The insecticide permethrin (in the synthetic pyrethroid family) is widely used on cotton, wheat, corn, alfalfa, and other crops. In addition, over 100 million applications are made annually in and around U.S. homes.
Permethrin, like all synthetic pyrethroids, is a neurotoxin. Symptoms include tremors, incoordination, elevated body temperature, increased aggressive behavior, and disruption of learning. Laboratory tests suggest that permethrin is more acutely toxic to children than to adults.
The U.S. Environmental Protection Agency has classified permethrin as a carcinogen because it causes lung tumors in female mice and liver tumors in mice of both sexes. Permethrin inhibits the activity of the immune system in laboratory tests, and also binds to the receptors for a male sex hormone. It causes chromosome aberrations in human and hamster cells.
Permethrin is toxic to honey bees and other beneficial insects, fish, aquatic insects, crayfish, and shrimp. For many species, concentrations of less than one part per billion are lethal. Permethrin causes deformities and other developmental problems in tadpoles, and reduces the number of oxygen-carrying cells in the blood of birds.
Permethrin has been found in streams and rivers throughout the United States. It is also routinely found on produce, particularly spinach, tomatoes, celery, lettuce, and peaches.
A wide variety of insects have developed resistance to permethrin. High levels of resistance have been documented in cockroaches, head lice, and tobacco budworm.
BY CAROLINE COX
Caroline Cox is JPR’s editor.
Permethrin is used to kill pest in-sects in agriculture,
home pest control, forestry, and in public health programs, including head
lice control. It was first marketed in 1973. Worldwide, the dominant use
of permethrin is on cotton, accounting for about 60 percent (by weight)
of the permethrin used.1 In the U.S., al-most
70 percent of the permethrin used in agriculture is used on corn, wheat,
and alfalfa.2 Over 100 million applications
of permethrin are made each year in U.S. homes, and over 18 million applications
are made in yards and gardens.3
Permethrin is a synthetic pyrethroid. Like most
members of this family of insecticides, it has four isomers, molecules
made up of the same atoms with different three-dimensional structures.
(See Figure 1)
Mode of Action
Permethrin, like all synthetic pyrethroids, kills
insects by strongly exciting their nervous systems. Permethrin makes the
nervous system hypersensitive to stimuli from sense organs. Rather than
sending a single impulse in response to a stimulus, permethrin-exposed
nerves send a train of impulses. This excitation occurs because permethrin
blocks the movement of sodium ions from outside to inside of the nerve
cells. Permethrin’s mode of action is similar to that of the organochlorine
insecticide DDT.5
Acute Lethal Dose
Permethrin’s LD50 (the amount
of permethrin that kills 50 percent of a population of test animals) is
variable. In a summary of nine oral LD50 tests using
rats, the LD50 varied from 430 milligrams per kilogram
of body weight (mg/kg) to over 4,000 mg/kg. Some of this variability occurs
because the proportions of isomers in the test materials vary. The cis
isomers are about ten times more toxic than the transisomers.6
Neurotoxicity
In mammals, permethrin has complex effects on the
nervous system. As in insects, it causes repetitive nerve impulses. It
also inhibits a variety of nervous system enzymes: ATPase, whose inhibition
results in increased release of the neurotransmitter acetylcholine 7;
monoamine oxidase-A, the enzyme which maintains normal levels of three
other neurotransmitters 8; and acetylcholinesterase,
the enzyme that breaks down acetylcholine.9
(Two large families of insecticides, the organophosphates and the carbamates,
are acetylcholinesterase inhibitors.) In addition, permethrin inhibits
a nervous system receptor, the GABAA receptor, producing
excitability and convulsions.10
Finally, permethrin inhibits respiration (the process by which cells use
sugars as an energy source) in a manner similar to other neurotoxic drugs.11
It is therefore not surprising that permethrin causes a wide variety of
neurotoxic symptoms.
