Synthetic pyrethroids

ISSN: 2231-6922 Review Article

Ind J Biol Stud Res Vol 3(1): 1-27

Synthetic pyrethroids: a brief review of effects on mammalian system toxicology Vijay Kumar Singh ………………………………………………………………………………………….. Department of Zoology, Faculty of Life sciences, Agra College, Agra. ABSTRACT The pyrethroids are the most useful insecticides that added deliberately to the environment and thus become hazardous to non-target organism including the higher mammalian groups. The toxicity of the pyrethroids as insecticides has received considerable attention during the last two decades and more because of the established utility and effectiveness and widespread use of these compounds for the improvement in agricultural output and the control of disease vectors. Although extensive data are available on the toxicity of the synthetic pyrethroids to animals, yet information pertaining to cytogenetic effects of pyrethroids are meager.

PYRETHROIDS AND TOXICITY Barnes and Verschoyle (1974) studied the toxicity of new pyrethroids insecticides, while Suzuki and Miyamoto (1974) metabolism of tetramethrin in house flies and rats in vitro, whereas Ueda et.al. (1974) reported photodecomposition of resmethrin and related pyrethroids. CAsida et.al. (1976) investigated structure-biodegradability relationship in pyrethroid insecticides, while White et. Al. (1976) the relationship between brain levels of cismethrin and bioresmethrin in female rats and their neurotoxic effects, whereas Elliott (1976) properties and applications of pyrethroids. Careton (1977) analysed effects of cismethrin on the rabbit nervous system, while Narahashi et. al. (1977) studied neurophysiology of structure-activity relation of pyrethroid, whereas Aldridge et. al. (1978) on the effect of DDT and the pyrethroids cismethrin and decamethrin on acetylecholine and cyclic nucleotide content in rat brain. Elliot et. al. (1978) reported the insecticidal activity of the pyrethrins and related compounds. Nashimura and Narahasi (1978) observed structure – activity relationships of pyrethroids based on direct action on nerve, whereas Casida et. al. (1979) reported comparative metabolism of pyrethroids derived from 3phenoxybenzyl and -cyano-3-phenoxy – benzyl alcohols while Madhukar and Matsumura (1979) reported that pyrethrins and synthetic prethroids cause induction of hepatic microsomes in rats. Ray and Cremer (1979) investigate the action of decamethrin on rats and reported that type II pyrethroids anttagonise Y-aminobutyric (GABA)- mediated inhibition, modulated nicotinic cholinergic transmission and markedly enhance adrenalin and noradrenalin release. Carlsonand Schoenig (1980) revealed induction of liver microsomal NADPH cytochrome-c-reductase and cytochrome P-450 by some new synthetic pyrethroids, while Gray et. al. (1980) the relationship between the pharmacokinetics of intravenous cismethrin and bioresmethrin and their mammalian toxicity. Lequesne et. al. (1980) assessed clinical and electrophysiological transient facial sensory symptoms following synthetic pyrethroid exprosure. McCorkle et. al. (1980) studied the effect of permethrin on the immune response of chickens, While Ray (1980) investigated an EEG of decamethrin

Synthetic pyrethroids: a brief review of mammalian system toxicology

induced choreoathetosis in the rat. Vershoyle and Aldridge (1980) reported structureactivity relationships of some pyrethroids in rats. Dyball (1982) reported inhibition by decamethrin and resmethrin of hormone release from the isolated rat neurohypophysis-a model mammalian neurosecretory system, while Glomot (1982) toxicity of deltamethrin to higher vertebrates. Gray and Rickard (1982) studied the toxicity of pyrethroids to rats after direct injection into the central nervous system, while Kolmodin-Hedman et. al. (1982) reported the effect of a synthetic pyrethroid detlamethrin on excitability changes following a never impulse, while Ray (1982) the contrasting actions of two pyrethroids (deltamethrin and cismethrin) in the rat. Ray (1982) explained the changes in brain blood flow associated with deltamethrin induced choreoathetosis in the rat, while Vijveberg and Bereken (1982) the action of pyrethroid insecticides on the vertebrate nervous system. Casida et al. (1983) reported mechanism of selective action of pyrethroid insecticides. Papadopoulon-Mourkidou (1983) analysed established prethroid insecticides, while Parker et al. (1983) toxicological and carcinogenic activity of fenvalerate in the B6C3F1 mouse. Rose and Dewar (1983) studied correlation between neuromuscular dysfunction and neurobiochemical abnormalities in rats after intoxication of four synthetic pyrethroids. Cagen et al. (1984) studied pyrethroid mediated skin sensory stimulation, while Canhn et al. (1984) pharmacological effects of deltamethrin on the CNS. Crofton and Reiter (1984) reported effects of two pyrethroid insecticides on motor activity and the acoustic startle response in the rat, while Knox et al. (1984) paresthesia from cutaneous exposure to a synthetic pyrethroid insecticide. Parket et al. (1984) evaluated chronic toxicity and carcinogenicity of fenvalerate in rats, while Prasada et al. (1984), in vitro effects of pyrethroid on rat brain and liver ATPase activities. Brodie (1985) studied neurotoxicology of deltamethrin after infusion into different sites in the neuraxis of freely moving rats. Desi et al. (1985) studied immunotoxicological effect of cypermethrin, while Flannigan et al. (1985), dermatological evaluation of synthetic pyrethroid insecticides. Ghiasuddinand Soderlung (1985) observed that pyrethroid insecticides are potent, stereospecific enhances of mouse brain sodium channel activation, while Gray (1985) pyrethroid structure toxicity relationships in mammals, whereas Lawrence et al. (1985) observed that interactions of pyrethroid insecticides with chloride ionophore associated binding sites. Leake et al. (1985) reported the comparative effects of pyrethroids on neurons of target and non-target organisms, while Malley et al. (1985) the effect of vitamin E and other amelioratory agents on the fenvalerate mediated skin sensation. Narahashi (1985) reported nerve membrane ionic channels as the primary target of pyrethroids, whereas Rashatwar and Matsumara (1985) interaction of DDT and pyrethroids with calmodulin and its significance in the expression of enzyme activities of phosophodiesterase. Soderlung (1985) studied pyrethroid-receptor interactions, stereospecific binding and effects on sodium channels in mouse brain preparation, while Staatz and Hosko (1985) effect of pyrethroid insecticides on EEC activity of conscious, immobilized rats. Thiebault et al. (1985) studied experimental intoxication by deltamethrin in the dog and its treatment, whereas Vijveberg and de Weille (1985) the interaction of pyrethroids with voltage – dependent Na channels, while Abalis et al. (1986) effects of insecticides of GABA – induced chloride influx into rat brain microsacs. Bloomquist et al. (1986) discussed inhibition of GABA stimulated chloride influx in mouse brain vesicles by polychloroalkane and pyrethroid insecticides, while Chinn and Narahashi (1986) stabilization of sodium channel states Ind J Biol Stud Res Vol 3(1), 2013 pp 1-27

