers to minimize
contact is essential. No pre-employment or periodic medical
examinations are required.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations - Pilots and loaders should have special training
in application methods and recognition of early warning symptoms of
poisoning, when using solvent containing formulations. Flagmen
should wear overalls and a broad brimmed hat and be well away from
the dropping zone when using solvent containing formulations.
3.7 LABELLING
Formulations in Category 5 - Minimum cautionary statement
CAUTION
This formulation contains methoprene. Keep the material out of reach
of children and well away from foodstuffs, animal feed and food
containers.
3.8 RESIDUES IN FOOD
Maximum residue limits for methoprene have not yet been recommended
by the joint FAO/WHO Meeting on Pesticide Residues.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General
Methoprene is a fatty-acid derivative of no known health hazard to
man. It may be absorbed from the gastrointestinal tract; through the
intact skin and by inhalation of spray mist.
4.1.2 Manufacture and formulation - TLV
No information. Closed systems and forced ventilation may be
required to reduce, as much as possible, the exposure of workers to
the chemical.
4.1.3 Mixers and applicators
When opening a container and when mixing, protective impermeable
boots, clean overalls, impermeable gloves and a respirator should be
worn. Mixing, if not mechanical, should always be carried out with a
paddle of appropriate length. Avoid contact to mouth and eyes.
Before eating, drinking or smoking, hands and other exposed skin
should be thoroughly washed with alkaline soap.
4.1.4 Other associated workers (including flagmen in aerial
operations)
Persons exposed to methoprene and associated with this application
should wear protective clothing and observe precautions as described
in 4.1.3.
4.1.5 Other populations likely to be affected
With good application practice other populations are not likely to
be exposed to significant amounts of methoprene which is essentially
non-toxic.
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Unprotected persons may enter treated areas immediately after
spraying without being exposed to a health hazard.
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGES
Residues in containers Should be emptied in a diluted form into a
deep pit taking care to avoid ground waters. The empty containers
need not be decontaminated, they should be burned or crushed and
buried below topsoil. Containers should not be used for any other
purposes.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning
No clinical or laboratory signs of toxicity to man or other animals
are known. Methoprene is only slightly toxic to mammals other than
man.
4.4.2 Treatment before a person is seen by a
physician
If a person shows signs of illness from exposure to formulations of
methoprene, supportive therapy should be given.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSTICS AND TREATMENT OF POISONING
5.1.1 General information
Methoprene is an organic acid derivative; a sesquiterpenoid compound
of no known health hazard to man. It may be absorbed from the
gastro-intestinal tract; through the intact skin; and by inhalation
of spray mist. It is readily metabolized via intermediatry metabolic
pathways.
5.1.2 Signs and symptoms
Methoprene is not sufficiently toxic to produce clearly recognizable
clinical and laboratory signs of toxicity in man or other mammals.
5.1.3 Laboratory
No information available.
5.1.4 Treatment
If a person shows signs of illness due to exposure to methoprene
formulations these are most likely due to the solvent, treat
accordingly.
5.1.5 Prognosis
Not applicable since acute poisoning is not expected even with large
ingested doses.
5.1.6 References to previously reported cases
None.
5.2 SURVEILLANCE TEST
None.
5.3 LABORATORY METHODS
References only are given.
5.3.1 Detection and assay of compound and residues -
L. L. Dunahm et al. (1975) J. Chromatogr. Sci.: 13(7), 334-336
L. M. Hunt & B. N. Gilbert (1976) J. Agric. Food Chem.: 24(3),
669-670
W. W. Miller (1975) Environ. Qual. Saf., Suppl.: Vol. 3, ISS
Pesticides, pp. 105-109
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