Effects of piperonyl butoxide on exploratory behaviour in female mice.

Previous studies reported that piperonyl butoxide (PBO) induces adverse effects on exploratory behaviour in male mice. However, no consistent effects of PBO treatment were observed in female mice. This study aimed to evaluate PBO's neurobehavioral effects in female mice. Female mice were exposed to PBO through diet to provide levels of 0 (control), 0.025%, 0.1%, and 0.4% from 5 to 12 weeks of age, and selected behavioural parameters were measured. The average female body weight showed no significant effect from PBO treatment through the experimental periods. Regarding multiple-T water maze performance at 10 weeks of age, no significant effect caused by PBO treatment was observed. Exploratory behaviour examination of 8-week-old female mice indicated that the average speed declined in a significant dose-related manner, and the longitudinal pattern indicated a significant difference between the control and high-dose groups. For exploratory behaviour examination at 11 weeks of age, the total exploration distance shortened in a significant dose-related manner, and the average speed declined similarly. These longitudinal patterns showed significant differences between the control and high-dose groups. The PBO dose levels in this study produced several adverse effects on exploratory behaviour in female mice.

Selection for imidacloprid resistance and mode of inheritance in the brown planthopper, Nilaparvata lugens.

BACKGROUND: Strong resistance to imidacloprid in Nilaparvata lugens (Stål) has developed in Southeast and East Asia. Although the mode of inheritance for resistance is very useful information for pest control, this information is unknown in N. lugens. Here, we established two resistant strains that were selected from field populations in Vietnam and the Philippines, and conducted crossing experiments to determine the inheritance pattern. RESULTS: The resistance ratio of 50% lethal dose (LD50 ) values for the two resistance-selected strains, i.e., resistant strains originating from Vietnam (VT-Res) and the Philippines (PH-Res), to their control strains were ∼ 8- and 157-fold, respectively. Reciprocal cross experiments between VT-Res and the susceptible strain (S-strain), and between PH-Res and the S-strain showed that the degree of dominance was 0.81 and 0.82, and 0.95 and 0.96, respectively. Analysis of the F2 populations and backcrosses to the parental strains indicated that resistance is a major-gene trait following Mendelian inheritance. The strength of the resistance was suppressed by pre-treatment with piperonyl butoxide, an inhibitor of cytochrome P450-monooxygenases. CONCLUSION: Our results suggest that imidacloprid resistance in N. lugens is autosomal and an almost completely dominant major-gene trait that is likely manifested by high expression levels of a detoxification enzyme. © 2019 Society of Chemical Industry.

Phthirus pubis Infestation of the Scalp: A Case Report and Review of The Literature.

Phthirus pubis usually infests the pubis, groin, buttocks and perianal region. It can sometimes infest the thighs, abdomen, chest, axillae and beard. Eyelashes and eyebrows may be involved in children. The involvement of the scalp is very rare. We describe a case of P. pubis infestation located exclusively on the scalp in an adult woman. Neither lice/nits nor skin lesions were observed elsewhere, including eyebrows, eyelashes, axillae, pubis, buttocks and perianal region (the patient was hairless in the axillae and pubis). A review of the literature is enclosed.

[Scabies of the nail unit in an infant]. / Scabiose de l'appareil unguéal chez un nourrisson.

BACKGROUND: There are no guidelines regarding the management of scabies in infants and recurrence is common at this age. We report the case of an infant with subungual hyperkeratosis and ungual lesions subsequent to classic scabies. PATIENTS AND METHODS: A 7-month-girl, treated 6 weeks earlier with esdepallethrin for scabies, consulted for acquired lesions on 3 toe nails. These nails were thickened and displayed subungual hyperkeratosis. Physical examination of the skin, the finger nails and mucous membranes was otherwise normal. Fungal analyses were negative, but direct microscopic examination revealed numerous larvae of Sarcoptes scabiei as well as ovular debris. The child was treated with urea 40% to obtain chemical avulsion of the nails, and with topical esdepallethrin and a quarter tablet of ivermectin orally; there was no follow-up of the child. DISCUSSION: Ungual scabies has already been reported in crusted scabies and very rarely in classic scabies. Subungual and ungual locations of S. scabiei may constitute a source of reinfestation with scabies in infants. Treatment is not well defined and currently involves chemical avulsion of the nails and the application of topical antiscabies treatment.