At relatively high doses, these neuro-toxic symptoms
of permethrin include tremors, incoordination, hyperactivity, paralysis,
and an increase in body temperature. These symptoms can persist up to three
days.12 Other behavioral effects have been observed
at lower doses. For example, sublethal exposure of mice to the permethrin-containing
insecticide Ambush increased activities like chewing 13
; sublethal exposure of rats to permethrin increased aggressive behavior,
agitation, and resistance to being captured 14 ; and
permethrin disrupted a learned feeding behavior in rats at doses of about
20 percent of the LD50. 15
Eye and Skin Irritation
Permethrin-containing products can be irritating
to both eyes and skin. For example, the agricultural insecticide Pounce
3.2 EC “causes moderate eye irritation.”16
Ortho Total Flea Control 2 and Solaris Flea-B-Gon Total Flea Killer Indoor
Fogger both cause “tearing, swelling, and blurred vision.”17,18
They also cause “redness, swelling, and possibly blistering” of the skin.17,18
Adams 14 Day Flea Dip “causes eye injury”19 and
“may cause al-allergic reactions”19 on
skin.
Effects on the Immune System
Experiments with laboratory animals indicate that
the immune system (used by living things to defend themselves from disease)
“appears to be a sensitive target for permethrin activity.” Ingestion of
permethrin reduces the ability of immune system cells called T-lymphocytes
to recognize and respond to foreign proteins. Doses equivalent to 1/100
of the LD50 , inhibited T-lymphocytes over 40 percent.
Permethrin ingestion also reduced the activity of a second type of immune
system cell, natural killer cells, by about 40 percent.20(See Figure
2.) In tests using mouse cell cultures, permethrin had similar effects
on the immune system, inhibition of two kinds of lymphocytes.21
Researchers concluded that “the immune system is exquisitely sensitive
… at exposure levels that cause no overt toxicity.”20
Effects on Reproduction
Permethrin affects both male and female reproductive
systems. It binds to receptors for androgen, a male sex hormone, in skin
cells from human males, causing researchers to “advise protection from
any form of contact or ingestion of the pyrethroids.”
22 Permethrin also binds to a different receptor,
called the peripheral benzodiazepine receptor, that stimulates production
of the male sex hormone testosterone.23
In addition, permethrin caused reduced testes weights in a long-term feeding
study of mice.24 In females, permethrin exposure
has caused embryo loss in pregnant rabbits24
and in pregnant rats.25
Mutagenicity
Permethrin was mutagenic (damaging to genetic material)
in three tests with human cell cultures, one with hamster cells, and one
with fruit fly larvae. In cultures of human lymphocytes (white blood cells),
permethrin exposure caused an increase in chromosome aberrations, chromosome
fragments,26 and DNA lesions.27
In hamster ovary cell cultures, permethrin exposure caused chromosome aberrations.28
Exposure to Ambush (a permethrin-containing insecticide) during larval
development increased sex-linked lethal mutations in fruit flies.29
Carcinogenicity
According to the U.S. Environmental Protection Agency
(EPA), permethrin is a possible human carcinogen (chemical that causes
cancer).30 EPA found that permethrin increased
the frequency of lung tumors in female mice, and increased the frequency
of liver tumors in male and female mice.24
The World Health Organization reports that permethrin increased the frequency
of lung tumors in females in two out of the three mouse studies it reviewed.
(See Figure 3.) Lung tumors
increased with increasing permethrin exposure in the third study, but the
increase was not statistically significant.31
There are no publicly available studies of the carcinogenicity
of permethrin-containing insecticide products.
