Document K65dJqBKwwNz37nx8g1MQK5gx

Plapp l POLYCHLORINATED BIPHENYL: AN ENVIRONMENTAL CONTAMINANT ACTS AS AN INSECTICIDE SYNERGIST MONS 0492`.9 Plapp 2 Abstract Bioassay experiments with houseflies demonstrated that the poly chlorinated biphenyl preparation known as Arochlor 1254 Is a powerful synergist for the carbamate Insecticide carbaryl. The mechanism of synergism Is unknown, but probably does not Involve the Inhibition of microsomal oxidase which Is usually responsible for Insecticide synergism. MONS 049250 Plapp 3 Ift recent years the widely used plasticizers known as polychlorinated biphenyls (PCB) have become recognized as DDT-like environmental con taminants (1). As with DDT and other chlorinated insecticides, PCB are environmentally persistent, subject to biological magnification, and are inducers of the microsomal enzyme systems which detoxify Insecticides and metabolize steroids (1,2). Some PCB, particularly materials containing small amounts of chlorine, are toxic to mammals and Insects (3). The potential health hazard of these materials has been emphasized by recent work which demonstrated that prior exposure of ducklings to PCB Increased their susceptibility to duck hepatitis virus (4). In the present report data are presented on a hitherto undescribed property which further relates PCB to insecticides. Tests with Arochlor 1254, a PCB preparation containing 54% chlorine, demonstrated that the material is a powerful synergist for the carbamate insecticide carbaryl against the housefly. Since nonperslstent insecticides such as carbaryl are widely used as replacements for the persistent chlorinated insecticides, any environmental contaminant which Increases its toxicity is a potential complicating factor In the development of this and,similar short residual insecticides. In this research houseflies were bioassayed by exposure to films of 1:5 (w:w) combinations of carbaryl and PCB and the toxicity if the com binations was compared to that of carbaryl only. We also tested 1:5 combinations of carbaryl and piperonyl butoxide, a standard insecticide synergist. In other experiments we measured the effect on the toxicity of carbaryl to houseflies after prior exposre to PCB or piperonyl butoxide. We also determined the effect of exposure to the 2 synergists HONS 049251 Plapp 4 on oxidative metabolism of several Insecticide chemicals by houseflies under In. vivo condi tions. Carbaryl and plperonyl butoxide were technical grade samples available in the laboratory (5). Arochlor 1254, was used as supplied by the manufacturer (6). GLC analysis confirmed its identity as a typical, multicomponent PCS preparation (7). Flies tested were an Insecticide susceptible strain (Orlando Regular) and a strain (Orlando DOT) highly resistant to chlorinated insecticides and possessing a low tolerance to carbaryl and other carbamate Insecti cides. The origin and resistance spectra of the strains have been described previously (8). Pint glass jars were coated on the Inner surface with measured amounts of the test chemicals. A water supply and food were placed In each jar, 20 flies of mixed sexes were introduced, and the jars were covered with cheesecloth and held 24 hours at which time mortality determinations were made. All experiments were replicated and LCSo values in micrograms per jar of carbaryl were estimated by computer analysis of the data. Results of the toxicity tests (Table 1) revealed that the PCB pre paration was highly active as a synergist for carbaryl. It increased the toxicity of the insecticide in the several tests by factors of 11- to 82-fold. With piperonyl butoxide, the degree of synergism was similar, ranging from 15- to 68-fold. Thus, PCB is approximately as active as plperonyl butoxide as a synergist for carbaryl. The degree of synergism was usually greater when flies were exposed simultaneously to carbaryl and the synergists, but was still significant when flies were exposed to the insecticide after preexposure to PCB or plperonyl butoxide. As HONS 049252 ' Is usual In synergism experiments, the Increase In toxicity was greater with the resistant than with the susceptible strain. Differences occurred In the time required for response of treated flies to PCB-carbaryl combinations as compared with pfperonyl butoxlde- carbaryl combinations. In tests with Orlando Regular flies, exposure to combinations of 1000 ug/jar each of carbaryl and synergist resulted In more rapid knockdown when piperonyl butoxlde was employed (50X In 2 hours) than when PCB was the synergist (50* In approximately 6 hrs.). After 24 hr preexposure to the synergists, the time required for response to carbaryl upon subsequent exposure was decreased to 1 hour for piperonyl butoxide and 1.25 hours for PCB. These results suggest that there may be differences In the mechanism by which the 2 compounds cause synergism. It Is thought that piperonyl butoxlde owes Its