Efficacy of pharmacokinetic interactions between piperonyl butoxide and albendazole against gastrointestinal nematodiasis in goats.

To test the hypothesis that modulation of hepatic microsomal sulphoxidation and sulphonation by the cytochrome P450 inhibitor piperonyl butoxide could increase bioavailability of albendazole, the present study was undertaken to understand the pharmacokinetics of albendazole in goats at a dose of 7.5 mg kg- 1 body weight with and without co-administration with piperonyl butoxide at 63.0 mg kg- 1 body weight. Plasma albendazole sulphoxide metabolite, the anthelmintically active moiety, reached its maximum concentration of 0.322 ± 0.045 µg ml- 1 and 0.384 ± 0.013 µg ml- 1 at 18 h and 24 h after administration of albendazole alone and co-administration of albendazole with piperonyl butoxide, respectively. Analysis of the data revealed statistically increased albendazole sulphoxide levels at 24 (P 0.05) in values of maximum concentration (normal and calculated) could be observed between groups of goats. However, values of time to reach the concentration maximum (normal and calculated), area under the concentration-time curve (0-∞ and calculated), minimum residence time, distribution half-life, elimination half-life and total area under the first movement of plasma drug concentration-time curve were significantly higher (P <  0.05) in plasma levels of albendazole sulphoxide in goats following single oral co-administration of albendazole with piperonyl butoxide. The faecal egg count reduction and lower 95% confidence limit for the group treated with albendazole alone were 97 and 68%, while for co-administration of albendazole and piperonyl butoxide the values were 99 and 97%, respectively. The ED50 for egg hatch was 0.196, indicating suspected resistance to benzimidazole anthelmintics. The drug combination proved efficacious against an albendazole-resistant nematode parasite population in goats.

Effects of Maternal Exposure to Piperonyl Butoxide (PBO) on Behavioral Development in F1-Generation Mice.

Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to provide dietary levels of 0% (control), 0.01%, 0.03%, and 0.09% during gestation and lactation periods, and selected reproductive and neurobehavioral parameters were measured in the F1 generation. There was no adverse effect of PBO on litter size, litter weight, or sex ratio at birth. The average body weights of male offspring decreased significantly in dose-related manners on postnatal days (PNDs) 0, 4, 7, and 14 (p = 0.0019, 0.0096, 0.033, and 0.038, respectively) during the lactation period. In female offspring, the average body weights decreased in dose-related manners on PNDs 0, 4, 7, and 14 (p = 0.0027, 0.0104, 0.0193, and 0.0062, respectively). The survival of dams slightly decreased (p = 0.0209) in the high-dose group during the lactation period. With respect to behavioral developmental parameters, surface righting on PND 7 of male and female offspring was delayed significantly in a dose-related manner (p < 0.001 in each). Swimming direction on PND 7 of male offspring was delayed significantly in a dose-related manner (p < 0.01), and for female offspring it was delayed significantly in the high-dose group (p < 0.05). Swimming head angle on PND 7 of male offspring was delayed significantly in a dose-related manner (p < 0.05). Spontaneous behavior examination in males indicated that rearing increased in the high-dose group in the F1 generation. The dose levels of PBO in the present study produced some adverse effects in neurobehavioral parameters in mice.

Retention and efficacy of ultra-low volume pesticide applications on Culex quinquefasciatus (Diptera: Culicidae).

