N,N-Diethyl Phenylacetamide (DEPA): A Safe and Effective Repellent for Personal Protection Against Hematophagous Arthropods

Repellents play an important role in protecting humans from the bites of insect pests. An effective and safe repellent will be useful in reducing human-vector contact and thereby help in the interruption of vector borne disease transmission. Because of the unavailability of m-toluic acid in India for the manufacture of N,N-diethyl m-toluamide (DEET), there is a need to develop an alternate effective and safe insect repellent. In total, 120 substituted amides were synthesized and tested for repellency at 1.0 mg/cm2 under laboratory conditions. Among these amides, N,N-diethyl phenylacetamide (DEPA), applied at 1.0 mg/cm2 in different oil bases, was found to exhibit promising repellency (6–8 h) in the laboratory when tested against Aedes aegypti (L.) The repellent DEPA was evaluated on army personnel in comparison with dimethylphthalate (DMP) and DEET against mosquitoes, black flies, and land leeches under field condition in the North-East Frontier area of India. Both DEPA and DEET displayed broad-spectrum repellency. DEPA was more effective than DMP against all test organisms. However, no significant difference was noticed between DEPA and DEET for repellency at 0.25 and 0.5 mg/cm2 against black flies and mosquitoes. DMP was the least effective among the three compounds in the field studies. The relative potency of DEPA in comparison with DEET and DMP for repellency against Phlebotomine sand flies also was determined. At 0.1 mg/cm2, both DEPA and DEET were found to be equally effective with a protection time from 4.37 ± 0.08 to 4.45 ± 0.15 h. Both compounds were significantly more effective than DMP. At 0.2 mg/cm2, DEPA and DEET provided protection times of 6.52 ± 0.08 and 7.15 ± 0.15 h, respectively. DEPA was formulated into a vanishing cream, a pharmacologically safe polymer-based liquid, and a liposphere lotion. The vanishing cream and the two-polymer liquid formulations enhanced protection times from 4.4 to 6.5 and 7.13 h, respectively, compared with an alcohol solution applied at 0.5 mg/cm2 on the forearm of human volunteers. Formulations of DEPA and DEET applied at 0.5 mg/cm2 on rabbits exposed to Ae. aegypti enhanced protection times compared with an alcohol solution and the liposphere lotion from 4.0 to 6.0 h and 4.0 to 5.0 h, respectively. Comparison of mean protection times of DEET and DEPA applied at a rate of 0.3 mg/cm2 to human volunteers exposed to Cx. quinquefasciatus under field conditions indicated that the lotion formulations of DEET and DEPA provided significantly (Duncan's multiple-range test, P < 0.05) higher protection times than did alcohol solutions. Toxicological studies revealed that DEPA is safe.