Pyrethroid Pesticides are documented to be Endocrine Disrupting Chemicals.

There are documented links in the medical literature between pyrethroids and

1. breast Cancer

2. testosterone decreases

3. childhood brain cancers

4. weakens and damages Blood-Brain-Barrier

5. neurological and cardiological damage, esp. to infants and children

6. thyroid damage and reduced intellectual performance

7. the ATP Energy Cycle and sensomotor -polyneuropathy

8. Lou Gehrig�s Disease (ALS), Parkinson�s, Multiple Scheloris

9. Synergistic effects with Malathion, Deet , etc.

Pyrethroid pesticides are documented to be a significant factor in ALS or to cause ALS like symptoms.

references:

[ Pesticide exposure and amyotrophic lateral sclerosis , NeuroToxicology , Volume 33, Issue 3, June 2012, Pages 457-462; https://www.sciencedirect.com/science/article/abs/pii/S0161813X12000770

(93) Selected pyrethroid insecticides stimulate glutamate uptake in brain synaptic vesicles. Neuroreport 1998 Oct 26;9(15):3519‑23; Vaccari A, Ruiu S, Mocci I, Saba P,Bernard B. Brodie.

The pyrethroids permethrin and cyhalothrin are potent inhibitors of the mitochondrial complex I. J Pharmacol Exp Ther 1997, Gassner B, Wuthrich A, Scholtysik G, Solioz M; May ;281(2):855‑60; Narahashi T.

Nerve membrane Na+ channels as targets of insecticides. Trends Pharmacol Sci 1992 Jun;13(6):236‑41; Zhao X, Dai S, Chen G.

Inhibition of glutamate uptake in rat brain synaptosome by pyrethroids. Chung Hua Yu Fang I Hsueh Tsa Chih 1995 Mar;29(2):89‑91; Receptors for gamma‑aminobutyric acid and voltage‑dependent chloride channels as targets for drugs and toxicants. FASEB J 1987 Oct;1(4):262‑71, Eldefrawi AT, Eldefrawi ME.;

HPLC Determination of Flumethrin , Deltamethrin, Cypermethrin, and Cyhalothrin Residues in the Milk and Blood or Lactating Dairy Cows. Journal of Analytical Toxicology, Volume 21, Number 5, September 1997, pp. 397 �402. D. Zuccari Bissacot and I. Vassilieff . ;

Topical application of synthetic pyrethroids to cattle as a source of persistent environmental contamination. J Environ Sci Health B 1997 Sep;32(5):729‑39, Gassner B, Solioz M.;

Patient Information Network, Exposure Survey of patients with ALS, http://members.aol.com/alspinpoint/results.html;

& Occupational exposures and amyotrophic lateral sclerosis; Am J Epidemiol 1997 Jun 15; 145(12):1076-88. McGuire, Longstreth et al, &; & Motor neuron disorder simulating ALS induced by chronic inhalation of pyrethroid insecticides; Doi H, Kikuchi H, Kira J et al; Neurology. 2006 Nov 28;67(10):1894-5; &

[A new method for early detection of neurotoxic diseases (exemplified by pyrethroid poisoning)], M�ller- Mohnssen H, Hahn K, Gesundheitswesen . 1995 Apr;57(4):214-22. German. Toxicology . 2007 Jan 18;229(3):194-205.;

Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids; Nasuti C, Cantalamessa F et al; Toxicology . 2007 Jan 18;229(3):194-205.; &

Effect of pyrethroid-based liquid mosquito repellent inhalation on the blood-brain barrier function and oxidative damage in selected organs of developing rats; Gupta A, Nigam D, Gupta A, Shukla GS, Agarwal AK; J Appl Toxicol . 1999 Jan-Feb;19(1):67-72; &

Review (Pesticide Health Effects), B Windham (Ed), www.flcv.com/pesticid.html

Motor neuron disorder simulating ALS induced by chronic inhalation of pyrethroid insecticides; Doi H, Kikuchi H, Kira J et al; Neurology. 2006 Nov 28;67(10):1894-5.

[A new method for early detection of neurotoxic diseases (exemplified by pyrethroid poisoning)], M�ller- Mohnssen H, Hahn K, Gesundheitswesen . 1995 Apr;57(4):214-22. German.

Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids; Nasuti C, Cantalamessa F et al; Toxicology . 2007 Jan 18;229(3):194-205. Epub 2006 Oct 29.