To combat mosquitoes and the public health hazards they present, spraying chemical adulticides is an efficient and timely control method for immediate reduction of adult populations. With the growing consciousness of environmental and public health concerns, effective mosquito control means not only maximizing the effectiveness (in terms of mosquito mortality rates) of the pesticide application, but also minimizing the unintended effects (health hazard and environmental pollution). A series of experiments was carried out to assess the efficacy and deposition of ultra-low volume (ULV) sprays on adult mosquitoes which included the influence of chemical type, spray volume, spray concentration, droplet size, and deposit location (where the droplets land on the mosquito). A modified Potter Tower was used to apply an extremely fine spray (volume median diameter ∼20 µm) on caged adult mosquitoes (Culex quinquefasciatus). Reslin (50 g/L bioresmethrin) was diluted in either water or D-C-Tron plus spray oil (782 g/L paraffinic petroleum oil), Twilight (89 g/L phenothrin) was diluted in D-C-Tron, and the mosquito mortality was assessed 24 h after spraying. A fluorescent tracer was added to the spray mixture to determine the amount of spray on mosquitoes. A fluorescent microscope was also used to view the deposit of droplets on mosquitoes. It was found that droplet retention and mortality were reduced with the larger droplet sizes. Large water-based droplets tend to bounce off adult mosquitoes. There is a tendency for droplets approximately 20 µm in size to be retained on the fine hairs on the mosquito. The largest spray deposit was found on the adult mosquito wings and the lowest deposit on the head. Mortality was higher for formulations diluted with oil compared to those diluted with water. ULV applications with ultra-fine sprays (VMD 20 µm) and oil-based products resulted in maximum target efficacy under laboratory conditions, at minimum cost, and with the minimum amount of chemical adulticides.

Evaluation of Three Commercial Backpack Sprayers with Aqualuer® 20-20 Against Caged Adult Aedes Aegypti.

Three commercially available backpack sprayers were evaluated with Aqualuer® 20-20 (20.6% permethrin, active ingredient; 20.6% piperonyl butoxide, technical) against caged adult Aedes aegypti in semifield trials in northeastern Florida. Two battery-powered sprayers, Birchmeier and Hudson, were compared with the standard hand-pump SOLO 425 sprayer, which is currently used in pest management operations. Physical characteristics, droplet analysis, and overall ease of use were documented. Multiple dilutions of the insecticide were also evaluated. The results indicated that the Birchmeier sprayer was the preferable machine in terms of its physical characteristics and operator use. There was no significant difference in percent mortality of the test mosquitoes between the sprayers. Multiple dilutions ranging from 1:9 to 1:1050 of the insecticide resulted in greater than 80% mean mortality.

Subacute oral toxicity of combinations of selected synthetic pyrethroids, piperonyl butoxide, and tetramethrin in rats.

In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes. Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days. During the study period, mortality and serious clinical findings were not observed in any animal. However, feed consumptions decreased in groups 1 and 3 (p < 0.05). Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0.05). Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups. Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0.05). The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver. It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.

Analysis of putative inhibitors of anthelmintic resistance mechanisms in cattle gastrointestinal nematodes.

Effects of the cytochrome P450 inhibitor piperonyl butoxide and the P-glycoprotein inhibitor verapamil on the efficacy of ivermectin and thiabendazole were studied in vitro in susceptible and resistant isolates of the cattle parasitic nematodes Cooperia oncophora and Ostertagia ostertagi. The effects of combined use of drug and piperonyl butoxide/verapamil, respectively, were investigated in the Egg Hatch Assay, the Larval Development Assay and the Larval Migration Inhibition Assay. The effects of piperonyl butoxide and verapamil as inhibitors of thiabendazole and ivermectin responses were particularly marked for larval development, where both inhibitors were able to completely eliminate all differences between susceptible and resistant isolates. Even the lowest concentrations of anthelmintics used in combination with inhibitors caused complete inhibition of development. Differences and/or similarities among responses in different isolates were only obtained in the two other assays: in the Egg Hatch Assay piperonyl butoxide caused a shift in concentration-response curves obtained with thiabendazole to the left for all isolates tested, changing relative differences between isolates. In contrast, an effect of verapamil in the Egg Hatch Assay was only apparent for benzimidazole-resistant isolates. In the Larval Migration Inhibition Assay only ivermectin was tested and piperonyl butoxide shifted the concentration-response curves for all isolates to the left, again eliminating differences in EC50 values between susceptible and resistant isolates. This was not the case using verapamil as an inhibitor, where curves for both susceptible and benzimidazole-resistant isolates shifted to the left in Ostertagia isolates. In Cooperia the picture was more complex with ivermectin-resistant isolates showing a larger shift than the susceptible isolate. Single nucleotide polymorphisms in the ß-tubulin isotype 1 gene were investigated. Significantly increased frequencies of resistance-associated alleles were observed for the codons 167 and 200 in one benzimidazole-resistant isolate but not in an isolate selected for benzimidazole resistance at an early stage of selection.

