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Comparison of detection sensitivity of immuno- and genotoxicological effects of subacute cypermethrin and permethrin exposure in rats.

Institoris L, Undeger U, Siroki O, Nehez M, Desi I.

Department of Public Health and WHO Collaborative Centre for Chemical Safety, Albert Szent-Gyorgyi Medical University, Szeged, Dom ter, Hungary. ist puhe.szote.u-szeged.hu

Immuno- and genotoxicological effects of a 28-day oral treatment by equitoxic (1/10, 1/25, 1/50 LD50) doses of cypermethrin (55.4, 22.2, and 11.1 mg/kg) and permethrin (125.7, 50.3, and 12.6 mg/kg) were compared on male Wistar rats. Humoral and cell-mediated immunity were investigated by PFC assay and delayed type hypersensitivity (DTH) reaction (footpad swelling assay), and the genotoxic effects were studied by structural and numerical chromosome aberrations in bone marrow cells. The experimental system also involved certain general toxicological (body weight gain, organ weights) and haematological [white blood cell (WBC), red blood cell (RBC), haematocrit (Ht) and cell content of the femoral bone marrow] investigations. Among the immune function assays, only DTH reaction decreased at the two higher cypermethrin (CY) doses. These doses also increased the number of numerical chromosome aberrations of the bone marrow cells but did not change the number of structural aberrations. All CY doses decreased the mean cell volume (MCV) of RBCs and the Ht value. The two higher doses also reduced the WBC count in the peripheral blood. Permethrin (PE), in the applied dose range, had no effect on the examined immune function parameters, but all three doses increased the number of numerical chromosome aberrations. A dose-dependent increase in the liver weight, decreased MCV value, and elevated cell content of the femoral bone marrow were also observed. Under these experimental conditions, examination of chromosome aberrations proved to be less sensitive in detection of exposure by cypermethrin than applied immune function assays did. Permethrin, on the contrary, increased the number of numeric aberrations at all dose levels but had no effect on the immune function parameters examined.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10513999&dopt=Abstract permethrin Elimite



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Elevated oxidase and esterase levels associated with permethrin tolerance in Anopheles gambiae from Kenyan villages using permethrin-impregnated nets.

Vulule JM, Beach RF, Atieli FK, McAllister JC, Brogdon WG, Roberts JM, Mwangi RW, Hawley WA.

Vector Biology and Control Research Centre (Kenya Medical Research Institute), Kisumu.

The permethrin tolerance (PT) of a population of the mosquito Anopheles gambiae (Diptera: Culicidae) increased following the introduction of permethrin-impregnated nets for malaria control in certain villages near Kisumu, western Kenya. Using a biochemical test that indirectly measures oxidases associated with permethrin resistance, we found that this population had higher oxidase levels than a comparison population from villages without impregnated nets. Mosquitoes from a colony of An. gambiae selected for PT, the RSP (reduced susceptibility to permethrin) strain, were exposed to permethrin with or without the oxidase inhibitor piperonyl butoxide (PB). Significantly higher mortality rates occurred when permethrin was synergized by PB, presumably by suppression of oxidases responsible for PT. An unselected (UNS) colony of An. gambiae that was more susceptible than RSP in a permethrin-susceptibility bioassay (i.e. LT50 22 min for UNS, vs. 42min for RSP) was compared with the RSP colony for levels of oxidases and esterases. The levels of both enzymes were very significantly higher in the RSP strain (P<0.0001). We speculate that use of impregnated nets selected for higher oxidase and esterase levels in An. gambiae to metabolize permethrin acquired from the nets. Both oxidase and esterase mechanisms could confer cross-resistance to other pyrethroids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10514048&dopt=Abstract permethrin Elimite



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Effects of permethrin at different temperatures on pyrethroid-resistant and susceptible strains of Anopheles.

Hodjati MH, Curtis CF.

London School of Hygiene and Tropical Medicine, UK.

The influence of temperature (16, 22, 28, 37 degrees C) on effects of permethrin was investigated for susceptible and pyrethroid-resistant strains of the mosquitoes Anopheles gambiae and An. stephensi (Diptera: Culicidae). Young unfed female adult mosquitoes were exposed to 0.25% permethrin test papers or to polyester netting treated with permethrin 500mg a.i./m2. The time to 50% knockdown (KT50) declined as temperature increased, i.e. there was a positive temperature coefficient of this effect of the pyrethroid. Resistance ratios (comparing KT50 values) between resistant and susceptible An. stephensi ranged between 2.5 and 4.4 at the different temperatures. Comparative tests of pyrethroid tolerance of different strains would be valid over the 22-28 degrees C range but, when using a discriminating dose to detect resistance, more precise temperature control is desirable. Mortality 24h after exposure to 0.25% permethrin of both susceptible and resistant strains of An. stephensi showed a negative correlation with temperature between 16 and 22 degrees C and a positive correlation at higher temperatures. In An. gambiae, however, the correlation was positive over the whole range. Irritancy of permethrin-treated netting to Anopheles females (measured as time lapse until first flight take-off, and the number of take-offs during 7.5 min exposure) was positively correlated with temperature in all four strains and was much greater for the susceptible than the resistant strains.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10608231&dopt=Abstract permethrin Elimite



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Modifications of pyrethroid effects associated with kdr mutation in Anopheles gambiae.

