Document 1Q6XD7bjwGDrR9XJJj26XK6Rj

Central Toxicology Laboratory Alderley Park Nr Macclesfield Cheshire SK10 4TJ Telephone Alderley Edge (0625) 58271 1 Imperial Chemical Industries Limited With the compliments of the author Regittered in England No.218019 RoflitteredOff.ee Imperial Chemical Homo Millbank London SW1P 3JF 03A322 SL 3O r i 7? m& nr ''Tn KJ Vol. 7. No. 3 Sacramento. California March 1976 Dr. Gordon appointed ARB member DR. ALVIN S. GORDON Governor Iidmund G. Brown Jr. on March S announced Trie appointment of Di. Ahm S. Gordon of Iriicinilas to the Air Resources Board. Dr. Gordon succeeds Dr. Ron;:! Sawyer. whoso resignation was effective Fehnury 29. Dr. G.-rdon was a civilian employee of the L.S. Navy ai China Lake from 1951 !' January, l**7ii; most recently. lie was head 0: the chemical kinetics branch, ii c.-eut ce Dr. Gordon, who is ol. teaches er.ctr.aei me ai the Lhiiversity of California at San I): .'go. He lias an out si and hie background for c.::'.ic`i*j.ion :n live work of Hie Air 1C "iicc, lie received his l`h 1). m k.;.v>a! eke mu' ry from New York ^rc.-T-ciy and Ills B S. from Polytechnic ! :.; nHe was a uvem'.'ei of the Air I'esovaces Iv .-.:d research c >m:-.'.it;..-e a-d i China Lake c !._ a re c_;.u. a. ; *otocm-ru-try Gradual reduction of lead in gasoline ordered by ARB The state Air Resources Board voted on February 19 to require oil companies to gradually reduce the amount of lead added to gasoline sold in California. The action, climaxing a decade of debate on the hazards of airborne lead, was taken after a lengthy hearing at Los Angeles City Hall. ARB Chairman Tom Quinn said the redaction of lead in gasoline is necessary to pTOtecl public health, especially cinlihen in heavily populated areas and alone freeway routes. "Many parks, playgrounds and apailme:'.', complexes near frees-, ays pose a serious health- piobitin for children because of large concentrations of air borne lead," Quinn said. "There is evi dence that children who live in some Southern California areas have)') tur.es more lead in their blood than is normal." The unanimous action by the ARB requires large oil refineries to phase down the average lead content of all gasoline March 30-31 meetings set for San Francisco Caliiormj Air Resources lio.:rd will meet March 30 and 31 in Man Francisco. Included on the agenda of the March 50 meeting will be a continued public Deanna or. ;>iocedu;cs bo certification of gasoline vapor rccoveiy sy steins r.t service stations, public lu .ting to consider adaption of ambient air quality stand.ads applicable io the Lake Tak.e Air Badi! only, and a review of the enforcement practices of ihe Bay Area .Air Pollution (Vu.i:ul District. T wo ambient air quality standards dif ferent iiom the rest ul tl.e Stale arc being Considered to: lake Tahoe' vi.-hihty reducing pari.cles jp.d carbon m-ino.snd-j. The S.m branci-cn ine-ct. will he (Cf::-.`..nta:.-d on pay.* 3) produced at each refinery ftorn present levels of around 1,85 grains per gallon to 0.4 by 1980. Lead reductions and eflective dales tiJopteJ are 1.4 grams per gallon (average) by January 1. 1977. 1.0 by January 1. 197.5. 0.7 by January 1. 1979, and 0.4 by January 1. 19S0. Since the reductions are based upon a pool average of gasoline produced at the re fineries. the companies will be able to offer premium and regular graJes for older cars. Smaller companies, producing less ibaii 20.000 barrel, per day. will be re quired to reduce average lead content m 1.7 grams per gallon by January 1, 1979. and 1.4 by January 1, 1950. Board member Mary Nichols com mented the phase-down is necessary t" achieve the State's air quality standard for lead of 1.5 mierngrams per cubic meter for a 30-d::y average. "Above,that level, independent medical evidence shows that there is a danger of permanent neurological damage to younger childien.'' she said. Spokesmen for some major oil com panies complained that action could C3USC economic hardship for them, but Qiiiutt responded that the companies had refused in ptov.de tl.e Air Resources Boaid with data t.