Studies on Saligenin Cyclic Phosphorus Esters with Title Insecticidal Activity : Part X. Synergism of Malathion against Susceptible and Resistant Insects
ETO, Morifusa; OSHIMA, Yasuyoshi; KITAKATA, Setuo; Author(s) TANAKA, Fumikazu; KOJIMA, Ken'ichi
Citation 防虫科学 (1966), 31(1): 33-38
Issue Date 1966-02-28
URL http://hdl.handle.net/2433/158466
Right
Type Departmental Bulletin Paper
Textversion publisher
Kyoto University m m fl ~ in 31 ~-I
~Wrff1lJ'Il:ar1tl-f-~ 24n~mO~0)~¥E~~l2;.R~t.:. c z hl2 Summary Bliss 0) probit r.tI~ t...t.:t.I~., -cmJ.1nt.... -( zcr:»: 1 iiJi Exploratory studies have been made with ~ I) O)rf:t~~r~rln1lt7Ja.Frf1~~3'Er!ftl:l2;J<~t.:. substituted benzyl esters of chrysanthemic acid M* :~~O)M*l2;U~'r Q c Table 1. sos 2 0) in search for effective insecticides. Of many benzyl tm< '"C" Studies on Saligenin Cyclic Phosphorus Esters with .Insecticidal Activity. Part X. Synergism of Malathion against Susceptible and Resistant Insects. Morifusa ETO, Yasuyoshi Osmsr», Setuo KITAKATA*. Fumikazu TANAKA* and Ken'ichi KOJIMA* (Department of Agricultural Chemistry. Kyushu University, Fukuoka and*Institute of Agricultural Chemicals, Toa Noyaku Co. Ltd., Odawara) Received November 30, 1965. Boiyu-Kagaku, 31, 33. 1965. 6. ~!llt1ofj' IJ If= ~iJ~ ~ AJM:r. A 7' )J,0)ii]f~ (t!HO¥fD r®~l!E.:i,;J: v:m;j/Ll!Emr1H~*{'rQ"7 :77'.i";; c 0)~l;1Jf'ffl] rrjJj'iT~' *tbm~ . ~t1J1m7-:::* • rnrf:15c-* • IN'M.l!-* (1L1H#J: n~mn1~ {t~~1. *mjffin~~~~fl:n~li1f~iYD 40. 11. 30 )'l:l]! ~ :7 :r:t ;;0)J1j1J 1l'm~ ~ -II 1.> L t 't'91l i; tt -CP 7.> tri-e-tolyl phosphate O)±~mt'J:{~;;qlPn~1l' ~tJ" HllO) -l} 9 7' =- ;;ro~ ~ A~:r. A 7"It-IC "?~,"(. ~:7:r:t;; t O)~~IJ{tm H~~tt;fd J: o:m;tlcfl 0) -1 x:»: :r.t ';1 ~ ~. P 3 ::J r«-11l' m p "(~JH L t..:. ll,l~:r. A 7"It-O) 7 9 1t-:m'.t;U= Ii. L t Icm;j;i:f'Jl IC~Jvnpti'it'J:1l'ff-v tz: 7 1t-4'- 1t-lt15'!;U=li:f1£Vtfililr.~vjJgp~~1JrFm ~~v tz: ll.tJtti v t":l~fr~ I1t, m:::rrWJt.. ~l;1JJi!Hi 7-methyl-2-phenyl-4H-l, 3, 2-benzodioxaphosphorin-2-oxide 't' a).,tz, LO) f, O)li:f1£Vtt'J:-1 :r./'{:r.IC~Jv, propyl paraoxon ~ Dibrom O)J: ? tJret?nj~IJJi!lJ: ~ f, lIWJ't' ih., tz: Certain organophosphorus compounds increase oitroi», it is metabolized in vivo to active anti the toxicity of malathion (O,O-dimethyl 5-(1.2 esterase agents. 1. e., saligenin cyclic phosphates biscarboethoxyethyl) phosphorodithioate) to marn 11,\2). A series of saligenin cyclic phosphorus esters mals!', EPN (ethyl p-nitrophenyl phenylphos have been synthetically preparedt3,!4landexamimed phonothionate)!' and TOCP(tri-c-tolyl phosphate)!' for biological activities. Aryl derivatives were are well known examples. For insects, particularly selective inhibitors of ali-eaterase!" and appeared resistant strains. several synergists of malathion to be synergistic with malathtonw, whereas small have been reported: propyl paraoxon (dipropyl alkyl derivatives were highly Insectlcidalr", p-nitrophenyl phosphate)4>, EPN and its oxoana Results of investigations on the synergistic loga> for house fly; tributyl phosphorotrithioate activities of some saligenin cyclic phosphorus and its some related substances for house fly and esters against resistant insects are presented in mosquitos-P ; EPN for mosquitov: Dibrom (1,2 this papar, It was observed that 7-methyl dibromo-2,2-dichloroethyl dimethyl phosphate) 2-phenyl-4H-l, 3. 