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Acute toxicological effects in rats treated with a mixture of commercially formulated products containing methyl parathion and permethrin.

The study examined the interactions between a commercial formulation of methyl parathion (CF-MP) and a commercially formulated product of permethrin (CF-PMT) in male rats. The acute toxicity (LD50 values) and brain cholinesterase activity were investigated as toxicological endpoints. Results indicated that CF-MP modified the acute toxicity of CF-PMT. When animals were treated with a mixture, the addition of 380 mg/kg of CF-MP reduced the LD50 of CF-PMT by only 9.0%; however, when rats received CF-MP at 464 mg/kg, the LD50 of CF-PMT was reduced by 37% (P < 0.001). Also, CF-PMT decreased the CF-MP-induced inhibition of cholinesterase activity by 50% (P < 0.05). It was interesting to observe that xylene, which is the most abundant component in the vehicle of both formulations, had no effect on the CF-MP-induced inhibition of the cholinesterase activity. There was no relation between lethality and the inhibition of the brain cholinesterase activity in rats treated with mixtures containing CF-MP+CF-PMT or with either commercially formulated product alone. Considering the increased toxicity observed in rats treated with CF-PMT+CF-MP, it would be advisable to investigate further the interactions between both pesticides.

Animals↗

Toxicity of microencapsulated permethrin to selected nontarget aquatic invertebrates.

Microencapsulated permethrin (penncapthrin) was evaluated under laboratory conditions for its toxicity toward several nontarget aquatic invertebrates. Average LC50 estimates for selected lotic invertebrates, based on a one hour dosing regime, were: 2.71 mg/L for Simulium vittatum, 4.59 mg/L for Hydropsyche spp., and 13.41 mg/L for Isonychia bicolor. In acute static tests with Daphnia magna, there was no significant difference (p less than or equal to 0.05) between the toxicity of penncapthrin at 96 h (LC50 range: 6.80-22.5 micrograms/L) and the EC formulation at 72 h (LC50 range: 0.6-21 micrograms/L). Comparatively, the toxicity of microencapsulated methyl parathion (penncap-m) was not significantly different from that of penncapthrin toward D. magna, the former having LC50 estimates ranging form 0.3-12.25 micrograms/L. LC50 estimates associated with Daphnia pulex ranged from 19 to 131 micrograms/L. The toxicity of penncapthrin and penncap-m toward D. pulex was difficult to determine because of frequent control mortality due to food deprivation resulting from the need to run tests for longer than 48 h. In successful tests, LC50 estimates ranged from 19 to 28 micrograms/L for penncapthrin and 0.08 to 25 micrograms/L for penncap-m after 72 h exposure. In long term toxicity tests, 95% of D. magna at 1 microgram/L, 44% at 10 micrograms/L, and 20% at 15 micrograms/L survived after 39 days exposure. Less than 15% of D. pulex survived over the same concentration range following 32 days exposure. Despite same drawbacks, long-term toxicity tests were more appropriate than short-term tests for evaluating microencapsulated pesticides because of reduced variability in LC50 estimates and lower control mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute toxicity of two pyrethroids, permethrin, and cypermethrin in neonatal and adult rats.

The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonyl butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (chi 2 = 5.97; p < 0.05) and PERM (chi 2 = 4.37; p < 0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.

Aging↗

High performance liquid chromatographic determination of diazinon, permethrin, DEET (N, N-diethyl-m-toluamide), and their metabolites in rat plasma and urine.

A rapid method was developed for the analysis of the insecticide (A) diazinon (O,O-diethyl O-2-isopropyl-6-methylpyridimidinyl) phosphorothioate, its metabolites (B) diazoxon (O,O-diethyl O-2-isopropyl-6-methylpyridimidinyl) phosphate, and (C) 2-isopropyl-6-methyl-4-pyrimidinol, the insecticide (D) permethrin [3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methylester], its metabolites (E) m-phenoxybenzyl alcohol, and (F) m-phenoxybenzoic acid, the insect repellent (G) DEET (N,N-diethyl-m-toluamide), and its metabolites (H) m-toluamide and (I) m-toluic acid in rat plasma and urine. The method is based on using C18 Sep-Pak cartridges (Waters Corporation, Milford, Mass., U.S.A.) for solid phase extraction and high performance liquid chromatography with a reversed phase C18 column, and absorbance detection at 230 nm for compounds A, B, and C, and at 210 nm for compounds D-I. The compounds were separated using a gradient from 1% to 99% acetonitrile in water (pH 3.0) at a flow rate ranging between 1 and 1.7 mL/min in a period of 17 min. The limits of detection were ranged between 20 and 100 ng/mL, while limits of quantification were 80-200 ng/mL. The relationship between peak areas and concentration was linear over a range of 100-1000 ng/mL. This method was applied to determine the above insecticides and their metabolites following dermal administration in rats.

