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. Permethrins mode of action
is similar to that of the organochlorine insecticide DDT.5
Acute Lethal Dose
Permethrins 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 injury19 and may cause
al-allergic reactions19 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 permethrins
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