Dipartimento di Medicina Sperimentale e Sanit� Pubblica , Universit� di Camerino , Via Scalzino , 62032 Camerino (MC), Italy. cinzia.nasuti@unicam.it

Estrogenicity of pyrethroid pesticides . J Toxicol Environ Health A. 2002 Oct 11;65(19):1419-35. Chen H, Wang X.,

The role of P450 metabolism in the estrogenic activity of bifenthrin in fish . Aquat Toxicol . 2014 Nov;156: 17-20. DeGroot BC, Brander SM.

(metabolites mostly responsible for estrogenic activity)

Pyrethroids are a class of insecticides involved in different neurological disorders. They cross the blood-brain barrier and exert their effect on dopaminergic system , contributing to the burden of oxidative stress in Parkinson's disease through several pathways. The aim of the present study was to evaluate the effect of neonatal exposition to permethrin and cypermethrin (1/10 of DL (50)) in rats from the eighth to the fifteenth day of life. Open-field studies showed increased spontaneous locomotor activity in the groups treated with permethrin and the one treated with cypermethrin, while a higher number of center entries and time spent in the center was observed for the cypermethrin-treated group. Lower dopamine and higher homovanillic acid levels were measured in the striatum from both treated groups. A reduction of blood glutathione peroxidase content was measured, while no change in blood superoxide dismutase was observed. Carbonyl group formation increased in striatum, but not in erythrocytes. Lipid peroxidation occurred in erythrocytes, but not in striatum. No changes in fluidity at different depths of plasma membrane were measured in striatum or erythrocytes. The activation of monocyte NADPH oxidase by phorbol esters (PMA) shows that superoxide anion production was reduced in the pyrethroid-treated groups compared to the control group. Our studies suggest that neonatal exposition to permethrin or cypermethrin induces long-lasting effects after developmental exposure giving changes in open-field behaviors, striatal monoamine level, and increased oxidative stress. Although the action of pyrethroids on various target cells is different, a preferential interaction with the extracellular side of plasma membrane proteins can be observed.

Med Sci Monit . 2006 May;12(5):BR169-73.

Bifenthrin causes neurite retraction in the absence of cell death: a model for pesticide associated neurodegeneration.

Nandi A , Chandil D , Lechesal R , Pryor SC , McLaughlin A , Bonventre JA , Flynnx K , Weeks BS .

Department of Biology aand Environmental Studies Program, Adelphi University, One South Avenue, Garden City, NY 11530, USA.

BACKGROUND: Bifenthrin is a synthetic pyrethroid insecticide derivative of naturally occurring pyrethrins from chrysanthemum flowers. Bifenthrin is considered relatively safe and therefore incorporated as the active ingredient in preparations sold over the counter for household use. Recent studies have raised concern that chronic exposure to pesticides in the home setting may increase the risk for neurodegenerative diseases. To address this concern, in the present study, bifenthrin is added to pre-differentiated PC12 and effect of bifenthrin on the retraction of existing neurites is observed a model for neurodegeneration. MATERIAL/METHODS: PC12 cells were differentiated with nerve growth factor for twenty-four hours and then treated with what was determined to be a sublethal dose of bifenthrin for up to an additional 48 hours. The percent of cells with neurites was assessed at various times before and after nerve growth factor treatment. Bifenthrin toxicity was determined using trypan blue exclusion. RESULTS: Bifenthrin was not toxic to PC12 cells at concentrations ranging from 1 x 10(-10) M to 1 x 10(-4) M. Twenty-four hours after nerve growth factor treatment, a maximum percent of cells had formed neurites and with a treatment of 1 x 10(-5) M bifenthrin, approximately 80% of these neurites retracted in within 12 additional hours and almost all neurites had retracted within 48 hours. Trypan exclusion showed that these cells were viable. CONCLUSIONS: These data show that bifenthrin can stimulate the retraction of neurites in the absence of frank toxicity.

Int J Dev Neurosci . 2004 Feb;22(1):31-7.

Mosquito repellent (pyrethroid-based) induced dysfunction of blood-brain barrier permeability in developing brain.

Sinha C , Agrawal AK , Islam F , Seth K , Chaturvedi RK , Shukla S , Seth PK .

Developmental Toxicology Division, Industrial Toxicology Research Centre, P.O. Box 80, Mahatma Gandhi Marg, Lucknow 226001, India.