Animals↗

Field trial of the efficacy of a combination of imidacloprid and permethrin against Tunga penetrans (sand flea, jigger flea) in dogs in Brazil.

In a field trial in Brazil 17 dogs penetrated by females of the jigger flea, Tunga penetrans, were topically treated with a combination of 10% imidacloprid and 50% permethrin (Advantix), while 17 dogs remained untreated. The follow-up controls on days 7, 14, 21 and 28 post-treatment clearly showed that, beginning from day 7, the flea load in treated dogs decreased, so that most of the dogs became free of tungiasis lesions, while in the untreated group the flea load remained high. Since the dogs distribute the flea eggs throughout the village, leading to a high incidence of tungiasis in humans, treatment of dogs probably also decreases the number of cases of tungiasis in the latter.

Animals↗

Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children.

The incidence of clinical attacks of malaria was significantly less in Gambian children aged 1-9 years who slept in villages where all the bed nets (mosquito nets) were treated with permethrin than in children who slept in control villages with placebo-treated nets. Significant differences in changes in spleen size and in packed cell volume were also observed between the 2 groups during the course of a rainy season. No side effect was noted. Treatment of bed nets with insecticide is a form of malaria control that is well suited to community participation and can readily be incorporated into primary health care programmes. Insecticide-treated nets may be more effective in areas of seasonal or low intensity transmission than in areas with heavy perennial challenge.

Animals↗

Scabies in nursing homes: an eradication program with permethrin 5% cream.

Permethrin 5% cream was used to treat scabies in three large nursing homes under a compassionate-plea protocol for chronic, therapy-resistant infestations. All residents, staff, and frequent visitors were treated whether or not symptomatic. Family members of these groups were treated either when symptomatic or directly exposed to scabies. Nine hundred ninety-five persons were treated, 202 of whom were diagnosed with scabies. Approximately 35% (111 of 313) of nursing home residents were diagnosed with scabies. These were patients in whom multiple treatments with other scabicides were unsuccessful. At the completion of the study, 195 patients were examined for efficacy of treatment. Of these, 91 (46.7%) had clearing of lesions with one medication application, 77 (39.5%) with two treatments, and 23 (11.8%) with three or more treatments. The overall cure rate was 98%. Adverse experiences occurred in 2.4% of cases and were mild (i.e., pruritus and rash).

Adolescent↗

An outbreak of lindane-resistant scabies treated successfully with permethrin 5% cream.

An outbreak of scabies in 12 persons, after contact with a hospitalized patient with lindane-resistant Norwegian scabies, is described. Resistance to treatment was documented in 7 of 10 patients treated with lindane. Of these, one responded to crotamiton 10% cream, and the remaining six were cured by a single treatment with permethrin 5% cream.

Adolescent↗

Isocratic reversed-phase liquid chromatographic method for the simultaneous determination of (S)-methoprene, MGK264, piperonyl butoxide, sumithrin and permethrin in pesticide formulation.

An isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method development for the simultaneous determination of five active ingredients (S)-methoprene, MGK264, PBO, sumithrin and permethrin in a new complex pesticide formulation is described. These active ingredients have similar polarities and contain isomers. The RP-HPLC method development approach began with the selection of a column based on the component structure information, bonded phase, and particle physical characteristics. Second, the mobile phase composition was changed to improve peak resolution and peak sensitivity, especially with analytes containing isomers. Choosing the match between the stationary phase and mobile phase composition, the developed RP-HPLC method not only can simplify the procedure appreciably but also significantly decrease total analysis time and increase peak height. The developed isocratic RP-HPLC method for the analysis of this new formulation was then validated for specificity, linearity, precision, and accuracy. The chromatographic peak identification was identified by LC-MS using the electrospray ionisation in the positive-ion mode.