2-benzodioxaphosphorin-2-oxide for green rice leafhopper!', Allofthesephosphorus (VII) was a quite effective synergist of malathion. compounds are known as inhibititors of ali-esterase or related hydrolases at least in vivo condition. Materials and Methods Although TOCP itself is not the inhibitor in Chemicals: Samples except Compound III were 33 Table 1. Joint action of saligenin cyclic phosphorus esters (I-VII) and some other phosphoric esters with malathion against susceptible house flies. Y,/"jO"f. . I II f- R '\,/" /0 CH2 Compound' LDGO (pg/!f ) with Cotoxicity No. R X Y alone malathion coefficient (1 : 1) Malathion 0.46 I OMe H 0.02 0.06 0.6 II OEt ° H 0.16 0.14 1.7 III OEt °S H 0.11 0:22 0.8 IV OPh H c. 10 (30%) 0.38 2.3 V O-o-Tol ° H c. 10 (40%) 0.26 3.4 VI Ph ° H c. 10 (6096) 0.36 2.5 VII Ph ° Me c. 10 (70%) 0.26 3.4 TOCP ° >10 ( 096) 0.90 1.0 Dibrom 0.03 0.008 7.1 Propyl paraoxon O. 10 0.11 1.5 Isopropyl paraoxon 0.22 0.06 4.9 Abbreviations for designating structures: Me=methyl; Et=ethyl ; Ph=phenyl ; Tol=tolyl, Numbers in parentheses are mortality percentage at 10 pg dose per insect. purified through column chromatography, distil They were kept at 25'. Mortality counts were lation or recrystallization. Materials included were made 24 hours after treatment. malathion, Dibrom, proply paraoxon, isopropyl Joint toxic action was tested by applying the paraoxon (diisopropyl p-nitrophenyl phosphate), mixture of malathion and synergist at a 1:1 ratio. TOCP and seven' derivatives of saligenin cyclic The joint action was evaluated by the cotoxicity phosphorus esters. The cyclic esters were prepared coefficient2o,211 of the mixture. The coefficient was by a reported method. 13,14> Their structures are calculated by the following equation (1). shown in Table 1 (I-VII). Cotoxicity coefficient=Actual toxicity index of Insects: Oriental house fly (Musca domestica a mixture/Theoretical toxicity index of a mixture vicina Macquart) and green rice leafhopper ...... (1) tNephotettix cincticeps Uhler) were used. The For some practically non-toxic compounds, a strains of house fly were: (1) Sapporo, a suscep modified simple equation (2) could be applied. tible strain and (2) Hokota, a diazinon-resistant Cotoxicity coefficiente-Llr., of malathion alone/ strain showing cross-resistance to malathion. LDGO of malathion in a mixture...... ·.... ·...... · ( 2 ) The strains of leafhopper were: (1) Odawara, a The cotoxicity coefficient is the number of times susceptible strain and (2) Koti, a malathion-re of increase (or decrease) in toxicity. sistant strain caught in a field of Koti prefecturew. In some experiments, this was used after further Results selection with malathion for several generations. The activity of saligenin cyclic phosphorus esters Test method: Acetone solution of test chemicals in joint action with malathion was examined in was topically applied to female adult insects. comparison with some phosphoric esters which For green rice leafhopper, a previously reported have been reported as synergists of malathion. micro techniquewwas used. Five replicate samples Results with susceptible house flies are shown in each of ten insects were used for each treatment. Table 1. Aryl derivatives of saligenin cyclic esters 34 IW J1l ft ~ til 31 ),J-I Table 2. Synergistic effect of saligenin cyclic phosphorus esters (I-VII) with malathion against resistant house flies in comparison with other phosphate synergists. LOo• (flg/ ~) Cotoxicity Compound with alone malathion coefficient (1 : 1) Malathion 2.54 I 0.15 0.06 4.7 II 0.40 0.22 3. 