synergistic activity to Its ability to Inhibit microsomal oxidative enzymes (9). PCB, on the other hand, would not be expected to act as synergists In the same way since they are considered to be microsomal Inducers rather than Inhibitors (1). To measure the effect of the synergists on microsomal oxidation we exposed Orlando DDT flies to films of PCB or piperonyl butoxide at a rate of 1,000 ug/jar for 24 hours and then to the cyclodiene Insecticides, aldrln and heptachlor at the sublethal dose of 10 ug/jar for 4 hours. Subsequent GLC analyses (7) revealed (Table 2) that exposure of flies to PCB resulted In an Increase In the amounts of aldrln oxidized to dledrin and heptachlor oxidized to h. epoxide to 145 and 153X of control values, respectively. Exposure to piperonyl butoxlde resulted In a reduction In oxidase activity of 28 to 50% for the 2 substrates. The results provide evidence that the mechanisms of synergism of PCB and piperonyl butoxlde must differ since their effects on the microsomal enzyme system appear to be ooooslte In nature. MONS 049253 Plapp 6 The possible significance of these findings is only speculative at present. If synergism related to PCB occurs with other insecticides and with mammals as well as with Insects, then unintentional exposure due / to environmental contamination might render nontarget organisms more susceptibl than expected to certain pesticides. Thus, PCB may increase the already high level of danger associated with the use of many Insecticides. Indeed, such a mechanism might explain some of the epidemics of poisoning that have occurred in farm workers exposed to apparently "safe" concentrations of certain highly toxic insecticides (10). ' MO/VS 04954 REFERENCES AND NOTES 1. R. W. Rlsebrough, P. Rleche, D.'P. Peakall, S. G. Herman, M. N. Kriven, Nature 220. 1098 0968). - 2. D. C. Holmes, 0. H. Simmons, J. O'G. Tatton, Ibid. 216, 227 (1967), R. W. Risebrough in Chemical Fallout, M, W. Miller and G. G. Berg, Eds. (Thomas, Springfield, 111. 1969), p. 5. 3. W. F. Von Oettingen, U. S.. Publ. Health Serv. Pub!. No. 414, 306 (1955), E. . Lichtenstein, K. R. Schulz, T. W. Fuhremann, T. T. Liang, J_. Econ. Entomol. 62, 761 (1969), D. B. Peakall, J. L. Lincer, BioScience 20. 958 (1970). 4.. M. Friend, 0. 0. Trainer, Science 170, 1314 (1970).' 5. Carbaryl is 1-naphthyl methyl carbamate, piperonyl butoxlde is a-[-(2-butoxy- ethoxy)ethoxy]-4,5-methylenedioxy-2-propyltoluene. 6. We thank Monsanto Chemical Co., St. Louis for the sample of Arochlor 1254 used in these experiments. 7. Gas chromatographic analyses were performed on a Micro-Tek Model 160 chromatograp equipped with a Ni63 detector. The 1/8" I.D. x 10' column contained 2X SE-30 and 3X QF-1 on Chromosorb W HP, 80/100 mesh. Column temperature was 209C and detector temperature was 260C. Dieldrln and heptachlor epoxide, the. metabolites of aldrln and heptachlor, respectively, were identified by cochromatography with authentic standards and by standard tic methods. 8. F. W. Plapp, R. F. Hoyer. J.. Econ. Entomol. 61, 768 (1967). 9. J. E. Caslda, Agr. Food Chem. 18, 753 (1970). MONS 049255 10. Personal communication, Nov. 1970 from Marlon Moses, R.N., Rodrigo Terronez Memorial Clinic, Delano, Calif.; testimony of T. H. Mllby, M.D., Chief, Bureau of Occupational Health and Environmental Epidemiology, Cal. Dept. Public Health, presented 9 Dec. 1970 before California. Assembly Committee on Agriculture. - 11. 1 thank G. Hold for assistance with the bioassays and W. H. Vance for Plapp 8 GLC assays. Approved as Technical Article _by the Director, Texas Agricultural Experiment Station and supported in part by USDA Regional Research Project, S-73. MQNS 049256 PIapp 9 Table 1. Toxicity of carbaryl and cartaryl isynergist combinations to susceptible (Orlando Regular) and resistant (Orlando DOT) houseflies. Treatment Orlando Regular Carbaryl IC5Q Increase (ug/jar) In toxicity Orlando DDT Carbaryl IC5Q Increase (ug/Jar) In toxicity Carbaryl only 1386 Carbaryl:PCB 1:5 96 Cartaryl:P1peronyl butoxlde 1:5 37 PCB for 24 hrs. then carbaryl 80 Plperonyl butoxlde for 24 hours,, 94 then carbaryl 14 X 37 X 17 X 15 X 4402 54 65 384 174 82 X 68 X 11 X 25 X Calculated as quotient of response of flies to carbaryl divided by response of flies to Indicated carbaryl:synerg1st combination. i MUNS 049257 . Plapp 10 Table 2. Microsomal oxidase activity in Orlando DDT flies untreated and after exposure to PCB or piperonyl butoxlde. Aldrin Epoxldase* Heptachlor epoxldase* Treatment X substrate Converted to dieldrln X substrate Activity as Converted to X of control h. epoxide Activity as X of control Control PC8 9 1000 ug/jar Piperonyl butoxlde 0 1000 ug/Jar 11.4 16.7 5.7 100 146 SO .- 34.6 52.8 24.8 100 . 153 72 |`Calculated from GLC scans by totaling recovery of substrate and product and then | calculating the X conversion. Results are averages of duplicate or triplicate assays. MONS 04925a