There are two molecular mechanisms which could explain
permethrin’s carcinogenicity. First, permethrin reduces the activity of
an enzyme involved in the breakdown of the amino acid tryptophan. This
can lead to the buildup of carcinogenic tryptophan breakdown products.32
Second, permethrin inhibits what is called “gap junctional intercellular
communication” (GJIC), chemical communication between cells. GJIC plays
an important role in the growth of cells, and some cancer promoting chemicals
inhibit GJIC.33
Other Chronic Effects
The liver is a sensitive target for permethrin effects. When EPA summarized
17 medium- and long-term laboratory studies that exposed rats, mice, and
dogs to permethrin, effects on the liver were noted at the “lowest effect
level” in all of them.24 Other chronic
effects in laboratory tests include enlarged adrenal glands at all doses
tested in a rabbit feeding study, and increased kidney weights at all doses
tested in a rat feeding study.24
Synergy
Synergy occurs between two or more chemicals when
their combined exposure causes more adverse effects than the sum of their
individual effects. A possible cause of the health problems reported by
30,000 veterans who served in the Persian Gulf War is exposure to a combination
of chemicals, including permethrin. The combination of permethrin, the
anti-nerve gas drug pyridostigmine bromide, and the insect repellent DEET
has been tested in laboratory animals. Neurotoxic symptoms, including decreased
activity, diarrhea, shortness of breath, tremors, inability to walk, and
damage to nerves, were observed in hens exposed to all three chemicals,
but not in hens exposed to permethrin alone. Permethrin with just pyridostigmine
bromide or just DEET also caused tremors and inability to walk, but symptoms
were not as severe.35
Other pesticides interact synergistically with permethrin
with in other species. Permethrin and the herbicide atrazine synergistically
induce growth of the soil fungus Pythium ultimum, 36
and permethrin and the insecticide amitraz are synergistically toxic to
the bollworm.37
Individual Susceptibility
Individuals vary in their susceptibility to permethrin, as has been
illustrated by the following research:
Beneficial Arthropods: As a broad spectrum insecticide, it is not surprising that permethrin impacts beneficial arthropods, those that are useful in agriculture. Examples include the following:
Birds: While permethrin’s acute toxicity to birds is low,50 it causes other ad-verse effects. Three-week dietary exposure of chickens reduced hemoglobin (oxygen carrying protein) levels, and red blood cell counts, while increasing the number of white blood cells.51 The reduction in hemoglobin occurred at the lowest dose tested, 33 mg/kg.51 Permethrin also caused decreased immune responses in chicks,52 and damaged mallard ovaries.53
Fish: Permethrin is highly toxic to fish.
This toxicity is due, in part, to the sensitivity of their nervous system.54
Fish also lack the enzymes that break down permethrin in other animals.55
The LC50 (the concentration
that kills 50 percent of a population of test animals) is less than 1 part
per million (ppm) for almost all fish species tested, and for some fish
is less than 1 part per billion (ppb). Agricultural permethrin products
called emulsifiable concentrates are about twice as toxic to fish as permethrin
alone. Small fish are less tolerant of permethrin than large fish, and
it is more toxic in cold water than in warm water.56
Fish also have a particular developmental stage when they are most susceptible.57
Sublethal effects on fish include abnormal swimming,
a reduced startle response, and loss of equilibrium.58
Permethrin bioconcentrates in fish, so that concentrations
in fish are higher than the concentration in the water in which the fish
live. Bioconcentration factors (the ratio between the concentration in
the fish and the concentration in the water) up to 113 have been measured
in brook trout,59
up to 613 in Atlantic salmon,59 and up
to 631 in rainbow trout.60
Complex effects of permethrin on fish have been
documented by the Canadian Forest Service in field studies. They found
that diets of trout and salmon were altered when permethrin killed the
insects these fish use as food. In some cases, diets were altered for a
year following treatment. Reductions in fish growth rates, and migration
to untreated areas followed; recovery required four months. The researchers
concluded that permethrin is “not an acceptable treatment for large-scale
use in forest areas containing fish-producing
water.”61
Amphibians: Permethrin disrupts the
growth and development of tadpoles. Exposure slowed growth for two to three
weeks, and increased the frequency of a tail abnormality. (See Figure
5.) The increase in this deformity occurred at the lowest concentration
of permethrin tested, 0.1 ppm. At this concentration tadpoles also responded
to prodding in a jerky and disorganized way, making them vulnerable to
predation. Tadpoles exposed to an even lower concentration (0.05 ppm) reduced
their feeding for several weeks after exposure.62
Permethrin also effects brain function in tadpoles.
