In vivo effect of diflubenzuron, administered via mineral salt supplementation, against Haematobia irritans and Rhipicephalus microplus parasitizing cattle.

This study involved two field trials with the aim of evaluating the efficacy of diflubenzuron, via mineral supplementation, against Haematobia irritans parasitizing cattle. Concomitantly with the main trial, a stall test was conducted to ascertain the effects of a different formulation with the same active ingredient against Rhipicephalus microplus, along with the action of diflubenzuron on the reproductive parameters of R. microplusfemales that had naturally detached from cattle. Against H. irritans, it was observed that the efficacy indexes fordiflubenzuron were low (≤ 31.3% or 44.6%) or null (0.0%) throughout the study. The anti- R. microplus efficacy of diflubenzuron, at weekly intervals, ranged from 0.0 to 13.7% over the entire experimental period. Null efficacy (0.0%) was registered for diflubenzuron in relation to the reproductive parameters of R. microplusfemales that had naturally detached from cattle. The different diflubenzuron formulations, administered via mineral salt supplementation, did not show satisfactory efficacy indexes against H. irritans and R. microplus parasitizing cattle, within the experimental design of the present study. In addition, this agent did not present any deleterious effects on the reproductive parameters of R. microplus females.

In vivo effect of diflubenzuron, administered via mineral salt supplementation, against Haematobia irritans and Rhipicephalus microplus parasitizing cattle / Efeito in vivo do diflubenzuron, administrado via sal mineral, contra Haematobia irritans e Rhipicephalus microplus parasitando bovinos

Abstract This study involved two field trials with the aim of evaluating the efficacy of diflubenzuron, via mineral supplementation, against Haematobia irritans parasitizing cattle. Concomitantly with the main trial, a stall test was conducted to ascertain the effects of a different formulation with the same active ingredient against Rhipicephalus microplus, along with the action of diflubenzuron on the reproductive parameters of R. microplusfemales that had naturally detached from cattle. Against H. irritans, it was observed that the efficacy indexes fordiflubenzuron were low (≤ 31.3% or 44.6%) or null (0.0%) throughout the study. The anti- R. microplus efficacy of diflubenzuron, at weekly intervals, ranged from 0.0 to 13.7% over the entire experimental period. Null efficacy (0.0%) was registered for diflubenzuron in relation to the reproductive parameters of R. microplusfemales that had naturally detached from cattle. The different diflubenzuron formulations, administered via mineral salt supplementation, did not show satisfactory efficacy indexes against H. irritans and R. microplus parasitizing cattle, within the experimental design of the present study. In addition, this agent did not present any deleterious effects on the reproductive parameters of R. microplus females.

Resumo O objetivo deste estudo foi avaliar a eficácia do diflubenzuron, administrado via suplementação mineral, contra Haematobia irritans parasitando bovinos, em dois testes à campo. Concomitantemente, foi realizado testes em estábulo para determinar os efeitos de uma formulação diferente, com o mesmo princípio ativo, contra Rhipicephalus microplus , bem como a ação do diflubenzuron nos parâmetros reprodutivos de fêmeas de R. microplus recolhidas após desprendimento natural do hospedeiro bovino. Contra H. irritans, foi observado que foram baixos (≤ 31,3% ou 44,6%) ou nulos (0,0%) os índices de eficácia do diflubenzuron. A eficácia anti-R. microplus do diflubenzuron, observada em intervalos semanais, variaram de 0,0% a 13,7% durante todo o período experimental. Com relação aos parâmetros reprodutivos das fêmeas de R. microplus recolhidas, foi observada eficácia nula (0,0%) para o diflubenzuron. Conclui-se que as diferentes formulações administradas via sal mineral no atual estudo, contra H. irritans e R. microplus parasitando bovinos, não apresentaram eficácia satisfatória. Este agente também não mostrou efeito deletério sobre os parâmetros reprodutivos de fêmeas de R. microplus.

Toxicological assessment of the anti-salmon lice drug diflubenzuron on Atlantic cod Gadus morhua.