Pyrethroid-based mosquito repellents (MR) are commonly used to protect humans against mosquito vector. New born babies and children are often exposed to pyrethroids for long periods by the use of liquid vaporizers. Occupational and experimental studies indicate that pyrethroids can cause clinical, biochemical and neurological changes, and that exposure to pyrethroids during organogenesis and early developmental period is especially harmful . The neurotoxicity caused by MR has aroused concern among public regarding their use. In the present study, the effect of exposure of rat pups during early developmental stages to a pyrethroid-based MR (allethrin, 3.6% w/v, 8h per day through inhalation) on blood-brain barrier (BBB) permeability was investigated. Sodium fluororescein (SF) and Evan's blue (EB) were used as micromolecular and macromolecular tracers, respectively. Exposure during prenatal (gestation days 1-20), postnatal (PND1-30) and perinatal (gestation days 1-20 + PND1-30) periods showed significant increase in the brain uptake index (BUI) of SF by 54% (P < 0.01), 70% (P < 0.01), 79% (P < 0.01), respectively. This increase persisted (68%, P < 0.01) even 1 week after withdrawal of exposure (as assessed on PND37). EB did not exhibit significant change in BBB permeability in any of the group. The results suggest that MR inhalation during early prenatal/postnatal/perinatal life may have adverse effects on infants leading to central nervous system (CNS) abnormalities, if a mechanism operates in humans similar to that in rat pups.

Neurological deficits induced by malathion, DEET, and permethrin, alone or in combination in adult rats.

Abdel-Rahman A , Dechkovskaia AM , Goldstein LB , Bullman SH , Khan W , El- Masry EM , Abou-Donia MB . J Toxicol Environ Health A. 2004 Feb 27;67(4):331-56.

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.

Malathion (O,O-dimethyl-S-[1,2-carbethoxyethyl] phosphorodithionate ), DEET (N,N-diethyl-m-toluamide), and permethrin [(+/-)-cis/trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylic acid (3-phenoxyphenyl) methyl ester] are commonly used pesticides. To determine the effects of the dermal application of these chemicals, alone or in combination, the sensorimotor behavior, central cholinergic system, and histopathological alterations were studied in adult male Sprague-Dawley rats following a daily dermal dose of 44.4 mg/kg malathion, 40 mg/kg DEET, and 0.13 mg/kg permethrin, alone and in combination for 30 d. Neurobehavioral evaluations of sensorimotor functions included beam-walking score, beam walk time, inclined plane, and grip response assessments. Twenty-four hours after the last treatment with each chemical alone or in combination all behavioral measures were impaired. The combination of DEET and permethrin, malathion and permethrin, or the three chemicals together resulted in greater impairments in inclined performance than permethrin alone. Only animals treated with a combination of DEET and malathion or with DEET and permethrin exhibited significant increases in plasma butyrlcholinesterase ( BChE ) activity. Treatment with DEET or permethrin alone, malathion and permethrin, or DEET and permethrin produced significant increases in cortical acetylcholinesterase ( AChE ) activity. Combinations of malathion and permethrin or of DEET and permethrin produced significant decreases in midbrain AChE activity. Animals treated with DEET alone exhibited a significant increase in cortical m2 muscarinic ACh receptor binding. Quantification of neuron density in the dentate gyrus, CA1 and CA3 subfields of the hippocampus, midbrain, brainstem, and cerebellum revealed significant reductions in the density of surviving neurons with various treatments. These results suggest that exposure to real-life doses of malathion, DEET, and permethrin, alone or in combination, produce no overt signs of neurotoxicity but induce significant neurobehavioral deficits and neuronal degeneration in brain.

Toxicol Lett. 1999 Jun 30;107(1-3):161-76.

Chronic sequelae and irreversible injuries following acute pyrethroid intoxication.

M�ller- Mohnssen H .

Physiological Institute, Ludwig Maximilians University, Munich, Germany.

For patients the author has observed, the majority of complaints following an acute pyrethroid intoxication disappeared after the end of exposure. Residuals frequently observed after more than 2 years 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 (paroxysmal tachycardia, pollakisuria , increased heat-sensitivity, orthostatic hypotonia and reduced exercise tolerance due to circulatory disorder). Non-neurological symptoms include deficiency of cellular and humoral immune system established by laboratory findings: opportunistic infections, especially Candida-infections of the gastro-intestinal tract, relapsing infections of the urinary and respiratory tract, the latter often aggravating to respiratory obstruction. Most of the patients exhibit positive epi- or intracutantest against pyrethroids or pyrethrines , and acquainted sensitivity also to other antigens. Many of these patients exhibit pathological autoimmune diagnostical findings and developed autoimmune diseases as for instance scleroderma-like syndrome, myasthenia-like syndrome with progredient muscle atrophy, autoimmun -hemolysis and autoimmun -thrombocytopenic purpura.

Hum Exp Toxicol . 1999 Mar;18(3):174-9.

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

Gupta A , Agarwal R , Shukla GS .

Predictive Toxicology Research Group, Industrial Toxicology Research Centre, Lucknow, India.

