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[Effects of renovation measures on the health status of persons, exposed to pyrethroids through carpets and flooring].

80 clients of a mobile unit for environmental quality testing were contacted after monitoring for potential toxic substances in their homes or places of work. Elevated concentrations of pyrethroids (in all cases at least permethrin) were found in these 80 cases in dust or materials, mainly because of pyrethroid treated carpetings. The clients were questioned whether they removed one or all of the contaminated carpets. Furthermore, they were questioned as to their state of health and the period of time which had passed since the carpets were removed. 75 of the 80 contacted clients had initially called the mobile unit for environmental quality testing because of health impairments, whereas 5 clients had done this only for preventive reasons. 47 (59%) of the contacted clients had removed all carpetings which were contaminated with permethrin. 8 (10%) clients had got rid of a part of the contaminated carpets and 25 (31%) clients did not remove any carpet. 39 (83%) of the clients who had removed all contaminated carpetings, described a complete or at least partial improvement of their complaints. The complaints of 6 (13%) clients did not improve despite removal of their carpets. The lowest concentration of permethrin that was assessed at the homes of clients, who, after removing all contaminated carpet floorings, described complete recovery, were 10-15 mg/kg dust and 15 mg/kg carpet, respectively. The effect of removing all contaminated carpetings on health improvement in comparison with the results of not removing any carpet was statistically significant (test: chi 2, p < 0.0001). The corrected contingency coefficient amounted to 0.71. In 3 cases, where the contaminated carpets had already existed for 5, 7 and 10 years in the homes of clients, there were still permethrin-concentrations of 115, 100 and 150 mg per kg dust. This result indicates that indoor contamination of permethrin is highly persistent.

Air Pollution, Indoor↗

Hydrolysis of pyrethroids by carboxylesterases from Lucilia cuprina and Drosophila melanogaster with active sites modified by in vitro mutagenesis.

The cloned genes encoding carboxylesterase E3 in the blowfly Lucilia cuprina and its orthologue in Drosophila melanogaster were expressed in Sf9 cells transfected with recombinant baculovirus. Resistance of L. cuprina to organophosphorus insecticides is due to mutations in the E3 gene that enhance the enzyme's ability to hydrolyse insecticides. Previous in vitro mutagenesis and expression of these modifications (G137D, in the oxyanion hole and W251L, in the acyl pocket) have confirmed their functional significance. We have systematically substituted these and nearby amino acids by others expected to affect the hydrolysis of pyrethroid insecticides. Most mutations of G137 markedly decreased pyrethroid hydrolysis. W251L was the most effective of five substitutions at this position. It increased activity with trans permethrin 10-fold, and the more insecticidal cis permethrin >130-fold, thereby decreasing the trans:cis hydrolysis ratio to only 2, compared with >25 in the wild-type enzyme. Other mutations near the bottom of the catalytic cleft generally enhanced pyrethroid hydrolysis, the most effective being F309L, also in the presumptive acyl binding pocket, which enhanced trans permethrin hydrolysis even more than W251L. In these assays with racemic 1RS cis and 1RS trans permethrin, two phases were apparent, one being much faster suggesting preferential hydrolysis of one enantiomer in each pair as found previously with other esterases. Complementary assays with individual enantiomers of deltamethrin and the dibromo analogue of cis permethrin showed that the wild type and most mutants showed a marked preference for the least insecticidal 1S configuration, but this was reversed by the F309L substitution. The W251L/F309L double mutant was best overall in hydrolysing the most insecticidal 1R cis isomers. The results are discussed in relation to likely steric effects on enzyme-substrate interactions, cross-resistance between pyrethroids and malathion, and the potential for bioremediation of pyrethroid residues.

Animals↗

Pyrethroids used indoor-ambient monitoring of pyrethroids following a pest control operation.