Increasing use of the chitin synthesis inhibitor diflubenzuron against the ectoparasitic salmon louse Lepeophtheirus salmonis in marine aquaculture has raised concerns over its environmental impacts. This study evaluated how diflubenzuron affects Atlantic cod Gadus morhua, a fish species often found near Atlantic salmon Salmo salar farms, focusing on uptake kinetics and hepatic transcriptional responses. Two experiments were conducted, one time-series trial in which the fish were given a daily dose (3 mg kg-1 fish) of diflubenzuron for 14 d followed by a 3 wk depuration period, and one dose-response trial with increasing concentrations (3, 10 and 50 mg kg-1 fish). The highest diflubenzuron concentrations were found in the liver at Day 15. No detectable levels of diflubenzuron were found in liver or muscle 3 wk after the end of the treatment. At the molecular level, small effects of diflubenzuron treatment on gene transcription were observed. In the time-series experiment, the strongest effects were seen at Day 8, with 2 transcripts being upregulated (bclx2 and cpt1a) and 8 transcripts being downregulated (gstp1, gstm1, gstt1, ugt1a, nat2, cat, p53 and slc16a9a). Five transcripts (cyp3a, cpt1a, ptgs2, elovl5 and mapk1) responded significantly to diflubenzuron exposure in the dose-response experiment. This study shows that diflubenzuron can be taken up by Atlantic cod, that it is rapidly cleared from the body and that when present this pharmaceutical causes only small effects on the expression of genes involved in detoxification pathways. Taken together, our data suggest that accumulated diflubenzuron at the levels studied would have a relatively small effect on wild Atlantic cod.

Determination of diflubenzuron residues in milk and cattle tissues / Determinação de resíduos de diflubenzuron em leite e tecidos bovinos

Diflubenzuron (DFB) is used to control ectoparasitic infestation by inhibiting larvae development in the manure and feces of treated animals. It is also currently been used to control tick infestations. In this study, milk and tissues from cattle treated orally with DFB for a 77-120 day period with a commercial product containing the compound were analyzed for the presence of residues. DFB residues were determined by using extraction with acetonitrile, cleanup with C18 SPE and chromatographic analysis by HPLC with UV detection (254nm). DFB was not detected in any of the analysed samples (<0.006mg kg-1 for fat, <0.014mg kg-1 for muscle, <0.015mg kg-1 for kidney, <0.016mg kg-1 for liver and <0.0006mg kg-1 for milk). In this manner, the use of this compound, according to the manufacturer's suggested doses may result in cattle milk, liver, kidneys, fat and muscles being considered safe regarding the presence of DFB residues.

O diflubenzuron (DFB) é um inibidor de desenvolvimento de insetos que inibe a síntese de quitina com atividade ovicida e larvicida e está sendo utilizado na pecuária para o controle do carrapato. Leite e tecidos provenientes de bovinos tratados por um período de 77 a 120 dias com um produto comercial contendo DFB foram analisados quanto à presença de resíduos. Os resíduos de DFB foram determinados utilizando-se extração com acetonitrila, limpeza por SPE C18 e cromatografia líquida de alta eficiência com detecção por UV (254nm). DFB não foi detectado em nenhuma das amostras analisadas (<0.006mg kg-1 para gordura, <0,014mg kg-1 para músculo, <0,015mg kg-1 para rim, <0,016mg kg-1 para fígado e <0.0006mg kg-1 para leite). Dessa forma, a utilização do princípio ativo conforme recomendado pelo fabricante e em níveis suficientes para se obter o efeito larvicida desejado deve resultar em leite, fígado, rins, gordura e músculos que podem ser considerados seguros para o consumo em termos da presença DFB.

Effect of sublethal dose of diflubenzuron and azadirachtin on various life table attributes of Culex quinquefasciatus (Diptera: Culicidae).

