Evaluation of compounds for insecticidal activity on adult mosquitos. 5. Toxicity to adult mosquitos and residual properties of some pyrethroids.

Bull. Org. mond. Sant; Bull. Wld Hlth Org. 11970, 42, 387-398 Evaluation of Compounds for Insecticidal Activity on Adult Mosquitos* 5. Toxicity to Adult Mosquitos and Residual Properties of Some Pyrethroids A. B. HADAWAY, F. BARLOW, J. E. H. GROSE, C. R. TURNER & L. S. FLOWER New pyrethrin-like compounds are compared with earlier synthetic pyrethroids and natural pyrethrins for intrinsic toxicity to adult mosquitos and for residual contact activity. Two of the compounds are at least as toxic as pyrethrin I to female Anopheles stephensi and Aedes aegypti. Residues of these compounds are very persistent in the dark or in very subdued lighting but they decompose on exposure to normal intensities of daylight and rapidly lose their insecticidal activity. The following 5 compounds were provided by Dr M. Elliott, Rothamsted Experimental Station, England: Trimethrin (2,4,6-trimethylbenzyl (±)-cis, transchrysanthemate): melting point 50°C-51°C. Pentamethrin (pentamethylbenzyl (+)-cis, transchrysanthemate): indefinite melting point but higher than 65°C. 2,4- dichlorobenzyl (+)-cis, trans-chrysanthemate: MATERIALS a greasy solid, melting point indefinite. Pyrethrins: a commercial extract containing 25 % 4-allylbenzyl (±)-cis, trans-chrysanthemate: boilw/w of total pyrethrins, supplied by Stafford Allen ing point 143°C at 0.02 mm of Hg. and Sons Limited, London, England. 4-allyl-2,6-dimethylbenzyl (±)-cis, trans-chrysanPyrethrin I: a sample provided by Dr Thain, themate: boiling point 150°C at 0.03 mm of Hg. Tropical Products Institute, London, England. Phthalthrin; tetramethrin; OMS-1011 (3,4,5,6Allethrin: a technical grade containing 92% of tetrahydrophthalimido-methyl (±)-cis, trans-chrysanthe allyl homologue of cinerin I; supplied by the themate). The technical-grade sample supplied by American Cyanamid Company, Princeton, N.J., the Sumitomo Chemical Company, Japan, was a USA. cream-coloured solid which melted over the range a-(±)-trans-allethrin: melting point 51°C-52°C, 65°C-70°C. It could be recrystallized from petroleum separated from technical allethrin. ether to give a white solid, melting point 72°C-74°C; Dimethrin; OMS-187 (2,4-dimethylbenzyl (+)-cis, this was presumably enriched in the trans- ester trans-chrysanthemate): a technical-grade sample (melting point 78'C). The technical-grade material supplied by McLaughlin, Gormley, King and Com- was used for volatility and toxicity measurements. Later, samples of the pure (±)-cis, trans- and the pany, Minneapolis, Minn., USA. 2-naphthyl (±)-cis, trans-chrysanthemate: in view (±)-trans- compound were supplied. of the sharp melting point, 80°C-81°C, probably OMS-JIlS (1,2,3,4-tetrahydro-6-naphthalene-memainly trans- isomer. thyl (+)-trans-chrysanthemate). The technical material supplied by the Sumitomo Chemical Com* From the Ministry of Overseas Development, Tropical pany, Japan, was a pale-yellow liquid and was used as received. Pesticides Research Unit, Porton Down, England. The generally low toxicity to mammals, and hence safety in use, of pyrethrins means that there is a considerable interest in synthetic pyrethrin-like compounds. Those prepared by Elliott and his colleagues (Elliott et al., 1965, 1967), together with some compounds from the World Health Organization programme for the evaluation of new insecticides, were therefore tested against adult mosquitos. 2480 387- 388 A. B. HADAWAY AND OTHERS Compound OMS-1116 (thiophthalimido-methyl (±)-transchrysanthemate). The technical material supplied by the Sumitomo Chemical Company, Japan, was a pink solid (melting point 110°C-116°C). It was recrystallized from petroleum ether and the pure compound (melting point 1140 C-1i 6°C) was used for measurements. OMS-1206; NRDC-104 (5-benzyl-3-furylmethyl (±)-cis, trans-chrysanthemate). Three samples of this compound were supplied by Dr M. Elliott and were tested over a period of about 18 months. The compound when received was a very pale-yellow solid which became discoloured on storage, but all the measurements were made with purified material. Dr Elliott also provided samples of some of the stereo-isomers of OMS-1206. NRDC-108 (5-benzyl-3-furylmethyl 2,2,3,3-tetramethylcyclopropanecarboxylate). This compound, synthesized and supplied by Dr M. Elliott (Elliott et al., unpublished data) is the ester of the same alcohol as NRDC-104 with 2,2,3,3-tetramethylcyclopropanecarboxylic acid. This acid does not show stereo-isomerism and the ester is a single substancea colourless crystalline material with a melting point of 36°C-37°C. Like OMS-1206, it became discoloured on storage but all measurements were made with colourless material of the correct melting point and the sample was recrystallized from methanol when necessary. Rate of loss (g/m2/day) OMS-187 Trimethrin OMS-101 1 OMS-1 115 OMS-1116 OMS-1206 (NRDC-104) NRDC-108 Under the conditions of this test, OMS-187 is relatively volatile but the remainder would be classified as of low volatility and potentially persistent insecticides. Toxicity by topical application Median lethal doses of compounds determined by the topical application of measured volumes of solutions in di-isobutyl ketone to the dorsal surface of the thorax of individual female Anopheles stephensi and Aedes aegypti mosquitos, 1-2 days old, are shown in Table 1. Of the synthetic pyrethroids, OMS-1206 (NRDC104), NRDC-108 and OMS-1011 (phthalthrin) were TABLE I MEDIAN LETHAL DOSES OF VARIOUS COMPOUNDS TO FEMALE MOSQUITOS Compound LD50 (ng/mosquito) An. Ae. aegypti stephensil RESULTS Volatility Glass-fibre filter-papers impregnated with compounds at a dosage rate of 1 g/m2 from acetone solutions were hung in a room at 25°C and a relative humidity of 50 %-55 % in darkness. The amounts of compounds remaining on the papers at different times after treatment were determined by extraction with 95 % ethanol or 40-60 petroleum ether, according to the method of analysis used. The analytical methods mainly depended on ultraviolet absorption properties but gas-liquid chromatography was also employed. Readings at several wavelengths in the ultraviolet method provided a check on possible decomposition. Neither form of analysis indicated any appreciable decomposition in the dark but this would not be true for residues stored in daylight. Rates of loss were of zero order and are shown in the following tabulation. There was no suggestion that the cis-isomer was appreciably more or less volatile than the trans-isomer for those compounds which were mixtures. 0.092 0.019 0.0025 0.0048 0.0020 0.0033 0.016 Pyrethrum (based on total pyrethrins) Pyrethrin I 1.8 4.0 1.1 Allethrin a-allethrin 7.0 2.5 19 15 - 13 52 41 OMS-187 (dimethrin) Trimethrin Pentamethrin 13 15 12 4-allyl-benzylchrysanthemate 9.5 4-allyl-2,6-dimethylbenzyl chrysanthemate 50 2,4-dichlorobenzyl chrysanthemate >150 2-naphthyl chrysanthemate 3.6 OMS-1011 26 OMS-1115 7.8 OMS-1116 0.9 OMS-1206 (NRDC 104) NRDC-108 1.0 50 25 17 150 >150 8. (...truncated)