Health Risks Linked to Pyrethroids

A review of the study, "Subchronic Dermal Application of N,N-Diethyl m-Toluamide (DEET) and Permethrin to Adult Rats, Alone or in Combination, Causes Diffuse Neuronal Cell Death and Cytoskeletal Abnormalities in the Cerebral Cortex and the Hippocampus, and Purkinje Neuron Loss in the Cerebellum," which was published in Experimental Neurology, Volume 172, November 2001.

Functional impairment of blood-brain barrier following pesticide exposure during early development in rats.

Study of Insecticide Neurotoxicity Yields Clues to Onset of Parkinson's Disease

BLACKSBURG, Va., March 24, 2003 -- A grant from the U.S. Army has led Virginia Tech researchers to discover that exposure to some insecticides may cause a cascade of chemical events in the brain that could lead to Parkinson's Disease.

Jeffrey R. Bloomquist, a neurotoxicologist and associate professor in the university's Department of Entomology, described his findings as part of the International Award for Research in Agrochemicals, a symposium honoring Robert M. Hollingworth, at the annual meeting of the American Chemical Society in New Orleans this week.

"We found low-level exposures set in motion a process with an early onset that develops slowly and is persistent," Bloomquist said. "More surprising is that high-level exposures resulted in few immediate effects that we could observe, but in the longer term there was a delayed effect."

The Virginia Tech researchers studied the levels of dopamine, dopamine transporter protein expression, and the levels of a synaptic protein (alpha-synuclein) in mice exposed to various doses of the insecticide permethrin. The increase in dopamine uptake indicated the mouse's system was reacting to a neurochemical insult caused by the presence of the insecticide. The slow response to high levels of exposure to pesticides is caused, Bloomquist thinks, to the system being overloaded and only after a period of a few weeks is it capable of responding to the insult in the same way as low doses.

In some individuals, dopamine-producing neurons may be challenged by genetic factors or by previous exposure to other neurotoxins. For individuals with a genetic predisposition, exposure to permethrin may trigger chemical events in the brain that result in an increased risk for damage to the area of the brain that is selectively damaged in Parkinson's disease.

The loss of motor skills, resulting in symptoms such as muscle rigidity, shuffling gait, and a rhythmic tremor, has been linked to the loss of dopamine production in the brain. That loss of dopamine is the major neurochemical expression of Parkinson's Disease.

"Our studies have documented low-dose effects of permethrin, doses below one-one thousandth of a lethal dose for a mouse, with effects on those brain pathways involved in Parkinson's Disease," he said. "We have found effects consistent with a pre-parkinsonsian condition, but not yet full-blown parkinsonism."

Bloomquist also found permethrin exposure resulted in an overproduction of the protein alpha-synuclein at low doses. The accumulation of the protein is a major component of the formation of the Lewy bodies, fibrous tangles observed in the brains of patients with Parkinson's Disease.

The studies so far have concentrated on two-week exposures in mice. Bloomquist hopes to continue the work, looking at longer-term exposure. He is also studying the effects of another widely used pesticide, chlorpyrifos.

Bloomquist and his co-investigator, Dr. Bradley Klein, are supported by a five year, $584,558 grant from the United States Army Medical Research and Materiel Command. One purpose of the Neurotoxin Exposure Treatment Research Program, under which the project was funded, is to determine if military operational and deployment exposures increase risks for neurodegenerative disease and, if so, determine means of protecting troops.

"Permethrin is used worldwide in agriculture and urban settings," Bloomquist said. "Widespread human exposure to this compound occurs, so its effects are not limited to soldiers."

Medical studies indicating health hazards from pyrethroid pesticides

Sumithrin (Anvil), Resmethrin (Scourge) and Permethrin belong to a class of pesticides known as synthetic pyrethroids. Pyrethroids are closely related to each other and therefore the following studies may relate to pyrethroids generally, not just the chemical(s) focused on in a particular study.

Links between pyrethroids and breast cancer

The link between pyrethroids and breast cancer is not proven much more research is needed in this area. But several studies indicate pyrethroids disrupt the endocrine system by mimicking the effects of the female hormone estrogen. This in turn can cause breast cancer in women and lowered sperm counts in men. When estrogen levels are elevated, old cells are not removed from the body and cell proliferation occurs, whether benign or malignant.

This study examined four pyrethroid pesticides. It concludes that the "studies imply that each pyrethroid compound is unique in its ability to influence several cellular pathways. These findings suggest that pyrethroids should be considered to be hormone disruptors, and their potential to affect endocrine function in humans and wildlife should be investigated." [Environmental Health Perspectives, Vol. 107, No. 3, March 1999, pages 173-177.]

