Document 2j5MBj7RRk45OdpX9Zpywzzjg

IFGTECHNirM r 'C.jmENT STAFF TEC' ~ ' L SERVICES REPORT SO. 402 WL F. Oc Jnch Chemical Company A OVWION OP THB a P OOOOM1CM COMPANY DEVELOPMENT CENTER 4% OVT CYALVATI`IN COMBUSTION TOXICOLOGICAL TESTING PART 5: CF a SERIES OF SYNTHETIC AND NATURAL BASED ON INCAPACITATION RESPONSE AND ANALYTICAL COMBUSTION GAS DATA PRODUCTS by G. F. Smith W. C. Bachtel (Corporate Toxicology) Conpletedi July 13, 1977 rtNfit He.: 502< Dote Issuedt August 10, 1977 Project No.: 2352 PT--TBUTION Akron w. i. Johnson *1. N. Strassburg J. I. Powell, Jr. L. B. Crider R. R. Blear'. J.A.TePas - t.M.J R. n. Kreeger *L.P.Arnold - B.J.XAsson R. J. Meyer - (3) C. s>. Flesdng m. m. o'Mere J. B.JKtlts r. JbrfHn - H. - (D Cleveland I.D.Soott - R.A.Krueger B.M.G.Zwicksr - N.B.lOha P.j.Donat - J.C.Heely - t.J.Beha *B .W. Harringtoa-A.I .Cleaenta-C.F .Krc F. E. Krause N. B. Becker B. L. Kent K. Greene - R. Rex B. Osborne if. Raasey c: L. Blackfan A. 1. Aabrose , * SBhaaidarer F. Malone Savege Friedberg Cleveland G. Tilley J. D. Tsssilli P. A. Rsquet R. B. C. R. j. p. Morrill D. P. Bnechtge Brecksvilla 1. J. Fawcett e.j. A. Stahl R. Wllgiag G. I. Thoapson C. B. Luftsr H.Tucker - A.R.Siebert - J.A.Olase R. R. Schlatsar D. B. Ley B. D. Dickens A. W. HeBows .A N. J. Rroenks BFG21956 r>m ABSTRACT The NBC is playing a key role :n the developrer.t if a firsgeneration bioassay combustion-inhalation testing protocol for the acceptance of materials. A protocol will be ready in Sep tember! 1977. in January, 1977 we reviewed the results of our bioassay testing program with M. Birky of the NBS. As a result of the meeting, M. Birky asked us to quantitatively evaluate a series of materials. Therefore, we have tested Geon 8750 'rigid PVC), polychloroprene, Geon 8750 with zinc ferrocyanide, Estane 58360 and red oak wood by incapacitation bioassay testing. I will summarize the results of this work in this report. Based on the mass of material which induces 50% incapacitation, tha materials ere ranked as follows (best performing material listed first)! Geon 8750 > Betens S8360 > polychloroprene > wood > Qaom 8750 SFC > polychloroprene ZPC. In the case of Geon 87S0, polychloroprene end red oek wood, carbon monoxide has been fomad to' ploy the dominant role in inducing the incapacitation pompom--. Zn the ease of Geon 8750 ZFC end polychloroprene VC* Wrosen cyanide appears to play the ooet important role is lad--inf incapacitation. In the case of Eatane 58360, the --0----i--tlem of csrbon monomide end hydrogen cyanide may be the ooot- --portent components in inducing incapacitation. *: BFG21957 EOOM9Z: '' " ^ Table of .ont'Tts 'b'jectives. . Conclusion* . III Introduction, Discussion. . 1.) Apparatus - Procedure .......................... 2.) Developing Dose-Response Curves . 3.) Comparison of Materials .................... 4.) Analytical Data ....................................... 5.) Relationship of Dose of Specific Components of Combustion Products to Mortality Hasard .............................. 6.) Relationship of Dose of Specific Components of Combustion Products to Incapacitation Hasard.................... I- Futura Plana, Nafarances. PAGE IS 2614003 . t: BFG21958 TABLE I Biological Pesponse to the Products of Combust ion............................................................................................. TABLE II Mass of Material Which Induces a 504 Pesponse for Various Bioresponses..................................................... TABLE III Time to Incapacitation Associated With the Mass of Material Which Induces 50% Incapacitation. . TABLE IV Hazard Index Values Calculated From Data in Table II and Table III.......................................................... TABLE V Ranking of Materials Based on Mass Which Induces 50% Response for Various Bioresponses ................... 1MLX VZ Mass of Material Which Induces a 50% Response for Various Bioresponses...................................................... TABLE VZZ Analytical and Biological Dose Data.......................... TABLE VIZI Dose for S0 Bioresponse....................................................... TABLE IX % 00'Kb at 50% Incapacitation......................................... 6 9 11 12 14 14 17 34 39 riOOBS 1 mow a List of Figures Beta Aeaponse Cure* for Geon *750 ............................. Aalatioeehip of CO-Kb to Atmospheric CO . . . 37 X. Objectives W\e objectives of the current round of bicassay testing aret 1.' To evaluate a series of polymeric and natural materials on tne basis of the incapacitation and .mortality bioresponse . 2.) To couple analytical gas measurements to combustion bioassay testing. 3.) Assess the role of specific toxicants in observed bioresponses. II. Conclusions 1. ) The ranking of the performance of a series of materials de pends on tha type of bioresponse used in the evaluation. 2. ) baaed on tha mass of notarial which induces 50% incapacita tion, tho notarials aro ranked aa follows (beat performing material Hated firat)t Goon 1750 > latane 51350 > polyehloroprane > red oak > Geon 1750 with sre > polychloroprana with STC. 3. ) Hill am the mesa of aatarlal which induces 50% mortality at the and of two weeks, the aaterlala are ranked aa followo (heat perianalaa materiai listed first)s red oak > Katana IttM > Mlfehioropreme > Geon 1750 > polychloroprane with Sf Vleon 1750 with src. .)4 750 appeara to be due to CO. Long rtallty fu Geon 750 appeara to be due to HC1. I.) polyahloroprene also generatas K1 upon oombusi aprtalltp and ineapacitatien for polychloroprane holHlhly One to CO. tinea on a gran for gran erabea only 2-3 tinea nere BC1 than does polya noPareto reduction of Kl generation fron PTC tioally inprova the conbustloo toxicological natality and ineapacltation for red oak appear to be