Benzoylphenyl ureas as veterinary antiparasitics. An overview and outlook with emphasis on efficacy, usage and resistance.

Six benzoylphenyl ureas are currently used in formulations approved as veterinary medicines: diflubenzuron for fly control mainly on cattle, lice and blowfly strike control on sheep, and lice control on farmed salmonids; lufenuron for flea control on dogs and cats and for lice control on farmed salmonids; triflumuron for lice and blowfly strike control on sheep; fluazuron for tick control on cattle; teflubenzuron for lice control on farmed salmon; and novaluron for fly and tick control on cattle and for flea control on dogs. Resistance to diflubenzuron and triflumuron has already been reported for sheep body lice and blowflies, and to fluazuron in cattle ticks. These and other minor veterinary usages, as well as the current status of resistance, are reviewed and perspectives for future opportunities are discussed based on unexplored potentials and threats posed by future resistance development.

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.

A method for eradicating amphipod parasites (hyperiidae) from host jellyfish, Chrysaora fuscescens (Brandt, 1835), in a closed recirculating system.

On 2 December 2006, a heavy infestation of the parasitic hyperiid amphipods Hyperia medusarum and Lestrigonus shoemakeri was discovered in the sea nettles (Chrysaora fuscescens) exhibit at the Tennessee Aquarium. Pretreatment trials that exposed moon jellyfish (Aurelia aurita) and sea nettles to therapeutic levels of diflubenzuron confirmed that the treatment would be tolerated by these species of jellyfish. The exhibit tank was dosed with a 0.03 mg/L concentration of diflubenzuron for 7 days, after which the medication was removed by filtration. An arbitrarily chosen subset from the sea nettle exhibit was sampled regularly over the next 8 wk to monitor the parasite population. The average number of amphipods per jellyfish sampled decreased throughout the treatment and sampling period. No live amphipods were observed 6 wk after the start of treatment, and no negative side effects were observed in the sea nettles. The use of diflubenzuron to eradicate hyperiid parasites from scyphomedusae is a safe and useful option when properly applied in a controlled environment.

The poultry red mite Dermanyssus gallinae (De Geer, 1778): current situation and future prospects for control.

The current importance of Dermanyssus gallinae, mainly in egg layer, in Europe is pointed out. The limits of conventional control methods are underlined (development of mite resistance--future insecticide legislation and animal welfare legislation). Alternative control methods such as feeding deterrents or biological control, are reviewed in the context of poultry pest management.

The efficacy of Diflubenzuron against the body louse (Damalinia limbata) of Angora goats.

The efficacy of an insect growth regulator, Diflubenzuron, to control biting lice (Damalinia limbata) on Angora goats was investigated. Lice on goats which were dipped in a concentration of 625 g Diflubenzuron to 1,000 1 water and then kept in quarantine was eradicated after a single treatment. Nymphs remained present on these goats up to 4 weeks and adult lice up to 8 weeks post-treatment. A single treatment provided greater than 90% reduction in nymphal stages from Week 6 to Week 16 post-treatment in treated goats continuously exposed to reinfestation. The treatment reduced adult louse infestations on these goats by 78-94% through Weeks 6-16 post-treatment. At the end of the trial (24 weeks post-treatment), these goats had 88% fewer nymphs and 84% fewer adult lice compared with untreated control goats.

Effects of the chitin synthesis inhibitor diflubenzuron on development of Ascaris suum and Haemonchus contortus.

The potential of the chitin synthesis inhibitor diflubenzuron (DFB) to alter the development of the parasitic nematodes (Ascaris suum and Haemonchus contortus was investigated. DFB given orally (10 mg kg-1 per day for 30 days) to sheep inoculated with H. contortus infective larvae did not prevent the establishment of adults or affect fecal egg output. However, there was a significant (greater than 90%) decrease in the number of infective larvae recovered from fecal cultures derived from lambs harboring H. contortus adults that were treated with DFB. DFB did not affect egg hatching. Oral administration (10 mg kg-1 per day for 20 days) of DFB to swine harboring adult A. suum adults had no effect on the adult worm burden or on egg morphology, but eggs removed from worms obtained from DFB-treated swine contained less chitin than eggs removed from untreated control swine. DFB also inhibited chitin synthesis in vitro in the isolated reproductive tract of A. suum adults. These results indicate that DFB at high doses can inhibit the subsequent development of H. contortus larvae in the feces. Since H. contortus larvae lack chitin, DFB may act on these larvae by a mechanism independent of a direct effect on chitin synthesis.

Simulation of fly-waves to assess the ability of diflubenzuron to protect sheep against flystrike by Lucilia cuprina.