1 III 0.20 0.10 3.6 IV >10 (10%) 0.55 9.2 V >10 (1096) 0.65 7.8 VI >10 (2596) 0.57 8.0 VII c. 10 (40%) 0.29 14.0 TOCP >10 ( 096) 3.44 1.5 Dibrorn 0.07 0.07 2.0 Propyl paraoxon 0.73 0.46 2.5 Isopropyl paraoxon 0.43 0.36 2.2 Numbers in parentheses are mortality percentage at 10/1g dose per insect. are synergistic with malathion. They increase 2-oxide (VII). Phenyl phosphate (IV) and phenyl the toxicity of malathion 2.3 to 3.4 times at a phosphonate(VI) arealmost same in the synergistic 1:1 mixing ratio. Their activities are more than activity. Alkyl derivatives of saligenin cyclic propyl paraoxon and less than Dibrom and iso phosphorus esters are much less synergistic (II) propyl paraoxon. The most active compounds or even antagonistic (I, III). TOCP known to among the tested cyclic esters are 2-(o-tolyloxy) potentiate the toxicity of malathion in mamrnalstt' -4H-1, 3, 2-benzodioxaphosphorin-2-oxide (V) did not show any effect to house flies. which is the active metabolite of TOCplI,12) and Synergism of saligenin cyclic phosphorus esters 7-methyl-2-phenyl-4H-1, 3, 2-benzodioxaphorin- with malathion in a resistant strain of house fly Table 3. Joint action of saligenin cyclic phosphorus esters (I-VII) with malathion against malathion susceptible green rice leafhoppers in comparison with some phosphate synergists. LOo• (pg/ ~) Compound with Cotoxicity alone malathion coefficient (1 : 1) ---- Malathion 0.003 I 0.008 0.004 1.1 II 0.069 0.003 1.9 III 1.892 0.005 1.2 IV 0.240 0.003 2.0 V 0.464 0.008 0.8 VI 0.218 0.005 1.2 VII 3.120 0.003 2.0 TOCP >10 0.005 1.2 Dibrom 0.208 0.005 1.2 Propyl poraoxon . 0.006 0.002 2.0 Isopropyl paraoxon 0.211 0.003 2.0 35 Table 4. Synergistic effect of some organophosphorus esters with malathion against green rice leafhoppers LDoo (pg/ ~) Compound with Cotoxicity alone malathion coefficien t (1 : 1) Malathion 0.021 (0. 048)* I 0.010 0.006 2.3 II 0.066 0.010 3.2 III >2 0.019 2.2 V (0.167) 0.015 2.2 VII >3 0.011 3.8 TOCP (>10) (0.083) 1.1 Dibrom 0.533 (0.069) 1.3 * Data in parentheses were obtained by using insects of 12th generation of Koti strain which had been selected under the pressure of malathion at LDoo• is demonstrated in Table 2. The strain, Hokota, Discussion was selected with diazinon. It showed more or less cross-resistance to all of tested phosphorus The present results indicate that aryl derivatives esters and was about 5 times resistant to mala of saligenin cyclic phosphorus esters synergize thion. For this strain synergistic activity of the insecticidal activity of malathion. The syn Dibrom and isopropyl paraoxon decreased and ergistic effect is remarkably enhanced in resistant activity of propyl paraoxon slightly increased. strains. This is interesting to note in comparison On the contrary the synergistic effect of saligenin with the fact that the effect of other phosphate cyclic phosphorus esters remarkably increased. synergists such as Dibrom and isopropyl paraoxon Even the alkyl derivatives acted as synergist of decreased in the resistant strain of house ,fly. malathion. Thus, all of present cyclic esters are Smallalkyl derivatives of cyclic esters are generally more active than other tested organophosphorus not synergistic with malathion in susceptible synergists. Aryl derivatives of cyclic esters are strains but are synergistic in resistant strains. very effective synergists. Cyclic phenylphospho The synergism appears to result primarily from nate of methylsaligenin (VII) is the most effective the inhibition of detoxication of malathion. synergist and increased the toxicity of malathion Malathion may be detoxified by either phosphatase 14 times. action or esterase action. The low toxicity of Results of tests on susceptible and resistant malathion to mammals is explained by the latter strains of green rice leafhopper are shown in mechanisms", It has been observed for a great Tables 3 and 4 respectively. The toxicity