Chromatography, High Pressure Liquid↗

The effects of pyridostigmine bromide, permethrin, and DEET alone, or in combination, on fixed-ratio and fixed-interval behavior in male and female rats.

Concurrent exposure to pyridostigmine bromide (PB), permethrin (PERM) and/or N,N-diethyl-m-toluamide (DEET) may have contributed to the development of a syndrome that appears to have afflicted military personnel who served during the Gulf War. The present experiment sought to evaluate the behavioral effects of these compounds alone, or in various combinations, in male and female rats. Subjects were exposed to a multiple fixed-ratio (FR) 50, fixed-interval (FI) 2-min schedule of reinforcement. PB dose-dependently decreased FR and FI response rates. FR responding was disrupted by lower doses and there were no differences between the sexes. PERM vehicle administration decreased response rates maintained by both schedules of reinforcement; this was offset by an increase in response rate after the administration of the intermediate dose of PERM. The highest dose of PERM decreased both FR and FI response rates. FR rates in male rats were more disrupted than those in female rats. Only the highest dose of DEET decreased FR and FI response rates in male and female rats. FR rates were more disrupted in female rats than in male rats. Synergistic effects were only observed when FI response rates decreased in male rats upon exposure to half the low dose of PB with half the low dose of PERM or half the low dose of PB with half the low dose of DEET. The results of this experiment thus show that small doses of PB, PERM and DEET disrupt well-established, schedule-controlled behavior in male and female rats in a schedule- and gender-dependent manner; schedule-dependent and gender-dependent synergistic effects were also observed. The mechanism by which the compounds exert these behavioral effects remains to be determined.

Animals↗

Determinants of the Permethrin Impregnated Bednets (PIB) in the Republic of Benin: the role of women in the acquisition and utilization of PIBs.

An important aspect of malaria control strategies has been the use of prophylactic measures such as impregnated bednets; however, adoption of this strategy has been slow and uneven. This study considers the factors determining Permethrin Impregnated Bednets (PIB) use in the context of a PIB promotion project in a rural area of Benin undertaken between 1992 and 1995. Quantitative data, on socio-demographic characteristics, malaria knowledge, attitudes, and practices, were gathered from 191 households of PIB users and non-users for comparative purposes using a questionnaire format. Qualitative data were collected from 23 focus group discussion sessions and 16 semi structured interviews. Women's income, men's educational level, and women's participation in communal organizations were the principal variables distinguishing user households from non-user households. Recourse to non-western medicine and, in particular, to medicinal teas which are considered preventive or curative correlates negatively with PIB use. The qualitative data shows that informants consider exposure to the sun, especially while engaged in agriculture work, a principal cause of malaria, and that PIB adoption is not considered justified in a context where there is a quasi chronic shortage of financial resources and where confidence in the efficacy of non-western medicine prevails. Because they have primary responsibility for the health of their families and are more aware of children's vulnerability to malaria, women are more inclined than men to want to buy PIBs. However, because the household head, who is most often male, sets family consumption priorities using family income, women often have to resort to using their own income, which is often considerably lower than that of men, to buy PIBs. Support for community initiatives which are directed to women's work, linked with intensive effort to sensitize men to the mechanisms of malaria transmission and the principal groups at risk, is seen as a means to increase PIB acquisition and use.

Bedding and Linens↗

Validated HPLC method for quantifying permethrin in pharmaceutical formulations.

An isocratic HPLC method for permethrin determination in raw material and pharmaceutical presentations as lotion and shampoo has been developed and validated following ICH recommendations. Cis and trans- isomers, impurities and degradation products are well separated. The chromatographic analysis were performed on a 4 microm particle C-18 Nova-Pak (Waters, Madrid, Spain) column (15 x 0.39 cm) kept in a Biorad column oven at 35 degrees C. Mobile phase consisted of methanol--water (78:22, v/v) at a flow rate of 1 ml/min. UV detection was performed at 272 nm and peaks were identified with retention times as compared with standards and confirmed with characteristic spectra using the photodiode array detector.