m. (JMthllty and ineapacltation for Geon 1750 with tre fKfctfdoxoprene with tre appear to be due to KM. I.) fire retarded with polychloroprane. This relatively high levels of MCM ewelutiea loth Mortality and Incapacitation appear inatloa of 00 * 2614005 II. Conclusion* L'nt : nueo For all of the mater lal s ir.v no evidence that 'Cl plays incapacitat ion. :jted so :ar. *e ~.s\e a -runor rale it. indue; Introduct ion We have recently completed a fifth round of bioassay testi.no of the combustion products of a series of natural and synthetic materials. This report describes the objectives of this work, the experiments, their results and the conclusions. A few years ago several model building codes began to include rules for the regulation of Mterials based on combustion product toxicity. In aest cases these restrictions did not go into effect because no taat procedure urns available for the evaluation of matarials. tinea the nmedsd bioassay tasting protocol did not axiat, tha National Bureau of Standards offered to develop a first generation test procedure before September, 1977. Merit Birky was given the responsibility of daveloping tha protocol. Part of tha rasearch for the development of the MBS bioessay testing protocol has been done by Professor Yves hlari# at tha University of Pittsburgh. Using a sensory irritation model, hlnrie has investigated the combustion products from s vide range of materials. In ordar to interpret the results of the experiments pith oophostion products, Marie has also studied the sensory ^nri atlw response to a number of pure geees. Marie has found, *%albg the sensory irritation nodal, that K1 is oma of the most " irritating gaams. Mcamae of this, the combustion products of PVC are vary irritating in Marie's sensory irritation nodal. On the basis efjltarie'dsensory irritation procedure, the performance of P*C mpuld hn hedged *sry inferior to the performance of most other ostealpTS is enson useage. until very recently, Marie's work has Been the dUv research available to Birky in support of the development of the needed bioassay testing protocol. Because of this, ttdkplns bean strongly Influenced by Merle's work and this has been reflected in preliminary versions of the protocol which Birky will misses in September. has been strongly influenced by Marie, this has pieced any restriction on which groups to him. Therefore, last January ws viaited with him soam aspects of our bioassay tasting bblieved that by revealing noma of the results w testing work that the results of Marie's brought into better perspective la Birky'a vise. Bpedlfically, wa wanted to familiarise rirky with our findings on the sensitivity of the renklna of a series of eaterinis as n function of tha details of tike test procedure, in 22614006 BfG21961 III. Introduction ' t'ont inued addition, our own work has shown that carbon monoxide is the most important component of the combustion products of PVC :n inducing incapacitation in the rotating cage experiment. Finally, we included results from our work on PVC with Zinc Ferro Cyanide to demonstrate that the protocol which we have used will detect s 'super toxic" material. We believed that the results of our experiences with this material would be of great interest and value to Birky because he has emphasized that an acceptable bioassay testing protocol must be sensitive to "super toxic* Mteriels. Birky was very interested in the correlation which we have found of incapacitation in the rotating cage with carbon monoxide, because he did not accept the implications of the result. Basi cally Birky believes that HC1 is very important in inducing incapacitation or lose of useful function in a fire victim. Since our work has shown that carbon monoxide and not HC1 is important in inducing test aniaml incapacitation in the rotating cage eepstlnat, Birky views this bioresponse es inadequate. This reflects the influence which Alarie has had on Birky. After hearing our presentation, Birky asked us to do soa nav experiments and to supply hin with seaples of pvc/zpc, which tested by Alaris. Birky wanted ua to test wood, PVC and an that the relative performance could be determined, tinoe Alaris would be testing PVC/XPC by sensory irritation, we bellsemC it mi assert-lal to test this material by incapacitation in the matatlng oifs experiment for comparison. To demonstrate that tli effect ef VC is not exclusive to PVC but that it would operate in any acid get generating polymer, polychloroprene end polyohleunpunPU/tFC were also tested. Birky's request to ue to do tbaes experiments indicated e genuine receptiveness to further Input, tinoe an input to Birky'a work is vital at this point, the unpnrVVBts burnt boon done. This report gives the results of the Nihiu of experiments done in response to Birky's request. iv. Discussion turn - Procedure air It, experimental conditions and procedure have Since the third round of testing*3'. Three hvu been madet 1.) static animals have been banting unit has been rebuilt based on nichroms diamantei end 3.) the squirrel cage air recircuhis been replaced with a parastaltic pump of the ns rate capacity. im m s z z BFG21962 V. I.' Apparatus - Procedure - Continued; The physical system consists of a <0 liter .r.halatior. chaster and a 20 liter combustion chamber interconnected by aair circulation system. The experimental conditions are roe same as previously used*. The partial recirculation of the atmosphere which is used in this procedure permits the fulfill ment of three critical criteria: 1.) the animals are exposed to air no hotter than 3 2C; 2.) test animal anoxia is prevented since the t 02 does not go below 18%; and 3.) a pseudo-stable atmosphere of combustion products is generated. The duration of the exposure is fifteen minutes for each