Permethrin

General

Permethrin, like all synthetic pyrethroids, is a neurotoxin.

Permethrin is used against a variety of pests, on nut, fruit, vegetable, cotton, ornamental, mushroom, potato, and cereal crops. It is used in greenhouses, home gardens, and for termite control. It also controls animal ectoparasites, biting flies, and cockroaches. It may cause a mite build-up by reducing mite predator populations!!
From: http://extoxnet.orst.edu/pips/permethr.htm

General effect

Permethrin is a neurotoxin to mammals as well. Symptoms include tremors, incoordination, elevated body temperature, increased aggressive behaviour, hyperactivity, and disruption of learning.
At relatively high doses, these neurotoxic symptoms of permethrin include paralysis. These symptoms can persist up to three days (International Programme on Chemical Safety. 1989).

Permethrin kills insects by strongly exciting their nervous systems. Rather than sending a single impulse in response to a stimulus, permethrin-exposed nerves send a train of impulses, similar to that of the organochlorine insecticide DDT (Vijverberg et al 1990). Membrane ATPases are a target of the neurotoxic effect of pyrethroid compounds (Kakko I et al 2003) which could explain the effect on the immune apparatus (Grosman N et al. 2005) (all found for rats).
Permethrin is a potent inhibitor of the mitochondrial complex ( Gassner, B. et al. 1997) and generates as such a wide variety of symptoms in rats.
In addition, permethrin inhibits a nervous system receptor, the GABAA receptor, producing excitability and convulsions ( Ramadan, A,A, et al. 1988).

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.

Chemistry

		Permethrin is a synthetic pyrethroid. Pyrethroid (pyrethrum) is a botanical insecticide for centuries extracted from chrysanthemum flowers, known as pyrethrum daisies (tropical flower).
Permethrin

Ban

Permethrin is banned as crop protector in the European Union (Directive 2000/817/EG European Commission december 27 2000).
The U.S. Environmental Protection Agency (EPA) has classified permethrin as a carcinogen because it causes lung tumours in female mice and liver tumours in mice of both sexes.

Research

DNA

In cultures of human lymphocytes (white blood cells), permethrin exposure caused an increase in chromosome aberrations, chromosome fragments, DNA lesions (Barrueco, C. et al. 1992, Surrallés, J. et al. 1995, Undeger U, Basaran N. 2005) and in hamster ovary cell cultures, permethrin exposure caused chromosome aberrations too (Barrueco, C. et al. 1994).

Cancer

The U.S. Environmental Protection Agency has classified permethrin as a carcinogen because it causes lung tumours in female mice and liver tumours in mice of both sexes ( U.S. EPA. 1997, U.S. EPA. Office of Pesticide Programs. Health Effects Division. 1997).
The onset of the development of human malignant breast tumours is associated with permethrin (Kasat K, et al 2002, Kakko I et al 2004).

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 build-up the level of carcinogenic tryptophan breakdown products ( El-Touky, M.A. 1989).
Second, permethrin inhibits what is called ‘gap junctional intercellular communication’ (GJIC), so the chemical communication between cells. GJIC plays an important role in the growth of cells, and some cancer promoting chemicals inhibit GJIC ( Tateno, C. et al. 1993).

Reproduction

Permethrin affects both male and female reproductive systems (Eil C. et al 1990). Permethrin might have estrogen-like effects on female rats, but antiandrogen-like effects on males (Kim SS et al 2005).

In addition, permethrin caused reduced testes weights in a longterm feeding study of mice (U.S. EPA. Office of Pesticide Programs. Health Effects Division. 1997).
Permethrin and the metabolite 3-phenoxybenzoic acid (3-PBA) displays antiandrogenic activity (Sun H, et al 2007).
Permethrin also binds to the peripheral benzodiazepine receptor, that stimulates production of the male sex hormone testosterone. (Ramadan, A.A. et al. 1988).
Permethrin may cause mitochondrial membrane impairment in Leydig cells and disrupt testosterone biosynthesis by diminishing the delivery of cholesterol into the mitochondria and decreasing the conversion of cholesterol to pregnenolone in the cells, thus reducing subsequent testosterone production (Zhang SY et al 2007).

