Document nO958Gn8z4V0OZG2BOQrNNLX

AR226-2849 ACUTE INHALATION TOXICITY STUDIES ON FOUR MIXTURES Haskell Laboratory Report Ho. 115-76 Report by: gess logist Approved by: _ tbs rochisGwicz Chief Inhalation Toxicology Section B A B :dhg jjate Issuei February 17, 1976 Company Sanitized. Does not contain TSCA OSI W) acute inhalation toxicity studies on four % fMIXTURES Haskell Laboratory Report No. 1 1 5 .7 6 Table of Contents INTRODUCTION I. Low Boilers Haske ! No. 9544 II. [Composite Haske No. 9542 Page No. 1 3 4 5 8 8 Company Sanitized. Does not contain TSCA CP,t ACUTE INHALATION TOXICITY S-rnntRS o n FOUR MIXTURES INTRODUCTION --- ____ ^ P \ Thee studies were aimed at providing a preliminary t ^ a s e f o i ^ v a i u a t i n g the potential hazard of the ^ - 1- Company Sanitized. Does not contain TSO/> "Bf Materials Tested Haskell Nos. I. II. III. IV. 9544 9542 9545 9543 Samples Ready for Testing 11/24/76 Submitted by Organic Chemicals Department, Jackson Laboratory a c u t e i n h a l a t i o n t o x i c i t v STUDIES ON FOUR' MIXTURES Haskell Laboratory Report No. 115-76 "6 Low Boilers A. Generation Procedure . test material was fed through a micrometer valve, from an C r 0Vide a constant drip rate into an iso flask heated to 60 C. Instantaneous evaporation occurred and the resultant vapors were swept into a 2 0 - liter battery jar, con taining the test animals, by a 5 liter /minute house air stream. Three exposures, each of four hours in duration, were conducted v?*ious concentration levels. Each exposure utilized 10 male ChR-CD rats ranging in initial body weight from 240 to 300 grams. B. Analytical Procedure *. A Hewlett Packard 5710A gas chromatograph, equipped with a flame ionization detector, was used for sample analysis. A ten S ? n by ^ " ei8llthJbI,eh stainless steel column, packed with 10% SE-30 on C h r o m a s o r # ^ was used at 70C. Analysis was performed C n ,`'"a iargeS: peak (n = i) in the chromatogram. Comparison was fcodrHbyrm ^n i"t?rinv n = 1 comP onent in standards and converting to the total low boiler concentration. One milliliter gaseous injections were employed in the analyses. . C. Results The data for the three exposures is presented below; TWA Concentration jmg/liter of low boilers) Fractional Mortality deaths/ten animals) Clinical S i m s 25 72 140 0/10 0/10 0/10 Hyperemia, labored respiration Hyperemia, labored respiration Hyperemia, labored respiration 2 'Company Sanitized. Does not contain "*'"`'vBI Practically no weight loss was observed in any test animal and all animals gained weight at a regular rate during the 14-day post exposure recovery period. D. Summary The approximate lethal concentration (ALC) for the~| Low Boiler Mixture (H#9544) is > 140 mg/liter for rats exposed for four hours. This value suggests that H#9544 is "practically non toxic" on an acute inhalation basis. II Composite % Generation Procedure Chamber atmospheres were generated by two different techniques. One method was to syringe drive the mixture through a one-quarter inch Teflori tube submerged in a heated mineral oil bath. The resulting vapors were swept into a 20-liter battery jar by a 5 liter/ minute house air stream. The chamber air composition achieved in this manner was similar to the weight percent composition in the sample solution. This might simulate an exposure at high process temperatures. A second generation technique employed was to force house air through a fritted disc immersed in the telomer solution (heated to 40C). The resulting air mixture achieved using the method is similar to the equilibrium vapor composition expected in normal storage situations. No dilution air was added in this case. Employing both generation techniques, five four-hour exposures, each using 10 male ChR-CD rats, were conducted. Rats tested ranged in initial body weight from 240 to 270 grams. B. Analytical Method A Varian 600B gas chromatograph, equipped with a flame ioniza tion detector, was used for sample analysis. A six-foot by oneeighth inch stainless steel column, packed with 10% FFAP on Chromasorb W, was employed. Samples were trapped in ethanol using midget impingers. Since chamber air composition varies with the generation technique, all concentrations are reported on the basis of the n = 3 component concentration (See Appendix A ) . C. Results and Discussion - With syringe drive generation, the n = 3 component levels remained relatively stable throughout the exposure, whereas, the "high-boiling" components of the sample precipitated out as a dust of varying concentration and particle size distribution. This factor probably contributed heavily to the non-linearity in the dose-response data in the accompanying table. . Using the bubbler generation technique, all of the extremely low boiling components of the sample appeared during the first 30 to 60 minutes of exposure and then disappeared (as evidenced by gas chromatographic monitoring). Stable levels of low boilers are not achieved by this generation technique. 