experiment. Since all exposures are of the same duration, meaningful comparisons of post axpoture mortality data can be made. The fifteen minute time period of the experiment is important for anothar reason. EXiring combustion, PVC raleases HC1 aarly, further heating results in ths svolution of CO. It is important that tha test snissls bs sspossd to ths products of all phases of ths decom position process. Ths fifteen minute exposure allows nearly complete cossbustion to occur. The inhalation chamber holds six rotating cages on e common drive shaft. One eniael is placed in each cage and tha cages are rotated at six KM by an electric motor. The bioresponsee which were dotosmined with their definitions ere: 1.) leoemeoitation - At the end of the IS minute exposure, EKTnfltaer of animals incapacitated out of six was determined. The result is reported as a percent. 2.1 yi-- H Tnoepncitetion - The tine at which incapacitation olcurred wee determined for each animal which fenNM Incapacitated. The tine interval during which laaftgMaltatlon occurred is reported. .)3 of aurs - At the end of the Pr o animals dead out of the orig- inu^ix wee <determined The result is reported se s .)4 Htaerrsn Mm ortality - if at the end of the ampoaure S*TTtwwo MiaSte were not deed, enough were saerithat two wore available for CO*8b determine surviving animals were returned to holding M thboervation. rood and water were available, . Heof two weeks, the cumulative number of Is deed out of the original six was determined. eecrlficed for CO*8b wore net Included in tho statistice. The result is expressed as e percent. 22614003 1.) Apparatus - Procedure - Continnuueedi Two expressions of the mass of material used in each experi ment are given: 1.) the actual weight of the sample used, and 2.) a concentration parameter -- the weight of 3ampie consumed divided by the volume of atmosphere in the experiment. This paraster facilitates intercomparison of results from various types of apparatus by accounting for differences of volume. The volume of our experiment is defined as 180 liters [40 20 15 minutes X (8 liters per minute flow rate)] . The results are shown in Table I. 2.) Developing Pose-Response Curves The evaluation of the performance of a material is based on the mass of eaterial which will induce 50% response. For a given material, as the seas increases, tha percent of the exposed asianls which will respond incraasea. A plot of tha parcent tee versus the ease of eatarial exposed it defined as a doss the eaas of eaterial which will induce 50% tee oaa be obtained directly froe such a curve. The nueerl- ttl soles of the ease of eaterial which induces SOI response on i 1.) tbe specific blorespooae in question. . .inee- ________jaortality, or other, and 2.) the properties of the r|lU A low or hifh tonic gea release. Zn a ccepariaon of eeterlalsf the eaterial with the largest value of 0% response is judged to be better or aefer. 5*.* idb bioreapooas has been teen in our previous itive response'*). Thet is, a --11 incre- __________ ? exposed will result in a change froe 01 , lift} be 1001 anieals responding. ideally, doss ed bv non-sero nee-100 percent responaee. d prqfiee because several axparieents nay oil a reege of aeapla weights which will of result. is order to have ths best date its national aureau of Standards, for this taban special efforts to define the with dse-sero, non-100 percent response data 1# illustrated in Figure I which shows the defined by the data free Table X for Goon 1750. the results for the ness of eatarial which 600frT92 rjf' BFG21964 TABLE X Biological Raaponaa to the Products of Coabuation Bart 1: Gaon 8750 Rigid PVC, SO nil Thick la Maas i copauaad of aniaala Time incapacitatlon occur* ain:sac % Mortality at and *0? at end of aapoaura two weeii 4.3 at" 1.) 11. 11.7 1S.0 33.3 IU 47.4 34.1 41.1 0 0 100 17 15(00 0 75 SO 9t30 - 11:30 so 100 3 11(30 - 14:30 33 75 100 11:00 - 13:45 66 100 inrTfir mi" rvc. is ail Thick 0 SO 7*45 - 13:00 so 7*00 - :40 44 41S - 10i30 190 2(40 - 4 (SO m It 30 - 5:45 0 0 0 0 0 50 50 0 0 0 50 75 0 17 U 100 - 12:15 11(45 - 14:45 9:30 - 12:15 9(25 - 12:40 5:00 - 6:15 0 0 0 33 50 100 0 0 0 33 100 100 o ro fris z . Mm A. Table I - (OMtiBMd) Eolychloropcese/PC, 20 all Thick pc p oar liter air of ulatli incapacitated 1.91 1.99 1.11 '1 *te t* |1| * Wg ' 1.9 5.3 4.4 4.T 9.1 9.2 U4 11.1 . , 0 0 . 17 99 199 199 199 199 tation occurs lata -12(45 3(59 - 7(09 3t45 - 7(20 1(59 - 10(90 2(19 - 3(15 1(15 - 2(45 at and of exposure 0 0 0 0 0 0 0 3 at end of two weals 0 0 0 0 0 25 0 93 15(99 12(45 llt4S 19(45 9(39 t99 14(59 15(90 14(29 9t5S 19(35 0 0 9 95 199 0 75 25 3 100 Mass of Material Which Induce! a SO* Response for Varr is Bioreaponses Materlal Bioresponses Mortality At End of At End of Incapacitation Exposure Two Weeks Jeon 8750 gm exposed 11 .2 12.5 <8.3 mg consumed per liter air 47.3 52.8 < 35.0 Peon 8750/XTC ge exposed eg conexeed per liter sir 1.45 6.3 2.7 11.6 2.5 10.1 4.5 22.4 8.1 40.2 7.9 37.2 2.7 10.8 2.7 10.2 e x o b ie z z fee WWI 3.9 20.8 9.0 22.3 9.4 50.0 9.1 48.4 8.1 30.2 7.7 34.4 3.) Comparison M Matorn Based on the data from Table II for tne mass -f material whion will induce 503 incapacitation, the materials are ranked aa follows (best performing material listed first Tear. 9750 > "state 53 360 > polychloroprene > Red Cak > Geon S150.'ZFC > pc 1yen.1 mrcprene 'ZFC. The performance of Geon 3050 is measarably superior to that of any of the other materials. The next best material is Estane 58360, more than twice as much Geon 8750 as Estane 5336C is required to induce 50% incapacitation. The three materials, Estane 58360, polychloroprene and red oak, for practi cal purposes are equivalent. The effect of cFC in imparting excessive toxicity to chlorine containing polymers is