House dust and airborne particles (PM) were sampled before (T1) and 1 day (T2), 4-6 months (T3) as well as 10-12 months (T4) after a pest control operation (PCO). Cyfluthrin was applied in 11, cypermethrin in 1, deltamethrin in three and permethrin in four interiors. The pyrethroid concentrations in house dust and PM were measured by GC/MS with a detection limit for all pyrethroids of 0.5 mg/kg house dust and of 1 ng/m3 PM for deltamethrin and permethrin and 3 ng/m3 PM for cyfluthrin and cypermethrin. A general background concentration of permethrin (95th percentile: 5.9 mg/kg) and cyfluthrin (95th percentile: 34.9 mg/kg) in house dust was found. In general, an appropriately performed PCO lead to an increase of pyrethroids in house dust as well as in PM, in some cases up to 1 year after application. One day after the application the cyfluthrin concentration increased significantly from 0.25 (T1) to 33.8 mg/kg house dust (T2) and up to 4.9 ng/m3 in PM. The permethrin concentration increased significantly from 4.3 to 70 mg/kg in house dust and up to 18.1 ng/m3 in PM, deltamethrin increased to 54.5 mg/kg and 20.8 ng/m3 and cypermethrin to 14 mg/kg and 45.7 ng/m3. Thereafter a continuous decrease could be observed during the time course of 1 year. After 1 year the permethrin concentration in house dust was still 1/5 of the T2 concentration, whereas for cypermethrin and cyfluthrin only 1/14 and 1/23 of the T2 concentration were found. Deltamethrin was not detected at all after T2. Moreover, the data of this study showed significant, positive correlations between pyrethroids in house dust and in airborne particles especially one day after PCO.

Air Pollutants↗

Lymphocyte DNA damage in rats exposed to pyrethroids: effect of supplementation with Vitamins E and C.

Pesticides have been considered potential chemical mutagens. In fact, some studies show that various agrochemical ingredients possess mutagenic properties inducing mutations, chromosomal alterations or DNA damage. Experimental evidence shows a marked correlation between mutagenicity and carcinogenicity and indicates that short-term mutagenicity tests are useful for predicting carcinogenicity. The present study on rat exposed to two pyrethroids, cypermethrin and permethrin, showed different lymphocyte DNA damage depending on the type of pyrethroid, the dose, and the period of treatment. Data obtained from comet assay showed that oral treatment with 150 mg/kg body weight/day of permethrin (corresponding to 1/10 of LD50) for 60 days, induced a significant increase in all comet parameters. No lymphocyte DNA damage was measured after treatment with 25 mg/kg body weight/day of cypermethrin (corresponding to 1/10 of LD50) for the same period. A higher dose of permethrin (300 mg/kg body weight/day), for a shorter period (22 days), did not induce lymphocyte DNA damage, while supplementation with 200 mg/kg of Vitamins E and C protected erythrocytes against plasma membrane lipids peroxidation. Moreover, treatment with Vitamins E and C maintained the activity of glutathione peroxidase, which was reduced in the presence of permethrin, and reduced the osmotic fragility, which had increased following permethrin treatment.

Animals↗

Neurotoxic action of six pyrethroid insecticides on the isolated sciatic nerve of a frog (Rana ridibunda).

The neurotoxic action of six pyrethroid insecticides, four type II, (flucythrinate, deltamethrin, fenvalerate, fluvalinate) and two type I (cis- and trans-permethrin) was compared on the isolated sciatic nerve of frog. The nerve was exposed to pyrethroids for 30 min and action potentials were recorded for more than 45 hr after exposure. From the plots of the amplitude of the compound action potential vs time, it was possible to estimate, for each compound, the minimum effective concentration, the concentration which is required to reduce the amplitude of the compound action potential to 50% of its control value (mEC50). Flucythrinate was the most toxic compound, while toxicity decreased in the value: deltamethrin > fenvalerate > fluvalinate >> cis-permethrin > trans-permethrin. Low neurotoxicity of cis-permethrin and trans-permethrin (type I pyrethroids) was expected. The neurotoxicity of type I pyrethroids is mainly due to an action at the synapse, which are not present in the frog sciatic nerve preparation. The relative potencies of the four type II compounds agree with their acute toxicity estimated using the LD50.

Acetone↗

Determination of pyrethroid residues in agricultural products by an enzyme-linked immunosorbent assay.

