Non-target toxicology of a new mosquito larvicide, trypsin modulating oostatic factor

Trypsin modulating oostatic factor (TMOF), a peptide hormone originally isolated from the ovaries of adult Aedes aegypti, is currently under commercial development as a new pesticide chemistry with a novel mode of action for the control of larval mosquitoes. The objective of the current research is to evaluate potential risks of the use of TMOF as an insecticide on non-target organisms. TMOF (YDPAP(6)) was degraded in vitro (as determined by HPLC and LC/MS) to DPAP(6), PAP(6), and then AP(6) by leucine aminopeptidase, a pancreatic enzyme found in the digestive system of vertebrates. The rate of degradation of TMOF and PAP6 was significantly greater than that of DPAP6, while no metabolism of AP6 was found. TMOF technical insecticide was produced on a commercial scale by recombinant yeast (heat-killed before application). The technical TMOF when administered in a single dose by gavage to male and female mice at 2000mg dry weight/kg body weight produced no negative effects as compared to controls up to 12 days after treatment. When male and female mallard ducks were treated by gavage with 1250mg dry weight of technical TMOF/kg body weight each day for 5 days, again no toxic effects were noted through 35 days after the last treatment. TMOF technical insecticide was also applied to the shaved skin of male and female rabbits at the rate of 2000mg/kg for 12 days, with no effect. The end point observations in these in vivo experiments were mortality; changes in growth rate, behavior, body structure, and color; and possible lesions observed during necropsy. Finally, Daphnia incubated with technical TMOF in rearing water at the level of 1.0 X 10(6) yeast cells/ml (10mg/ml) also demonstrated no negative effects on mortality, growth, molting, time to first brood, and production of viable neonates. It appears from these studies that TMOF can be degraded by vertebrate digestive proteases and technical TMOF is not toxic to the non-target organisms examined. (C) 2004 Elsevier Inc. All rights reserved.