demonstrated in the performance of Geon 8750/ZFC and polychloroprene/ZFC. Nearly ten times as much Geon 8750 as Geon 8750/ZFC or polychloro prene/ZFC is required to induce 504 incapacitation. We have seen as shorn in Table II that for different materials there are substantial differsnces in the mass of material which induces a SOI response. Likewise deferent materials there may be substantial difference* in the time at which response occurs. This phenomenon has served smny workers in ?his field as a basis from which to evaluate end ra.ik materials. For sxample. Smith end Crane*4' of tlM FAA evaluate eateriels on the basis of tins to incapacitation (t^), ell materials compered at equal mass. Smith end Crane believe that this parameter nay have some relation ship to the amount of time which would be available to escape a burning environment. Thus, the greater ti is, the better the materiel. Ibis approach is valid and indeed both parameters (ti and mesa which induces incapacitation) are important in any com- pleea account of the toxicological properties of a aaterial. This philosophy is belne implimeoted into the latest results from the University of MlObipan propram*5'. In our previous rounds of inonpaeitation bioessay testing, no substantial differences of tbm tlam to incapacitation were noted for the materials which were tested. For asp fives ssterial, samples of relatively low weight wenld indues no rssppsse. in the case of samples which induced inoapncltetdsm of sons of the animals, incapacitation occurred at about 12-19 trinutes. Mulatively heavy samples induced incapacita tion at about 9-12 sdmutes. However, dramatically different behavior mms observed for the two ZFC containing aaterials eval- this round of testing. This is illustrated in Table III t^gaimb to incapacitation corresponding to the ness ,vhiiS^rndmces 90% incapacitation. The data in Table Ited from the results of Table I. incapacitation Liar in the case of the ZFC containing materials. added dimension to the hasard of these aaterials. fcrate the combined effect ef the mass of materiel which imdumes Incapacitation and the tine to incapacitation, the folloviao hasard index equation is offered: Hasard Index 1 IC50 X ti (1) Tine TABLE I t Incapacitation Aisociated with the Masa of Material Which induce* 501 Incapacitation- ~lfistimated from Data in Table I) Material Geon 8750 Polychloroprene Red Oak Estane 58360 Geon 8750/lFC Polychloroprene/ZFC tx, Bin, 13 13 14 14 8 5.S It must be emphasized that the purpose of Equation (1) it purely illustrative. ZC$p i tha aau which indues* 50% incapacitation. Vm lagfar tha value of tha haaard index for a particular notarial, the praetor tha tanlaological haaard. Iha hazard indax value fci Mbs Mb aatariala ara shewn in Table XV. latad on tha ratalta in Wild nr, tha laaot hatazitaa aotarial out of tha tlx la separated m the aoai hatardooa by a factor of about twenty. Tha worst parforalnp -- nod therefore tha least acceptable -- aatarlals ara tho too tPC oontalhinp eompounds. Our r*TffY ofejeetive in this round of teatin? was to obtain aahonl ineapoOwpaion dots for the six selected aatarlals. Merit ftthy of tho efwSlaves that loan of survival response or inoaposltatioa is tho he. t bioresponse to use in tho assosmont of ooohustioa psodoet haaard^*'. Phis philosophy will almost certainly bd refloated loathe hioaasay test lap protocol whioh tha MM la 100 of soda proupe and ropulstory spanclas to lillty. Also tha Incspec1tatloo response relation to tha haaard of tho roal fire sapacitatlon of a fire victim represents tha 'hm cannot remove himself. If tha victim cannot in virtually certain, mpwaver an n secondary f testlap. wo havo attempted to aloo ohtnin (at and of exposure and at and of two waaha poet tho six selected oatoriale.. This was considered to bo importoot for tho followinp reason. Several important workers la tha field base their evaluations of the performance of aatar lals on tha mortality response'"**'. Secondly, Alaria evaluates 1L. TABLE '.a za rd ralculatoi f:or 5ata !ex .diues Ta:: 1 c* II ar.d Table Material Geon 8750 Polychloroprene Red Oak Eatane 58360 Geon 8750/ZFC Polychloroprene/ZFC Hazard Index .4 . setsriel a not only on tho beats of sensory irritation but also on the mortality response, these workers consider the aortality hSsard am ld^ortant parameter in the total toxicological equation. Thesefed, Respite the fact that Birky considers incapacitation to he^Utt most eseful hioreaponse for the evaluation of the cou sts of eateriala, the snrtality response to cos&usaay shM up as, at least, a part of the final pro* reason, it is important to have sons basic under* performance of oar saterials with respect to the ils are svaluetsd and coopered on the basis of 50% nortality. The results are listed in sST%S for tho ness of notarial which induces 50% tl nest be considered as estinates. This is >r Sh&ality response is relatively less sensitive Material contested than is the incapacitation is. It is necessary to sake large changes in ness in order to effect the percent nortality. itermination of the mass of satsrial which induces relatively less precise than the determination trial which induces 50% incapacitation. Also, to anticipate the correct ranqe of aaea of eater- .Mcoperly span the ranqe of nortality response in stvo week post exposure nortality results. Be* resistsnos to disease as a resul* of the contention I also confuse the two week post exposure nortality these reservations in aind, a coaqtarison can be node. 2614016 ::m... BFG21971 3.' Compare so r. ->f Ma-enals - ->r. : r. ,,e Based on the lata :n Table II for r-.e rj * - : r.duce 50% mortality at the end of two wee<s, t -.*? , r . 1 are ranged as follows (bets perf ormir.:; material l.^ted :.r.= * Sed Oak > Estane 58 360 > polychloroprene > 3eo-. 