Vijay Kumar Singh

by deltamethrin in mouse neuroblastoma cells. Desi et al. (1986) carried out immunoneuro-and general toxicological animal studies on a synthetic pyrethroid, cypermethrin. Edwards et al. (1986) worked on comparative toxicity of ciscypermethrin in rainbow trout, frog, mouse and quail, while Forshaw and Ray (1986) the effects of two pyrethroids, cismethrin and deltamethrin, on skeletal muscle and the trigeminal reflex system in the rat. Hiromori et al. (1986) observed the therapeutic effects of methocarbamol on acute intoxication by pyrethroids in rats. Hutson and Longan (1986) reported the metabolic fate of pyrethroids (WL85871; a mixture of two isomers of cypermethrin) in rats, while Narahashi (1986) mechanisms of action of pyrethroids on sodium and calcium channel gating. Sherby et al. (1986) studied effects of pyrethroids on nicotinic acetylcholine receptor binding and function. Smith and Stratton (1986) observed the effects of synthetic pyrethroid insecticide on nontarget organisms, while Squiban et al. (1986) observed the action of deltamethrin, a synthetic pyrethroid. Staatz and Hosko (1986) studied interaction of pyrethroids with mammalian spinal neurons. Chalmers et al. (1987) reported the neurophysiological study of the sites of action after deltamethrin intoxication, whereas Crofton and Reiter (1987) motor activity and the acoustic startle response in the rat after pyrethroid intoxication. Forshaw et al. (1987) studied the effects of 2 types of pyrethroid on rat skeletal muscle, while Mckillop et al. (1987) a quantitative assessment of pyrethroid-induced paraesthesia in the guinea pig flank model. Anadon et al. (1988) reported the microsomal enzyme induction by permethrin in rats, while Devan and Murray (1988) involvement of peripheral-type benzodiazepine receptors in the proconvulsant actions of pyrethroid insecticides. He et al. (1988) revealed the effects of pyrethroid insecticides on subjects engaged in packaging pyrethroids, while Hijzen and Slangen (1988) effects of type I and type II pyrethroids on the startle response in rats. Ishmael and Litchfield (1988) studied chronic toxicity and carcinogenic evaluation of permethrin in rats and mice, whereas Lister and Ray (1988) the role of basal forebrain in the primary cholinergic vasodilation in rat neocortex produced by systemic administration of cismethrin. Ogata et al. (1988) observed blocking of GABA – activated chloride channels after deltamethrin intoxication, while Ramadan et al. (1988) action of pyrethroids on GABA. Tamang et al. (1988) reported in vivo immuno-suppresson by synthetic pyrethroid (cypermethrin) pesticides in mice and goats, while Wright et al. (1988) reported classification of the actions of 10 pyrethroid insecticides in the rat, using the trigeminal reflex and skeletal muscle as test systems. Bradbury and Coats (1989) revealed comparative toxicology of prethroid insecticides Joy (1989) observed the type I and type II pyrethroids increased inhibition in the hippocampal dentate gyrus of rat. U.S.E.P.A. (1989) published pesticide fact sheet for cypermethrin. Aldridge (1990) observed toxicological properties of pyrethroids and their neurotoxicity. Cabral and Galendo (1990) AND Cerbral et al. (1990) studied carcinogenicity of fenvalerate and deltamethrin in mice and rats respectively. Coats (1990) studied mechanisms of toxic action and structure activity relationships for organochlorine and synthetic pyrethroid insecticides. Eriksson et al. (1990a and b) observed the behaviour and effects on cholinergic system after neonatal exposure to DDT and its fatty acid conjugate respectively. Forshaw and Ray (1990) reported a novel action of deltamethrin on membrane resistance in mammalian skeletal-muscle and non-myelinated nerve-fibres, whereas Gupta (1990) toxicity of cypermethrin in mice, rats and rabbits, Joy et al. (1990) revealed characteristics of the prolonged inhibition produced by a range of Ind J Biol Stud Res Vol 3(1), 2013 pp 1-27