The exposure of sublethal doses (25% emergence inhibition) of diflubenzuron (DFB) (0.0002 mg/liter) and azadirachtin (AZD; 0.0079 mg/liter) insect growth regulators was provided to late third- early fourth instars of Culex quinquefasciatus till emergence of adults to find out the effects on various biological and life table attributes of adults, and comparison was made with control (CTL) as well. Life expectancy of both males and females of DFB survivors was significantly less in comparison with AZD and CTL ones; however, it was nonsignificantly different between CTL and AZD. In all treatments, males were shorter lived than females of their respective treatments. DFB survivors showed significant reduction in number of blood-fed females, resulting in minimum of oviposition days, total number of egg rafts, total number of eggs, eggs per egg raft, eggs per female life span, and eggs per female per day than survivors of both AZD and CTL significantly, but these parameters did not differ significantly between CTL and AZD, except eggs per egg raft. The net reproductive rate, intrinsic rate of increase, and finite rate of increase were significantly less in DFB than rest of the survivors, whereas doubling time for generation was significantly high; however, difference in mean generation was not significant among them. This study reveals that DFB has the potency to affect severely the various life table attributes at sublethal dose, but AZD does not have such effectiveness at similar sublethal dose against Cx. quinquefasciatus.

Effectiveness of pyriproxyfen and diflubenzuron formulations as larvicides against Aedes aegypti.

The efficacy of technical pyriproxyfen and diflubenzuron was evaluated at the laboratory level against Aedes aegypti, where we achieved adult emergence inhibition (EI50) values of 0.048 and 1.59 ppb (microg/liter), respectively. We compared these data with values obtained for temephos. We prepared emulsifiable concentrate formulations of pyriproxyfen and diflubenzuron in the laboratory and obtained EI50 values of 0.01 and 0.02 ppb, respectively. We also obtained 100% adult emergence inhibition with 0.1% slow-release sand formulations of pyriproxyfen and diflubenzuron. In a simulated field study, the granular sand formulations of pyriproxyfen, diflubenzuron, and temephos remained active for over 4 mo. In a field study, a 0.2% granular formulation of diflubenzuron and 1% temephos showed a similar performance.

Laboratory evaluation of diflubenzuron as a feed-through for control of immature sand flies (Diptera: Psychodidae).

The benzoylurea chitin synthesis inhibitor diflubenzuron was evaluated as a rodent feed-through for the control of immature stages of Phlebotomus papatasi Scopoli (Diptera: Psychodidae). The development and survival of second instars of P. papatasi larvae that were fed feces from Syrian hamsters, Mesocricetus auratus, that had been fed a diet containing 0, 8.97, 89.7, or 897 ppm diflubenzuron was evaluated. No pupation or adult emergence occurred when larvae were fed feces from hamsters that were fed diets containing diflubenzuron. The mortality of sand flies fed feces from treated hamsters was coincident with pupation of the controls, suggesting a specific effect on the larval-to-pupal molt. The results of this study suggest that a control strategy using rodent baits containing diflubenzuron for phlebotomine sand flies and zoonotic cutaneous leishmaniasis may be possible.

Safety of elevated dosages of a 0.24% diflubenzuron pellet administered orally to horses.

The safety of a feed-thru pellet formulation containing the insect growth regulator diflubenzuron (0.24%) for control of manure-breeding flies (Musca domestica L. and Stomoxys calcitrans L.) in horses was evaluated. Pellets were administered orally at 0, 1, 3, and 5 times the clinical dosage (0.12 to 0.20 mg/kg) on a daily basis for 31 consecutive days. Variables examined included daily clinical observations, hematology, coagulation, serum chemistry, acetylcholinesterase inhibition, body weights, and physical examinations. Horses remained healthy throughout the study, and no adverse reactions or events related to the pellets were observed. Statistically significant differences (P < or = 0.10) between dose groups (0x, 1x, 3x, and 5x) were observed for only four of the 44 serum chemistry and hematologic variables measured, none of which was dose related. Diflubenzuron can be safely administered orally to horses at 0.12 to 0.20 mg/kg for control of manure-breeding flies.

Effects of boric acid, fipronil, hydramethylnon, and diflubenzuron baits on colonies of ghost ants (Hymenoptera: Formicidae).

Laboratory colonies of the ghost ant, Tapinoma melanocephalum (F.) were administered sugar solution (10%) baits containing the insecticides boric acid, fipronil (REGENT), hydramethylnon (SIEGE), or diflubenzuron (DIMILN). Colonies were exposed to the baits for 21 d, and development of workers, queens, and brood (larvae and pupae) was observed for 4 wk. Fipronil (0.05%) caused 100% mortality in all colonies the first week. With boric acid (0.5%), 100% mortality of workers, queens, and brood was reached at the end of the third week. With hydramethylnon (2%), 83% of the colonies disappeared at the end of the fourth week, but some queens were still alive 9 wk after the trial started. Diflubenzuron (1%) behaved similarly to the control, although in some colonies, the brood production increased, whereas in other colonies, the queens disappeared. In the control colonies, workers, queens, and brood were always observed even up to 9 wk.

