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At least 1,009 records · Page 56Linked to original sources
PubMed2000

Reduction in skin permeation of N,N-diethyl-m-toluamide (DEET) by altering the skin/vehicle partition coefficient.

Reported adverse side effects after using N,N-diethyl-m-toluamide (DEET)-containing mosquito repellent products appear to be the result of significant absorption of DEET through human skin. The overall objective was to develop formulations of DEET with significantly reduced permeation using the basic principles and model of skin permeation based on Fick's laws of diffusion at steady state. Ternary phase diagrams of DEET with water and semipolar solvents, ethanol, PG and PEG 400, showed an increase in the aqueous solubility of DEET. This resulted in a linear decline in octanol/water PC with an increase in the concentration of the solvent. Permeation of DEET across human skin was studied from vehicles containing various amounts of PG and PEG 400 using an infinite dose technique and Franz diffusion cell. DEET's flux reduced with increasing PG concentration and the flux from 90% PG was 9.9+/-2.1 microg/cm(2) h, 6-fold lower than flux of pure DEET control, 63.2+/-24.5 microg/cm(2) h. Flux was reduced 6-fold from 60% PEG 400 solution, and permeation of DEET was totally prevented from 90% PEG 400 which was very viscous. However, a combination of 60% PEG 400 with 30% PG not only reduced permeation 9-fold but was suitable as a vehicle for formulation. The decrease in flux and permeability of DEET with increasing concentration of solvent appeared to be a direct result of decrease in skin/vehicle PC and octanol/water PC. This study clearly demonstrates that alternative formulations can be developed for DEET aimed at reduced permeation and toxicity unlike the current formulations some of which contain ethanol which has been shown to enhance permeation of DEET. A similar approach can be used for developing formulations of other industrial and occupational agents to prevent their skin permeation when a user may be exposed to them.

Algorithms↗
PubMed1997

Percutaneous absorption and disposition studies of methotrexate in rabbits and rats.

The absorption and disposition of methotrexate (MTX) in the plasma, synovial fluid (SF), skin, and muscle tissue were studied following administration of a topical MTX gel in rabbits and rats. In rabbits, MTX concentrations in the plasma increased steadily toward the peak (5.9 +/- 2.8 ng mL-1) which appeared at approximately 2 h postdose and declined with the elimination half-life of 4.48 +/- 1.74 h. At 1 h after the topical dose, the MTX concentrations in the skin (49.0 +/- 19.8 micrograms g-1), muscle (12.7 +/- 3.3 ng g-1), and SF (19.2 +/- 10.1 ng g-1) underneath the dosed stifle joint were significantly higher (p < 0.05) than those of the untreated stifle joint, indicating the potential therapeutic value of topical delivery of MTX for rheumatoid arthritis. A large fraction (approximately 59%) of MTX which was found in the skin at 1 h postdose was present in the stratum corneum, indicating its extensive binding capacity for MTX. The MTX concentrations in the muscle and SF of the dosed stifle joint at 1 h postdose were 1.8 and 2.6 times higher than those in the dosed elbow joint, respectively, reflecting the effect of dose site on the permeation of MTX. Using a new filter paper method, the amounts of SF obtained from the elbow and stifle joints of four rabbits were 26.3 +/- 8.3 and 48.8 +/- 5.2 mg, respectively. A significant enhancer effect of N,N-diethyl-n-toluamide (DEET) on the disposition of MTX in the stratum corneum of rabbit ear was observed (p < 0.05) by the tape-stripping method. In rats, the gel containing 4% DEET resulted in a twofold increase in the permeation of MTX into the muscle over the 4 h period postdose. A modified HPLC method with a linear calibration curve (r > 0.999) over the range of 2-50 ng mL-1. quantitation limit of 0.5 ng mL-1, and mean recovery of approximately 87% was used for the quantitation of MTX in the tissue and fluid samples.

Animals↗
PubMedDate not supplied

A bioassay for insect deterrent compounds found in plant and animal tissues.