pyrethroids in the rat hippocampus, while Oortgiesen et al. (1990) blocking of detalmethrin-modified sodium current in cultured neuroblastoma cells. Vijverberg and Bereken (1990) studied neurotoxicological effects and the mode of action of pyrethroid insecticides. Chen et al. (1991) reported an epidemiologic-study on occupational acute pyrethroid poisoning in cotton farmes, while Chugh et al. (1991) effect of fenvalerate and endosulfan on behavioural despair and forced locomotor – activity in albino mice. Eriksson and Fredriksson (1991) studied neurotoxic effects of two pyrethroids, bioallethrin and deltamethrin on immature and adult mice specifically changes in behavioural and muscarinic receptor variables, while Gomes et al. (1991) pyrethroids insecticides effect on physical and behavioural development of rats. He et al. (1991) reported changes of nerve excitability and urinary deltamethrin in sprayers, while Husain et al. (1991) neurotoxicological effects of a pyrethroid formulation, fenvalerate in rats. Furthermore, Hutson and Millburn (1991) noticed enzyme mediated selectivity of an organophosphate and a pyrethroid on various animals. Effects of pyrethroid insecticides on hepatic microsomal eyzymes in rats were noticed by Krechniak and Wrzensiowska (1991), while Maity and Poonia (1991) worked on learning and memory traces in rats after fluvalinate treatment, however, Moretto (1991) observed effects on spraymen and inhabitants of sprayed houses after indoor spraying with the pyrethroid insecticide lambda cyhalothrin. Ray (1991) repored about the pesticides derived from plants and other organisms. Modulation of nerve membrane sodium – channel activation by deltamethrin was reported by Brown and Narahashi (1992), whereas 3-generation reproductive studies of a synthetic pyrethroid-cyhalothrin was carried out by Deshmukh (1992) and pyrethroid insecticide-induced alterations in mammalian synaptic membrane-potential were reported by Eells et al. (1992). Eriksson et al. (1992) gave exposure of DDT to neonatal mice which induced permanent changes in brain muscarinic receptors and behaviour in adult mice, while Lessenger (1992) exposed 5 office workers inadvertently to cypermethrin. Lukowiez-Ratajezak and Krechniak (1992) observed effects of delthemethrin on the immune system in mice. Varshneya et al. (1992) noticed immunotoxic responses of cypermethrin as synthetic pyrethroid insecticides in the rats. Abdelkhalik et al. (1993) studied the teratogenic effects of deltamethrin in rats and activation of phosphoinositide protein kinae-c-pathway in rat brain tissue by pyrethroids was reported by Enan and Matsumura (1993), while Forshaw and Ray (1993) reported inactivation of a voltage dependent choride channel in nie 115 neuroblastoma cells by protein kinase-c and pyrethroid deltamethrin, whereas Forshaw et al. (1993) inhibition of a neuronal voltage-dependent chloride channel by the type-II pyrethroid deltamethrin. Ginsburg and Narahashi (1993) noticed differential sensitivity of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels to the insecticide allethrin in rat dorsal root ganglion neurons, while enhancement of alterated hepatic foci in rat lever and inhibition of intercellular communication in vitro by the pyrethroid insecticides fenvalerate, flucythrinate and cypermethrin was recorded by Hemming (1993), however, effects of pyrethroid insecticides on gap junctional intercellular communications in balb/c3t3 cells by dyetransfer assay were analysed by Tateno et al. (1993). Effects of a pyrethroid type II pesticide on conditioned behaviour of rats and toxicology of pyrethroids and their relevance to human health were recorded by Moniz et al. (1994) and Perger and Szadkowski (1994) respectively, while Sheets et al. (1994) observed age-dependent differences in the susceptibility of rats to deltamethrin. Siroki et al. (1994) reported immunotoxicological effects of SCMF a Ind J Biol Stud Res Vol 3(1), 2013 pp 1-27