Permethrin has a chemical structure that interacts with the cellular estrogen receptor (McCarthy AR et al 2006).
Permethrin inhibits the estradiol metabolism in the liver (Usmani KA, et al 2006).

Pesticide-induced injury (permethrin) can occur very early in development (mice, rats, rabbits) ( Spencer, F. et al 1982, Greenlee AR et al 2004, U.S. EPA. Office of Pesticide Programs. Health Effects Division. 1997); Permethrin exposure has caused embryo loss in pregnant rabbits (U.S. EPA. Office of Pesticide Programs. Health Effects Division. 1997) and in pregnant rats ( Spencer, F. and Z. Berhane. 1982).

Immune system

Permethrin ingestion reduces, already at a low dose, the ability of T-lymphocytes to recognize and respond to foreign proteins and reduces the activity of natural killer cells. In tests using mouse cell cultures, permethrin had similar effects on the immune system: Inhibition of two kinds of lymphocytes (Blaylock, R.L. et al. 1995, Stelzer, K.J. et al. 1984).

Topical permethrin exposure produces systemic immune effects in mice. Permethrin decreased thymic weight and cellularity. A single topical dose of permethrin also depressed the splenic T-cell proliferative response to mitogen, the splenic macrophage hydrogen peroxide production, and splenic B lymphocyte-specific antibody production (Punareewattana K et al 2001, Prater MR et al 2002, Prater MR et al 2003, Prater MR et al.2005). Institóris L et al (2001) and Olgun S et al (2004) state that permethrin is a potent immunotoxicant.

Behaviour, brain

In mammals, as well in insects, permethrin inhibits a variety of nervous system enzymes: ATPase, whose inhibition results in increased release of the neurotransmitter acetylcholine (Al-Rahji, D.H. 1990, Kakko I et al 2003) and permethrin inhibits monoamine oxidase-A, the enzyme which maintains normal levels of three other neurotransmitters (Rao G.V. et al 1993.); And finally permethrin inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine ( Rao, G.V. et al 1995).

DOPAMINE

A low dose of permethrin can reduce the amount of dopamine transporter immunoreactive protein in the caudate-putamen (in mice brain) (Karen DJ et al 2001, Bloomquist JR et al 2002, Gillette JS 2003, Pittman JT et al 2003).
Permethrin increases the levels of dopamine transporter (DAT) protein in the striatum of mice, which may render neurons more vulnerable to toxicant injury (Gillette JS et al 2003, Elwan MA et al 2005).
The affected dopaminergic neurotransmission caused a decrease in open field behaviour (mice) (Karen DJ et al 2001).

DYSFUNCTIONAL BEHAVIOUR

Sublethal exposure of rats to permethrin increased aggressive behaviour, agitation, resistance to being captured (McDaniel, K.L. et al 1993); ) and disrupted a learned feeding behaviour in rats ( Peele, D.B. and K.M. Crofton. 1987).
Insecticides like permethrin may well be linked to Parkinson's disease (Karen DJ et al 2001, Pittman JT et al 2003).

BRAIN METABOLISM

Permethrin stimulates the uptake of glutamate in rat cortical synaptic vesicles, the brain stem (Hudson PM et al 1986, Vaccari A et al 1998) but Wu J. (1999) found the opposite.
Permethrin induces a dose dependent decrease in the serum levels of thyroid hormones T4, T3, fT4 and fT3 and an increase in the serum TSH levels. Permethrin treatment reduced both the levels of T4 and T3 in homogenates of the cerebral cortex and hippocampus (Wang S et al 2002).
In vitro, Permithrin had no significant effects on the activity of GABAT (gamma-aminobutyric acid transferase) in rat brain; in vivo!!!, permethrin may have different effects on the activity of GABAT in rat brain, which deserve further study (Ji ZY, et al 2003).