A general field bioassay for detecting biologically active compounds in plants and insects has been developed and tested for efficacy and sensitivity. Methanolic extracts, in sucrose solution, of 20 plant and six caterpillar species were offered to the ponerine ant Paraponera clavata and the feeding preferences observed. The bioassay resulted in the detection of nine plant and three caterpillar species with ant-deterrent extracts, and 11 plant and three caterpillar species with neutral or attractant extracts. All of the plants showing ant-deterrent characteristics which had been chemically investigated in our laboratory, or for which chemical literature was available, contained secondary metabolites of known deterrence. Both naturally occurring and artificial differences in chemical concentrations could be detected using the bioassay. The method provides a means of screening plants and insects for compounds that are insect anti-feedants or that can modify insect behaviour.

Animals↗
PubMed2006

Behavioural response of Colorado potato beetle (Leptinotarsa decemlineata) larvae to selected plant extracts.

Potato leaves were treated with 2, 20 or 200 g kg(-1) solutions of extracts of five plant species collected in Turkey, and then exposed to larvae of Colorado potato beetle, Leptinotarsa decemlineata (Say). During the first 24 h of exposure, leaf consumption was not affected by 2 g kg(-1) extracts, whereas significantly more leaf tissue remained on leaves treated with 20 g kg(-1) extracts of Arctium lappa L., Bifora radians M Bieb, Humulus lupulus L. or Xanthium strumarium L. than on untreated control leaves. Feeding was not affected by the 20 g kg(-1) extract of Verbascum songaricum Schrenk ex Fisch & Mey. Extracts of all species at 200 g kg(-1) reduced larval feeding, with H. lupulus and X. strumarium providing the greatest protection. Observations of larval behaviour over the first 15 min of exposure to these extracts revealed that the interaction of beetles with leaf tissue was significantly affected by plant extracts. Feeding frequency was not affected by 2 g kg(-1) extracts but was reduced by all higher concentrations. Feeding was inhibited completely by 20 g kg(-1) of H. lupulus extract and reduced significantly compared with the controls by all other extracts. Suppression of feeding was caused by all extracts at 200 g kg(-1), with V. songaricum providing 91% reduction in feeding duration. Rejection behaviour, in which larvae did not return to the leaf after their interaction with it, was rare on 2 g kg(-1) extracts but seen in over 60% of larvae on 20 g kg(-1) extracts and over 80% on 200 g kg(-1) extracts. The present results demonstrate that these extracts have significant ability to protect potato leaves for up to 24 h by prevention of feeding behaviour by L. decemlineata. Further studies are needed to determine the potential of these plant extracts, or their active components, for use in biologically based pest management strategies.

Animals↗
PubMed2003

Acaricidal effects of cardiac glycosides, azadirachtin and neem oil against the camel tick, Hyalomma dromedarii (Acari: Ixodidae).

The cardiac glycoside, digitoxin, from Digitalis purpurea L (Scrophulariaceae), a cardiac glycosidal (cardenolide) extract from Calotropis procera (Ait) R Br (Asclepiadaceae), azadirachtin and neem oil from Azadirachta indica A Juss (Meliaceae) were tested for their effects against larvae and adult stages of the camel tick, Hyalomma dromedarii Koch (Acari: Ixodidae). The contact LC50 values of the first three materials against adults were 4.08, 9.63 and >40.7 microg cm(-2), respectively, whereas the dipping LC50 values of the four materials were 409.9, 1096, >5000 and >5000 mg litre(-1), respectively. Contact and dipping LC50 values of the extract and azadirachtin against larvae were 6.16, >20.3 microg cm(-2) and 587.7 and >2500 mg litre(-1), respectively. Azadirachtin had no effects on egg production or feeding of adults up to 5000 mg litre(-1); however at 2500 mg litre(-1), it caused significant reduction in feeding activity of larve, prolonged the period for moulting to nymphal stage, and caused 60% reduction in moultability. Results of the two cardiac glycoside materials are comparable with those of several commercial acaricides. The risks and benefits associated with the use of cardiac glycosides are considered.

Animals↗
PubMed2001

Subchronic dermal application of N,N-diethyl m-toluamide (DEET) and permethrin to adult rats, alone or in combination, causes diffuse neuronal cell death and cytoskeletal abnormalities in the cerebral cortex and the hippocampus, and Purkinje neuron loss in the cerebellum.

