Comparative cost-effectiveness of ivermectin versus topical organophosphate in feedlot yearlings.
(1/23)
A replicated-pen field trial was performed under commercial feedlot conditions in western Canada to determine the cost-effectiveness of administering ivermectin to yearling beef cattle upon entry to the feedlot after the grazing season, and to establish the level of trichostrongylid gastrointestinal parasite infection in this population, as estimated by fecal egg counts. Six thousand eight hundred and eighty-three, mixed breed, yearling steers were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: Ivermectin, which received topical ivermectin (0.5%) at the rate of 1.0 mL/10 kg body weight; or Fenthion, which received topical fenthion (20%) at the rate of 12 mL/295 kg body weight. There were 15 pens in each experimental group. Final weight, weight gain, average daily gain, and dry matter intake to gain ratio were significantly (P < 0.05) improved in the Ivermectin group as compared with the Fenthion group. There were no significant (P > or = 0.05) differences in initial weight, days on feed, or daily dry matter intake between the experimental groups. The geometric mean fecal egg counts at the time of allocation were 14.7 eggs/5 g and 16.6 eggs/5 g for the Ivermectin and Fenthion groups, respectively (P > or = 0.05). There were no significant (P > or = 0.05) differences in morbidity or mortality between the experimental groups. In the economic analysis, the significant improvements in feedlot performance in the Ivermectin group resulted in a net economic advantage of $4.20 CDN per animal. (+info)
Analysis of the use of fenthion via epicutaneous in dogs for Rhipicephalus sanguineus control.
(2/23)
The action of fenthion was studied in a 15% epicutaneous formulation upon Rhipicephalus sanguineus, which may transmit pathogens to men and other animals, such as Ehrlichia, Babesia and Ricketsia. Dogs were artificially infected for the trial. The fenthion bioassays were begun four months after artificial infestation. The test group, having a mean of 186 ticks per dog, received the formulation dosage according to body weight on the neck region. Tick counts were performed, considering diameters > or = 2mm, during 11 days of treatment, in the most affected body areas: back, ears and paws. Before the application of fenthion in the dogs, it were observed an average 43.3% ticks in the ears, 38.1% in the back area and 17.6% in the paws. The number of ticks in dogs decreased by 36.2%, 63.8%, 82.7%, 67%, 40% and 4.9%, respectively on days 1, 2, 3, 5, 7, 9 and 11 after treatment. R. sanguineus anti-tick activity, lower than that officially recommended, was verified. The number of ticks increased progressively after the 5th day, demonstrating residual insecticide inefficacy. The results obtained did not indicate the use of this formulation, at the tested dosage, as an elective measure for R. sanguineus control. (+info)
Topical insecticide treatments to protect dogs from sand fly vectors of leishmaniasis.
(3/23)
We compared the susceptibility of sand fly vectors to four topical insecticide treatments applied to domestic dogs, a reservoir of human leishmaniasis. Dogs were exposed to sand flies pretreatment and at 1 week, 1 month, and 2 months posttreatment. Sand fly bloodfeeding and survival rate of both fed and unfed flies were significantly reduced by the permethrin, deltamethrin, and fenthion treatments, but diazinon had no effect. The survival rate of bloodfed sand flies was reduced by up to 86% with deltamethrin collars. The antifeeding effect suggests that deltamethrin collars may be recommended to dog owners to protect their pets from sandfly- borne diseases. The combined effects on sand fly feeding and survival indicate that epidemiologic, community-based trials are warranted to test whether deltamethrin collars could reduce the incidence of canine and, hence, human leishmaniasis. (+info)
In vitro metabolism of fenthion and fenthion sulfoxide by liver preparations of sea bream, goldfish, and rats.