-u costs of removing lead from gasoline. "The oil companies have gros.ly exag gerated the problem and made it vary difficult fur ns to do u:..- j.ih." lie s.nd. "They have attempted to mislead u, and interfere vvith our ettoits to act m the public interests." While voting in favor of the reduction. Board member Dr. Robert Sawyer said. "I v.jiii in go on record as favoring i complete elm:..tation of lead from gaso line in the yeai s ahead." Under (he new control,, the ARB esiiui.it.the suite will Iv aide in jclu-- 1.* lit slmulai J, 9-. :'.-;C:-|!t >: the tune u: the South Coast \:r I?.wit!: the e\ce;.t:.i;i ot the !.en..c, area vvk.cii has IcC* ede.l Cs^epti. .:,a..y u ! ".id levels SL 034323 'r.J. Anaesth. (1979), 51, 417 2us~ ^ -r>v ' *tA--W^A. MUTAGENICITY OF INHALATION ANAESTHETICS: TRICHLOROETHYLENE, DIVINYL ETHER, NITROUS OXIDE , /, --------------------------END CYCLOPROPANE* Ufic ^ J. M. Baden, M. Kelley, R. I. Mazze and V. F. Simmon SUMMARY The mutagenic potential of trichloroethylene, divinyl ether, nitrous oxide and cyclopropane was assessed in vitro by microbial assay employing two histidine-dependent strains of Salmonella typhinturiums TA1535 and TA100. Anaesthetic agents in various concentrations were incubated with bacteria in the presence or absence of an enzyme system prepared from enzyme-induced rat liver. Nitrous oxide and cyclopropane were not mutagenic, whereas diviny] ether gave a strongly positive response. Results for trichloroethylene were equivocal. These and previous studies with the salmon ella system, together with mutagenicity studies using different test systems, indicate that modem inhalation anaesthetic agents are unlikely to be mutagenic. Among the suggested hazards of operating room contamination by anaesthetic gases is an increased frequency of malignancies in female anaesthetists (Cohen et al., 1974). It is therefore appropriate to screen the anaesthetic agents for possible carcinogenic potential. The salmonella-microsome test (Ames, McCann and Yamasaki, 1975) is an assay that has hroved useful in the detection of chemical carcinogens W mutagens. We used this procedure to test halothane, and four halogenated ethers--methoxyflurane, isofivrane, enflurane and fluroxene (Baden et al., 1976, 1977)--for mutagenic activity; only fluroxene (2,2,2-trifluoroethyl vinyl ether) was mutagenic (Baden et al., 1978). In the present study we have tested the volatile anaesthetics trichloroethylene and divinyl ether and the gaseous anaesthetics, nitrous oxide and cyclopropane, to determine their mutagenic potential. METHODS The methods and materials used for testing anaes thetic agents in the salmonella assay system have been reported in detail elsewhere (Baden et al., 1976) and are summarized below. The anaesthetics tested were commercially available preparations. Trichloro ethylene and divinyl ether were greater than 99.5% pure as assayed by gas chromatography. Bacterial preparation Two histidine-dependent strains of Salmonella typhimurium, TA1535 and TA100, were used (Ames, McCann and Yamasaki, 1975). For each experiment, inocula from stock cultures grown overnight at 37 CC were used in a nutrient broth. Metabolic system A mammalian metabolic activation system, S-9 mix, was prepared from the livers of male SpragueDawley rats sacrificed 5 days after i.p. injection of 500 mg kg-1 of Aroclor 1254, a polychlorinated biphenyl. Aroclor is a potent inducer of the mixedfunction oxidase system. Each assay was conducted both with and without the metabolic activation system. Jeffrey M. Baden, m.b., b.s., f.f.a.r.c.s., m.r.c.p. (u.k.); Merijean Kelley, ph.d.; Richard I. Mazze, m.d.; Anesthesiology Service (112A), VA Hospital, 3801 Miranda Avenue, Palo Alto, California 94304, U.S.A. VINCENT F. Simmon, ph.h.. Microbial Genetics Program, Stanford Research Institute International, Menlo Park, California, U.S.A. Correspondence to J. M. B. * Presented at the 1978 Annual Meeting of the American Society of Anesthesiologists, Chicago, Illiniois. 