Vijay Kumar Singh

new pyrethroid pesticide in mice. Rekling and Theophilidis (1995) studied the effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motorneurons in a brain stem slice from newborn mice, while Soderlung and Knippe (1995) actions of insecticides on sodium-channels-multiple-target sites and sitespecific resistance, however, Song and Narahashi (1995) reported selective blocking of tetramethrin – modified sodium channels by (±) alpha – tocopherol (Vitamin E). Investigation of immunotoxicity of supercypermethrin forte in the wistar rat was done by Tulinska et al. (1995). Neurological investigations in 23 cases of pyrethroid intoxication were repoted by Altenkirch et al. (1996), while Bain and LeBlanc (1996) reported interaction of structurally diverse pesticides with the human MDRI gene product p-glycoprotein, whereas effect of permethrin on pentobarbitone – induced sleeping time and hepatic microsomal constituents in mice was noticed by Shah et al. (1996). Song et al. (1996) investigated the interactions of tetramethrin, fenvalerate and DDT at the sodium channel in rat dorsal root ganglion neurons, while Song and Narahashi (1996a) differential effects of the pyrethroid tetramethrin on tetrodotoxinsensitive and tetradotoxin-resistant single sodium channels. Modulation of sodium channels of rat cerebellar purkinje neurons by the pyrethroid tetramethrin was repoted by Song and Narahashi (1996b). Gassner et al. (1997) reported permethrin and cyhalothrin as potent inhibitors of the mitochondrial complex. Holton et al. (1997) observed effects of the tremorgenic pyrethroid, bifenthrin, and of anaesthesia and found that increasing or decreasing nervous activity modulates the severity of the gliovasuclar lesions of 1, dinitrobenzene in the rat, while Kostka et al. (1997) reported effect of permethrin and DDT on the activity of cytochrome P-450 1A and 2B molecular forms in rat liver. Meola et al. (1997) did laser cytometric analysis of permethrin toxicity in insect and mammalian epithelial cells. Patro et al. (1997) studied neurotoxicological effects of deltamethrin on the postnatal development of cerebellum of rat, whereas Ray et al. (1997) actions of pyrethroid insecticides on voltage-gated chloride channels in neuroblastoma celols, however, effect of exposure to the synthetic pyrethroid insecticide cypermethrin on rat peripheral blood lymphocyte dopamine receptors was studied by Ricci et al. (1997). Santoni et al. (1997) observed prenatal exposure to cypermethrin modulates rat NK Cell Cytotoxic functions, while insecticide cytotoxicity and CYP 1A/2 induction in primary human and rat hepatocyte cultures were observed by Sousa et al. (1997), whereas Trainer et al. (1997) reported high affinity binding of pyrethroids to the alpha subunit of brain sodium channels. Cantalamessa et al. (1998) investigated influence of neonatal treatment with the pyrethroid insecticides cypermethrin on the development of dopamine receptors in the rat kidney, while Pauluhn and Machemer (1998) reported comparison of animal model and human data of assessment of pyrethroid induced paraesthesia. Condes Lara et al. (1999) studied effects of cypermethrin on the electroencephalographic activity of the rat, whereas Forshaw et al. (1999) the role of volage-gated chloride channels in type II prethroid insecticide poisoning. Functional impairment of blood-brain barrier following pesticide exposure during early development in rats was reported by Gupta et al. (1999), while Santoni et al. (1999) observed alterations of T-cell distribution and functions in prenatally cypermethrin exposed rats and found possible involvement of catechalomaines. Forshaw et al. (2000) studied the role of voltage-gated chloride channels in type II pyrethroid insecticides poisoning, while Oesch et al. (2000) worked on metabolic detoxification. Saxena and Sharma (2000) reported the effect of metabolic detoxification. Saxena and Sharma (2000) reported the effect of synthetic pyrethroid on behaviour pattern in Rattus norvegicus. Sheets (2000) reported age Ind J Biol Stud Res Vol 3(1), 2013 pp 1-27


dependent differences in susceptibility to organophosphorus and pyrethroid insecticides, while Soderlung et al. (2000) differential sensitivity of sodium channel isoforms and sequence variants to pyrethroid insecticides. Giray et al. (2001) reported prevention of cypermethrin-induced oxidative stress in rat brain and liver by Vitamin or allupurinol.

PYRETHROIDS AND METABOLISM Casida et al. (1971) investigated oxidative metabolism of pyrethrin in mammals, while Ueda et al. (1971) metabolism of (+) trans and (+) CIS resmethrin in rats. Miyamoto (1976) studied degradation, metabolism and toxicity of synthetic pyrethroids, while Soderlund and Casida (1977a), effects of pyrethroid structure on rates of hydrolysis and oxidation by mouse liver microsomal enzymes, whereas Soderlund and Casida (1977b) substract specificity of mouse-liver microsomal enzymes in pyrethroid metabolism. Ruzo et al. (1978) reported metabolism of decamethrin in rats, whereas Ruzo et al. (1979) decamethrin metabolites from oxidative, hydrylytic and conjugative reactions in mice. Chambers (1980) introduced the metabolism of pyrethroids, while Crawford et al. (1981) reported balance and tissue retention study regarding metabolism of cis and trans-cypermethrin in rats. Differential toxicity of trans-permethrin in rainbow trout and mice in terms of role of biotransformation and role of target organ sensitivity were reported by Glickman et al. (1982) and Glickman and Lech (1982) respectively. Graillot and Hoellinger (1982) studied covalent bindings with liver proteins of two pyrethroids isomers cismethrin and bioresmethrin, while Eadsforth and Baldwin (1983) human dose-excretion after pyrethroid insecticide, cypermethrin intoxication. Ghaisuddin and Soderlund (1984) reported hydrolysis of pyrethroid insecticides by soluble mouse brain esterases, while Rhodes et al. (1984) the bioaccumulation and biotransformation of cis, transcypermethrin in the rat. Mumtaz and Menzer (1986) worked on comparative metabolism and fate of fenvalerate in Japanese quail (Cotuemix coutarnix japonica) and rats (Rattas norvegicus), while Woollen et al. (1992) investigated differences in urinary metabolite profiles following oral and dermal cypermethrin administration in man, however, Anadon et al. (1996) studied toxico-kinetics of deltamethrin and its UHO metabolite in the rat.