3 ': ' > . . - chlcroprene/ZFC > Geon 8750/2FC. The rank of Geon 9'3I -as based on results obtained in the third round of testir.a the mass of Geon 8750, which induced 50% mortality at toe e-o of two weeks, was 6.1 grams. In the current round, samples low enough in mass to define this result were not used. Essentially equivalent performance is observed for red oak, Estane 58360, polychloroprene and Geon 8750. The performance of Geon 8750 2FC and polychloroprene/ZFC is significantly inferior to that of the other four materials. Again the effect of ZFC in imparting excessive toxicity to chlorine containing polymers is demonstrated in the performance of Geon 87S0/ZFC and polychloroprene/2FC. These results for the ranking of the materials based on the three bioresponses are suimsarized in Table v. Table v shows that Geon <750 outperforms rod oak on the basis of the incapacitation response but red oak outperforms Geon 8750 on the basis of the mortality at the end of two weeks response. This reversal of performance is due to the role different components of the com bustion products pley in inducing different bioresponses, we have previously seen that CO plays the dominant role in inducing incapacitation*3'. Since wood generates more CO than PVC does, PVC outperforms wood on the basis of the incapacitation response. On the other hand, our earlier work has also shown that HC1 plays a vary important role in inducing mortality. Since PVC generatea BC1 and wood does not, wood outperforms Pvc on the basis of the mortality response. The role of specific components of combustion products in inducing response will be discussed in greeter detail in e later section of this report. One of the major conclusions from our earlier work*9'10' is that while using only one bioresponse (death), the details of the conditions of cashustion of ths samples have a pronounced effect on the ranking of e series of neterials. The results of this mead of teeti4fe demonstrate that the ranking of a series of depends strongly on which specific incapacitation used for the evaluation. Earliar this year, Birky erne results from Alaria and Jounay for the ranking basad on the sensory irritation type mpwa ults are sunamrised in the first two Of fbhln VI and show that on ths basis of this response. of wood is superior to the performance of pvc by a factor of about one hundred. For comparison, our results for the performance of wood, PVC end polyurethane based on incapaci tation in the rotating cage are given in the third column of Table VX. These results show tliat the performance of PVC is acre than e factor of two superior to the performance of wood. This reversal of the order of ranking of wood and PVC wee surprising. 22614017 BFG21972 TA3^: Ranking* of Materials lased or. Mass Which Induce* $0% Response'Tor VariouJ TTorespcr.ses Material don 8750 Polychloroprene latane 513(0 Had Oak aeon 7S0/src PolyhloroprM/src __________________Biorespomei _ Mortal At 4nd of Incapacitation Expoaura At End of Two Weeks 4 3 22 4 21 5 46 ( 4S Beet perttmlnp Material * l Materials raa|4 Identically when they have the ease value ef MM which lndnoes 50% renponae. TABLB VI Mtie^f haterla 1 Which Induces a 50% teaponee asns-- teneery irritation 0.5 SO 50 lloreeponeea Jounay xnoepecifcation Seneory in Betetiag Irritation _____Case 0.5 47 (( 21 30 22 8T0VT92 BFG21973 3.) Comparison 3: Mater :j is inueji cut is 'o', i-.e to J1 f: er-.-r.cos >: * . J -tails : * we sample * - st lor.. 9j t tie r 11 . s '"o iat: -n .if the f .10 * v j? ojcr. ; - p a citation oicresponse : s sensitive to different individual chemi cal components of the combustion ^ases. Alarie has shown that HC1 is much more important than CO m inducing sensory irritation. Our own work has shown that CO is much more important than HC1 -n inducing incapacitation in the rotating cage. Since PVC generates HC1 and wood does not, and wood generates more CO than PVC, eval uation by incapacitation in the rotating cage shows wood worse than PVC. Our results suggest that the importance of HC1 in a real fire situation may have been greatly overemphasised. This issue must be further investigated. However, as shown in Table VI, our work has established that the ranking of a series of materials depends on which type of bioresponse is used for the eveluetion. Since all incapacitation bioresponses do not rank all materials in roughly the same order, for a bioassay testing protoool to be used to control the acceptability of materials, it ia critical to establish which bioresponae moat realistically models the reel fire heserd. Merit Birky must decide which type of bioresponae moat closely models the hazard of a real fire situation. Cur input to him on the basis of the work reported here should be useful in that it desnnstrates that not all in capacitation bioresponses are equivalent. One feature of e bioresponae which adequately models the real fire hasard ia that it will detect materials which are excessive!,, toxic. Based on incapacitation in the rotating cage, addition of SPC to Geon I7S0 increases the toxicity by more than a factor of tan. Thus, it appaars that the incapacitation bioresponae, as determined in the rotating cage, is sensitive to "super toxicants". 4.) analytical Data Our bloassey testing program has been coupled with a program of analytical gee iMaaurements. Through correlation of bioresponses dose specific consonants of combustion products, it .e to Sfetolfy the components most important in inducing A baste understanding of the factors contributing to bioresponses enhances the reliability of our work, such information serves as a basis for for the guidance of programs for the develop- snteriels. Tbs gases we have monitored included CO, HC1 end HO. Samples for CO were collected in vaccutainers, carried beck to ALTC and analysed by OC. The BC1 content of the atmosphere was determined om-site using e chloride ion selective electrode method. The details ef the procedures for CO and BC1 have been reported0'9'10' The procedure for the determination of the HO content of the 22614019 BFG21974 4 .) Anal yt ica 1 Ha - a - 1 Co n - : r. .ed ' a'mospner* was the same as the HC1 procedure except that t.