Submitted to: U.S. Army Center for Health Promotion and Preventative Medicine
Publication Type: Government Publication
Publication Acceptance Date: October 22, 2001
Publication Date: November 1, 2001
Interpretive Summary: Serious diseases such as West Nile Virus, Lyme Disease, malaria, dengue fever, yellow fever and typhus are transmitted to humans by blood-feeding ticks, mosquitoes and lice. There is a need to develop new compounds as protectants against these disease carriers. A new compound, DM-156-2, proved to effectively repel biting mosquitoes in an in vitro bioassay. The problem was that, although preliminary assay identified DM-156-2 as a candidate insect repellent, further research and development of it was impossible because its safety for topical application to animals was unknown. Toxicological studies reported here proved that the compound was nontoxic in a series of animal tests, and this has cleared the way for its further entomological evaluation using human subjects. This is an important step in the eventual development and use of the compound as a new repellent to protect humans against blood-feeding arthropods that carry disease.
The purpose of the study was to determine the acute toxicity of the candidate repellent DM-156-2 in animals using a battery of short-term toxicity tests. It was found that the repellent is nonirritating to the skin and eyes of rabbits. It is not a photochemical irritant in rabbits nor does it produce skin sensitization in guinea pigs. The oral approximate lethal dose (ALD) in male rats is 1480 mg/kg. The dermal ALD in guinea pig is greater than 5000 mg/kg. The Salmonella-Escherichia coli/Mammalian- Microsome Reverse Mutation Assay was negative in the presence and absence of S9 activator. The collective results indicate that DM-156-2 is relatively nontoxic when applied to the skin of animals. No adverse effects in humans are anticipated following a single dermal exposure therefore, the compound was cleared for further entomological studies using human subjects.