PYRETHROIDS AND BIOCHEMISTRY Cremer et al. (1980) observed regional changes in brain glucose utilization in rats given a pyrethroid insecticide, while Hutson (1981) progress in pesticide biochemistry. Lock and Berry (1981) reported biochemical change in the rat cerebellum following cypermethrin administration. Brodie and Aldridge (1982) reported elevated cerebellar cyclic GMP levels during the deltamethrin-induced motor syndrome, while Cremer and Seville (1982) comparative effects of two pyrethroids deltamethrin and cismethrin on plasma catecholamines and on blood glucose and lactate, however Staatz et al. (1982) reported a pharmacological study of pyrethroid neurotoxicity in mice. Correlation between cerebeller cyclic GMP and motor effects induced by deltamethrin was studied by Brodie (1983). Forshaw and Bradbury (1983) reported pharmacological effects of pyrethroids on the cardiovascular system of the rat, while Cremer and Seville (1985) changes in regional cerebral blood flow and glucose metabolism associated with symptoms of pyrethroid toxicity. Rickard and Brodie (1985) studied correlation of blood and brain levels of the neurotoxic pyrethroid deltamethrin with the onset of symptoms in rats, while Hudson et al. Ind J Biol Stud Res Vol 3(1), 2013 pp 1-27

Vijay Kumar Singh

(1986) neurobehavioural effects of permethrin, associated with alterations in regional level of biogenic amine metabolites and amino acid neurotransmitters. Brooks and Clark (1987) investigated enhancement of norepinephrine release from rat brain synaptosomes by alphacyano pyrethroids, whereas de Boer (1988) changes in plasma corticosterone and catecholamine contents induced by low doses of deltamethrin in rats. Eells and Dubocovich (1988) changes in plasma corticosterone and catecholamine contents induced by low doses of deltamethrin in rats. Eells and Dubocovich (1988) observed enhanced neurotransmitter release from rabbit strial slices after pyrethroid treatment, whereas Shakoori et al. (1988) the effect of six months feeding of cypermethrin on the blood and liver of albino rats, while Ahmer (1989) subacute toxicity of cypermethrin in rats, whereas Catinot et al. (1989) effects on rats of subacute intoxication with deltamethrin via an osmotic pump. He et al. (1989) worked on clinical manifestations and diagnosis of acute pyrethroids poisoning, while Hassan et al. (1990) effects of some insecticides on several enzymes of tryptophan metabolism in rats. Gray et al. (1992) reported toxicological profile of fluvalinate – A synthetic pyrethroid, whereas Malviya et al. (1993) perinatal effects of two pyrethroid insecticides on brain neurotransmitter function in mice exposed to deltamethrin and hydrocortisone, while Ahlbom et al. (1994) induced dose response changes in brain muscarinic receptors and behaviour in neonatal and adult mice after neonatal exposure of a type I pyrethroid (bioallethrin). Effects of deltamethrin on catecholamine secretion of bovine chromaffin cells were reported by Bickmeyer et al. (1994), while effect of deltamethrin on regional brain polyamines and behaviour in young rats was studied by Husain et al. (1994). Majumdar et al. (1994) worked on subacute toxicity of fenvalerate in broiler chicks regarding concentration, cytotoxicity and biochemical profiles. Dixit (1995) reported the efficacy of cypermethrin on blood and liver biochemistry of Rattus norvegicus, while Saxena (1995) cybil induced blood morphological changes in albino rats. Yamano and Morita (1995) observed effects of pesticides on isolated rat hepatocytes mitochondria and microsomes. Box and Lee (1996) worked on a systemic reaction following exposure to a pyrethroid insecticide, while Hassouna et al. (1996) systemic application of pyrethroid insecticide and reported evoked differential expression of c-Fos and c-Jun proteins in rat brain. Verma (1996) reported effect of cypermethrin on certain brain biochemical parameters in albino rat. Ayub Shah and Gupta (1997) did biochemicotoxicological study on permethrin in rats, while Doneriya (1997) reported response of albino rat to decis (a synthetic pyrethroid) on liver biochemistry, whereas Eltawil and Abdel Rahman (1997) of the effect of cypermethrin on isolated male and female rat hepatocytes. Garg et al. (1997) studied biochgemical and physiological alterations following short term exposure to fluvalinate, a synthetic pyrethroid, while Saxena and Saxena (1997) haemogram in albino rat after cybil intoxication. Saxena and Saxen (1997) reported serum protein level as an indicator of cybil toxicity in Rattus norvegicusk, while Saxena (1997) observed effect of deltamethrin on brain biochemistry of Rattus norvegiccus after hafen 20EC intoxication. Yadav (1997) studied the effect of synthetic pyrethroid, fevnvalerate 20EC, on liver biochemistry of Rattus norvegicus, while Diel et al. (1998) in vitro effects of the pyrethroid Sbioallethrin on lymphocytes and basophils from atopic and nonatopic subjects. Garey and Mary (1998) observed estrogenic and antiprogestagenic activities of pyrethroid insecticides, whereas Patel et al. (1998) hyperglycaemia in cypermethrin induced toxicity in crossbred calves. While Santoni et al. (1998) cypermethrin induced alteration to thymocyte distribution and functions in prenatally exposed rats. Saxena (1998) observed haemotobiochemistry of albino rat after intoxication of cybil, a Ind J Biol Stud Res Vol 3(1), 2013 pp 1-27


