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. PermethrinÂ’s mode of action is similar to that of the organochlorine insecticide DDT.5
Acute Lethal Dose
PermethrinÂ’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