N,N-Diethyl m-toluamide (DEET) and permethrin have been implicated as potential neurotoxic agents that may have played an important role in the development of illnesses in some veterans of the Persian Gulf War. To determine the effect of subchronic dermal application of these chemicals on the adult brain, we evaluated histopathological alterations in the brain of adult male rats following a daily dermal dose of DEET (40 mg/kg in 70% ethanol) or permethrin (0.13 mg/kg in 70% ethanol) or a combination of the two for 60 days. Control rats received a daily dermal dose of 70% ethanol for 60 days. Animals were perfused and brains were processed for morphological and histopathological analyses following the above regimen. Quantification of the density of healthy (or surviving) neurons in the motor cerebral cortex, the dentate gyrus, the CA1 and CA3 subfields of the hippocampus, and the cerebellum revealed significant reductions in all three treated groups compared with the control group. Further, animals receiving either DEET or permethrin exhibited a significant number of degenerating (eosinophilic) neurons in the above brain regions. However, degenerating neurons were infrequent in animals receiving both DEET and permethrin, suggesting that neuronal cell death occurs earlier in animals receiving combined DEET and permethrin than in animals receiving either DEET or permethrin alone. The extent of neuron loss in different brain regions was similar among the three treatment groups except the dentate gyrus, where neurodegeneration was significantly greater with exposure to DEET alone. The neuron loss in the motor cerebral cortex and the CA1 subfield of all treated groups was also corroborated by a significant decrease in microtubule associated protein 2-immunoreactive elements (15-52% reduction), with maximal reductions occurring in rats receiving DEET alone; further, the surviving neurons in animals receiving both DEET and permethrin exhibited wavy and beaded dendrites. Analysis of glial fibrillary acidic protein immunoreactivity revealed significant hypertrophy of astrocytes in the hippocampus and the cerebellum of all treated groups (24-106% increase). Thus, subchronic dermal application of DEET and permethrin to adult rats, alone or in combination, leads to a diffuse neuronal cell death in the cerebral cortex, the hippocampal formation, and the cerebellum. Collectively, the above alterations can lead to many physiological, pharmacological, and behavioral abnormalities, particularly motor deficits and learning and memory dysfunction.

Administration, Cutaneous↗
PubMed1995

Pharmacokinetics of 2-ethyl-1,3-hexanediol. III. In vitro skin penetration comparisons using the excised skin of humans, rats, and rabbits.

Excised skin from Fischer 344 rats, New Zealand White rabbits, and human females (obtained from mammoplasty patients) were compared for their in vitro skin penetration potential with 2-[14C]-ethyl-1,3-hexanediol (EHD). EHD was applied as both an undiluted dose and a 3% v/v aqueous dose using a flowthrough skin penetration chamber design and was analyzed over 0-6 hr. The undiluted dose was equivalent to a 150 mg/kg dose used in vivo with rats (Frantz et al., Drug Metab. Dispos. 20(1), 6-18, 1992), but normalized on a per cm2 surface area basis, and applied under occluded conditions (covered as for in vivo studies). Undiluted applications of EHD did not substantially penetrate skin, with effluent recoveries of approximately 0.9% of the applied dose for human skin, 2-4% for rat skin, and 3-6% for rabbit skin. By comparison, nonoccluded human skin showed lower effluent radioactivity (0.6%), which was attributed to EHD evaporation from skin. With undiluted EHD, approximately 97% of the recovered 14C was an unabsorbed dose for human skin, with 94% for rat skin and 85% for rabbit skin (expressed as a percentage of the recovered dose). Based on HPLC analysis of effluent samples, 99-100% of the undiluted [14C]EHD penetrated rat, rabbit, and human skin in the unmetabolized form. In contrast, approximately 5% of the applied aqueous dose was recovered in the effluents for human skin, while 6-9% appeared in effluents for rat skin; rabbit skin was not evaluated for aqueous doses. The fraction of unabsorbed aqueous EHD dose totaled 53% of the applied dose for human skin and 63% for rat skin. Evaporative loss of undiluted [14C]EHD was also measured (captured on activated charcoal) in separate experiments and compared with a known standard chemical, N,N[14C]diethyl-m-toluamide (DEET). Evaporation of EHD was clearly a competing factor with penetration, particularly for human skin preparations, and evaporative losses were similar to those seen in previous studies. Penetration of skin was also greater for both EHD and DEET when evaporation was not permitted (stopped chamber). Permeability constant (kp) values were calculated using the pseudo steady-state slopes from plots for cumulative mg/cm2 penetration vs time. For undiluted EHD, human skin had the slowest penetration rate, while rabbit skin kp values were the largest. The kp values for water solutions of EHD on rat and human skin demonstrated a slightly higher penetration, with values of the same order of magnitude as that observed for a concurrently run [14C]ethanol control. The minimal skin penetration observed in vitro in this study, taken together with in vivo percutaneous pharmacokinetic studies (Frantz et al., 1992) and the known percutaneous toxicology of EHD, suggests that penetration through human skin and systemic adverse effects should be minimal.