Effects of short-term oral combined exposure to environmental immunotoxic chemicals in mice.

People are constantly exposed to environmental chemicals through contact with the atmosphere or by ingestion of food. Therefore, when conducting safety assessments, the immunotoxic effects of combinations of chemicals in addition to toxicities produced by each chemical alone should be considered. The objective of the studies reported here were to demonstrate the combined effects of three well-known environmental immunotoxic chemicals -- methoxychlor (MXC), an organochlorine compound; parathion (PARA), an organophosphate compound; and piperonyl butoxide (PBO), an agricultural insecticide synergist -- by using a short-term oral exposure method. Seven-week-old Balb/cAnN mice received daily oral exposure to either one or two of the environmental immunotoxic chemicals for 5 consecutive days. On Day 2, all mice in each group were immunized with sheep red blood cells (SRBC), and their SRBC-specific IgM responses were analyzed by using an enzyme-linked immunosorbent assay and plaque-forming cell assay. T- and B-cell counts in the mouse spleens were also assessed via surface antigen expression. Mice that received MXC + PARA and PBO + MXC treatment showed marked decreases in SRBC-specific IgM production and T- and B-cell counts compared with those in mice that received vehicle control or the corresponding individual test substance. This suggests that simultaneous exposure to multiple environmental chemicals increases the immunotoxic effects of the chemicals compared to individual exposure.

Sex-, tissue-, and exposure duration-dependent effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part I: oxidative and neurotoxic potentials.

Earlier research has evidenced the oxidative and neurotoxic potential of imidacloprid, a neonicotinoid insecticide, in different animal species. The primary aim of this study was to determine how metabolic modulators piperonyl butoxide and menadione affect imidacloprid's adverse action in the liver and kidney of Sprague-Dawley rats of both sexes. The animals were exposed to imidacloprid alone (170 mg kg⁻¹) or in combination with piperonyl butoxide (100 mg kg⁻¹) or menadione (25 mg kg⁻¹) for 12 and 24 h. Their liver and kidney homogenates were analysed spectrophotometrically for glutathione peroxidase, glutathione S-transferase, catalase, total cholinesterase specific activities, total glutathione, total protein content, and lipid peroxidation levels. Imidacloprid displayed its prooxidative and neurotoxic effects predominantly in the kidney of male rats after 24 h of exposure. Our findings suggest that the observed differences in prooxidative and neurotoxic potential of imidacloprid could be related to differences in its metabolism between the sexes. Co-exposure (90-min pre-treatment) with piperonyl butoxide or menadione revealed tissue-specific effect of imidacloprid on total cholinesterase activity. Increased cholinesterase activity in the kidney could be an adaptive response to imidacloprid-induced oxidative stress. In the male rat liver, co-exposure with piperonyl butoxide or menadione exacerbated imidacloprid toxicity. In female rats, imidacloprid+menadione co-exposure caused prooxidative effects, while no such effects were observed with imidacloprid alone or menadione alone. In conclusion, sex-, tissue-, and duration-specific effects of imidacloprid are remarkable points in its toxicity.

Suppressive effect of liver tumor-promoting activities in rats subjected to combined administration of phenobarbital and piperonyl butoxide.