-e absorbing solution was iilute NaOH and the electrcde was a ryar. lon selective electrode. Simultaneous measurements of MCI and HCN were not possible in the case of materials which generate both because cyanide interferes with the chloride ion selective electrode. In these cases, measurements were made only for HCN content. During the course of each exposure experiment, suffic ient samples were taken in order to adequately define the nature of the concentration-time profiles of the gases. At the end of each IS minute exposure, blood samples were taken from the two weakest animals for CO*Hb determination. The concentrationtime data is used to calculste the total dose to which the test animals are exposed during the course of the experiment. The dose is directly related to the integral of the concentration time profile and this parametsr has bean daterminad for each gas in asch sxperiment. The results srs given in Table vii. Proa the date in Table XX and Table VXX, we are able to deduee the doee of CO'Hb, CO, HC1, and HCN associated with SOI response fer each material. The results srs givsn in Table vili. The best wey to deteralne the significance of CO, BC1, end HCN in inducing bioresponse would be to coapare the results from Table VXII eith the results Of experiments where response is induced with pare pease. However, we do not have the required pure gasbloresponse imfensetlon. But by investigating a series of materials whieh have differing coaposition of the combustion prodoete* it is passible to identify the important components in inducing blorespouse. When tbe same high dose of a specific toxi cant fraa at least two different source materials induces the same r da that that toxicant is When low doses for all i bioresponse to s particular aatarial, lilpa Of two conclusions is possible: 1.) the combina tion of toaieaats is important, or 2.) sows other component un accounted for is responsible. of Pose of Specific Components of Combustion i to mortality riaiard at the end of the exposure with Geon 8750, the iO S4% and the dose of RC1 is 105,000 ppa-ninute. in the tflua round of bioassay testing, Geon 8750 and "Geon 87235 were both estimated on the basis of tha mortality response at tha and of tha aapoaure. The levels of co*Hb were 65% and 58% and the levels of IC1 were 5f,000 ppa-ninute and 44,000 ppa-ainuta, respec tively. These results suggest that in tha presage of BC1 mortality la laisuoed at the sad of the exposure with 60-45% CO-lb. The rssponea is apparently soaewhat insensitive to the level of aci sines we have found 44,000-105,000 ppn minute at the end-point. BFG21975 > 11, I1 ,,< o o o Oo eft* e N *4 OB oi r* % % eH 9 * *> 04 ft* m * e 9 ffBtft 9ft ftft <4 9 r* 9 * CBft 04 ft ft ft mO 9 9 oft o O O OB * 04 04 9 <0ft wt in m % 04 os <N 04 o * o CB o 9 O OS 9ft OSft 0* 9 ft 9ft OS in 9 fB :XI' e ee e 9 m ft r9*ft 9 ftft <n o ^m r9t * 9ft o o *ft 0* m e f9tft o S0 9O 99 99 A ft % X f* ** rm 9 9 t 9 f 0* tn 04 9 8 i 9* a1 1 1 ! % %% v * * % 04 ! 1 I * s M .9 ftl i ft :t 9ft ifttft it J*J4JI t a BFG21977 , :&* 55 5) a *>-& , V. 2261402a. -t*b Acs** 4-j V II - (C ontinued) (C ontinued) 9TO17T9ZZ T ib i* V II - (C ontinued) IZ0M 9Z T able V II - (C o n tin u e d ) BZOVfSZ s* at I*S mtmj * * mt mi imtm# 25 C s: OI : U Q.' i| oOO' O H in oe o% r* vO oo o Oo in <N o o &S % %% ON <N in in r* ri/*> in in r* p-* ^ vO N rPs^i --. ^ vO j r- * ^I ; r- oo O o oo o o <e IN O in o IN ; ^ <0 -- m IN IN %% IK 1 , IN V *> 5 iXl - = 9) > a1 f*- HaVM oiw IrN* IiNn *h r* Oo Mol irn* oo oo flD 9> Oo Oe n* ^ IN m 00 in r* o u 1 oo o r* o % % in r* V 8. a o ** 0 %% oe r~ v < Mi i I 1 Ol a 1(1 I oCh o* rv n* m nO* M ss (i 2614029 21, =i o or* IN /% <N IN in so %% IN IN oo * & m O oo <N in m N %* fn \ft IN *r ^4 o o o y IN %%% OB IN IN o p* u" IN p* o oo o t/1 < r- O on <0 %% % ** * p* ^ N1 o o% U1 N oo kP -H <N * kP o ee o ^ r* m in e * %% in o w* * O O IN *4 IN oe e in m <*> mo f* eo e 88 e*e * vJ" li '(W st ss BFG21985 T a b le V II - (C o n ti nueil I C 0^T9? T a b le V I I - (C o n tin u e d ) BFG21987 2614032 G ram a b x |> o s e d ( 6 2 -7 l . s * CO Ub 33. 30000 ^ ^o 04 O* in OOOOO ^^ ^o --t m in oo rsflD9nn 04 in ^ m^ o oo 04 in ^<4 m a r> in % -4 % o* 04 m 04 o * rthf OH %% 04 0n* r0>4 o*to* om ro orf> o < r* HM* f4n ^ Ba.. 11 Uo"> fs oinn% oo o O00B 04 04 <ione* 04 o 04 04 m * o^% * hnhh omr o * e* o * % o ir%t o <rfnt t M T *b l V ll - (C o n tin u e d ) Z.l)VT9Z s it z * ti j i >rr4B A BFG21992 :ablf. vi : i Dose for 50< Bioresponse Incapacitation Material CO Mb % 15 min CO ppm-min 15 min HC1 ppm-min 15 m l r. i ppra-mi r. Gaon 8750 58 37,000 92,000 - Gaon 8750/xrc 21 4,500 - 3,633 Polychloroprana 53 41,000 7,500 - Pol yehloropram/IFC 12 1,400 - 3,500 tad Ota S9 38,000 - - Batana 58340 45 24,000 - 2,400 Mortality at End of Bxpoaura 5 OBM 750 QMB 97M/SFC t4 42,000 105,000 10 1,500 - 4,800 folyoklroprna 0 75,000 24,000 - FolyekloropraM/IK 20 8,00 - 7,800 tad Ota 0 92,000 - - Batata SISM 70 39,000 4,4 00 >ks 7 SO < 47 20 < 27,000 7,100 < 43,000 m 4,200 75 49,000 20 a, 100 7 90,000 07 37,000 22,000 - - 7,800 3,800 261403S 43039 BFG21993 3 l t . 0 P. 5 ' ! ..1' u' ?r~TT7c r s T3 MoFl `i ?.ar .1 - !