To determine cypermethrin and permethrin in agricultural products, a competitive enzyme-linked immunosorbent assay (ELISA) method was employed. The matrix interferences were minimized by direct dilution of the extracts. No further cleanup was needed. A minimum matrix effect with a 1:10 dilution of white wine for cypermethrin and a 1:200 dilution of red and white wines, fruits, and vegetables for permethrin was found when phosphate-buffered saline containing 40% methanol was employed as the diluent. Good recoveries of spiked levels were observed. The mean percentage recoveries of cypermethrin spiked in white wine and permethrin spiked in red and white wines were 99.7, 74, and 78%, respectively. The mean percentage recoveries of permethrin spiked in apple, banana, cucumber, lettuce, onion, and peach were 99.2, 105, 70.2, 97.5, 94.4, and 89.4%, respectively. Validation of the ELISA method with permethrin-spiked lettuce and peach was carried out using gas chromatography with mass spectrometry, resulting in a good recovery and correlation.

Agriculture↗

Toxicity of six pesticides to common frog (Rana temporaria) tadpoles.

Amphibian species inhabiting agricultural areas may be exposed to pesticides during their aquatic larval phase. We tested the toxicity of six commonly used pesticides on Rana temporaria spawn and tadpoles. In acute tests, tadpoles were exposed to relatively high concentrations of azoxystrobin, cyanazine, esfenvalerate, MCPA ([4-chloro-2-methylphenoxy] acetic acid), permethrin, and pirimicarb for 72 h. Chronic exposure tests were performed from fertilization to metamorphosis with azoxystrobin, cyanazine, and permethrin at concentrations similar to those found in surface waters in agricultural areas in Sweden. The most lethal pesticides in the acute exposure were azoxystrobin, permethrin, and pirimicarb. Also, negative effects on the growth of the tadpoles were observed with azoxystrobin, cyanazine, and permethrin. The chronic exposure at lower pesticide concentrations did not result in increased mortality or impaired growth. However, we found a positive effect of permethrin on growth and size at metamorphosis. The results suggest that the examined pesticides can inflict strong negative effects at high concentrations but have no or relatively weak effects on R. temporaria spawn or tadpoles at concentrations found in Swedish surface waters.

Animals↗

Comparative evaluation of new synergists containing a butynyl-type synergophore group and piperonyl butoxide derivatives.

Cross-substituted derivatives of piperonyl butoxide (PBO) and MB-599 (proposed common name: verbutin) were synthesized and investigated as carbofuran and permethrin synergists against housefly, Musca domestica L. The majority of PBO and MB-599 derivatives were significantly more potent synergists for carbofuran than for permethrin. PBO, the most important representative of this series was not the most potent synergist for carbofuran or for permethrin. Cleavage of the methylenedioxy ring of methylenedioxyphenyl (MDP) polyether compounds resulted in complete loss of synergistic activity with both insecticides, but it could be restored or even improved by incorporating an alkynyl ether moiety into the molecule. The improved synergistic activity was found to be closely associated with the 2-butynyloxymethyl side-chain, suggesting that this can be regarded as a characteristic synergophore group. MB-599, one of the most promising compounds bearing this group showed considerably higher activity with carbofuran (synergist ratio, SR = 37.8) than with PBO (SR = 6.4). There was no significant difference between synergistic activities of MB-599 (SR = 4.6) and PBO (SR = 4) for permethrin.

Alkynes↗

Pyrethroid insecticide residues on vegetable crops.

Pyrethroid insecticides were applied on various vegetable crops as foliar treatments to determine dissipation rates. On Chinese broccoli (Guy Lon), Chinese mustard (Pak Choi) and Chinese cabbage (Kasumi, napa), fenvalerate was persistent with residues of 0.10, 0.14 and 0.11 mg kg-1, respectively, by day 21. Cypermethrin residues on head lettuce were below 0.1 mg kg-1 by day 10 but on the leafier romaine and endive varieties it was more persistent and required 14-19 days to dissipate below this concentration. After three applications, residues of cypermethrin in harvested carrots and of permethrin in eggplant were not detected on the day of application. On asparagus, deltamethrin and cypermethrin residues declined to less than 0.1 mg kg-1 by days 1 and 2, respectively; permethrin was more persistent, requiring more than 2 days to decline to less than 0.1 mg kg-1. Deltamethrin on dry (cooking) and Spanish onions was not detected on the day of application. On tomatoes, the concentration of permethrin was 0.093 mg kg-1 on the day of application and declined to about 0.05 mg kg-1 after 2-4 days. In general, permethrin, cypermethrin and deltamethrin residues declined to acceptable concentrations within an acceptable pre-harvest interval. Fenvalerate may be too persistent on these speciality crops unless a maximum residue limit > 0.1 mg kg-1 is permitted.