(4/23)
The in vitro metabolism of fenthion and its sulfoxide (fenthion sulfoxide) in sea bream (Pagrus major) and goldfish (Carassius auratus) was investigated and compared with that in rats. Fenthion was oxidized to fenthion sulfoxide and the oxon derivative, but not to its sulfone, in the presence of NADPH by liver microsomes of sea bream, goldfish, and rats. These liver microsomal activities of the fish were lower than those of rats but were of the same order of magnitude. The NADPH-linked oxon- and sulfoxide-forming activities of liver microsomes of the fish and rats were inhibited by SKF 525-A, metyrapone, alpha-naphthoflavone, and carbon monoxide. The oxidizing activity to fenthion sulfoxide was also inhibited by alpha-naphthylthiourea. Several cytochrome P450 isoforms and flavin-containing monooxygenase 1 exhibited these oxidase activities. Fenthion sulfoxide was reduced to fenthion with liver cytosol of the fish and rats upon addition of 2-hydroxypyrimidine, N(1)-methylnicotinamide, or butyraldehyde, each of which is an electron donor of aldehyde oxidase, under anaerobic conditions. The activity was inhibited by menadione, beta-estradiol, and chlorpromazine, which are inhibitors of aldehyde oxidase. The activities in the fish livers were similar to those of rat liver. Aldehyde oxidase purified from the livers of sea bream and rats exhibited the reducing activity. Thus, fenthion and fenthion sulfoxide are interconvertible in fish and rats through the activities of cytochrome P450, flavin-containing monooxygenase, and aldehyde oxidase. (+info)
Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.
(5/23)
We investigated the endocrine-disrupting actions of the organophosphorus pesticide fenthion and related compounds and the influence of metabolic transformation on the activities of these compounds. Fenthion acted as an antagonist of the androgenic activity of dihydrotestosterone (10(-7)M) in the concentration range of 10(-6)-10(-4)M in an androgen-responsive element-luciferase reporter-responsive assay using NIH3T3 cells. The antiandrogenic activity of fenthion was similar in magnitude to that of flutamide. Fenthion also tested positive in the Hershberger assay using castrated male rats. Marked estrogenic and antiestrogenic activities of fenthion and related compounds were not observed in MCF-7 cells. When fenthion was incubated with rat liver microsomes in the presence of NADPH, the antiandrogenic activity markedly decreased, and fenthion sulfoxide was detected as a major metabolite. The oxidase activity toward fenthion was exhibited by cytochrome P450 and flavin-containing monooxygenase. Fenthion sulfoxide was negative in the screening test for antiandrogens, as was fenthion sulfone. However, when fenthion sulfoxide was incubated with liver cytosol in the presence of 2-hydroxypyrimidine, an electron donor of aldehyde oxidase, the extract of the incubation mixture exhibited antiandrogenic activity. In this case, fenthion was detected as a major metabolite of the sulfoxide. Metabolic interconversion between fenthion and fenthion sulfoxide in the body seems to maintain the antiandrogenic activity. (+info)
Evaluation of xenobiotic N- and S-oxidation by variant flavin-containing monooxygenase 1 (FMO1) enzymes.
(6/23)
The flavin-containing monooxygenase gene family (FMO1-6) in humans encodes five functional isoforms that catalyze the monooxygenation of numerous N-, P- and S-containing drugs and toxicants. A previous single nucleotide polymorphism (SNP) analysis of FMO1 in African-Americans identified seven novel SNPs. To determine the functional relevance of the coding FMO1 variants (H97Q, I303V, I303T, R502X), they were heterologously expressed using a baculovirus system. Catalytic efficiency and stereoselectivity of N- and S-oxygenation was determined in the FMO1 variants using several substrates. The I303V variant showed catalytic constants equal to wild-type FMO1 for methimazole and methyl p-tolyl sulfide. Catalytic efficiency (V(max)/K(m)) of methyl p-tolyl sulfide oxidation by R502X was unaltered. In contrast, methimazole oxidation by R502X was not detected. Both H97Q and I303T had elevated catalytic efficiency with regards to methyl p-tolyl sulfide (162% and 212%, respectively), but slightly reduced efficiency with regards to methimazole (81% and 78%). All the variants demonstrated the same stereoselectivity for methyl p-tolyl sulfide oxidation as wild-type FMO1. FMO1 also metabolized the commonly used insecticide fenthion to its (+)-sulfoxide, with relatively high catalytic efficiency. FMO3 metabolized fenthion to its sulfoxide at a lower catalytic efficiency than FMO1 (27%) and with less stereoselectivity (74% (+)-sulfoxide). Racemic fenthion sulfoxide was a weaker inhibitor of acetylcholinesterase than its parent compound (IC(50) 0.26 and 0.015 mM, respectively). The (+)- and (-)-sulfoxides were equally potent inhibitors of acetylcholinesterase. These data indicate that all the currently known FMO1 variants are catalytically active, but alterations in kinetic parameters were observed. (+info)
A physiologically based pharmacokinetic model of organophosphate dermal absorption.