*: - . -j i ot HC1 roqui r<j `liar.or levels : ;.l : . . r mortal iry at the end oi the exposure. Apparent 1 ., wit r. i- r below 24.000 ppm-minute, it does not stror.ql, :n n* r 11 ute mortality at the end of the exposure. This is seen for pol - prer.e and red oak. where % CO-Hb is 80 for both. Carbc-. -o1 x. ie is probably the most important component of the combustion products of polychloroprene and red oak in inducing mortality at the end of the exposure. Low % CO-Hb is seen for Geon 8'50/ZFC and poly- chloroprene/ZFC. We were not able to make measurements: however, it is likely that the level of HC1 is significar.tiy higher for Geon 8750/ZFC than for polychloroprene/ZFC at 50% mortality at the end of the exposure. The HCN levels are 6,800 ppm-minute and ',800 ppm-minute respectively. These results suggest that HCN is probably the most important component in the decomposition products of Geon 8750/ZFC and polychloroprene/ZFC in inducing mortality at the end of the exposure. Moderate levels of CO-Hb and of HCN are seen for Kstane 51380. This suggests that in the case of Estane 58360, both carbon monoxide and HCN contribute to inducing mortality at the end of the exposure. Comparison of tha results for all materials, except Geon 8750, for mortality at tha and of tha exposure and at the end of two weeks shows insignigieant differences. This is because for, these materials after tha and of tha exposure, no further fatalities occur T*"' the saaM factors responsible for mortality at the end of the exposure are responsible for aortality at tha end of two weeks. The case of Ceon 8750, howeear, is draMtically different. During the two week post exposure holding period, fatalities continue to occur. This delayed mortality feature appears to be characteristic of pvc. The component of the ccaiubstion products of Geon 8750 responsible for the mortality responee during the two week post exposure holding period appears to be the MCI. This is seen in comparison of tha results froai Geon 8750 and from polychloroprene for mortality at the end of two weeks. For Geon 8750, the level of HC1 is higher while the level of % CO-Hb is lower than the corresponding levels from polychloropreee. Xt is further very interesting to note that tha parformanca of (plyehloroprene is diffarant from tha characteristic parformanca of lie in that significant numbers of post exposure sertalities do act occur. Since poet exposure mortalities in the case of PVC are due to HC1, this suggests that if the evolution of HC1 from pvc oould be reduced to the level of evolution of HC1 from polychloro prene, the performance of PVC on the basis of mortality at the end of two weeks could be dramatically improved. Data in Table vix shows that Geon 8750 tvolves only 2-3 times mors HCi per gram than does polychloroprene. 22614039 BFG21994 S.) Relationship ot Dose -jf Specific Components of 'o-.~. ,s.; ;n Products to Mortality Hazard - t Con.t1 n jed For the current round of bio assay testing t .ne turpose of tr. e proceeding analysis is to substantiate the ranking and evaluation, of the series of materials in part (3) of the Discussion section. It is not adequate to 3imply evaluate a material on the basis of animal response to the combustion products. It is necessary to have som understanding of how the response is induced by tne combustion products. This gives a more complete account of the potential toxicological properties of a material beyond a simple rank ordering of a series from "worst" to "best". Two materials which are ranked equivalently may be evaluated differently if their mode of action is different. Fairly or not, carbon monoxide is considered an acceptable hazard of a fire situation, h material which induces response via carbon monoxide is considered more acceptable than a material which has s different mode of action. Coupling analytical tasting to bioasaay tasting also has ths effect of enhancing the reliability of the bioresponse results. <.) halatlonahlp of Dose of Specific Compontnts of Combustion Products to Incapacitation Hazard In the current round of testing, we have evaluated a series of chlorine containing and other materials which spans a wide range of ohlorlne content. . . .red oak 0% to pvc 50%. Thus, a batter evaluation of tho role of RC1 in inducing incapacitation can oe code coopered to the third round of testing'3' where only pvc com pounds were used. The range of HC1 at incapacitation is 0-92,900 for rod oak, polyehloroprene, and Gaon 1750. This lack >rrelation of loeol of HC1 with the incapacitation response rates thet K1 is not Important in inducing the incapacitareepemse. aowever, the range of % CO-Hb associated with 50% lnsameeltetion for those throe materials is in the range 53-59% CO*Se. The oarbon monoxide levels are in the range 37,000-41,000 koto. This tenonstratee that incapacitation is primarily for rod oak, polyehloroprene, and Gaon 1750. it (thet K1 le not important in inducing incapacitation km? Itelns^Mp* experiment) suggests that the importance of Situation say be overestimated. However, this investigation. between atmospheric carbon nonoxIda and t in Figure IX. Figure XX includes the results from cseh emperiaant conducted in this round of testing. The relationship defined by the data in Figure XX demonstrates that the ooaXmation components, other than CO, have a negligible affect on tho uptake of 00. Low values of I CO'Hb are associated with incapacitation in the oass of Goon 1790/fPC and polychloroprene/lFC. These materials generate hydro gem eyenlde upon heating, however; and the level of WOM la 3,did ppg-mlamte and 3,500 ppm-minute from doon 1750/XPC BFG21995 2614040 FIGURE 2 Relationship of I CO-Hb to Atmospheric CO < n - r-'O1 . ~ "i i. orop rene / ZFC respoctivo I . i* ir.c,ip.r-:,at;:n. T-.v i-* parts 2 arid 4 of Table VII snows '.-.a' nydrcger. cvar.:2e is venerated early from Geon 8750/ZFC ar.d polychlorrprer.e :FJ f?.lowed by rapid clearing from the c.namber. The data m parts 2 a.