Chandre F, Darriet F, Duchon S, Finot L, Manguin S, Carnevale P, Guillet P.

Laboratoire de Lutte contre les Insectes Nuisibles, Institute for Research & Development (IRD formerly ORSTOM), Montpellier, France. chandre ipr.ird.ci

Effects of knockdown resistance (kdr) were investigated in three pyrethroid-resistant (RR) strains of the Afrotropical mosquito Anopheles gambiae Giles (Diptera: Culicidae): Kou from Burkina Faso, Tola and Yao from Cote d'Ivoire; compared with a standard susceptible (SS) strain from Kisumu, Kenya. The kdr factor was incompletely recessive, conferring 43-fold resistance ratio at LD50 level and 29-fold at LD95 level, as determined by topical application tests with Kou strain. When adult mosquitoes were exposed to 0.25% permethrin-impregnated papers, the 50% and 95% knockdown times (KdT) were 23 and 42 min for SS females, compared with 40 and 62 min for RS (F1 Kou x Kisumu) females. On 1% permethrin the KdT50 and KdT95 were 11 and 21 min for SS compared with 18 and 33 min for RS females. Following 1 h exposure to permethrin (0.25% or 1%), no significant knockdown of Kou RR females occurred within 24 h. Permethrin irritancy to An. gambiae was assessed by comparing 'time to first take-off' (TO) for females. The standard TO50 and TO95 values for Kisumu SS on untreated paper were 58 and 1044 s, respectively, vs. 3.7 and 16.5 s on 1% permethrin. For Kou RR females the comparable values were 27.3 s for TO50 and 294 s for TO95, with intermediate RS values of 10.1 s for TO50 and 71.9 s for TO95. Thus, TO values for RS were 2.7-4.4 times more than for SS, and those for RR were 7-18 times longer than for SS. Experiments with pyrethroid-impregnated nets were designed to induce hungry female mosquitoes to pass through holes cut in the netting. Laboratory 'tunnel tests' used a bait guinea-pig to attract mosquitoes through circular holes (5 x 1 cm) in a net screen. With untreated netting, 75-83% of laboratory-reared females passed through the holes overnight, 63-69% blood-fed successfully and 9-17% died, with no significant differences between SS and RR genotypes. When the netting was treated with permethrin 250mg ai/m2 the proportions that passed through the holes overnight were only 10% of SS vs. 40-46% of RR (Tola & Kou); mortality rates were 100% of SS compared with 59-82% of RR; bloodmeals were obtained by 9% of Kou RR and 17% of Tola RR, but none of the Kisumu SS females. When the net was treated with deltamethrin 25 mg ai/m2 the proportions of An. gambiae that went through the holes and blood-fed successfully were 3.9% of Kisumu SS and 3.5% of Yaokoffikro field population (94% R). Mortality rates were 97% of Kisumu SS vs. 47% of Yaokoffikro R. Evidently this deltamethrin treatment was sufficient to kill nearly all SS and half of the Yaokoffikro R An. gambiae population despite its high kdr frequency. Experimental huts at Yaokoffikro were used for overnight evaluation of bednets against An. gambiae females. The huts were sealed to prevent egress of mosquitoes released at 20.00 hours and collected at 05.00 hours. Each net was perforated with 225 square holes (2 x 2 cm). A man slept under the net as bait. With untreated nets, only 4-6% of mosquitoes died overnight and bloodmeals were taken by 17% of SS vs. 29% of Yaokoffikro R (P<0.05). Nets treated with permethrin 500 mg/m2 caused mortality rates of 95% Kisumu SS and 45% Yao R (P<0.001) and blood-feeding rates were reduced to 1.3% of SS vs. 8.1% of Yao R (P<0.05). Nets treated with deltamethrin 25 mg/m2 caused mortality rates of 91% Kisumu SS and 54% Yao R (P<0.001) and reduced blood-feeding rates to zero for SS vs. 2.5% for Yao R (P>0.05). (ABSTRACT TRUNCATED)

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Selection of permethrin resistance in the malaria vector Anopheles stephensi.

Chakravorthy BC, Kalyanasundaram M.

Vector Control Research Centre, Indira Nagar, Medical Complex Pondicherry, India.

The laboratory strain of Anopheles stephensi, a well-known urban malaria vector, was selected with permethrin, a synthetic pyrethroid at LD90 level up to five generations. The selection resulted in the development of resistance in F5 generation to the tune of 13-fold to permethrin and cross-resistance to the tune of 7-fold to cypermethrin, 9-fold to alphamethrin, and 10-fold to deltamethrin. The development of cross-resistance to 4% DDT was also noticed. The susceptibility status against 5% malathion was maintained throughout the five generations. The synergistic effect of piperonyl butoxide with permethrin did not overcome the development of resistance. The development of resistance showed a significant relationship between hatchability and different generations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1286731&dopt=Abstract permethrin Elimite