0007-0912/79/050417-05 $01.00 Desiccator incubation experiments Bacteria-seeded glucose-minimal plates with or without S-9 mix were placed in 9-litre, air-tight desiccator jars. Liquid or gas volumes of anaesthetics were added to the desiccators to give desired concen trations, which were verified at the beginning and end of exposure using an infra-red gas analyser. The concentrations, 10% tolerance, ranged from 0.1 to Macmillan Journals Ltd 1979 SL 034324 . ` j" -- .... - . ; 4,,` 7 ,* /" 5, ,v <' `-7 xL 'V*>+ ' .mum,tin,,i. ' rj, J V.".' 7 X .'V.-,-: -a--'*** 418 BRITISH JOURNAL OF ANAESTHESIA 30% for divinyl ether, 0.1 to 10% for trichloro ethylene and 1 to 81 % for nitrous oxide and cyclo propane. The concentrations did not change signifi cantly with time. Vinylidenc chloride 3% was used as a positive control. The bacterial plates were exposed to the test compound in sealed desiccator jars for 8 h at 37 JC then the plates were removed from the desiccators and incubated for a further 40 h at 37 CC. Colonies on each plate were counted. Tripli cate plates were prepared at each test concentration, and each experiment was performed at least twice. Liquid incubation experiments Bacterial cells, with or without S-9 mix, and various amounts of test chemical were added to sterile, 15-rnl stoppered tubes and rotated on a wheel for 2 h at 37 'C. The air phase concentrations for a particular anaesthetic, in the air spaces above the reaction mixtures, were the same as those used in the desic cator experiments. Concentrations were measured at the beginning and end of exposure, using an infra-red gas analyser, and were found to vary by not more than 10% with time. Aliquots of the test sample were added to tubes of top agar, mixed and poured onto glucose-minimal medium plates. 2-Anthramine 2.5 ng per plate was used as a positive control. The plates were incubated for 2 days at 37 cC in air and colonies were counted. Triplicate plates were pre pared at each test concentration, and each experiment was performed at least twice. Chemicals The source and purity of chemicals were as follows: trichloroethylene, Aldrich Chemical Co. (Milwaukee, Wisconsin), 99%--contains no trace of 1-2 epoxybutane or epichlorohj'drin; divinyl ether, Marshallton Chem. Co. (Winston, Salem, N.C.) 99.9%; nitrous oxide, Liquid Air, Inc. (San Fran cisco, California), 99%; cyclopropane, Liquid Carbonic (San Carlos, California), 99.9%. Analysis of data The numbers of revertant colonies on treated plates were compared with the numbers of spontan eous revertant colonies on plates exposed to room air. Statistical analysis was by t test; Pc 0.05 was considered significant. RESULTS Nitrous oxide and cycloprane did not increase the number of revertants in strain TA100 when assayed either in desiccators or in liquid incubation (table I). Similar negative results were obtained with strain TA1535. In contrast, plates exposed to the positive controls, vinylidene chloride or 2-ar.thramine showed 2.4-14.4-fold increases in the number of revertant colonies. Divinyl ether was mutagenic to strains TA100 and TA1535 in desiccator and liquid incubation. In desiccators, a dose-dependent increase in revertants occurred in the absence of metabolic system at vapour Table I. Mutagenicity, Salmonella tvphimurium strain TA 100 (mean ntonber of recertaut colonies per plate SE.M, n = 6) Nitrous oxide Cyclopropane Concn (vol %) Without S-9 With S-9 Without S-9 With S-9 Desiccator 0 1 3 9 `27 81 Vinylidene chloride 3% 144 2 16 167 3 158+14 153 + 7 16217 144 *20 669 63 167 + 8 177 + 8 178 + 18 147 7 155 + 9 160 + 10 403 + 34 167 12 144+11 149+10 166+10 168 8 125+14 886 56 183 16 157 + 12 157 + 8 153+10 181 16 122 + 9 6C4 + 37 Liquid 0 1 3 9 27 SI 2-anthramine 2.5 pg/plate 115 10 1C4 10 89 6 83 + 5 98 + 8 92 9 107+10 117 10 9S 11 103 15 1104 101 3 99 11 1122 93 92 1 91+5 91+7 SC+ 2 96 + 6 91+5 117 + 8 90 5 S46 86*3 $9 7 86 6 92 7 1299 166 Si 03*3gs ML Fig TA. trict ir.cr coni abo' Tri. >Da Fig Sim trie: incr CG7T oru 2.5- co: svs gro TA 1UTAGENICITY OF INHALATION ANAESTHETICS 400- .2 g 300- 3 U *----- Divinyl Ether with S-9(rt.6) # -~o Divinyl Ether without S-9(/j6) --Trichloroethylene with S-9(o15) * - -- Trichloroethylene without S-9(n*15) occurred only in the presence of the S-9 mix. Results are shown for strain TA100 in figures 1 and 2. Trichloroethylene did not increase the number of revertants in strain TA1535 or when assayed by liquid incubation. In desiccators, however, with the metabolic system present, the mean number of revertants of TA100 was increased approximately 30% above background (149+12, ?i = 15) at 1% (19613, n=l5) and 3% (1946, m= 15) vapour concentrations (fig. 1.). These increases were statistic ally significant (Pc0.01). 