synsthetic pyrethroid, while Singh (1998) effect of synthetic pyrethroid on liver biochemistry of Rattus norvegicus. Talts et al. (1998) observed changes in behaviour and muscrinic receptor density after neonatal and adult exposure to bioallethrin, while Kale et al. (2000) reported early hepatic changes in rats induced by permethrin in comparison with DDT, while Krishnappa et al. (2000) on the effect of lambda cyhalothrin on biochemical parameters in male rats, however Prakash et al. (2000) studied neurotoxicological effect of fenvalerate in postnatal rats following passive exposure. Kumar (2001) reported biochemical alterations in rat brain following typeII pyrethroid intoxication.

PYRETHROIDS AND GENOTOXICITY Schmid et al. (1971) discussed basic aspects of the methodology of chemical mutagenesis. Matter (1976) reported problems of testing drugs for potential mutagenicity, while Tates and Natarajan (1976) carried out a correlative study on the genetic damage induced by chemical mutagens in bone marrow and spermatogonia of mice. Matsuoka et al. (1979) carried out chromosomal aberration tests on 29 chemicals combined with S9 mix in vitra, while Behere and Bhunya (1980) observed in vivo effects of commercial herbicide, amiben, on bone marrow and germ cells of mice. Chatterjee et al. (1982) reported effects of synthetic pyrethroid, Sumicidin, on mammalian chromosomes. Polakova et al. (1983) evaluated the mutagenic effects of decamethrin, whereas Pluijmen et al. (1984) mutagenicity of synthetic pyrethroids in Salmonella typhimurium strains and in V79 Chinese hamster cells. Effect of pyrethroid on lymphocytic mitogenic responsiveness was studied by Stelzer and Michel (1984). Amer and Aboul Ela (1985) reported cytogenetic effects of pesticides and found induction of micronuclei in mouse bone marrow by cypermethrin and rotenone, while Bradley (1985) cytotoxicity as a mechanism of carcinogenesis. Amer et al. (1987) studied effect of the synthetic pyrethroid insecticide cypermethrin on the mitosis of Vicia faba, while Bhunya and Behere (1987) relative genotoxicity of trichloroacetic acid (TCA) as revealed by different cytogenetic assays viz-bone marrow chromosome aberration, micronucleus and sperm-head abnormality in the mouse. Bradley et al. (1987) reported relationship among cytotoxicity, lysosomal break down, chromosome aberrations and DNA double strand breaks, whereas Hoellinger et al. (1987) cytotoxicity, cytogenotoxicity and allergenicity of certain pyrethroids. Bhunya and Pati (1988) evaluated genotoxic effects of a synthetic pyrethroid insecticide cypermethrin in mice in vivo, while Puig et al. (1988) cytogenetic damage induced in cultural human lymphocytes by the pyrethroid insecticides cypermethrin and fenvalerate. Carbonell et al. (1989) reported mitotic arrest induced by fenvalerate in human lymphocyte cultures, while Patia and Bhunya (1989) cytogenetic effects of fenvalerate in mammalian in vivo test system. Puig et al. (1989) analysed cytogenetic damage induced in cultured human lymphocytes by pyrethroid insecticides cypermethrin and fenvalerate. Bhunya and Pati (1990) observed effect of deltamethrin, a synthetic pyrethroid, on the induction of chromosome aberrations, micronuclei and sperm abnormalities in mice, while Surralles et al. (1990) induction of mitotic micronuclei by the pyrethroid insecticide fenvalerate in cultured human lymphocytes. Barrueco et al. (1992) reported cytogenetic effects of permethrin in cultured human lymphocytes, while Caballo et al. (1992) cytogenetic damage induced in CHO cells by the pyrethroid insecticide fenvalerate, whereas Dolara et al. (1992) sister chromatid exchanges in human lymphocytes induced by dimethoate, omethoate, deltamethrin, benomyl and their Ind J Biol Stud Res Vol 3(1), 2013 pp 1-27