Chromatography, High Pressure Liquid↗

Immunotoxicological investigation of subacute combined exposure by permethrin and the heavy metals arsenic(III) and mercury(II) in rats.

Effects of combined 28 days of oral exposure to the insecticide Permethrin (Pe), alone or in combination with arsenic-III (As) or Hg-II (Hg), were investigated on certain toxicological (body weight, organ weights), haematological (white blood cell (WBC) and red blood cell (RBC) counts, haematocrit (Ht), mean cell volume (MCV), cell content of the femoral bone marrow) and immune function (IgM-PFC, delayed-type hypersensitivity (DTH) reaction) parameters of male Wistar rats. Immunotoxic (H = high) and NOEL (L = low) doses of the three substances were determined in preliminary experiments under identical experimental conditions. In the present study, the immunotoxic dose of Pe (126 mg/kg) was combined with the NOEL dose of As (3.33 mg/kg) or Hg (0.40 mg/kg), and the NOEL dose of Pe (12.6 mg/kg) with the immunotoxic dose of As (13.3 mg/kg) or Hg (3.20 mg/kg). A separate group of animals, treated with the appropriate high dose component only, was used as internal control. Significant interactions were observed in the liver weight of the animals treated with Pe(H)-As(L) or As(H)-Pe(L), in the cell content of the femoral bone marrow in case of Pe(H)-As(L) and Pe(H)-Hg(L) combinations, as well as in the number of PFCs formed from 10(6) spleen cells in the Pe(H)-As(L) and in the maximum of DTH reaction in the Hg(H)-Pe(L) combination. The results show that combined exposures by the investigated substances modify the toxic (including immunotoxic) effects of the single compounds. These findings rise the probability that the interactions observed can also be present in human situations altering the health hazard of this three chemicals.

Animals↗

Diversion of Anopheles gambiae from children to other hosts following exposure to permethrin-treated bednets.

Permethrin-treated bednets reduce mortality and morbidity from malaria in Gambian children. However, it is not certain how this effect is achieved, as neither mosquito numbers nor the human blood index of indoor-resting female Anopheles gambiae Giles sensu lato (Diptera: Culicidae) mosquitoes have been reduced when treated bednets were introduced into a community. One possibility is that insecticide-treated bednets divert mosquitoes from children to adults. To investigate this hypothesis, a cross-over trial with insecticide-treated bednets was undertaken in two small Gambian villages. To differentiate mosquitoes that had fed on children from those that had fed on adults, all children in the study villages were immunized with rabies vaccine before the trial. Using the detection of rabies antibody in a bloodmeal as an indicator that a mosquito had bitten a child, it was found that the percentage of blood-fed mosquitoes caught indoors that had bitten a child fell significantly from 30.8% to 9.2% and from 28.0% to 6.9% in each village after insecticide-treated bednets were introduced. To investigate the possibility that some diversion to animals had occurred, a PCR analysis for human beta-globin DNA was undertaken on selected samples. The results of this investigation were confusing, as some rabies-antibody positive bloodmeals were negative for human DNA. This may have been due to cross-reacting antibodies in animal sera and/or DNA degradation by digestion in the mosquito. Although good evidence for diversion of mosquitoes away from children was obtained, it remains uncertain whether diversion was mainly to adult humans, to animals or to both.

Adult↗

An observer-blinded study of 1% permethrin creme rinse with and without adjunctive combing in patients with head lice.