Actividad biológica del diflubenzuron sobre Blattella germanica (Dictyoptera: Blattellidae) / Biological activity of the diflubenzuron has more than enough Germanic Blattella (Dictyoptera: Blattellidae)

Se realizó un estudio con la cepa Ameijeiras de Blattella germanica (Dictyoptera: Blattellidae), mantenida en el laboratorio desde el año 1994 y susceptible a los insecticidas propoxur, malation y cipermetrina. Esta cepa fue tratada con 4 concentraciones diferentes de diflubenzuron (Dimilin, OMS 1804), suministradas a través del alimento a ninfas de primer estadio de desarrollo, con el objetivo de determinar su efecto sobre la supervivencia, el fenotipo y el período de desarrollo ninfal de esta especie. Se determinó la línea de regresión dosis-mortalidad y se obtuvieron los valores de CE50 = 0,042 por ciento y CE95 = 0,357 por ciento. Se observaron efectos subletales en las ninfas tratadas con las 4 concentraciones probadas, mientras que los efectos morfogenéticos en los adultos solo aparecieron en los que fueron expuestos a las concentraciones más altas (0,25 y 0,4 por ciento). El período de desarrollo ninfal mostró un incremento altamente significativo al aumentar la concentración del inhibidor (F = 11,64; p <0,001). >(AU)

Effect of diflubenzuron on flight of adult aquatic insects (Plecoptera, Trichoptera) following emergence during the second year after aerial application.

With Malaise traps, we monitored the flight of adult Plecoptera and Trichoptera following emergence from headwater streams in the Fernow Experimental Forest, WV, during the second year after application of diflubenzuron. We placed five traps at various distances from each stream during May through September of 1991, 1992, and 1993. We collected pretreatment samples during the first year. In May 1992, diflubenzuron was applied to two watersheds, and the other two watersheds were used as untreated references. The 1992 study tested the effects of diflubenzuron that fell directly into the streams or were washed into the stream during the first year. For 1993, we tested the hypothesis that diflubenzuron affected adult flight following emergence during the year following abscission and possible ingestion of the treated leaves. The analysis compared the regressions of the number of adults caught in each trap versus distance of the trap from the stream among years and between treatments for each species. The flight of the stonefly Leuctra ferruginea (Walker) was reduced in the treatment watersheds compared with the reference watersheds during the year following abscission of the treated leaves. Adult flight of other species did not decrease in the treatment watersheds during 1993. These results show a relatively small effect of diflubenzuron on these aquatic insects; however, our study involved only a single application of diflubenzuron. Additional research may be needed to predict the possible effects of multiple applications of diflubenzuron over several years as often occurs during actual efforts to suppress gypsy moth, Lymantria dispar (L.).

Pharmaceutical development of a parenteral formulation of the investigational anticancer drug clanfenur.

A stable parenteral dosage form for the investigational cytotoxic drug clanfenur was designed, and the bulk drug was characterized by its nuclear magnetic resonance, mass spectrometry, infrared, and ultraviolet spectra. The 1H and 13C spectra show clanfenur to be a mixture of two stereoisomers. Because of poor solubility in aqueous solution and precipitation in co-solvent, surfactant, or emulsion systems, a two-pump infusion system was developed for intravenous administration. Clanfenur, solubilized in a Cremophor EL/ethanol (1:1, w/v) solution (concentration, 15 mg/mL), can be simultaneously infused with 5% dextrose infusion fluid. Total doses of up to 1,680 mg of clanfenur (and 56 g of Cremophor EL) theoretically can be administered to patients over a 6-hour period. From accelerated stability testing of clanfenur in the Cremophor EL/ethanol (1:1, w/v) formulation, a shelf life of 3.5 years at 4 degrees C and of 4 months at 25 degrees C is calculated.

Effects of diflubenzuron and clanfenur on mouse bone marrow cells.