Phenobarbital (PB) is a cytochrome P450 (CYP) 2B inducer, and piperonyl butoxide (PBO) is a CYP1A/2B inducer. These inducers have liver tumor-promoting effects in rats. In this study, we performed a rat two-stage liver carcinogenesis bioassay to examine the tumor-promoting effect of PB and PBO co-administration. Male rats received an intraperitoneal injection of N-diethylnitrosamine (DEN) for initiation. Two weeks after DEN administration, rats were given PB (60 or 120 ppm in drinking water), PBO (1,250 or 2,500 ppm in diet) or 60 ppm PB+1,250 ppm PBO for 6 weeks. One week after the PB/PBO treatment, all rats were subjected to a two-thirds partial hepatectomy. To evaluate the effect of the combined administration, we used two statistical additive models. In the isoadditive model, the average values of the area of GST-P positive foci in the PB+PBO group were significantly lower than those in the High PB or High PBO groups. In the heteroadditive model, the net values of Cyp1a1 mRNA level and microsomal reactive oxygen species (ROS) production in the PB+PBO group were significantly lower than the sum of those in the Low PB or Low PBO groups. On the contrary, there was no interactive effect in the PCNA-positive hepatocyte ratio, mRNA levels of Cyp2b1/2, Gstm3, Gpx2 and Nqo1, and the level of thiobarbituric acid-reactive substances in the PB+PBO group. These results suggest that PB and PBO co-administration causes suppressive effects in liver tumor-promoting activity in rats resulting from inhibited microsomal ROS production because of suppression of CYP1A induction.

In vitro and in vivo evaluation of cypermethrin, amitraz, and piperonyl butoxide mixtures for the control of resistant Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) in the Mexican tropics.

A study was conducted to evaluate the efficacy of cypermethrin, amitraz, and piperonyl butoxide (PBO) mixtures, through in vitro laboratory bioassays and in vivo on-animal efficacy trials, for the control of resistant Rhipicephalus (Boophilus) microplus on cattle in the Mexican tropics. Also, to examine mechanisms of resistance to cypermethrin in this tick population, the frequency of a mutated sodium channel gene (F1550I) was determined using a PCR assay. Results of laboratory bioassays using modified larval packet tests revealed that cypermethrin toxicity was synergized by PBO (from 46.6-57.0% to 83.7-85.0% larval mortality; P<0.05). The cypermethrin and amitraz mixture showed an additive effect (from 46.6-57.0% to 56.0-74.3% larval mortality). Strong synergism was observed with the mixture of cypermethrin+amitraz+PBO and this mixture was the most effective killing resistant tick larvae in vitro (96.7-100% of larval mortality). Tick larvae surviving exposure to cypermethrin or mixtures either with amitraz and PBO in vitro showed 2.9-49.6 higher probability to present the mutated allele than those killed by acaricide treatment (P<0.05). In the in vivo trial, the mixtures containing cypermethrin+PBO (80.6-97.3%), and cypermethrin+amitraz (87.0-89.7%) were more efficacious than cypermethrin alone (76.3-80.5%). The highest level of efficacy was obtained with the mixture of cypermethrin+amitraz+PBO, which yielded >95% control that persisted for 28 days post-treatment against R. microplus infesting cattle when tested under field conditions in the Mexican tropics. Although this mixture is a potentially useful tool to combat pyrethroid resistance, a product based on an acaricide mixture like the one tested in this study has to be used rationally.

Exploratory trial to determine the efficacy of the PYthon and the PYthon Magnum slow-release insecticide ear tags for the control of midges (Culicoides spp.), attacking sheep and cattle and flies attacking cattle.

This study investigated the prophylactic action of the chemical combination zeta-cypermethrin and piperonyl butoxide, administered by means of slow-release insecticide-impregnated ear tags, against biting midges (Culicoides spp) attacking sheep and against midges, horn flies (Haematobia irritant), stable flies (Stomoxys calcitrans), and houseflies (Musca domestica) attacking cattle. Treated sheep and cattle were protected 100 percent against blood-feeding midges for two months and there was a clear reduction in the number of midges collected from treated animals. Three days after the ear tags were attached to cattle, the number of horn flies on the cattle was reduced to practically zero and remained at a low level until the end of the trial (day 85). There was also a strong reduction in the numbers of stable flies and houseflies counted.

The importance of modelling the spread of insecticide resistance in a heterogeneous environment: the example of adding synergists to bed nets.