1. The effect of certain pesticides on the functional integrity of the developing blood-brain barrier (BBB) was studied following single and repeated exposure, and after subsequent withdrawal in rats. 2. Ten-day-old rat pups exposed orally to quinalphos (QP, organophosphate), cypermethrin (CM, pyrethroid) and lindane (LD, organochlorine) at a dose of 1/50th of LD50, showed a significant increase in the brain uptake index (BUI) for a micromolecular tracer, sodium fluorescein (SF), by 97, 37 and 72%, respectively, after 2 h. Residual increases in the BUI were found even after 3 days of the single treatment of QP (28%) and LD (23%). 3. Repeated exposure for 8 days (postnatal days (PND) 10-17) with QP, CM and LD increased the BBB permeability by 130, 80 and 50%, respectively. Recovery from these changes was complete in QP and LD-treated animals after 13 days (PND 18-30) of withdrawal. However, CM showed persistent effects that were normalized only after 43 days (PND 18-60) of withdrawal. 4. A single dose reduced to 1/100th of LD50 also increased BUI in 10-day-old rat pups following QP (20%) and CM (28%) exposure at 2 h. 5. An age-dependent effect of these pesticides was evident from the study showing higher magnitude of BUI changes in 10-day-old rats as compared to that in 15-day-old rats. Furthermore, adult rats did not show any effect on BBB permeability even at a higher dose (1/25th of LD50) of these pesticides given alone or in combination with piperonyl butoxide (600 mg/kg, i.p. ) for 3 consecutive days. 6. This study showed that developing BBB is highly vulnerable to single or repeated exposure of certain pesticides . The observed persistent effects during brain development even after withdrawal of the treatment may produce some neurological dysfunction at later life as well.

Predictive Toxicology Research Group, Industrial Toxicology Research Centre, Lucknow, India.

Pesticides have been implicated in various neurological disorders in humans and experimental animals. Our earlier studies have demonstrated a high vulnerability of developing blood-brain barrier (BBB) towards very low level exposure of quinalphos, cypermethrin and lindane. Earlier it has been observed that a cypermethrin-induced increase in the BBB permeability of neonatal rats was found to be persistent, requiring a longer period of withdrawal for complete recovery. These observations lead us to investigate the effect of a commonly available liquid mosquito repellent (MR) containing a pyrethroid compound, allethrin (3.6% w/v), on the functional integrity of the developing BBB and on certain parameters of oxidative damage in brain, liver and kidney. Two-day-old rat pups were allowed to inhale the MR (18 h per day) for 8 days (postnatal days (PND) 2-9). Rats exposed to MR were further withdrawn from the exposure for 8 days (PND 10-17) to study whether the changes induced following inhalation are reversible. Results of the study have shown a significant increase in the BBB permeability (45%) of the MR-exposed rat pups to a micromolecular tracer, sodium fluorescein (mol. wt. 376), used for the quantitative assessment of the BBB permeability, suggesting a delayed maturity of the BBB system. Brain glutathione (GSH) levels were also decreased (17%) in the exposed individuals. The oxidatively damaged end-products of lipids, measured as lipid hydroperoxides and conjugated dienes, were found to be increased in brain (42%, 16%), liver (34%, 20%) and kidney (68%, 29%), respectively. The oxidative product of protein, measured as protein carbonyls, was also increased significantly in liver (43%) and kidney (16%) of the MR-exposed rat pups as compared to age-matched controls. The biochemical changes that occurred in the BBB permeability and the oxidatively damaged end-products following MR inhalation in neonatal rats were, however, found to be completely recovered except for an increase in brain GSH (28%) level. The results suggest the possibility of health risk due to exposure to pesticide-based mosquito repellents, especially when exposure takes place in individuals at an early age.

Neurotoxicity resulting from coexposure to pyridostigmine bromide, deet , and permethrin: implications of Gulf War chemical exposures.

Abou-Donia MB , Wilmarth KR , Jensen KF , Oehme FW , Kurt TL . J Toxicol Environ Health. 1996 May;48(1):35-56.

Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA. donia@acpub.duke.edu

Of the three-quarters of a million service personnel involved in the Persian Gulf War, approximately 30,000 have complained of neurological symptoms of unknown etiology. One contributing factor to the emergence of such symptoms may be the simultaneous exposure to multiple agents used to protect the health of service personnel, in particular, the anti-nerve agent pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methylpyridinium bromide), the insect repellent DEET (N,N-diethyl-m-toluamide), and the insecticide permethrin (3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester). This study investigated neurotoxicity produced in hens by individual or simultaneous exposure to these agents (5 d/ wk for 2 months to 5 mg/kg/d PB in water, po; 500 mg/kg/d DEET, neat, sc ; and 500 mg/kg/d permethrin in corn oil, sc ). At these dosages, exposure to single compounds resulted in minimal toxicity. Combinations of two agents produced greater neurotoxicity than that caused by individual agents. Neurotoxicity was further enhanced following concurrent administration of all three agents. We hypothesize that competition for liver and plasma esterases by these compounds leads to their decreased breakdown and increased transport of the parent compound to nervous tissues. Thus, carbamylation of peripheral esterases by PB reduces the hydrolysis of DEET and permethrin and increases their availability to the nervous system. In effect, PB "pumps" more DEET and permethrin into the central nervous system. Consistent with this hypothesis, hens exposed to the combination of the three agents exhibited neuropathological lesions with several characteristics similar to those previously reported in studies of near-lethal doses of DEET and permethrin. If this hypothesis is correct, then blood and liver esterases play an important "buffering" role in protecting against neurotoxicity in the population at large. It also suggests that individuals with low plasma esterase activity may be predisposed to neurologic deficits produced by exposure to certain chemical mixtures.

Neurotoxicology. 1996 Summer;17(2):415-31.

Systemic application of pyrethroid insecticides evokes differential expression of c- Fos and c-Jun proteins in rat brain.

Hassouna I , Wickert H , el- Elaimy I , Zimmermann M , Herdegen T .

II. Institute of Physiology, University of Heidelberg, Germany.

Expression of the c- Fos and c-Jun transcription factor was investigated by immunocytochemistry in the thalamus, hypothalamus, hippocampus and cortex of adult rats following intraperitoneal application of proconvulsant doses of the pyrethroid insecticides, cypermethrin and permethrin. Pyrethroid insecticides are used world-wide and their uptake, e.g., by nutrition and inhalation evokes severe neurological symptoms in animals and humans, but their effects on neuronal gene expression has not been elucidated. Cypermethrin induced a strong expression of c- Fos and c-Jun in all the thalamic nuclei, except the ventro -posterior complex and substantia nigra, and in all the hypothalamic nuclei. In general, the immunoreactivities (IR) persisted for 8 h on their maximal levels, and were still above control levels after 24 h in several thalamic and hypothalamic areas. c- Fos -IR was strongly increased in all cortical layers with a predominance in the superficial layers II-IV, whereas c-Jun-IR was only slightly increased. In the hippocampus, cypermethrin induced a weak expression of c- Fos , but not of c-Jun, in the dentate gyrus and CA-3 area. Permethrin that has a lower pharmacological potency, evoked a similar pattern of c- Fos and c-Jun expression, however, intensity and persistence of the neuronal labeling were less pronounced. Our results demonstrate that the neurotoxic effects of pyrethroid insecticides comprise molecular genetic alterations in the brain such as early and lasting induction of Fos and Jun transcription factor proteins. These changes in the neuronal program are prominent in the hypothalamus and thalamus that are involved in the regulation of the autonomic and visceral nervous systems.

Gesundheitswesen . 1995 Apr;57(4):214-22; [A new method for early detection of neurotoxic diseases (exemplified by pyrethroid poisoning )] M�ller - Mohnssen H, Hahn K;

Medis-Institut des GSF- Forschungszentrums f�r Umwelt und Gesundheit, Oberschleissheim .

Comment in:

This pilot-study should contribute to the question whether Pyrethroid intoxication can be distinguished from other diseases by characteristic clinical symptoms. The results show that the characteristics of the intoxication do not consist in singular symptoms but in combinations and correlations of symptoms, i.e. of central-neurological with peripheral- and autonomic-neurological as well as with characteristic immunological disturbances. Neurological symptoms consist in cerebro -organic disfunctions, locomotory disorders reminiscent of multiple sclerosis or M. Parkinson, and sensory, motoric and vegetative polyneuropathy , leading, for instance, to cardiovascular regulatory disorder like sympathicotonia or, orthostatic hypotonia. Non-neurological symptoms include immunosuppression with consecutive opportunistic infections, like candida albicans, most frequently of the alimentary tract, but also dermal and mucosal swellings, lichen- ruber -like efflorescences , loss of hair, conjunctivitis. Other symptoms are: hypoglycaemic crises inhibition of fertility, disturbances of blood clotting, and most frequently in children, suspected hematopoetic disorders.

Utility of a neurobehavioral screening battery for differentiating the effects of two pyrethroids, permethrin and cypermethrin; McDaniel KL, Moser VC, Neurotoxicol Teratol . 1993 Mar-Apr;15(2):71-83.

ManTech Environmental Technology Inc., Research Triangle Park, NC 27709.

