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Pesticides

Permethrin

Technical Summary

September 2007

INTRODUCTION

Permethrin is one of many synthetic pyrethroids developed for use as an insecticide based on the chemistry of pyrethrum flowers (certain Tanacetum species). It is used in household insect foggers and sprays, flea dips and sprays for cats and dogs, ornamental garden and turf products, repellent/insecticide for clothing, mosquito abatement products, termite treatments, agricultural products, lice shampoos, body lotions for scabies control, and aircraft cabin insect control. Pyrethroid insecticides are some of the most widely used pesticides in the world because they are believed to be less harmful to humans than other pesticides.

Permethrin can be inhaled into the lungs, absorbed through the skin or ingested. The most dangerous route is inhalation, as this allows the chemical to move directly to target sites (e.g., the brain) without being metabolized by the liver and other organs. A more recent exposure route is through clothing impregnated for mosquito repellent.

Permethrin is comprised of two isomers, with the cis isomer being ten times more toxic than the trans isomer. The toxicity of permethrin varies with the trans/cis ratio, which is commonly 60/40 in agricultural use.

Permethrin exerts its primary toxic effects directly on the nervous system. It interferes with normal propagation of the nerve impulse along the axon (the action potential), by prolonging the open-time of sodium channels, thus provoking repetitive after-discharges. Studies in mice and rats show that sub-lethal intoxication leads to aggression, hypersensitivity to external stimulation, whole-body tremor, convulsions, and paralysis.

In an effort to gather information on the potential impact of permethrin on human health, we conducted an extensive search of the scientific literature published in academic journals. This was done through searches of online databases (Web of Science and PubMed) using terms such as ‘permethrin, pyrethrins, and pyrethroids.’ Abstracts were read and studies that were not relevant (e.g., pest control studies), were removed from our list. We then attempted to acquire every article of interest either in hard copy or pdf form. In addition to searching scientific journals, we also viewed government web sites for information such as toxicological reports from the Agency for Toxic Substances and Disease Registry, material safety data sheets (MSDS), and EPA publications. Although it is our goal, we cannot claim to have obtained every piece of relevant information on the topic of interest. Access to publications is sometimes limited, for example, by the date of publication (older articles are more difficult to obtain) or by monetary cost of obtaining the article.

This process resulted in 108 studies on the potential health effects of permethrin. These studies were read, analyzed, and categorized in an Excel spreadsheet (with complete citations), according to the specific health endpoints studied.

SUMMARY

The graph below (Figure 1) shows the number of findings on the most widely researched healthrelated endpoints. Shaded bars indicate whether or not there were significant effects of permethrin, effects only in combination with other chemicals, or no effects.

figure 1

Central and Peripheral Nervous System Effects

The most common finding in studies of the nervous system was a decrease in acetylcholinesterase (AChE) activity. This occurred in the midbrain, brainstem, cerebellum, cerebral cortex, hippocampus, and the hypothalamus. AChE is an enzyme that breaks down acetylcholine at the synaptic cleft, allowing cholinergic neurons to return to their resting state after activation. Without AChE, post-synaptic neurons experience repetitive firing. Various effects on the dopaminergic system were also documented, primarily in the corpus striatum. Molecular/metabolic actions include effects on Ca+ and  Na+ levels, and c-fos and BDNF gene expression in the brain. 

Behavioral Effects

Behavioral studies of rats and mice showed permethrin-induced impairments in balance, strength, and speed. Studies also found reduced response to conditioned behavior, enhanced startle response, and various sensorimotor effects. One study found behavioral effects in the offspring of mice given permethrin prior to mating (transgenerational effects).

Immune System Effects

Every one of the 15 studies that we found on the immune system showed significant effects. This included studies using rats, mice, and in vitro human studies. The most common findings included reduction or inhibited production of thymocytes, T-cells, and lymphocytes. Results indicated that permethrin led to the death and/or reduced production of blood cells necessary to fight bacteria and viruses, and remove waste products from the blood.

Female Reproductive System Effects

Of the seven studies that showed estrogenic effects, four looked at permethrin effects on MCF-7 human breast cancer cells. Results were consistent with research on endocrine disrupting chemicals showing effects, such as cell proliferation, at low doses but not at higher doses.

Effects on the Liver

The most commonly found effects were increased liver weight and increased liver enzyme activity.

DNA Effects

Several effects on the DNA of mice, rats, and humans are reported, including strand breakage, DNA fragmentation, chromosomal aberrations, and other individual study findings.

Effects on the Blood

Studies of the effects of permethrin on the blood showed decreases in mean cell volume, increases in bone marrow cell count and various specific effects on red blood cells.

Skin Effects

Five of the eight studies of the effects of permethrin on the skin were done in combination with other chemicals, including the insect repellent DEET. Various effects were found, including increased or decreased skin absorption and diminished cutaneous immunity. Studies of permethrin alone found diminished immunity, paraesthesia (prickling/tingling), and dysaesthesia (abnormal sensations).

Male Reproductive System Effects

One study of permethrin and the male reproductive system found reduced tissue weight in the prostate, seminal vesicles, penis, and Cowper’s gland of the rat. A recent study of cis-permethrin showed reductions in sperm count and motility, reduced testosterone levels, and cell damage. Two studies looking at permethrin in combination with DEET found mechanisms at the cellular level that could explain the results of the above studies.

Respiratory System Effects

Of the three studies that looked at the health effects of permethrin following inhalation, one found no effects (in the guinea pig), one found genotoxic effects in in vitro human mucosal cells, and one found a slight elevation in benign lung tumors in mice.

Effects on the Heart

We found two in vitro studies on the heart. One showed molecular effects on the bovine heart tissue and one showed impaired cell viability on the smooth muscle of the rabbit heart.

A Note on Cancer

Very few studies have been performed in recent years on the cancer-causing potential of permethrin. A 1994 review by the U.S. Army concluded that permethrin is a “possible human carcinogen” based on early studies in rodents. In 2006 the EPA also classified permethrin as “likely to be carcinogenic in humans,” based on mouse studies showing evidence of lung and liver tumors related to permethrin.

COMMENTS

The overall pattern shown in Figure 1 reveals a broad range of possible health effects of permethrin. Notably, permethrin appears to exhibit the characteristics of an endocrine disruptor, based on effects found in the female and male reproductive systems. Endocrine disruptors are chemicals that interfere with the communication system of glands, hormones and cellular receptors that control how the body is constructed from conception to birth, and how it functions throughout life. The classic pattern of endocrine disruptors is that they show adverse effects at extremely low doses, even when higher doses show no effects. Disorders that have increased in prevalence in recent years such as unusual male gonadal development, infertility, ADHD, autism, intellectual impairment, diabetes, thyroid disorders, and childhood and/or adult cancers are now being linked to prenatal exposure to endocrine disruptors. In addition, the studies that demonstrated impairment of white cell production (thymocytes, T-cells, and lymphocytes) cannot be ignored in light of the increasing prevalence of immune and autoimmune disorders such as multiple sclerosis, lupus, Crohn’s disease, Type 1 diabetes, and rheumatoid arthritis. In sum, permethrin exists in our homes, on our food, where we work and where we play, and now even in the clothing we wear. Its effects are not immediately obvious, making it appear harmless. However, like many other chemicals we have learned not to fear, it has the potential to cause long term damage to critical systems, including the developing systems of our children. People who are particularly susceptible to the effects of permethrin include children, pregnant women, and people with compromised immune systems or liver problems. Until research proves otherwise, we must be aware of, and use caution, in exposing ourselves to the potential harm caused by permethrin.