Crops, Agricultural↗

Pyrethroid tolerance in Culex pipiens pipiens var molestus from Marin County, California.

In May 2001 a sample of Culex pipiens pipiens variety molestus Forskål from Marin County, California, collected as larvae and reared to adults, was found to show reduced resmethrin and permethrin knock-down responses in bottle bioassays relative to a standard susceptible Cx. pipiens quinquefasciatus Say colony (CQ1). Larval susceptibility tests, using CQ1 as standard susceptible, indicated that the Marin mosquitoes had LC50 resistance ratios of 18.3 for permethrin, 12 for deltamethrin and 3.3 for pyrethrum. A colony of Marin was established and rapidly developed higher levels of resistance in a few generations after exposure to permethrin as larvae. These selected larvae were shown to cross-resist to lambda-cyhalothrin as well as to DDT. However, adult knock-down time in the presence of permethrin, resmethrin and pyrethrum was not increased after increase in tolerance to pyrethroids as larvae. Partial and almost complete reversion to susceptibility as larvae was achieved with S, S, S-tributylphosphorotrithioate and piperonyl butoxide (PBO), respectively, suggesting the presence of carboxylesterase and P450 monooxygenase mediated resistance. Insensitive target site resistance (kdr) was also detected in some Marin mosquitoes by use of an existing PCR-based diagnostic assay designed for Cx. p. pipiens L mosquitoes. Carboxylesterase mediated resistance was supported by use of newly synthesized novel pyrethroid-selective substrates in activity assays. Bottle bioassays gave underestimates of the levels of tolerance to pyrethroids of Marin mosquitoes when compared with mortality rates in field trials using registered pyrethroid adulticides with and without PBO. This study represents the first report of resistance to pyrethroids in a feral population of a mosquito species in the USA.

Animals↗

Efficacy of insecticide mixtures against larvae of Culex quinquefasciatus (Say) (Diptera: Culicidae) resistant to pyrethroids and carbamates.

The efficacy of insecticide mixtures of permethrin (pyrethroid) and propoxur (carbamate) was tested by larval bioassays on two strains of Culex quinquefasciatus (Say), one resistant to pyrethroids and the other resistant to carbamates. The method consisted in combining one insecticide at the highest concentration causing no mortality (LC0) with increasing concentrations of the second one. The concentration-mortality regression lines were determined for permethrin and propoxur alone and in combination, and synergism ratios (SR) were calculated in order to determine the magnitude of an increase or decrease in efficacy with use of the mixtures. With the pyrethroid-resistant strain (BK-PER), the results showed that propoxur at LC0 significantly enhanced the insecticidal activity of permethrin (SR50 = 1.54), especially on the upper range of the concentration-mortality regression. Conversely, when permethrin at LC0 was tested with propoxur against the carbamate resistant strain (R-LAB), an antagonistic effect was observed (SR50 = 0.67). With the BK-PER strain, an increased oxidative detoxification (MFO) appeared to be the main mechanism responsible for the synergistic interaction. Nevertheless, antagonism in the R-LAB strain is probably due to a physiological perturbation implying different target sites for pyrethroid (ie sodium channel) and carbamate insecticides [ie acetylcholinesterase (EC 3.3.3.7) and choline acetyltransferase (EC 2.3.1.6)].

Animals↗

Pesticides induced oxidative stress in thymocytes.

The role of oxidative stress in immune cell toxicity caused by the pesticides lindane, malathion and permethrin was investigated in thymic cells from C57BL/6 mice. Thymocytes treated with any of these pesticides (concentrations ranging between 50-150 microM) were found to generate both superoxide ((*)O(2) (-)) and H(2)O(2). The production of (*)O(2) (-) was detected with hydroethidine-ethidium bromide assay. H(2)O(2) production was monitored with a flow cytometric fluorescent (DCFH-DA) assay. All three pesticides stimulated (*)O(2) (-) release after 5 min exposure. Lindane and permethrin, but not malathion, continued to have significant (p < or = 0.05) effects on (*)O(2) (-) generation following 15 min of exposure. The lindane + malathion mixture was found to cause more-than-additive increase in (*)O(2) (-) production compared to individual pesticide treatments (at both 5 and 15 min). However, the effect of the lindane + permethrin mixture was not significantly different than individual components of this mixture. The effects of these pesticides on levels of antioxidant enzymes were also investigated, and only mixtures were found to have significant (p < or = 0.05) effects. Thus, lindane + malathion and lindane + permethrin mixtures increased total superoxide dismutase (SOD) specific activity, had no effect on catalase levels and inhibited GSH-peroxidase and GSH-reductase specific activities. Although the results of these studies do not explain the mechanism of action of these pesticides on the generation of (*)O(2) (-) and H(2)O(2), it is worthy of note that mixtures of these chemicals have oxidative responses greater than those of single chemicals.