The ability of a neurobehavioral screening battery to differentiate the effects of two pyrethroids, permethrin and cypermethrin, was assessed in this experiment. Although the structures of these pesticides differ only in the alpha- cyano group, the behavioral syndromes associated with the Type I and II pyrethroids are quite different. The tests included a functional observational battery which is a series of subjective and quantitative measures of neurological function and behavior, and an automated measure of motor activity. Our results verified previous reports in the literature describing these different syndromes, i.e., aggressive sparring behavior, fine to whole-body tremor, hyperthermia, and decreased motor activity for the Type I pyrethroid permethrin, and pawing, burrowing, salivation, whole body tremor to choreoathetosis, hypothermia, and lowered motor activity for the Type II pyrethroid cypermethrin. In addition, we report that permethrin produced decreased grip strengths, increased resistance to capture, increased reactivity to a click stimulus, and induced head and forelimb shaking and agitated behaviors, whereas cypermethrin produced pronounced neuromuscular weakness and equilibrium changes, retropulsion, lateral head movements, alterations in responses to various stimuli, and increased urination. Although there were similarities in some effects (e.g., decreased motor activity), the pesticides differed sufficiently in their overall behavioral profiles, and severity and time course of effects, to discriminate these two compounds. Thus, this type of screening approach is sensitive enough to differentiate these pyrethroids for hazard identification purposes.

Changes in myelinated nerve fibers and skeletal muscle of rats exposed to high doses of permethrin.

Cavaliere MJ , Maeda MY , Shih LW , Puga FR . Biomed Environ Sci. 1990 Jun;3(2):139-45.

Instituto Adolfo Lutz, S�o Paulo, Brazil.

Neurological signs and segmental demyelination in a cervical nerve were observed in rats treated orally with permethrin (300 mg/kg/day) for 5 days. Inflammatory and degenerative signals were recorded in the diaphragm muscle. These effects were more intense with the trade grade than with the technical grade product. The possible influence of the percentage of cis:trans isomers on the intensity of the observed effects is discussed.

�Fatal Asthma in Child from Anti-flea Shampoo�, Western J of Medicine, 2000, 173:86-87.

& Khera KS, Whalen C, Angers G, Teratogenicity study on pyrethrum and rotenone in pregnant rats, J Toxicol Environ Health 1982 Jul;10(1):111‑9; & J Appl Toxicol 1996, 16(5):397-400; & Garey J, Wolff MS, Estrogenic and antiprogestagenic activities of pyrethroid insecticides. Biochem Biophys Res Commun 1998 Oct 29;251(3):855‑9 & Go V, Garey J, Wolff MS, Pogo BG. Estrogenic potential of certain pyrethroid compounds in the MCF‑7 human breast carcinoma cell line. Environ Health Perspectives, 1999, 107(3):173-7.

Wu A and Liu Y, 2003, Prolonged expression of c- Fos and c-Jun in the cerebral cortex of rats after deltamethrin treatment, Brain Research: Molecular Brain Research, 110: 147-151; & Yu XM, 2006, The role of intracellular sodium in the regulation of NMDA-receptor-mediated channel activity and toxicity, Molecular Neurobiology, 33:63-80; & Doble A, 1996, The pharmacology and mechanism of action of riluzole , Neurology 47(Supp 4): S233-241; &( c) Valentine WM, 1990, Toxicology of selected pesticides, drugs and chemicals: Pyrethrin and pyrethrin pesticides, The Vetinary Clinics of North America, Small Animal Practice, 20:375-382.

Pyrethroids can elicit a range of immunotoxic and neurotoxic effects in humans and other mammals, and their exposure may contribute to reproductive dysfunction, developmental impairment and cancer ^22,24

Permethrin and cypermethrin showed dose-dependent cytotoxicity. The most toxic pyrethroid was cypermethrin followed by permethrin and natural pyrethrin. This study confirms that the cell toxicity was dependent on the chemical structure and pyrethroids without an ? - cyano group shows the weakest physiological effect ²⁶ . Treatment with cypermethrin caused significant decreases in ejaculate volume, sperm concentration, total sperm output, sperm motility and plasma testosterone ²⁷ . Three different mechanisms are involved usually during interference with hormone receptor by EDCs which includes (1) binding and activating the estrogen receptor; (2) binding without activating the estrogen receptor; and (3) binding with other receptors ³⁶ . For example pyrethroid compounds (permethrin, cypermethrin, fenvalerate and deltamethrin) at high concentrations inhibited the binding of estradiol to rat uterus cystolic estrogenic receptors (ERs) in a competitive binding study and suggested that signaling pathways other than ERs are involved in mediating pyrethroid induced or inhibited MCF-7 cell proliferation and pyrethroid insecticides may alter the conformation ER without binding to it. Approximately 27% (696 of 2,588) of the workers who sprayed pure pyrethroids reported having experienced symptoms such as abnormal facial sensations (paresthesia), dizziness, headache, nausea, loss of appetite, blurred vision, and tightness of the chest. Eight of these workers were diagnosed with mild acute pyrethroid poisoning, characterized in part by listlessness and muscular fasciculations. GABA receptors are the target sites for several insecticides; including chlorinated cyclodienes (e.g. endosulfan ) and phenylpyrazoles (e.g. fipronil). There is a relationship between exposure to certain neurotoxic pesticides such as pyrethroids during pregnancy and subsequent problems in children. Such a connection is suspected between learning and developmental disorders in children ⁵³ . Certain pesticides may also interrupt the neurological development process particularly during critical period and induce harmful effects on sensory, motor and cognitive functions for example Aziz et al., ⁵⁴