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mixtures. Ghosh et al. (1992) evaluated cytotoxic effects of Sumicidin, a type II synthetic pyrethroid, on mice in vivo at 6, 12 and 24 hrs. after exposures, whereas Herrera et al. (1992) effects of permethrin on the inductonof sister chromatic exchanges and micronuclei in cultured human lymphocytes. Amer et al. (1995) studied induction of chromosomal aberrations and sister chromatic exchange in vivo and in vitro BY the insecticide cypermethrin, while Geeta and Devi (1993a) induction of chromosomal aberrations in spermatogoneal cells of mouse by cypermethrin. Geeta and Devi (1993b) reported cytogenetic effects of fenvalerate in germ cell of mice, whereas Agarwal et al. (1994) cytogenetic effect of deltamethrin on rat bone marrow. Barrueco et al. (1994) observed the induction of structural chromosomal aberration in human lymphocyte cultures and CHO cells by permethrin, while Scassellati et al. (1994) evaluated the toxic and genotoxic risk from work related exposure to chemical compounds, whereas Dianovsky and Sivikova (1995) observed DNA damaging effects of cyclophosphamide on human blood cells in vitro studies with the single cell get test (comet assay, while Jha and Singh (1995) clastogenicity of lanthanides which induced chromosomal aberrations in bone marrow cells of mice in vivo. Surralles et al. (1995) studied induction of micronuclei by five pyrethroid insecticides in whole blood and isolated human lymphocyte cultures, where as Kornuta et al. (1996) genotoxic effects of pesticides. Nakano et al. (1996) evaluated the genotoxic potential of flumethrin in mouse bone marrow by chromosomal analysis and micronucleus test, while Chauhan et al. (1997) in vivo induction of sister chromatic exchange in mouse bone marrow following oral exposure to commercial formulations of alpha cyano pyrethroids. Oxidative liver DNA damage in rats treated with pesticide mixtures was reported by Lodovici et al. (1997), while micronuclei formation in bone marrow cells of rats treated with meothrin (synthetic pyrethoid) was reported by Oraby (1997). Pendzich et al. (1997) observed sister chromatic exchanges and high frequency cells in men environmentally and occupationally exposed to ambient air pollutants. Sings et al. (1997) carried out in vitro cytotoxicity studies of alphamethrin, butachlor and monocrotophos in MDBK cell culture, while Mukhopadhyay et al. (1998) reported genotoxicity of sennosides on the bone marrow cells of mice, whereas Villarini et al. (1998) in vitro genotoxic effects of the insecticide deltamethrin in human peripheral blood leukocytes and described DNA damage (comet assay) in relation to the induction of sister chromatic exchanges and micronuclei. Institoris et al. (1999) reported sensitivity of immuno- and genotoxicological effects of subacute cypermethrin and permethrin exposure in rats. Nehez et al. (2000) reported simultaneous action of cypermethrin and two environmental pollutant metals, cadmium and lead, on bone marrow cell chromosomes of rats insubchronic administration. PYRETHROIDS IN COMBINATION Casida et al. (1966) reported metabolism of methylene-C14 dioxyphenyl compounds in relation to their synergistic action. Casida (1970) reported mixed function oxidase involvement in the biochemistry of insecticide synergists. Kamienski and Casida (1970) reported importance of demethylenation in the metabolism in vivo and in vitro opf methylene dioxyphenyl synergists and related compounds in mammals while, Douch and Smith (1971) metabolism of m-tert-butyl-phenyl Nmethyl carbamate in insects and mice, whereas Spoljar et al. (1971) observed response of hepatic microsomal mixed function oxidases to various types of insecticide chemical synergists administered to mice. Abernathy and Casida (1973) Ind J Biol Stud Res Vol 3(1), 2013 pp 1-27


reported esterase cleavage in relation to selective toxicity of pyrethroid insecticides. Abernathy et al. (1973) evaluated substrate specificity and toxicological significance of pyrethroid hydrolyzing esterases of mouse liver microsomes, whereas Jao (1973) detoxification of resmethrin and tetramethrin by insect and mouse esterases in relation to synergist action .Yamamoto (1973) investigated mode of action of synergists in enhancing the insecticidal activity of pyrethrum and pyrethroids, while Jao and Casida (1974) esterase inhibitors as synergists for (+)-transchrysanthemate insecticide chemicals. Gaughan et al. (1980) worked on pesticide interactions and reported effects of organophosphorus pesticides on the metabolism, toxicity and persistence of selected pyrethroid insecticides, while Bradbury et al. (1981) protection against pyrethroid toxicity in rats with mephenesin. Marei et al. (1982) analysed the persistence of permethin, cypermethrin, deltamethrin and fenvalerate in fat and brain of treated rats, while Soderlund et al. (1982) selective inhibition of separate esterases inrat and mouse liver microsomes hydrolyzing malathion, trans-permethrin and cispermethrin. Bradbury et al. (1983) emphasized the action of mephensin and other agents on the effects produced by two neurotoxic pyrethroids in the intact and spinal rat. Davaud et al. (1986) reported PK 11195 antagonism of pyrethroid induced proconvulsant activity, while Joy and Albertson (1991) interactions of GABA-A antagonists with deltamethrin, diazepam, pentobarbital and SKF 100330A in the rat dentate gyrus, whereas Cantalamessa (1993) acute toxicity of two pyrethroids, permethrin and cypermethrin in neonatal and adult rats. Wester et al. (1994) reported human in vivo percutaneous absorption of pyrethrin and piperonyl butoxide, while Durairaj and Selvarajan (1995) synergistic action of organophosphorus pesticides on fish, Oreochromis mossambicus. Ortiz et al. (1995) investigated acute toxicological effects in rats treated with a mixture of commercially formulated products containing methyl parathion and permethrin, while Paul and Simonin (1995) studied comparision of the toxicity of a synergized and non-synergised insecticide to young trout. Kulshrestha (1996) observed effect of synergized and non-synergised pyrethroid on serum cholesterol, total lipid and phospholipids in Rattus norvegicus, while Singh (1996) response of liver and serum phosphatases to a pyrethroid and synergised pyrethroid in Rattus norvegicus. Comparative evaluation of toxicity of carbaryl, cypermethrin and malathion of testes in mice was carried out by Venkateshwarlu et al. (1997). Vijjan et al. (1997) reported interaction of neem based pesticide formulation with deltamethrin, a pyrethroid insecticide in rates. Saxena and Singh (1999) observed toxicity of cybil and synergised cybil on Rattus norvegicus, while Bhattacharya (2000) comparative dose response relationship of certain synthetic pyrethroids in Rattus norvegicus. Kakko et al. (2000) reported that piperonyl butoxide potentiates the synpatosome ATPase inhibiting effect of pyrethrin, while Chaudhary (2001) individual effect of -cyhalothrin and in combination with piperonyl butoxide on certain blood elements of albino rat. Singh and Saxena (2001) reported effect of cybil (Cypermethrin 25EC) and cybil-sevin (carbaryl 50EC) combinations on liver and serum phaphatases in wistar albino rats, while Yang et al. (2001) repetitive nerve stimulation and stimulation single fibre electromyography studies in rats intoxicated with single or mixed insecticides.