DEVELOPMENT

Activity-dependent gene expressions in cerebellar neuronal cells can be repressed by permethrin both in vitro and in vivo, and suggest that lactational exposure to pyrethroids (permethrin) might affect the postnatal development of the mammalian brain (rat pups). (Imamura L et al 2002).
Permethrin can induce a significant risk to the offspring following treatment of F0-mice before mating. Significant differences in the development of reflexes, swimming ability, and open field activity were evident in the offspring (Farag AT et al 2006).

Synergism

Permethrin exposure has been linked to both Parkinson’s disease and Gulf War illness (Plapp Jr FW 1999, Karen DJ et al 2001).

One contributing factor to the emergence of such symptoms may be the simultaneous exposure to multiple agents, impregnated in soldiers' uniforms used to protect their. In particular, the anti-nerve agent pyridostigmine bromide, the insect repellent DEET, and the insecticide permethrin.
Of the three-quarters of a million service personnel involved in the Persian Gulf War, approximately 30,000 (4%) have complained of neurological symptoms of unknown aetiology (Abou-Donia MB et al 1996).

Numerous tests do support the conviction that the combination of permethrin and DEET is disastrous. Test animals were hens (neurotoxic) (Abou-Donia MB et al 1996) and rats.
There was an altered metabolim of cortisol (Abu-Qare AW et al Nov 2001), increased levels of oxidative stress were demonstrated (Abu-Qare AW et al april 2001) and killed rat brain cells (Abu-Qare AW et al Jun 2001). Also were seen: Different behaviour, disruption of the BBB (blood brain barier), decreased m2 muscarinic acetylcholine receptor ligand binding density in rat brain and altered sensorimotor and locomotor activities (Abu-Qare AW et al 2003). So significantly slower locomotion rate and lowered thigmotaxis (remaining in the ‘center zone’) (Hoy JB et al 2000 a, Hoy JB et al 2000 b).

Together with pyridostigmine bromide and stress the effect is even stronger. More disruption of the BBB and neuronal cell death in the cingulate cortex, the dentate gyrus, the thalamus, and the hypothalamus. Other regions of the brain, although they demonstrated some neuronal cell death, did not exhibit disruption of the BBB (Abdel-Rahman A, et al 2002).
As these areas of the brain are respectively important for the maintenance of motor and sensory functions, learning and memory, gait and coordination of movements, such alterations could lead to many physiological, pharmacological, and behavioural abnormalities, particularly motor deficits and learning and memory dysfunction (Abdel-Rahman A et al Jan 2004, Feb 2004).

Individual susceptibility

It appears children may be more sensitive to permethrin than adults. Permethrin is almost 5 times more acutely toxic to 8-day-old rats than it is to adult rats (Cantalamessa, F. 1993). The Pentagon was warning family members not to send U.S. troops in the Persian Gulf flea and tick collar designed for pets. They can cause dangerous pesticides to be absorbed through the skin. The main ingredient in most flea collars is permethrin http://www.headlice.org/news/2003/troopcollars.htm. The Natural Resources Defense Council is pointing out that products intended to kill fleas and ticks can also poison pets and the people who handle them. Particularly toddlers, who's normal behaviour bring them in close contact with their pets http://www.nrdc.org/health/effects/pets/execsum.asp.

Since sulphates are involved in one of the major pathways to break down permethrin, individuals with defects in sulphate-related enzymes may be less able to break down permethrin, leading to increased susceptibility to motor neuron disease ( Pall, H.S. et al. 1987, Steventon, G.B., R.H. Waring, and A.C. Williams.1990).
Individuals with genetic variants of the enzyme pseudocholinesterase having reduced activity, are at higher risk of adverse effects from exposure to certain chemicals. This including the permethrin combination, implicated in symptoms seen in Gulf War veterans ( Abou-Donia, M.B. et al. 1996 abstract).

References Permethrin

Literature references Permethrin.
Internet references Permethrin.