Animals↗

Topical application of synthetic pyrethroids to cattle as a source of persistent environmental contamination.

Following the application of permethrin or cyhalothrin to cattle for the control of ectoparasites, the occurrence and persistence of these chemicals was assessed on the animals and in their environment. The release of permethrin from ear tags containing 1 g of the drug on cattle was followed for 65 days and lead to concentrations of 5 to 35 micrograms of permethrin per gram of hair on the shoulders. On the flanks of the animals, the corresponding values were 10 times lower. Across the 1.5 acre pasture, high concentrations of permethrin were measured at various locations and long after treatment: 6 micrograms/g on bark of a birch after one week, 5 micrograms/g on a pole of the fence after two weeks, 1 microgram/g in grass from a resting site of the animal after six weeks, and 0.5 microgram/g in bark of a pine tree after three month and two weeks after the animals had left the pasture. In similar assays, cyhalothrin applied to milk cows as a pour-on preparation was monitored. One week following treatment with 0.2 g/animal, hair cut from the shoulders contained 5 micrograms/g of the insecticide, which disappeared with a half-life of 12 days. Dust collected two weeks after the pour-on treatment from the milk barn where the cows were milked twice daily contained 47 micrograms/g of cyhalothrin, which disappeared with a half-life of 44 days. These results show that synthetic pyrethroids used on farm animals can be the source of widespread and persistent contamination.

Administration, Topical↗

Extended selections for pyrethroid resistance in the German cockroach (Dictyoptera: Blattellidae).

Selection experiments with a pyrethrins-susceptible and a pyrethrins-resistant strain of German cockroaches, Blattella germanica (L.), were conducted for 17 generations with either permethrin or fenvalerate as the selecting agent. Large nymphs were left on treated glass surfaces for extended periods of time each generation. Mortality was assessed at 24 h. The level of resistance was determined periodically by time-mortality testing. The VPI-susceptible strain served as the basis for comparison. The pyrethrins-susceptible strain developed resistance to pyrethrins early in the selection process; this strain ultimately became resistant to allethrin, phenothrin, permethrin, fenvalerate, cyfluthrin, and cypermethrin. Fenvalerate caused faster development of resistance than did permethrin. The pyrethrins-resistant strain, selected with fenvalerate, quickly became resistant to allethrin, permethrin, phenothrin, and fenvalerate. Ultimately, it developed resistance to all nine pyrethroids tested.

Animals↗

Susceptibility of stable flies (Diptera:Muscidae) from southeastern Nebraska beef cattle feedlots to selected insecticides and comparison of 3 bioassay techniques.

Insecticide susceptibility of field populations of stable flies, Stomoxys calcitrans (L.), was assayed using 3 exposure techniques: treated filter papers, treated glass petri dishes, and topical applications. Both topical applications and residual exposure to treated glass surfaces were suitable for testing susceptibility of stable flies to permethrin, stirofos, or methoxychlor. Residues on filter papers yielded inconsistent results with stirofos and methoxychlor. Significant concentration-mortality regression lines were generated with permethrin residues on filter papers, but approximately 1,000 times more insecticide was required to produce a toxic response when compared with permethrin residues on glass. Because of higher variability in response and the greater amount of insecticide required, residues on filter papers do not appear appropriate to test insecticide susceptibility in stable flies. Paired comparisons of field (F) and susceptible (S) stable flies resulted in field to susceptible ratios significantly > 1.0 only when the flies were treated topically, which suggests that topical application is more sensitive than residues on glass for the insecticides tested. Topical treatment with permethrin resulted in one FS(LD90) of 1.8-fold. Topical treatment with methoxychlor resulted in one FS(LD90) of 3.4-fold. However, the magnitude of these ratios is not larger than the significant differences observed within the susceptible laboratory colony from one generation to another. Intense exposure to insecticides is not known to have occurred in these field populations, indicating that the observed differences are the result of natural variation among stable fly populations and unrelated to prior selection with insecticides.