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Chauhan, L.K.S., D.K. Agarwal, V. Sundararaman. 1997. In vivo induction of sister chromatic exchange in mouse bone marrow following oral exposure to commercial formulations of alpha-cyano pyrethroids. Toxicol Lett. 93(2-3): 153157. Chen, S.Y., Z.W. Zhang, F.S. He, P.P. Yao, Y.Q. Wu, J.X. Sun, L.H. Liu and Q.G.Li. 1991. An epidemiologic-study on occupational acute pyrethroid poisoning in cotton farmers. Brit. J. Ind. Med. 48: 77-81. Chinn. K. and T. Narahashi. 1986. Stabilization of sodium chennal states by deltamethrin in mouse neuroblastoma cells. J. Physiol. (Lond.) 380: 191-207. Chou, T.C. and P. Talalay. 1994. Quantitative analyses of dose-effect relationships, the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme. REgul. 22: 27-55. Chugh, Y., A. Sankaranarayanan and P.L. Sharma 1991. Effect of fenvalerate and endosulfan on behavioural despair and forced locomotor-activity in albino mice. Asia Pacific J. Pharmacol. 6: 31-35. Coats, J.R. 1990. Mechanisms of toxic action and structure-activity relationships for organochlorine and synthetic pyrethroid insecticides. Environ. Health. Perspect. 87: 255-262. Condes Lara, M., A. G. Guerrero and L. V. Riveroll. 1999. Effects of cypermethrin on the electroencephalographic activity of the rat: A model of chemically induced seizures. Neurotoxicol. Teratol. 21: 293-298. Crawford, M.J., A. Croucher and D.H. Hutson. 1981. Metabolism of cis and transcypermethrin in rats : balance and tissue retention study. J. Agric. Food. Chem. 29: 130-135. Cremer, J.E., V.J. Cunningham, D.E. Ray and G.S. Sarna. 1980. Regional changes in brain glucose utilization in rats given a pyrethroid insecticide. Brain Res. 194: 278-282. Cremer, J.E., and M.P. Seville. 1982. Comparative effects of two pyrethroids deltamethrin and cismethrin on plasma catecholamines and on blood glucose and lactate. Toxicol. Appl. Pharmacol. 66: 124-133. Cremer, J.E., and M.P. Seville. 1985. Changes in regional cerebral blood flow and glucose metabolism associated with symptoms of pyrethroid toxicity. Neurotoxicol. 6: 1-12. Crofton, K.M. and L.W. Reiter. 1984. Effects of two pyrethroid insecticides on motor activity and the acoustic startle response in the rat. Toxicol. Appl. Pharmacol. 75: 318-328. Crofton, K.M. and L.W. Reiter. 1987. Pyrethroid insecticides and the gammaaminobutyric acid A receptor complex : motor activity and the acoustic startle response in the rat. J. Pharmacol. Exp. Ther. 243: 946-954. Deshmukh, P.B. 1992, 3-Generation reproductive studies of a synthetic pyrethroid – cyhalothrin. Toxicol. Lett. 64(5): 779-781. Desi, I., L., Varga, I. Dobronyi and G.Y. Sklenarik. 1985. Immunotoxicological investigation of the effect of a pesticide : cypermethrin. Arch. Toxicol. Suppl. 8: 300-304. Desi, I., L., I. Dobronyi and L. Varga. 1986. Immuno, Neuro- and general toxicologic animal studies on a synthetic pyrethroid: cypermethrin. Ecotoxicol. Environ. Safety. 12: 220-232. Devaud. L.L., P. Szot and T.F. Murray. 1986. PK 1195 antagonism of pyrethroid-induced proconvulsant activity. Eur. J. Pharmacol. 121: 269-273.


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