3 Company Sanitized. Does no! contain tsca 031 The following table tabulates the results achieved using both generation techniques. B Analytical TWA Concentration (mg/liter of n3 component) r 2.8 Syringe drive;'; 37.5 generation . 17.3 i Bubbler gnration 95 I ( 122 L D, Summary Fractional Mortality (# deaths/ ten animals) 0/10 3/10 0/10 _Cliuieal Symptoms and Comments None Salivation and labored respira tion. Cloud of white dust filled chamber and covered walls. All deaths occurred during exposure. Yellow discoloration of rat fur correlated with low boiler appearance in gas chromatograms (in first 30 to 60 minutes). Labored respiration, salivation, hyperemia and red nasal dis charge were also observed. In four-hour exposures, S H H B B f C c m p o s i t e (H#9542) was administered to rats using t W T 'differllt generation techniques. f yrTngS drive> where high boilers precipitated out in the lines and chamber as a dust, the ALC for H#9542 is about 17 mg/liter (n = 3 concentration^IJnder such conditions, this ALC value suggests that t h e l ^ l l ^ ^ H c o m p o s i t e is "slightly toxic" on an acute inhalation Basis. ' Osing the bubbler generation method, where the very low boilers come off early in the exposure, t h e f c ^ W c o m p o s i t e appears to be practically non-toxic" to rats exposed for four hours as indicated by an ALC > 122 mg/liter (n = 3 concentration). III. A. Generation Procedure The test material was syringe driven through a Teflorf- tube immersed i , a 160eC oil bath. The vaPo r i z e < M | i t f then entered a 10 liter / m m . house air stream and was delivered t ^ a 20-liter battery jar containing ten male ChR-CD rats ranging in initial body weight from 240 to 300 grams. Three exposures were run at different B, Analytical Procedure . ^ Varian 600B gas chromatograph, equipped with a flame ioniza tion detector, was employed for sample analysis. A three-foot by one-eighth inch stainless steel column packed with 107. SE-30 on Chromasorh- W was used at room temperature. One milliliter gas samples were directly injected into the column. - 4- 'Company Sanitized. Does not contain Tra cal C. Results rhe data from these exposures table: is presented in the following Analytical TWA Concentration _ (mg/liter BL Olefin) 45.8 204 433 D. Summary Fractional Mortality (# deaths/ten animals) 000///111000 Clinical Signs None None None . C for Crude (ffip9545) is greater than 433 mg/liter for Tats exposed tor four hours, Under our test condi- tions, this material is acute inhalation basis. considered to be "relatively harmless" on an IV* ^^^Composite A. Generation Procedure . In 1S:shl of the Problems e^gerienced with syringe driving such methode% (reieren?e tll0^ p i * i ^ omPosite discussion), the bubbler method of generation waS employe " i n this test. Chamber concentra- txons were varied by adjusting the ratio of air bubbled through the telomer solution to the amount of dilution air or bv altering teleaner solution temperature. This method of generation more closely approximates the equilibrium vapor composition o-e would expect over d iquia, . B, Analytical Procedure The procedure employed was identical to that used for Composite. The only variation was that the column oven wa grammed from 50-80C at 4C/min. ' C. Results and Discussion Similar thel ] p B B ^ 2 o n i p o s i t e bubbler exposures, high con centrations o f low filming components were observed immediately upon start up of exposure and gradually disappeared over the first hour of S o w " 6 (SeS IiSUrC X)* TeSt reSults are P^sented in the table 5 Company Sanitized. Does not contain TSCA CB! Exposure 1 2 3 4 5 6 7 8 8a Analytical TWA Concentration (mg/liter of L ~ 3 componenti 2.0 6.8 7.7 4.8 6.0 7.6 8.7 (12.5) (12.5) 50- 70 50-70 50-70 130-140 130-140 130-140 130-140 130-140 130-140 Fractional Mortality _(ff deaths/IQ ratst 0/10 20//1100 0/10 2/10 ( 820///111000) (/10) Clinical signs + ff * * * * * None For lU,,etratLn, L r S sle" " " P#r:tt,3i% hi`!l;rt " "" '-tious. rats died during the f i r s ^ 4 5 mi i-8 fc,12*5 mS/liter, eight of ten ' rats, removed fio re. j f I|,Sure- *" romaiuiag effects immediately and suffprprf f ' started recovering from placed it the c S e S ^ TM " SZ " * other rats ere due to" S % S T Z Z Z L ' Z Z Z f be m l S L l f feit mortalities w t e 130-140C. ' f?.-t? Perf 1pire " P o rats appeared to *' '" Parable ft.ctiooal d "L bth cemPerature ranges - 50-706C and 0. Summary Under these experimental copdi t-inne n has a four-hour Alt of about 6.0 m g <!#9543> tion). This value is consider-,? m * , " 3 cSPonent: concentra tion basis. considered moderately toxic" on an acute inhala- t Mild to moderate salivation *a;?vi\r hyperemia, and red discharg^ arould , e i f "Ser "d 1" " i j ; 1" rl"atl0" land later, red discharge from the yellow r d" o o i " t ^ f e' ^ derate 6 - 6- .Company Sanitized. Does not contain TSCA C iComoanv SoniiiraH nte*>b* Appendix A * tea ** See Appendix A Organic Chemicals Department 8- ?@pp&n?S-a-n--it-i.s-ed, Does not contain TSCA CBS