Animals↗

Laboratory studies of susceptibility and resistance to insecticides in Pediculus capitis (Anoplura; Pediculidae).

The susceptibility of local head lice to permethrin, sumithrin, deltamethrin, and carbaryl was determined by laboratory bioassays in field-collected colonies. Head lice collected from the infested heads of children 6-12 yr old were tested within 3 h of collection. The longest survival of control insects in the laboratory was obtained by keeping them in the dark at 18 degrees C and 70-80% RH. The base line susceptibility data obtained for insects collected from children not treated for lice, the reference colony, showed that deltamethrin caused the highest mortality of the insecticides tested (LC50, 0.06%). Permethrin, sumithrin, and carbaryl showed no significant difference in mortality (superposition of confidence intervals), being 10 times lower than that caused by deltamethrin. All field-collected lice required a higher LC50 of permethrin than the reference colony. Resistance levels varied from 3 to > 100 for colonies that were taken from children treated with anti-lice products. Lice colonies with permethrin resistance showed resistance to sumithrin and deltamethrin, but resistance was not observed to the carbamate carbaryl.

Animals↗

Acaricide resistance in northern fowl mite (Ornithonyssus sylviarum) populations on caged layer operations in Southern California.

Southern California caged layer operations were visited over 3 yr. Northern fowl mites from 26 field populations were tested for acaricide resistance using a capillary pipette and glass dish bioassay. One was a susceptible field population with no pesticide exposure for over 30 yr (reference site for resistance ratio calculation). Technical and commercial formulations of malathion, carbaryl (Sevin), permethrin, and a commercial formulation of tetrachlorvinphos/dichlorvos (Ravap) were tested. Malathion did not have high activity for mites relative to other materials, but resistance to both technical and commercial formulations was low (< 5x). Resistance to other materials was moderate to extreme. Frequency of carbaryl resistance (> 10x) was higher with the commercial (88%) than the technical material (41%); 19% of the populations had resistance > 100x to commercial carbaryl. Frequency of Ravap resistance (> 10x) was 68%; 8% of populations had resistance > 100x. Frequency of permethrin resistance (> 10x) was 72% for the technical material and 88% for the commercial formulation. Extreme permethrin resistance (> 1,000x) was observed in 56 and 50% of mite populations assayed using the technical and commercial formulations, respectively. Among sites, resistance to permethrin was uncorrelated with resistance to other chemicals, suggesting a different resistance mechanism. Resistance to carbaryl and Ravap was highly correlated [r = 0.76 at the LC50 level (concentrations estimated to be lethal to 50% of the test population) and r = 0.99 at the LC95 level], suggesting a common resistance mechanism. Producers currently depend completely on pesticides to control mite infestations. Mite resistance to registered materials emphasizes the need for integrated control measures.

Agriculture↗

The potential of some synthetic pyrethroids for control of the cattle tick (Boophilus microplus).

As part of a continuing programme to aid in the development of new acaricides, the potentials of three synthetic pyrethroids, permethrin, cypermethrin and decamethrin, were assessed against a range of resistant strains of the cattle tick (Boophilus microplus). The compounds were shown to be acaricidal, with decamethrin the most effective, giving efficient control of susceptible and organo-phosphorus resistant strains of the cattle tick at concentrations as low as one fifth of those previously used for any commercial acaricide. However higher concentrations were required for satisfactory control of the DDT-resistant strain. Permethrin-selection of a field strain containing a low percentage of DDT-resistant ticks led to rapid development of resistance to a level equivalent to that of the DDT-resistant strain. Further selection increased resistance to permethrin to a higher level than that shown in the DDT-resistant strain. This increased resistance to permethrin appears to be restricted mainly to this compound and is not associated with a marked increase in resistance to cypermethrin, decamethrin or DDT. The potential of organo-phosphorus compounds to potentiate the pyrethroids when the two classes of compounds are used as mixtures against the pyrethroid-resistant and susceptible strains was confirmed.

Animals↗