(7/23)
The rate and extent of dermal absorption are important in the analysis of risk from dermal exposure to toxic chemicals and for the development of topically applied drugs, barriers, insect repellents, and cosmetics. In vitro flow-through cells offer a convenient method for the study of dermal absorption that is relevant to the initial processes of dermal absorption. This study describes a physiologically based pharmacokinetic (PBPK) model developed to simulate the absorption of organophosphate pesticides, such as parathion, fenthion, and methyl parathion through porcine skin with flow-through cells. Parameters related to the structure of the stratum corneum and solvent evaporation rates were independently estimated. Three parameters were optimized based on experimental dermal absorption data, including solvent evaporation rate, diffusivity, and a mass transfer factor. Diffusion cell studies were conducted to validate the model under a variety of conditions, including different dose ranges (6.3-106.9 microg/cm2 for parathion; 0.8-23.6 microg/cm2 for fenthion; 1.6-39.3 microg/cm2 for methyl parathion), different solvents (ethanol, 2-propanol and acetone), different solvent volumes (5-120 microl for ethanol; 20-80 microl for 2-propanol and acetone), occlusion versus open to atmosphere dosing, and corneocyte removal by tape-stripping. The study demonstrated the utility of PBPK models for studying dermal absorption, which can be useful as explanatory and predictive tools that may be used for in silico hypotheses generation and limited hypotheses testing. The similarity between the overall shapes of the experimental and model-predicted flux/time curves and the successful simulation of altered system conditions for this series of small, lipophilic compounds indicated that the absorption processes that were described in the model successfully simulated important aspects of dermal absorption in flow-through cells. These data have direct relevance to topical organophosphate pesticide risk assessments. (+info)
Electroretinographic changes induced by organophosphorus pesticides in rats.
(8/23)
Electroretinographic changes induced by organophosphorus pesticides (OPs) were studied in rats. Male Wistar rats were intraperitoneally injected with fenthion, chlorpyrifos, fenitrothion, dichlorvos or chlorfenvinphos at doses of 0.01 mmol/kg and/or 0.05 mmol/kg. The electroretinogram (ERG) was recorded at 5 hours and 2 days after the administration, and brain and retinochoroid cholinesterase (ChE) activities was assayed at 3 days after the injections. The brain and retinochoroid ChE activities were reduced in rats treated with the OPs. Notably, the reduction of ChE activities by fenthion, chlorpyrifos and dichlorvos were similar. The administration of OPs induced a change in the ERG, characterized by alteration of the amplitudes of a- and b-waves. Nevertheless the ChE activities in the brain and retinochoroid were inhibited by all of the OPs, the OPs affected the amplitude of ERG differently. Fenthion and chlorpyrifos decreased the amplitudes; dichlorvos and chlorfenvinphos increased; and fenitrothion transiently decreased at 5 hours but increased 2 days after the injection. These results indicate that a factor or factors other than inhibition of ChE activities contributes to the alteration of ERG induced by OPs. (+info)