100- 0.1 o.z 0.3 0.5 0.7 1 23 Anaesthetic (%) 10 20 30 Fig. 1. Revertant colonies of Salmonella typhtmurium, strain TAlOOj after desiccator incubation with divinyl ether and trichloroethylene. Divinyl ether produced a dose-dependent increase in the number of revertant colonies at vapour concentrations greater than 1%; the maximum increase above background was 2.5-3.5-fold when S-9 was added, [richloroethylene produced a 30";, increase in the number of revertant colonies only in the presence of S-9. 300f 200- Ctviryl Ether with S-9 (n= 6) --5 Diviny! Ether without S-9 (,> 6) --- Trichloroethylene with S-9 (n-15) Trichloroethyiene without S-9 (-;= 15) 0.2 0.3 0.5 0.7 1 2 3 5 7 JO Anaesthetic ("1) Fig. 2. Revertant colonics of Salmonella typhimurinm, strain TA100, after Iiqiud incubation with diviny] ether and trichloroethylene. Divinyl ether produced a dose-dependent increase in the number of revertant colonies in vapour concentrations greater than 1%. The increase was seen only in the presence of S-9 and reached a maximum of 2.5-fold above background. Trichloroethylene did not increase the number of revertants above background. concentrations greater than 1%; when the metabolic system was added, there was an increase above back ground of 8-11-fold for TA1535 and 2.5-3.5-fold for TA100. In liquid incubation, a mutagenic response DISCUSSION In the present study, the most significant findings occurred with Hivinvl ether which was mutagenic to both strains ofsalmonella. Both the gases, nitrous oxide and cyclopropane, were not mutagenic while the results of the trichloroethylene tests were equi- 4c' vocal. In similar studies of halothane, enflurane, >1 methoxyflurane and fluroxene, only fluroxene (2,2,2-trifluoroethyl vinyl ether) was mutagenic (Baden et al., 1978). Fluroxene, however, gave positive results only in liquid incubation, whereas divinyl ether was mutagenic in both liquid and desic cator incubation. In the desiccator assay, divinyl etiter was mutagenic without the metabolic systems, although its activity was enhanced when metabolizing enzymes were present. This finding indicates that both divinyl ether and one or more of its metabolic products are mutagenic. In the past it has been assumed that the toxic effects of anaesthetic agents were produced only by reactive anaesthetic metab olites. Either divinyl ether was directly mutagenic or salmonella metabolized the anaesthetic to a mutagen. Many other compounds containing the vinyl moiety are mutagens (McCann et al., 1975) presumably because this group is highly reactive and can be oxidized to an epoxide (Bartsch et al., 1975). show riwtfc is or wily weakly, mipwiig. A 30% in crease in revertant colonies occurred reproducibly at 1 and 3% vapour concentrations in desiccator assays with strain TA100. Some authors (Chiu et al., 1978) would not regard this as a positive result, believing that at least a 100% increase in the number of revertant colonics is needed before mutagenicity is is established. Waskell (1978), who has also tested trichloroethylene in the salmonella system, concluded that it was not mutagenic. However, the test con ditions used were not the same as in the present study. On the other hand, Simmon, Kauhanen and Tardiff (1977), in a study using metabolic activation r llfl SL 034326 K, '.