BACKGROUND: Insecticides are an effective and practical tool for reducing malaria transmission but the development of resistance to the insecticides can potentially compromise controls efforts. In this study a mathematical model was developed to explore the effects on mosquito populations of spatial heterogeneous deployment of insecticides. This model was used to identify important parameters in the evolution of insecticide resistance and to examine the contribution of new generation long-lasting insecticidal bed nets, that incorporate a chemical synergist on the roof panel, in delaying insecticide resistance. METHODS: A genetic model was developed to predict changes in mosquito fitness and resistance allele frequency. Parameters describing insecticide selection, fitness cost and the additional use of synergist were incorporated. Uncertainty and sensitivity analysis were performed followed by investigation of the evolution of resistance under scenarios of fully effective or ineffective synergists. RESULTS: The spread of resistance was most sensitive to selection coefficients, fitness cost and dominance coefficients while mean fitness was most affected by baseline fitness levels. Using a synergist delayed the spread of resistance but could, in specific circumstances that were thoroughly investigated, actually increase the rate of spread. Different spread dynamics were observed, with simulations leading to fixation, loss and most interestingly, equilibrium (without explicit overdominance) of the resistance allele. CONCLUSIONS: This strategy has the potential to delay the spread of resistance but note that in an heterogeneous environment it can also lead to the opposite effect, i.e., increasing the rate of spread. This clearly emphasizes that selection pressure acting inside the house cannot be treated in isolation but must be placed in context of overall insecticide use in an heterogeneous environment.

In vitro - in vivo correlation of gene expression alterations induced by liver carcinogens.

Although cultivated hepatocytes are widely used in the studies of drug metabolism, their application in toxicogenomics is considered as problematic, because previous studies have reported only little overlap between chemically induced gene expression alterations in liver in vivo and in cultivated hepatocytes. Here, we identified 22 genes that were altered in livers of rats after oral administration of the liver carcinogens aflatoxin B1 (AB1), 2-nitrofluorene (2-NF), methapyrilene (MP) or piperonyl-butoxide (PBO). The functions of the 22 genes have been classified into two groups. Genes related to stress response, DNA repair or metabolism and genes associated with cell proliferation, respectively. Next, rat hepatocyte sandwich cultures were exposed to AB1, 2-NF, MP or PBO for 24h and expression of the above mentioned genes was determined by RT-qPCR. Significant correlations between the degree of gene expression alterations in vivo and in vitro were obtained for the stress, DNA repair and metabolism associated genes at concentrations covering a range from cytotoxic concentrations to non-toxic/in vivo relevant concentrations. In contrast to the stress associated genes, no significant in vivo/in vitro correlation was obtained for the genes associated with cell proliferation. To understand the reason of this discrepancy, we compared replacement proliferation in vivo and in vitro. While hepatocytes in vivo, killed after administration of hepatotoxic compounds, are rapidly replaced by proliferating surviving cells, in vitro no replacement proliferation as evidenced by BrdU incorporation was observed after washing out hepatotoxic concentrations of MP. In conclusion, there is a good correlation between gene expression alterations induced by liver carcinogens in vivo and in cultivated hepatocytes. However, it should be considered that cultivated primary hepatocytes do not show replacement proliferation explaining the in vivo/in vitro discrepancy concerning proliferation associated genes.

Estimation of the percutaneous absorption of permethrin in humans using the parallelogram method.

The objective of this study was to develop an estimate of the percent dermal absorption of permethrin in humans to provide more accurate estimates of potential systemically absorbed dose associated with dermal exposure scenarios. Piperonyl butoxide (PBO) was used as a reference compound. The human percutaneous absorption estimate was based on the assumption that the ratio of in vivo dermal absorption (expressed as a percentage during a given time period) of permethrin through rat skin to in vitro dermal absorption through rat skin was the same as the ratio of in vivo dermal absorption in humans to in vitro dermal absorption with human skin, known as the parallelogram method. The ratio of dermal absorption by in vitro rat skin to absorption by in vitro human skin ranged from 6.7 to 15.4 (for a 24-h exposure period) with an average of 11. Data suggest in vivo human dermal absorption values for permethrin ranging from 1.4 to 3.3% when estimated based on 24-h in vivo rat values, and 2.5 to 5.7% based on 5-d in vivo rat values. The parallelogram method used to estimate dermal absorption of permethrin and PBO is supported by results from several other compounds for which in vivo and in vitro rat and human dermal absorption data exist. Collectively, these data indicate that estimating human dermal absorption from in vitro human and rat plus in vivo rat data are typically accurate within ±3-fold of the values measured in human subjects.