Diflubenzuron (DFB) and Clanfenur (CFN) belong to a group of compounds called Benzoylphenyl Ureas (BPUs). Several BPUs regulate cell growth in insects and/or inhibit growth of B-16 murine melanomas. In view of potential clinical use for these compounds, DFB and CFN were selected as examples of BPUs and tested for effects on hematopoiesis in C57Bl/6 mice housed in a conventional environment. DFB and CFN exhibit anti-tumor activity in mice, cause little or no morbidity and mortality and rather than causing bone marrow suppression, which is usual for anti-cancer drugs, these agents stimulate hematopoiesis in vivo and in vitro. Stimulation in vivo was evidenced by increased (up to 112%) peripheral blood granulocytes 6 days after a single injection and enhanced granulopoiesis (approximately 25%) in bone marrow up to 18 days after treatment. That effects of DFB and CFN were on hematopoietic stem cells were indicated by 47% and 48%, respectively, increases in numbers of CFUs and 97% and 95%, respectively, increases in CFUgm. Further, bone marrow cells treated in vitro contained about twice the number of CFUs and CFUgm as control bone marrow cells. Almost all of the increase in number of spleen colonies, whether derived from donors treated in vivo or bone marrow cells treated in vitro, was accounted for by a corresponding increase in number of undifferentiated colonies. These data indicate that DFB and CFN treatment enhance numbers of pluripotential stem cells both in vivo and in vitro. The mechanism of enhancement, direct or indirect, remains to be determined.

Effect of an insecticide controlled-release bolus on a milk antibiotic residue test.

Following the use of diflubenzuron controlled-release insecticide boluses in a dairy herd, there was a concern that post-calving cows were testing positive on a milk antibiotic residue test for more milkings than they had prior to the use of diflubenzuron. A field trial was conducted to examine for possible effects of diflubenzuron milk residues on the milk antibiotic residue test, Delvotest-P. Data of 24 cows in the treatment group and 29 cows in the control group were analyzed. There was no significant difference in the number of milkings after calving in which the milk tested positive on the milk antibiotic residue test between the treatment (2.75 +/- .94) and control (2.97 +/- 1.05) groups when cows in all lactations were analyzed or when analyzed by lactation (1, 2, and greater than or equal to 3). It was concluded that the use of diflubenzuron boluses had no effect on the milk antibiotic residue test.

Tissue distribution of 14C-diflubenzuron in Atlantic salmon (Salmo salar).

Diflubenzuron is a potent inhibitor of chitin synthesis, with potential use against salmon lice infestations. The absorption, distribution and elimination of the substance in Atlantic salmon was examined after a single, oral dose of 75 mg/kg bodyweight. The kinetic properties were studied by whole-body autoradiography, liquid scintillation counting and thin layer chromatography, using a 14C-labelled isotope of the substance. The drug was poorly absorbed from the intestine, but reached a concentration of more than 4 micrograms/g in the mucus layer of the skin 2 days after administration. If maintained for several days, this concentration is probably sufficient to control all moulting stages of sea lice in Atlantic salmon. The main route of excretion was via the bile.

[Effect of difluron (dimilin) on larvae, imagines and eggs of Epilachna varivestis Muls. through application to the host plant]. / Uber die Wirkung von Diflubenzuron (Dimilin) auf Larven, Imagines und Eier von Epilachna varivestis Muls. bei Applikation über die Wirtspflanze.

Dimilin active ingredient diflubenzuron) is an insecticide influencing the chitin synthesis. The paper investigates its effect under application via the host plant. After oral intake with the food, the larvae of Epilachna varivestis Muls. (Mexican bean beetle) could not carry out the next molting and died. Imagines which had taken up Dimilin laid fewer eggs than untreated beetles, and no larvae hatched from the eggs. Direct treatment of the cluster of eggs with Dimilin also affected their development, depending on the degree of concentration. Freshly laid eggs were more susceptible than older ones. Contact with the treated non-host plant Vicia faba also caused disturbances in the development. The sensitive phase in the second instar lies between 24 and 48 hours after the previous molt. 3 to 6 hours exposition time are sufficient to inhibit the molting of the larvae, 9 hours suppressed the molting completely. The concentration limit for larvae of Epilachna varivestis lies between 1.0 and 2.5 ppm.