--Vi 1 c'-f i 420 BRITISH JOURNAL OF ANAESTHESIA systems prepared from both mice and rats, concluded that trichloroethylene was a weak mutagen. This conclusion is supported by the high frequency of hepatocellular carcinoma in B6C3F1 mice treated with commercial trichloroethylene (National Cancer Institute, 1976). Unfortunately, the test samples used in the mouse studies were stabilized with carcino genic epoxides (Henschler et al., 1977) and were given in large quantities into the stomach. Thus the mutagenic and carcinogenic potential of trichloro ethylene remains uncertain. FH HH ii ii F-C-C-D-C=C-H ii FH FLUROXENE HH HH ii ii H-C=C-0-C=C-H DIVINYL ETHER Fig. 3. Structural formulae of fluroxene and divinyl ether. Table II. Mutagenicity tests: A = salmon ella--Ames test; B = sister chromatid exchange', C = fibroblast~%-azagnanine Agents Positive Negative Halothane Nitrous oxide Chloroform Enflurane Methoxyflurane Isoflurane Cyclopropane Diethyl ether Trichloroethylene Fluroxenc Divinyl ether Ethylvinyl ether -- -- -- -- ----- - -- -- A? A, B A, B B A, B, C A, B, C A, B, C A, B, C A, B A, B A, B Aj B A, B -- -- Two other mutagenicity test systems have been used recently to test anaesthetics and in general have confirmed the findings of studies in the saimonellamicrosome assay (table II). Sturrock (1977) reported negative results for halothane, chloroform, nitrous oxide and enflurane, using the cultured Chinese hamster fibroblast-8-azaguanine system. The effect of anaesthetics on sister chromatid exchange in Chinese hamster ovary cells also has been measured (Stevens et al., 1977). Nitrous oxide, diethyl ether, trichloroethylene, halothane, enflurane, isoflurane, methoxyflurane and chloroform had no effect, where as divinyl ether, vinyl ethyl ether and fluoroxene gave positive results. The salmonella-microsome assay has proved useful in the detection of carcinogens as mutagens. Approxi mately 85% of known animal and human carcinogens examined in this system were mutagenic and nearly all mutagens are carcinogenic (Ames, McCann and Yamasaki, 1975). Our results with the salmonella assay have been supported by data from the Chinese hamster fibroblast-S-azaguanine and sister chro matid exchange systems. Based on all the evidence. we conclude that fluroxene and divinyl ether contain ing the vinyl moiety (fig. 3) arc potential carcinogens. These studies also suggest that the modern inhalation anaesthetic agents, nitrous oxide, halothane, en flurane, cyclopropane and methoxyflurane, are not carcinogenic. ACKNOWLEDGEMENT This study was supported in part by the VA Hospital, Palo Alto, California. REFERENCES Ames, B. N., McCann, J., and Yamasaki, E. (1975). Methods for detecting carcinogens and mutagens with the salmonella mammalian microsome mutagenicity test. Mutation Res., 31, 347. Baden, J. M., Brinkenhoff, M., Wharton, R. S., Hitt, B. A., Simmon, V. F., and Mazze, R. I. (1976). Mutagenicity of volatile anesthetics: halothane. Anesthesiology, 43, 311. ------ Kelley, M., Simmon, V. F., Rice, S. A., and Mazze, R. I. (1978). Fluroxene mutagenicity. Mutation Res., 58, 183. ------------- Wharton, R. S., Hitt, B. A., Simmon, V. F., and Mazze, R. 1. (1977), Mutagenicity of halogenated ether anesthetics. Anesthesiology, 46, 346. Bartsch, H., Malaveille, C., Montesano. R., and Tomatis, L. (1975). Tissue-mediated mutagenicity of vinylidene chloride and 2-chlorobutadiene in Salmonella typhimurium. Nature {Land.'), 255, 641. Chiu, C. W., Lee, L. H,, Wang, C. Y., and Bryan, G. T. (1978). Mutagenicity of some commercially available nitro compounds for Salmonella tvpkimunum. Mutation Res., 58,11. Cohen, E. N., Brown, B. W., Bruce, D, L., Cascorbi, H. F., Corbett, T, H., Jones, T. W., and Whitcher, C. E. (1974). Occupational disease among operating room personnel', a national study. Report on an Ad Hoc Committee on the Effect of Trace Anesthetics on the Health of Operating Room Personnel, American Society of Anesthesiologists. Anesthesiology, 41, 321. Henschler, D., Eder, E,. Neudecker, T., and Mctzler, M. (1977). Carcinogenicity of trichloroethylene: fact or artifact ? Arch. Toxicol., 37, 233. SL 034327 Ml MUTAGENICITY OF INHALATION ANAESTHETICS McCann, J., Choi, E., Yamasaki, E., and Ames, B. N. (1975). Detection of carcinogens as mutagens in the salmonella/ microsome test: Part 1, Assay of 300 