The actions of benzophenanthridine alkaloids, piperonyl butoxide and (S)-methoprene at the G-protein coupled cannabinoid CB1 receptor in vitro.

This investigation focused primarily on the interaction of two benzophenanthridine alkaloids (chelerythrine and sanguinarine), piperonyl butoxide and (S)-methoprene with G-protein-coupled cannabinoid CB(1) receptors of mouse brain in vitro. Chelerythrine and sanguinarine inhibited the binding of the CB(1) receptor agonist [(3)H]CP-55940 to mouse whole brain membranes at low micromolar concentrations (IC(50)s: chelerythrine 2.20 µM; sanguinarine 1.10 µM). The structurally related isoquinoline alkaloids (berberine and papaverine) and the phthalide isoquinoline ((-)-ß-hydrastine) were either inactive or considerably below IC(50) at 30 µM. Chelerythrine and sanguinarine antagonized CP-55940-stimulated binding of [(35)S] GTPγS to the G-protein (IC(50)s: chelerythrine 2.09 µM; sanguinarine 1.22 µM). In contrast to AM251, both compounds strongly inhibited basal binding of [(35)S]GTPγS (IC(50)s: chelerythrine 10.06 µM; sanguinarine 5.19µM). Piperonyl butoxide and S-methoprene inhibited the binding of [(3)H]CP-55940 (IC(50)s: piperonyl butoxide 8.2 µM; methoprene 16.4 µM), and also inhibited agonist-stimulated (but not basal) binding of [(35)S]GTPγS to brain membranes (IC(50)s: piperonyl butoxide 22.5 µM; (S)-methoprene 19.31 µM). PMSF did not modify the inhibitory effect of (S)-methoprene on [(3)H]CP-55940 binding. Our data suggest that chelerythrine and sanguinarine are efficacious antagonists of G-protein-coupled CB(1) receptors. They exhibit lower potencies compared to many conventional CB(1) receptor blockers but act differently to AM251. Reverse modulation of CB(1) receptor agonist binding resulting from benzophenanthridines engaging with the G-protein component may explain this difference. Piperonyl butoxide and (S)-methoprene are efficacious, low potency, neutral antagonists of CB(1) receptors. Certain of the study compounds may represent useful starting structures for development of novel/more potent G-protein-coupled CB(1) receptor blocking drugs.

The effects of cypermethrin pour-on and piperonyl butoxide on Triatoma infestans under laboratory conditions.

The effect of exposing Triatoma infestans to chickens treated with cypermethrin pour-on combined with piperonyl butoxide (PBO) was studied. Four groups of treated chickens and one control group were used. Each treatment received 1 or 2 ml of the cypermethrin formulation with and without PBO. Independent groups of nymphs were fed 1, 7, 15, 30, and 45 d after the treatment application. Blood intake was estimated after each feeding occasion. Up to 15 d after the pour-on application, high mortality was observed in all nymphs fed on treated chickens (> 93% +/- 12), and lower than the nymphs of the control group (< 33% +/- 15). After 30 d of the pour-on application, there was significantly different mortality between the treatment with 1 ml (80% +/- 9) and 2 ml (> 96% +/- 5); no difference was observed between groups with or without PBO addition. After 45 d of the pour-on application, the treatments did not show significant differences (77% +/- 7), although all treatments showed higher mortality than the control group (10% +/- 9). Up to 45 d after the pour-on application, blood intake by nymphs exposed to treated chickens (0.85 +/- 0.96 mg/nymph) was lower than blood intake by nymphs exposed to control chickens (6.7 +/- 5 mg/nymph). This study shows that cypermethrin pour-on produces high mortality and reduces the blood intake of third-instar nymphs of T. infestans up to 45 d after the insecticide application to chickens. PBO did not produce a detectable effect.