22.Endocrine Disruption and Perspective Human Health Implications: A Review, S. Poongothai , R. Ravikrishnan , Department of Toxicology, International Institute of Biotechnology and Toxicology, The Internet Journal of Toxicology� ISSN: 1559-3916, http://www.ispub.com/journal/the_internet_journal_of_toxicology/volume_4_number_2_48/article/endocrine_disruption_and_perspective_human_health_implications_a_review-17.html

24. Liu P, Song X, Yuan W, Wen W, Wu X, Li J, Chen X. Effects of cypermethrin and methyl parathion mixtures on hormone levels and immune functions in Wistar rats. Arch Toxicol 2006; 80; 449-457. ( s )

26Kakko I, Toimela T, Tahti H. The toxicity of pyrethroid compounds in neural cell cultures studied with total ATP, mitochondrial enzyme activity and microscopic photographing. Environ Toxicol Pharmacol 2004; 15: 95-102. ( s )

27. Yousef MI, El- Demerdash FM, Al- Salhen KS. Protective role of isoflavones against the toxic effect of cypermethrin on semen quality and testosterone levels of rabbits. J Environ Sci Health B 2003; 38: 463-478.

36. Hanke W, Jurewicz J. The risk of adverse reproductive and developmental disorders due to occupational pesticide exposure: an overview of current epidemiological evidence. Int J Occup Med Environ Health 2004; 17: 223-243. ( s )

41. Chen HY, Xiao J, Hu G, Zhou J, Xiao H, Wang X. Estrogenicity of organophosphorus and pyrethroid pesticides. J Toxicol Environ Health 2002; 65: 1419-1435. ( s )

53. Shafer TJ, Meyer DA, Crofton KM. Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs. Environ Health Perspect 2005; 113: 123-136. ( s )

54. Aziz MH, Agrawal AK, Adhami VM, Shukla Y, Seth. PK. Neurodevelopmental consequences of gestational exposure (GD14-GD20) to low dose deltamethrin in rats. Neurosci Lett 2001; 300: 161-165.

Spraying is the least effective means of controlling West Nile virus, Dr. KathleenToomey of the AAFP and CDC says, for a number of reasons. It's expensive, it kills beneficial insects, it's ineffective in wooded and foliated areas, and even if spraying kills adults, new mosquitoes will emerge within days, she says. Physicians should lobby to have public areas and home property kept free of standing water, where the mosquitoes breed. Persons who become infected are usually infected by mosquitoes in close proximity to their homes, she adds. AAFP is one of the largest national medical organizations, representing more than 94,700 family physicians, family medicine residents and medical students nationwide.

The American Academy of Family Physicians, http://www.aafp.org/fpr/20020900/2.html

Selective effects of insecticides on nigrostriatal dopaminergic nerve pathways. Bloomquist JR, Barlow RL, Gillette JS, Li W, Kirby ML. Neurotoxicology. 2002 Oct;23(4-5):537-44.

Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg 24061-0319, USA. jbquist@vt.edu

Abstract

A degeneration of the nigrostriatal pathway is a primary component of Parkinson's disease (PD), and we have investigated the actions of insecticides on this pathway. For in vivo exposures, C57BL/6 mice were treated three times over a 2-week period with heptachlor, the pyrethroids deltamethrin and permethrin, or chlorpyrifos. One day after the last treatment, we observed that heptachlor and the pyrethroids increased maximal [3 H]dopamine uptake in striatal synaptosomes from treated mice, with dose-dependent changes in Vmax displaying a bell-shaped curve. Western blot analysis confirmed increased levels of dopamine transporter (DAT) protein in the striatum of mice treated with heptachlor and permethrin. In contrast, we observed a small, but statistically significant decrease in dopamine uptake by 100 mg/kg chlorpyrifos. For heptachlor, doses that upregulated DAT expression had little or no effect on serotonin transport. Permethrin did cause an upregulation of serotonin transport, but required a 30-fold greater dose than that effective on dopamine uptake. Other evidence of specificity was found in transmitter release assays, where heptachlor and deltamethrin released dopamine from striatal terminals with greater potency than other transmitter types. These findings confirm that insecticides possess specificity for effects on striatal dopaminergic neurotransmission.