chemicals. Proc, Natl. Acad. Sci. U.S.A., 72, 135. National Cancer Institute (1976). Carcinogenesis Bioassay of Trichloroethylene. Technical Report Scries No. 2. CAS No. 79-01-6, NCI-CG-TR-2. DHEW Publica tion No. (NIH) 76-802. Washington, D.C., Super intendent of Documents. Simmon, V. F., Kauhanen, K., and Tardiff, R. G. (1977). Mutagenic activity of chemicals indentified in drinking water; in Progress in Genetic Toxicology, Proceedings of the Second International Conference on Environmental Mutagens (eds E. Scott, B, A. Bridges and F. H. Sobels), p. 249. Amsterdam: Elsevier/North Holland Biomedical Press. Stevens, W. C. ,White, A. E., Takehisa, S., Eger, E. I. n, and Wolff, S., (1977). Sister chromatid exchanges induced by inhaled anesthetics; in American Society of Anes thesiologists Abstracts of Scientific Papers, p. 495. Sturrock, J. E. (J 977). Lack of mutagenic effect of halothane or chloroform on cultured cells using an azaguanine test system. Br. J. Anaesth., 49, 207. Waskell, L. (1978). A study of the mutagenicity of anes thetics and their metabolites. Mutation Res., 57, 141. DIE MUTATIONSFAHIGKE1T DER INHALATIONSNARKOSE: TRICHLORATHYLEN, DIVINYLATHER, LACHGAS UND ZYKLOPROPAN ZUSAA1MENFASSUKG Es wurde das mutagene Potential von Trichlorathylen, Divinylather, Lachgas und Zyklopropan in vitro mittels Mikrobenanalyse beurteilt, in dcr zwei histidin-bezogene StSmme von Salmonella typhimurium, TA1535 und TA100, verwendet wurden. Narkosemittel in verschiedenen Konzentrationen wurden mit Bakterien in der Gegemvart Oder Abwesenhcit eines Enzymsystems inkubiert, das von, in Rattenleber herbeigefiihrten Enzymcn hergestellt wurde. Lachgas und Zyklopropan waren nicht mutagen, tvohingegen Divinylather eine stark positive Reaktion ergab. Fiir Trichlorathylen waren die Ergebnisse zweidcutig. Diese und vorangehende Studien mit dem SalmonellaSystem deuten zusammen mit Mutationsfahigkeitsuntersuchungen, die andere Testsysteme venvenden, darauf hin, dass es unwahrscheinlich ist, dass moderne Inhalationsnarkosemittel mutagen sind. MUTAGENICITE DES ANESTHESIANTS PAR INHALATION: TRICHLOROETHYLENE, ^THER DIVINYLE, PROTOXYDE D'AZOTE ET CYCLOPROPANE RESUME On a evalue in vitro le potentiel mutaginique du trichloro ethylene, de l'ether divinyle, du protoxyde d'azote et du cyclopropane par cssai de conformite microbien a l'aide de deux souches de Salmonella typhimurium TA1535 et TA100, dependant d'histidine. Des agents anesthesiants, en diverscs concentrations, ont iti mis a incuber avec des bacteries, en presence ou en 1'absence d'un systeme d'enzyme prepare a partir de foie de rat traitd aux enzymes inductiblcs. Lc protoxyde d'azote et le cyclopropane n'ont pas mutageniques, alors que l'ether divinyle a donn6 une forte reaction positive. Les resultats obtenus avec le trichloroethylene ont ct6 equivoques. Ces 6tudes, ainsi que les preccdentes, effectuces avec le systeme de salmonella, de mcme que les etudes de mutagnicite effecruies .4 l'aide de differents systemes d'essais, indiquent que les anesthisiants modernes par inhalation ne sont de toute vraisemblance pas mutageniques. MUTAGENICIDAD DE ANE3TESIAS POR INHALACION: TRICLOROETILENO, ETER DIVINILICO, OXIDO NITROSO Y CICLOPROPANO SUMARIO Se evaluo el potencial mutaginico de trocloroetileno, dter divinilico, 6xido nitroso y ciclopropano in vitro mediante evaluacidn microbial, empleando dos cepas de Salmonella typhimurium dependientes de histidina, TA1535 y TA100. Sc incubaron diversas concentraciones de agents ancstisicos con bacteria en la presencia o ausencia de un sistema dc enzimas preparado con higado de rata inducido con enzimas. El 6xido nitroso y el ciclopropano no fureon mutagenicos, mientras que el iter divinilico dio una respuesta positiva fuerte. Los resultados del tridoroetileno fueron ambiguos. Tanto estos como los estudios anteriores realixados con el sistema de salmonella, juntamente con estudios de mutagenicidad que se valieron de pruebas diferentes, indican que es poco probable que los agentes anestfsicos modernos por inhalacion sean mutagenicos. m j-vy&HjV&7 SdZ' SL 034328 gfeii -v* =.