Animals↗
PubMed2000

The toxicity of a neem insecticide to populations of culicidae and other aquatic invertebrates as assessed in in situ microcosms.

Microcosm trials were conducted with the botanical insecticide Margosan-O(R) to assess the potential hazards of the product to aquatic organisms. Laboratory chronic bioassays with water from the treated microcosms were conducted to provide an estimate of the residual effect of Margosan-O. Results from chronic tests showed Margosan-O toxicity to be greater in the laboratory exposures than in situ with Culicidae larvae exposed to the same concentrations. Residue analyses of the active ingredient, azadirachtin, determined that it had a half-life of 36 to 48 h in water exposed to natural sunlight. Two applications of Margosan-O at the recommended application rate for pests did not harm aquatic invertebrates that are categorized as planktonic and filter feeding (Culex sp. and Daphnia sp.). However, the benthic invertebrate (Chironomus riparius) was affected by multiple applications of neem. These results show that the use of Margosan-O and possibly other neem extracts in or near aquatic environments could lead to disturbances in benthic populations and may cause decreases in numbers of organisms that are important in food web and nutrient cycling processes.

Animals↗
PubMed2002

Genotoxicity studies on permethrin, DEET and diazinon in primary human nasal mucosal cells.

Possible genotoxic effects exerted by three widely used pesticides, permethrin, N,N-diethyl-m-toluamide (DEET) and diazinon, in primary human nasal mucosal cells were investigated. Primary nasal mucosa cells were prepared from tissue biopsies taken from 21 patients who underwent nasal surgery. Cells were exposed to 0.5-1.0 mM concentrations of permethrin, DEET and diazinon for 60 min. Genotoxic effects were detected by the alkaline microgel electrophoresis assay ("comet assay"). Within the concentration range, no significant cytotoxic effects were observed, but all three tested pesticides showed a significant genotoxic response that was concentration dependent. More pronounced genotoxic effects were observed in mucosal cells from the middle turbinate than in the inferior turbinate. The results provide some evidence for the potential carcinogenicity of these agents to human nasal mucosal cells. This should be further investigated.

Adult↗
PubMed2005

Components of honeybee royal jelly as deterrents of the parasitic Varroa mite, Varroa destructor.

The parasitic mite Varroa destructor Anderson & Trueman reproduces on the immature stage of the honeybee, Apis mellifera L. Mites are found more often on drone brood than worker brood and only infrequently on queen brood. We investigated the chemical basis for the low incidence of mites on queen brood. V. destructor mites were deterred by a crude extract of royal jelly, a glandular secretion produced by nurse bees and fed to queen larvae. Bioassay-driven fractionation of the crude extract via column chromatography resulted in one active fraction that was as active as the crude extract. Compounds in the active fraction were identified using gas chromatography (GC) and coupled gas chromatography/mass spectrometry (GC-MS). Before injection, compounds were esterified with MeOH/sulfuric acid, followed by silylation of any hydroxyl groups present. The active fraction contained at least 22 compounds, all fatty acids, several of which contained an additional hydroxyl group on the alkyl chain. Synthesis of some of these compounds that are not commercially available is described. A synthetic mixture containing most of the compounds in the active fraction was as active as the active fraction in the bioassay.

Animals↗