This study on pyrethroids concludes ³Chronic exposure of humans or animals to pesticides containing these compounds may result in disturbances in endocrine effects.² [Journal of Steroid Biochemistry, March 1990; 35(3-4): 409-14.]

A report issued in June 2000 by the Royal Society in England and written by a group from Cambridge University called for international cooperation to deal with the dangers posed by endocrine-disrupting chemicals, including pyrethroids, and recommends reducing human exposure to these chemicals.

Synergistic effects on endocrine disruptions

This study, conducted by six scientists at three Tulane medical institutions, suggests that combinations of chemicals could have much greater effect than the individual chemicals would on their own, even when an individual chemical has relatively low potential for endocrine disruption by itself. The study found "The synergistic interaction of chemical mixtures with the estrogen receptor might have profound environmental implications. These results may represent a previously uncharacterized level of regulation of estrogen-associated responses." ["Synergistic Activation of Estrogen Receptor with Combinations of Environmental Chemicals," Science Magazine.]

Links between pyrethroids and childhood brain cancers

A study of pesticides and childhood brain cancers has revealed a strong relationship between brain cancers and compounds used to kill fleas and ticks, according to a report published in Environmental Health Perspectives. The study concludes "The specific chemicals associated with children's brain cancers were pyrethrins and pyrethroids (which are synthetic pyrethrins, such as permethrin, tetramethrin, allethrin, resmethrin and fenvalerate) and chlorpyrifos (trade name: Dursban)." [Janice M. Pogoda and Susan Preston-Martin, "Household Pesticide sand Risk of Pediatric Brain Tumors," Environmental Health Perspectives, Vol. 105, No. 11 (November 1997), pages 1214-1220.] The EPA, in June 2000, halted sales of Dursban.

Links between pyrethroids and neurological damage

This study, conducted by the Physiological Institute at Ludwig Maximilians University in Munich, Germany, found that although "a majority of complaints following an acute pyrethroid intoxication disappeared after the end of exposure," several effects were still seen in patients after more than two years. Among these long-term symptoms were "(1) cerebro-organic disorders (reduced intellectual performance with 20%-30% reduction of endurance during mental work, personality disorder), visual disturbances, dysacousia, tinnitus; (2) sensomotor-polyneuropathy, most frequently in the lower legs; (3) vegetative nervous disorders," including increased heat-sensitivity and reduced exercise tolerance due to circulatory disorder. The study concludes "Many of these patients exhibit pathological autoimmune diagnostical findings and developed autoimmune diseases." [Toxicology Letters 1999 June 30; 107(1-3): 161-76.]

This study, conducted by the Department of Environmental Toxicology at Uppsala University in Sweden studied mice, not humans, but found that "low-dose exposure" to pyrethroids resulted in "irreversible changes in adult brain function in the mouse" when exposed during the growth period. This occurred at levels of exposure less than what was found to affect adult mice. The study also found "neonatal exposure to a low dose of a neurotoxic agent can lead to an increased susceptibility in adults to an agent having a similar neurotoxic action, resulting in additional behavioral disturbances and learning disabilities." [Neurotoxicology 1997; 18(3): 719-26.]

A series of investigations conducted at Northwestern's Department of Molecular Pharmacology and Biological Chemistry in Chicago, has found neurological damage from pyrethroids. One study, conducted by international expert Toshio Narahashi, finds nervous-system damage from pyrethroids to be comparable to DDT. This study found that "Detailed voltage clamp and patch clamp analyses have revealed that pyrethroids and DDT modify the sodium channel to remain open for an extended period of time." The result of this damage is "potent effects on the nervous system." ["Nerve membrane ion channels as the target site of environmental toxicants," Environmental Health Perspectives, 1987 April;71:25-9.]. A separate study found that pyrethroids cause "membrane depolarization, repetitive discharges and synaptic disturbances leading to hyperexcitatory symptoms of poisoning in animals." This study found that only 1% [Pharmacol Toxicol 1996 July; 79(1): 1-14.]

Links between pyrethroids and thyroid damage

A study conducted by four scientists on a variety of pesticides found a connection to thyroid damage, although this study was conducted on rats and not on humans. The study concludes "exposure to organochlorine, organophosphorus, and pyrethroid insecticides for a relatively short time can suppress thyroid secretory activity in young adult rats." The study also said a decrease in body weight seen "suggests that pyrethroid insecticides can inhibit growth rate." [Journal of Applied Toxicology, Vol. 16, No. 5, pages 397-400, 26 references, 1996.]

Maryland Pesticide Network

DEET and Permethrin: A Dangerous Combination.