Sheep were exposed to mass-released gravid females of the sheep blowfly, Lucilia cuprina, in a fly-proof animal house at various times after treatment with the insecticide diflubenzuron (1000, 1500 and 2500 ppm a.i.). Untreated sheep were similarly exposed as controls, while sheep treated with either diazinon (400 ppm a.i.) or cyromazine (1000 ppm) were used as standards for comparison. Before exposure, groups of sheep were wetted by simulating rainfall in the animal house in order to increase their susceptibility to flystrike by L. cuprina. In one trial, sheep jetted with either diflubenzuron or cyromazine (both at 1000 ppm) were protected against flystrike for at least 110 days. At 1500 ppm, diflubenzuron performed significantly better with no bodystrike occurring in the group until the end of the trial at 170 days. Under more severe fly pressure in a second trial diflubenzuron at concentrations up to 2500 ppm provided the same protection as diazinon (approximately 56 days), but performed significantly better thereafter. No cross-resistance to diflubenzuron was found in diazinon-resistant field populations of L. cuprina in laboratory bioassays. The data show that diflubenzuron would be suitable as a prophylactic treatment for flystrike.

Role of metabolism in effects of diflubenzuron on growth of B16 melanomas in mice.

The insect growth regulator diflubenzuron (DFB), which also inhibits growth of experimental tumors in mice, was studied to determine the influence of in vivo microsomal metabolism on its antitumor activity. DFB inhibits chitin synthesis and growth of imaginal epidermis in insects and suppresses melanogenesis and uptake of nucleosides in mouse melanoma cells, but the means of cell growth regulation and the role of metabolism of DFB in such regulation have not been established. Five daily injections of DFB (total of 4000 mg/kg) into C57BL/6 mice with B16 melanomas induced an acute 11-20% decrease in tumor volume and a 2-3 day increase in the initial tumor volume doubling time (Td), but at mid-treatment tumors regained maximum (control-like) rate of volume increase. Tumors in mice conditioned with a mixed function oxidase inhibitor (CoCl2) and treated with DFB did not decrease in mean volume, but their rate of volume increase was reduced by about 75% and the Td was increased by 4.2 days. In contrast, induction of mixed function oxidase with 3-methylcholanthrene (3-MC) or beta-napthaflavone (B-NF) enhanced the effects of DFB by a factor of 1.5 to 2.0. Therefore, aromatic hydroxylation of DFB may be required for tumor growth regulation. Three metabolites of DFB--two hydroxylated forms and a scission product, 4-chlorophenylurea (CPU), were also tested for tumor growth regulation. CPU was ineffective; a form oxidized at the 3 carbon of the phenyl ring (3-OH-DFB) was only marginally effective; but the 2-carbon form (2-OH-DFB) induced a 24% decrease in mean tumor volume and a 2.4 day increase in Td. Pretreatment with 3-MC and treatment with 2-OH-DFB also resulted in a 24% decrease in tumor volume and a 2.2 day increase in Td, but also reduced tumor volume increase to 20% between the 5th and 10th days after the initial 2-OH-DFB injection, compared to a 125% increase without 3-MC. Further, 3-MC pretreatment caused the otherwise marginally effective 3-OH-DFB to become almost as effective as 2-OH-DFB. These data support our previous report that DFB alters tumor growth and show that mixed function oxidase enhances effects of DFB, 2-OH-DFB and 3-OH-DFB.

Effects of diflubenzuron on growth of malignant melanoma and skin carcinoma tumors in mice.

The insect growth regulator diflubenzuron (DFB), which may also inhibit growth of imaginal epidermal cells in insects, was studied for antitumor activity in two mouse tumor models of epidermal origin. DFB inhibits chitin deposition, but the mechanisms by which DFB controls chitin deposition or regulates growth of insect epidermal cells are unknown. A single injection of 20 mg (800 mg/kg) of DFB into C57BL/6 mice with B16 malignant melanomas or AKR mice with skin tumors (CA 1025) induced a rapid (24 h) decrease in tumor volume in 78% and 66% of the tumors, respectively. In contrast, 85% of the melanomas and 91% of skin tumors in control mice increased in volume during the same 24-h period. Tumor volume decreased by as much as 55% for about 1% of the tumors, but the median decrease was 20% for both types of tumors. Since control tumors concommitantly increased, DFB-treated tumors decreased, relatively, to 60% of the volume of matched control tumors. After the initial volume decrease, both types of tumors resumed exponential growth resulting in an average growth curve delay, calculated for 12-14 days, of about 2.0 days. Subsequent treatment of melanomas with DFB 24 h after the initial treatment resulted in a further decrease in relative tumor volume to 40-50% of control tumor volume and a growth curve delay of 2.6 days. The most effective regimen used was 5 daily, 20-mg doses of DFB. Melanomas decreased to 40% of control tumor volume after the third injection and the mean growth curve delay was extended to 4.3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

[Results of exposure to synthetic insect development inhibitors in Psoroptes cuniculi (Psoroptidae) mites]. / Rezul'taty vozdeistviia sinteticheskimi ingibitorami razvitiia nasekomykh na kleshchei Psoroptes cuniculi (Psoroptidae).

Results of the effect of synthetic analogs of juvenile hormones of insects, dimiline, altozide and altozare, on the mite P. cuniculi have been shown. It has been noted that repeated coverings of mites in Petri dishes and rabbits' skin with 0.005--5% emulsions of altozide, 0.005--10% emulsions of altozare and 0.25--8% suspensions of dimiline cause no changes in their morphology and metamorphosis. 1--4% emulsions of altozide and altozare and 2--8% suspensions of dimiline have been found to have an acaricide effect and cause 100 per cent mortality of mites within 48 hours.