-.-. 4 of Table I shows that incapacitat ion occurs very early :n the case of Geon 8750/ZFC and polychlcroprene/"ZFC . These observations suggest that HCN is the most important component of the combustion products from Geon 8750/ZFC and polychloroprene/ZFC m inducing incapacitation. Moderate levels of % CO-Hb and HCN at incapacitation are seen for Estane 58360. This suggests that both CO and HCN are important in inducing incapacitation. Estane 58360 contains polychloroprene as a flame/drip retardant. Upon thermal degradation, this releases HC1 which may have the effect of increasing HCN release. This effect has been shown in our enalyticel testing program at ALTC(11). Our primary bioassay testing objective has been to evaluate and rank materials on the besis of dose-response testing. As a secondery goal, wo have coupled enalyticel testing with the bioresponse test ing to determine the role of specific components of combustion products in inducing bioresponse. Unfortunately, the optimum experi mental procedure for the achievement of the primary goal does not allow a highly accurate correlation of analytical and bioresponse date. This discrepancy comes about in the following way. We have asserted that carbon monoxide is important in inducing incapacitation bacause 50% incapacitation is associated with a level of carboxyhemoqlobin of 53-58% COHb in our experiments. The data which this is baaed on contains minor inaccuracies. All measurements of % CO*Hb are made on blood sasples taken from animals after the end of the IS minute exposure. However* comparison of the date in Table IZ with the data in table I shows that for any material, for the mass of material which induces 50% incapacitation, the incapacitation response takes place significantly sooner than 15 minutes. The problem arises from the fact that during the time period between when the snlmsl becomes incapacitated and the time when thg blood is taken, the r*rfl'1 continues to load carbon monoxide. The result is tirnt artificially high values of % COHb are associated with 50% inoappoltation in Table VIII. The magnitude of the discrepancy is not Mfisms and does not alter any of our conclusions. This is demooRootmt aa follows. For each of the three materials, Geon 8750, polflaoroprOM and red oak. . . . where it has been asserted the CO is tbs combustion component important in inducing incapacitation by chnncat incapacitation occurred at or very near 15 minutes for one of the samples. The carboxyhemoglobin values from thews experiments should very closely approximate the correct value of % CO*Hb to be associated with 50% incapacitation. The pertinent data taken froe Tables X and VXX is given in Table IX. For coepariaon, data is inolmtfed from Table VIII. This data shows that the results in BFG21997 Zft)trT2>ZZ *1 39 TABLE IX I CO-Hb at 501 Incapacitation Material Soon 1750 Polychloropreoa had Oak Results from Sample with Incapacitation at IS Minutes Maas of Sample, gm CO-Hb % 9.9 54 4.9 47 3.1 55 Results from Table VIII CO-Hb % 58 53 59 table VIZI aey ba artificially high by 4-6%. The results in the af Sabi# ZXhre in good agreement with the work of Using pan atefeoa aonoxide, incspscitatioo in the rotating safe experiment was inducsd at 49% CO-ab. She sainal incapacitation responses to of a series of awtarials spanning a VO hare found that at 90% iacaby the oonbustion products of Soon or rod oak wood, or pure CO gas -- the dalasit is about 47-95%. This suggests Ip noct laportant cosmonaut of the caaaetafials in inducing incapacitation in oust bo an integral part of any prograa f improved Materials, evaluation of natarOa the ranking but also on the nature of 'll is induced. Zn particular, it is iaportant Barton aoaaaido is aost iaportant in inducing #__ _____at la based on % CO-Mb results, la order to establish this result, additional experiments are required to define the dose-response relation- *" experiments, the exposure would bs ooo- s occurs, at that a blood collected for % CO* 2614043 BFG21998 40 . References * M . M. 0'Mara, "Presentat in of Bioassay Worx to S'BS " : 2 . 1 3/ -7 6 . :. \ *4 . M . O'Mara, "Overview of Meeting with Dr. M. 9ir < y Combustion Toxicology", IOC, 1/14/77. 3.) G. F. Smith and w. C. Bachtel, "Combustion Toxicological Testing - Pert III: Evaluation of Materials Based on Incapacitation Response and Analytical Gas Data", Staff Technical Report *388, Decamber, 1976. 4.) P. w. Smith, C. R. Crane, D. C. Sanders, J. K. Abbott and B. R. Endicott, "Materials Toxicology Evaluation by Direct Animal Exposure", Proceedings of the International 5.) G. P. Smith, "Status of the University of Michigan Caafeus- tioa Product Toxicity Program", BPGCD Meeting Report, 5/25/77. 6.) N. M. Birky, "Philoeophy of Testing for Assessment of Toxi cological Aspects of fire Exposure", J. Combustion toxicology. 3, 5 (1974). -------------------------- 7.) If. J. Potts and T. S. Lederer, "A Method for Comparative Testing of Smoke Toxicity", J. Combustion Toxicology, 4, 1X4 (1977). ------------------------------------------- t.) J. B. Terrill, R. B. Montgooery and C. T. Reinhardt, Pire Technology. U. 95 (1977). -------- 9.) M. N. G'Mrrb end W. C. Bechtel, "Combuetion Toxicological Teetias - Pert 2< Oombined Biological Response and Analytical 4sa Data on 12 Key Materials", Staff Tech nical Beport #34, April, 1974. 10.) N. 0*HBXa, "Basults of tha Exposure of Teet Rats to the mimxOeaBmstios Products from 8FGCC Products", Staff TechReport #352, October, 1975. 11.) Bii' 6*lhgmt amt g. P. Smith, "Toxic Gas Evolution from v'' MBp Vtodects", BPGCD Technical Report, to be 12.) S. C. P a, et.al., "Behavioral Aesesaewati raids Intoxication in tbs Evaluation of Behavioral Poiata", Prooaedings of tha Xatematiooal fympoeit oFT^Bustiar im. 2614044 ,v> BFG21999