of number of organophosphorus compounds that malathion to the susceptible insects increased synergism of malathion in mice and the degree twice by the addition of cyclic ethyl phosphate of in vivo inhibition of ali-esterase are generally (II) or phenyl phosphate (IV) of saligenin, cyclic related--w. For insects, high esterase activity phenylphosphonate of methylsaligenin (VII), hydrolysing malathion is considered to be respon propylparaoxon or isopropyl paraoxon. Synergistic sible at least partly for malathion-resistance in effect of saligenin cyclic phosphorus esters in some strains of mosquito (Culex tersalisi», house creased in the resistant leafhopper but less than fly (Musca domestica L.) 0> and green rice leaf· in the resistant house fly. They enhanced the hopper!'. On the other hand, Oppenoorth and toxicity of malathion 2.2 to 3.8 times. Difference Asperenv proposed that the detoxication in some in the synergistic activity against the leafhoppers organophosphate-resistant strains of house fly was between alkyl and aryl derivatives is not so due to "mutant ali-esterases", All of these enzymes distinctive as against house flies. are inhibited by selective ali-esterase inhibitors 36 such as propyl paraoxonl,B> and oxo analog of controlled for possibilities to increase the toxicity EPNB>. Thus these inhibitors synergize malathion of malathion to mammals and to cause ataxia!', against the resistant insects. The authors!" have shown that aryl derivatives Summary .of saligenin cyclic phosphorus esters are the Seven saligenin cyclic phosphorusesters including selective inhibitors of ali-esterase, whereas small the principal active metabolite of tri-o-tolyl alkyl derivatives are not so selective to ali-esterase phosphate, which is known as a potentiator of inhibition. This appears to be responsible for malathion, were examined for synergism of mala theirdifference in synergistic properties. Although thion using susceptible and resistant strains of an active metabolite of TOCP, 2-0-tolyloxy-4H house fly and green rice leafhopper. Aryl deriva 1, 3, 2-benzodioxaphosphorin-2-oxide (V) 1I,1Zl; tives of cyclic esters showed high activity, showed high synergistic activity with malathion, particularly against resistant strains. Alkyl TOCP itself was not effective. TOCP may be derivatives showed low synergism against resistant slowly metabolized in house fly. Therefore, TOCP strains. The most effective synergist among tested should be previously applied before treatment chemicals was 7-methyl-2-phenyl-4H-l,3,2-benzo with malathion. Its homologous ester, di-e-tolyl dioxaphosphorin-2-oxide. It was more effective phenyl phosphate synergized with malathion in against resistant house flies than some known house flies by its previous application 24 hours phosphate synergists, such as propyl paraoxon before'malathion treatments". and Dibrorn. Plapp28> of U. S. D. A., Corvallis, Oregon tested our samples of saligenin cyclic phosphorus esters References Cited with his own susceptible and organophosphate' 1) "Castda, J. E., Baron, R.L., Eto, M. and Engel, resistant strains of house fly (Musca domestica) 1. L.: Biochem. Pharmacol., 12, 73 (1963). and mosquito (Culex tarsalis). A strain of house 2) Frawley, J. P., Fuyat, H, N., Hagan, E. C., fly was 120 times resistant to malathion and Blake, J. R. and Fitzhugh, O. G.: ]. Pharma another strain was 10 times resistant to parathion. col. Expt], Therap., 121, 96 (1957). The resistant strain of Culex tarsalis was 100 3) Murphy, S. D., Anderson, R.L. and DuBois, times resistant to malathion. No cross-resistance K. P.: Proc. Soc. Exp. BioI. Med., 100, 483 to saligenin cyclic phosphorus esters was observed (1959). in ,both resistant strains of house fly. Thus, 4) Oppenoorth, F.1. and Asperen, K. V. : Ent. Salioxon (I) 17> and its thiono analog (Salithion) 17) Exp. Appl., 4, 311 (1961). were very effective insecticides against them. 5) Matsumura, F. and Hogendijk, C.1. : ibid. However, cross-resistance to them was present 7, 179 (1964). in the malathion-resistant mosquitoes. Cyclic 6) Plapp, F. W. and Eddy, G. W.: Science, 134, butyl phosphate (VIII), phenyl phosphate (IV) 2043 (1961). and phenylphosphonate (VI) of saligenin and 7) Plapp, F. W., Bigley, W. S., Chapman, G. A. phenylphosphonate of methylsaligenin (VII) were and Eddy, G. W. : ]. Econ. Entomol., 56, 643 only moderately effective as synergists for malathion (1963). against the malathion-resistant house flies. Against 8) Matsumura, F. and Brown, A. W. A. : ibid., the resistant mosquitoes, Compounds VII and VIII 54, 1176 (1961). were quite effective as malathion synergists. On 9) Kojima, K., Ishizuka, T. and Kitakata, S. : the other hand, Salithion was found to be quite Botyu-Kagaku, 28, 17 (1963). synergistic with parathion against parathion' 10) Aldridge, W. N. : Biochem. I., 56,185 (1954). resistant flies. 11) Casida, 1. E., Eto, M. and Baron, R.L. : The recent development of malathion-resistance PVature, 191, 1396 (1961). in green rice leafhopper in some regions of this 12) Eto, M., Casida, 1. E. and Eto, T. : Biochem. country'!' requires the effective synergists of Pharmacol., 11, 337 (1962). malathion. Their use, however, must be carefully 13) Eto, M. and Oshima, Y. : Agr. Biol. Chem., 37 26, 452 (1963). 20) Sun, Y. P. and Johnson, E. R.: J. Econ. 14) Eto, M., Kinoshita, Y., Kato, T. and Oshima, Entomol., 53, 887 (1960). Y.: tu«, 27, 789 (1963). 21) Sun, Y. P. and Johnson, E. R. : I- Agr. Food 15) Eto, M., Hanada, K., Namazu, Y.and Oshima, Chem., 8, 261 (1960). Y.: tu«, 27, 723 (1963). 22) DuBois, K. P. : Advanc. Pest Control Res., 16) Eto, M., Eto, T. and Oshima, Y.: ibid., 26, 4, 332 (1961). 630 (1962). 23) Krueger, J. R. and O'Brien, R. D. : ]. Econ. 17) Eto, M., Kinoshita, Y., Kato, T. and Oshima, Eniomol., 52, 1063 (1959). Y. : Nature, 200, 171 (1963). 24) Casida, J. E. : Biochem. Pharmacol., 5, 332 18) Kojima, K., Kitakata, S.,·· Shiino, A. and (1961). Yoshii, T.: Boiyu-Kagaku, 28, 13 (1963). 25) Eto, M., Matsuo, S. and Oshima, Y. : Agr. 19) Kitakata S., Shiino, A. and -Kojirna, K.: Bioi. Chem., 12, 870 (1963). ibid., 28, 29 (1963). 26) Plapp, F. W. : Personal communication (1964). A Case of Control of Sanitary Insect Pests by Bell 47-G2 Helicopter Dusting in Japan. Masayoshi GOIIDA, Seiroku SAKAI, Haruo MIURA*, 'Hldeo KOIZUMl* and Syiiitu NAKAGOSlII. (Institute for Agricultural Chemicals, Yashima Chemical Industry Co., Ltd. Tomitake-Nagano, Nagano, and Hongo-Mura Public Health Section, Higashichikuma, Nagano") Received December 8, 1965. Botyu-Kagaku 31, 38, 1966. (with English Summary, 47.) 7. --:)"~" I) ::i ~ 7- -~$~1ii(:~.Qiti~~!R(ljjMto) 1 f§~ ~EIl~~' MitHr1A • :=::lrtHil:K* • INt~!fJ* • r:ptlh~~ (/\t'tl1~~I~n~~ttmJEm, **~Hl*fil!:ilI!) 40. 12. 8 ~11l! iIIH1iO)J.>;lmli'1i~O).rr.J'Jh'J>;, li'1i~~HtH.';.t~Ir., 3mO)m;'ilHt1fttU~~!UilJj-a,"'{)V 47-G2 M" 1) ::l"f ~ -"t'?i!i=f:IlI':H'lilt, 'to)Iifjillf<:wJ*~WIa1tltt::. -&!l!fj1;:Hn*m~~fllllffil.*O)i1Htjitllt 'ttLlr.l!ilIt~ "t 0 7l /ll{:(p168~'£ "t'WIafi It tz, ~~itIlO);i:tJ:'lf!UI;1. rv x: O)m~, .m113"t' ~ ;I -1 x: J~.:r. >-1 .:r. J~.:r.>:t :t -1 .:r. J~.:r., m~"t' -1 x: J~ x:>:t :t -1 x: J~.:r. > ~ ;I -1 .:r. 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