OBJECTIVES: To determine if NIX (Warner Lambert Healthcare, Morris Plains, NJ) 1% Permethrin Creme Rinse Lice Treatment (1% PLT) without combing will effectively treat >/=95% of patients on day 2 or on day 15; to determine whether combing influences efficacy. STUDY DESIGN: A randomized, observer-blinded study enrolled 95 infested adults and children. All patients were treated with 1% PLT on day 1 and, if still infested, on day 8. One third of households were randomized to the combing group and two thirds to the no-combing group. Efficacy was assessed by: (1) visual inspection on days 1, 2, 8, 9, and 15 and, (2) shampooing/straining on days 2, 9, and 15. The target efficacy was 95%. RESULTS: In the no-combing group, the lice-free rate was 83.1% on day 2 (95% CI, 71.0-91.6), 45.8% on day 8 (before second treatment) (95% CI, 32.7-59.2), 77.6% on day 9 (95% CI, 64.7-87.5), and 78.3% on day 15 (95% CI, 65.8-87.9). Adjunctive combing did not improve efficacy on any day. CONCLUSIONS: In this population, 1% PLT was significantly less than 95% effective and suggests resistance to 1% PLT. The failure of nit removal combing by nonprofessional caregivers to improve efficacy demonstrates the unreliability of combing as adjunctive treatment in this setting.

Adolescent↗

Percutaneous absorption of cis- and trans-permethrin in rhesus monkeys and rats: anatomic site and interspecies variation.

Dermal absorption of cis- and trans-permethrin isomers was determined in rhesus monkeys and Sprague-Dawley rats. Four 14C radiolabels were used (cis alcohol, cis cyclopropyl, trans alcohol, and trans cyclopropyl). One microcurie of each radiolabel was applied to either the forehead or forearm of rhesus monkeys or to the midlumbosacral region of the rat. Urine was collected for 7 or 14 d. Correction factors for incomplete urine excretion were derived from measurements of radiolabel in the urine following im injection of an equivalent dose. It was noted that the total im dose recovered in the urine of both species was lower for the cis isomer than for the trans isomer. There was no significant difference between the dermal absorption of the cis isomer and that of the trans isomer in monkeys. The forehead, however, was more permeable for both isomers than the forearm (alcohol- and cyclopropyl-labeled cis and trans isomers, respectively, showed permeation in forehead, cis 28 +/- 6%, 24 +/- 6%, trans 21 +/- 3%, 14 +/- 4%, forearm, cis 9 +/- 3%, 9 +/- 3%, trans 12 +/- 3%, and 5 +/- 2%). There was no difference between absorption of the isomers (cis 46 +/- 4%, trans 43 +/- 5%) in rats, but absorption was significantly greater than in monkeys. The IM urinary t1/2 values in monkeys and rats were similar for both isomers (0.8-1.1 d).

Animals↗

Efficacy of a permethrin-based acaricide to reduce the abundance of Ixodes dammini (Acari: Ixodidae).

Permethrin-impregnated cotton was distributed to reduce abundance of immature Ixodes dammini Spielman, Clifford, Piesman & Corwin feeding upon white-footed mice (Peromyscus leucopus) and questing on vegetation at a private resort site (The Crane Reservation of The Trustees of Reservations in Ipswich, Mass.) located in coastal New England. This test constituted the first independent evaluation of the efficacy of this commercial product (Damminix). Over a 3-yr period, 2,000 applicator tubes containing treated cotton were distributed over the 7.3-ha site in 5 regularly scheduled applications. Mice removed treated fiber from the tubes and transported it to their nests. Within 3 wk of the first application, virtually all mice in the treated site were rendered free of ectoparasites. After the first season of application, no nymphal host-seeking I. dammini could be found on vegetation. Visitor and employee complaints about deer tick bites or ticks found on skin and clothing had been attributed to the site before treatment, but not thereafter. We confirmed the efficacy of Damminix for reduction of the abundance of vector ticks and thereby contributed to the protection of humans against Lyme disease at this site.

Animals↗

Control of Oropsylla hirsuta, a plague vector, by treatment of prairie dog burrows with 0.5% permethrin dust.

Permethrin, a pyrethroid insecticide, applied on two plots with a pressurized hand-held duster at mean rates of 2.3 and 4.0 g per burrow, was used to determine control levels for Oropsylla hirsuta fleas, a vector of bubonic plague, in black-tail prairie dog, Cynomys ludovicianus, burrows in northern Colorado during the summer of 1988. Burrows were sampled by "flagging" at day 0 and weeks 1, 3, 6, 9, and 12 to determine the mean number of fleas per burrow and percentage of burrows with at least one flea. The 4.0 g per burrow rate was highly effective (P less than 0.001) in controlling fleas for a period of 3 mo, whereas the 2.3 g per burrow rate was not.

Animals↗