Concentrations of 0.25 ppm decreased the amounts of two specific proteins
in the brain, while increasing the total amount of protein. One of the
proteins is associated with learning. Activity of several nervous system
enzymes, including acetylcholinesterase, decreased.63
Other Aquatic Animals: Permethrin
is very highly toxic to lobster; the LC50
is less than 1 ppb.64 It is highly toxic
to oyster larvae, with an EC50 (the concentration
causing abnormal development in half of the larvae) of less than 1 ppm.65
Permethrin bioconcentrates in oysters, with a bioconcentration factor of
1900. 66 Water fleas are also very sensitive
to permethrin exposure; LC50s of several
species are about 1 ppb.67 Permethrin
also caused “severe mortalities” of two kinds of zooplankton, cladocerans
and copepods with recovery taking about 3 months.68
Mysid shrimp are killed by permethrin at concentrations
so low that they cannot be detected in water (the LC 50 is 0.02 ppb). This
means that “any detection of these insecticides in estuarine waters would
likely be associated with adverse effects.”66
Another animal that is very sensitive to permethrin is crayfish; LC50s
for the red swamp crayfish vary from 0.4 to 1.2 ppb. Researchers concluded
that “even the lowest operational treatment level used for insect management
would seriously impact crayfish populations.”67
Residues on Food
The Food and Drug Administration’s (FDA’s) monitoring
program routinely finds permethrin on food. In 1996, it was the 13th most
commonly detected pesticide.68 Similar
results were found in monitoring of 14 fruits and vegetables by the U.S.
Department of Agriculture; permethrin was the 10th most frequently detected
pesticide and was often found on spinach (60 percent of the samples tested)
and tomatoes (11 percent of the samples tested).69 Permethrin was also
frequently found on celery and lettuce.70
Permethrin has also been found in baby food: FDA’s
1996 monitoring found it in 12 percent of the samples tested. The Environmental
Working Group found permethrin was the most commonly detected pesticide
in peach baby food (44 percent of the samples tested) and was also found
in plums (11 percent of the samples tested).71
Contamination of Water
Permethrin has been found in ground and surface
water. The U.S. Geological Survey has found permethrin in streams and rivers
in the Mississippi River Basin, 72 the
Central Columbia Plateau (Washington and Idaho),73 the Georgia-Florida
Coastal Plain,74 the San Joaquin-Tulare
Basin (California),75 and the Ozark Plateau
(Arkansas and nearby states).76 Permethrin
has also been found in groundwater in Virginia.76
Drift
Drift, pesticide movement during application away
from the target area, has been measured for two types of permethrin applications:
aerial and back pack mistblower. Aerially applied permethrin drifted 180-240
meters (590- 790 feet) under conditions “highly conducive” to drift.78
These researchers sug-gested using buffers of 150 meters (490 feet). Back
pack mistblower applications of permethrin drifted 150 meters.79
Persistence
According to EPA, permethrin’s half-life (the amount
of time required for half of the original amount of a chemical to break
down or move away from the study site) was 17 days in a North Carolina
agricultural soil and 43 days in Illinois.80
When used as a termiticide, permethrin persists longer; soil concentrations
did not decline during the first year.81
Permethrin also persists longer in tree needles, foliage, and bark, up
to 363 days.82 The ability of permethrin
to persist in the environment was graphically illustrated by a study of
an application of permethrin ear tags to cattle. Permethrin was found on
all surfaces analyzed, not only on the cattle, but also on the bark of
trees in their pasture, on a fence pole, and in grass. Some residues were
found three months after the ear tags were applied.83
Resistance
Resistance (the evolution of a strain of insect that is able to tolerate
a particular insecticide) to permethrin has been documented in a wide variety
of insects. These species include pear psylla,84fall
army-worm, 85 German cockroach,86
spotted tentiform leafminer,87 diamondback
moth,88 house fly,89
stable fly,90 head lice,91-93
and tobacco budworm.94 Many
of these species are resistant to other synthetic pyrethroids as well as
permethrin. The level of resistance is less than tenfold in some of the
species but high levels of resistance have been observed in cockroaches
(45-fold),86lice (up to 385-fold)91
and budworm (1400-fold).94
Inert
Ingredients
Like most pesticide products, permethrin insecticides contain ingredients
that are typically claimed as trade secrets by pesticide manufacturers.
Limited information about “inerts” in permethrin products is available.
Examples include:
COALITION FOR ALTERNATIVES TO PESTICIDES/NCAP
P. O. B O X 1 3 9 3, E U G E N E, O R E G O N 9 7 4 4 0 /
(5 4 1 )3 4 4 -5 0 4 4
JOURNAL OF PESTICIDE REFORM/ SUMMER 1998 - VOL.18, NO. 214l
I N S E C T I C I D E F A C T S H E E T
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