Pesticide link to Parkinson's

Permethrin repels mosquitoes

� Exposure to some insecticides may cause a cascade of chemical events in the brain that could lead to Parkinson's Disease, researchers have found.

� A team from Virginia Polytechnic Institute studied levels of key chemicals in the brain of mice exposed to various levels of the insecticide permethrin.

� They found that the insecticide stimulated a reduction in levels of an important transmitter chemical called dopamine.

� Parkinson's symptoms such as the muscle rigidity, shuffling gait, and a rhythmic tremor have been linked to the loss of dopamine production in the brain.

� The researches also found that exposure to permethrin was linked to increased production of a protein called alpha-synuclein.

� This protein is a major component of fibrous tangles called Lewy bodies, which are found in the brain of patients with Parkinson's.

� Exposure to low levels of the insecticide seemed to have a more immediate effect than exposure to higher doses.

� But the researchers believe this could be because high levels simply overwhelm the delicate systems within the brain, which takes time to come to terms with and react accordingly.

� DDT action

� Researcher Dr Jeffrey Bloomquist said a tiny dose - less than one thousandth of that needed to kill a mouse - was enough to produce effects on the brain.

� However, he said that while mice exposed to permethrin had shown Parkinson's-like symptoms, they had not developed the full blown disease.

� The researchers now plan to examine the effects of longer term exposure permethrin, and of exposure to another widely used pesticide, chlorpyrifos.

� Permethrin is used to treat clothes to repel and kill ticks and mosquitoes.

� It acts in a similar way to DDT by strongly exciting the nervous systems of insects.

� The chemical is toxic at high levels and classified as a possible carcinogen by the US Environmental Protection Agency.

� A spokeswoman for the UK Department for Environment Food and Rural Affairs said the use of permethrin was due to be phased out under an ongoing European Union review.

� She told BBC News Online: "DEFRA is sponsoring research into a possible link between Parkinson's disease and pesticides.

� "This was not one of the pesticides that was being looked at, but we are interested in these results and will pass them on to the research team."

� The results of the research were presented at a meeting of the American Chemical Society.

12. Mosquito repellent (pyrethroid-based) induced dysfunction of blood-brain barrier permeability in developing brain. Int J Dev Neurosci . 2004 Feb;22(1):31- 7; Sinha C, Agrawal AK, Seth PK et al; & Behavioral and neurochemical effects induced by pyrethroid-based mosquito repellent exposure in rat offsprings during prenatal and early postnatal period. Sinha C, Seth K, Agrawal AK et al. Neurotoxicol Teratol . 2006 Jul-Aug;28(4):472-81.

13. ( a)Immunohistochemical changes in the mouse striatum induced by the pyrethroid insecticide permethrin. Pittman JT, Dodd CA, Klein BG. Int J Toxicol . 2003 Sep-Oct;22(5):359-70; & (b)Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids. Nasuti C, Gabbianelli R, Falcioni ML, Di Stefano A, Sozio P, Cantalamessa F. Toxicology. 2007 Jan 18;229(3):194-205; & (c)Pyrethroid pesticide-induced alterations in dopamine transporter function. Elwan MA, Richardson JR, Guillot TS, Caudle WM, Miller GW. Toxicol Appl Pharmacol . 2006 Mar 15;211(3):188-97; & (d) Influence of dermal exposure to the pyrethroid insecticide deltamethrin on rat brain microanatomy and cholinergic/dopaminergic neurochemistry. Tayebati SK, Di Tullio MA, Ricci A, Amenta F. Brain Res. 2009 Dec 8;1301:180-8;

14. Insecticide-induced lupus erythematosus. Curtis CF. Int J Dermatol. 1996 Jan;35(1):74-5.

15. Effects of dermal sub-chronic xposure of pubescent male rats to permethrin (PRMT) on the histological structures of genital tract, testosterone and lipoperoxidation. Issam C, Zohra H, Monia Z, Hassen BC. Exp Toxicol Pathol . 2010 Apr 7; & (b) Chronic toxicity and cytotoxicity of synthetic pyrethroid insecticide cis-bifenthrin. Wang C, Chen F, Zhang Q, Fang Z. J Environ Sci (China). 2009;21(12):1710-5.

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