Document wqz1zznBNLeyqG0K887xoJNeJ

AR226-2849 LCUTE INHA: r ^ ^H----------' <-- -' Haskell Laboratory Report Ho.115-76 Report by: /\ /W^- 4 /^M^M^ yBfTic^A. BAgess Assistant Toxicologist Approved by: /V:tJ^^i\~^^'' -^^-^^g^-c Henzy J^.^-ochiEiowi.ez Chief ;' Inhalation Toxicology Section v BAB;dhg 2ate Issued. February 17, 1976 Company Sanitized. Does not contain TSCA C38 ACUTE INHALATION TOXICIIY STUDIES ON FODR^UMBBHiy MIXTURES CT D Haskell Laboratory Report No, 115-76 'Cable of Contents INTRODUCTION --------{LoBwoilers Hask'eTT No. 9544 iComposite HasESTf No. 9542 III. I CCrruuddeej "Haskell No. _9_ 5455 ^ HBH Composite skeli No. 9543^ Appendix A: Appendix B; Wt % Page No. 1 ^5 Jompany Sanitized. Does not contain TSCA '."Bi ACUTE INHALATION TQXICITY STDDIES -1^--^--^--^--^------JL Hasfcell Laboratory Report No, 115-76 INTRODUCTION limited. TBhe6e cuosxeicoicfypdoatteantaiavlailable on^l^fHmfmH Is materials at Parhersburg assd exposure situations Chansbers Works, the t^^fchese acute inhalation studies were initiated at subsequent Haskell Labora toitray. basTehefsoer setuvdalieusatiwnegrethaeimpedotaetntpiarol vhidaiznagrd a opf rtehlieminary Company Sanitized. Does not contain TSCfl "B? Materials Tested w Boilers '.amposite ------fifCrude omposCT'e Haskell Nos. I. 9544 II. 9542 III. 9545 IV. 9543 Samples Ready for Test-ing 11/24/76 Submitted by TRsnsicalsDep artment, Jackson Laboratory Haskell Laboratory Report No. 115-76 [Low Boilers A, Generation Procedure The test material was fed through a micrometer valve, from an inverted gas cylinder, to provide a constant drip rate into an iso thermal flask heated to 60C, Instantaneous evaporation occurred and the resultant vapors were swept into a 20-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 at various 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 571QA gas chromatograph, equipped with a flame ionization detector, was used for sample analysis. A tea foot by one-eighth inch stainless steel column, packed with 10% SE-30 on Chromasorif W, was used at 70C. Analysis was performed oa She largest peak (n = 1) in the chromafcogram. Comparison was made by monitoring the n = 1 component in standards and converting to the total low boiler concentration. One millilifcer gaseous injections were employed in the analyses. C. Results The data for the three exposures is presented below; TWA. Concentration (mg/liter of low boilers) 25 72 140 Fractional Mortality (j^ deaths/ten animals) 0/10 0/10 0/10 Clinical Signs Hyperemia, labored respiration Hyperemia, labored respiration Hyperemia, labored respiration igfifflpany Sanitized. Does not conMr --"31A W Practically no weight loss was observed in any test animal and all animals gained weight at a regular rate during the 14-day postexposure recovery period, D, Summary ^- t The approximate lethal concentration (ALC) for theBflPHI^RI 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. ffConipos ite Generation Procedure Chamber atmospheres were go-nerated by two different techniques. One method was to syringe drive the mixture through a one-quarter inch Teflon^ 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 ionization 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 ind 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 ths noa-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 not coniam TSCA C^t The following table tabulates the results achieved using both generation techniques. Analytical TWA Concentration (ing/liter of _Tl33 component) '-2.8 Syringe drive; 37"5 generation .- - 95 Bubbler generation 122 Fractional Mortality (# deaths/ ten animals) 0/10 3/10 0/10 Clinical Symptoms and Comments. None Salivation and labored respira tion. Cloud of white dust filled chamber and covered walls. All deaths occurred during exposure. FYellow 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. D. Summarv In four-hour exposures, fiBBH------|CG!aposi.te(H??9542) was administered to rats using t(ro'different generation techniques. With syringe drive, where high boilers precipitated out in the lines and chamber as a dust, the ALC for H#9542 is about 17 ing/liter (n su = gg 3 es t c s oncen that ttrhaet iJo n--) . --D--qg^gCJr osmupcohs co ite n i d s i tion "sl s, ig this htly t A o LC xic v " alue on a n acute inhalation oasis, Using the bubbler generation method, wh^.e the very low boilers come off early in the exposure, Che^m^J^QComposite appears to be "practically non-toxic" to rats exposed rot four hours as indicated by an ALC > 122 mg/liter (n = 3 concentration). Generation Procedure The test material was syringe driven through a Teflon'"' tube immersed i i a 160" C oil bath. The vaporizecfU------fthen entered a 10 liter/min, house air stream and was delivered to a 20-liter battery jar containing ten male ChR-CD rats ranging in initial body weight from 240 to 300 grains. Three exposures were run at different concentration levels. B. Analytical Procedure A Varian 600B gas chromatograph, equipped with a flame ionization detector, was employed for sample analysis. A three-foot by one-eighth inch stainless steel column packed with 107. SE-30 on Chromasorl^ W was used at room temperature. One milliliter gas samples were directly injected into the column. .Company Sanitized. Doss not contain ^^e. CE C. Results table-The data from these exposures is presented in the following Analytical TWA. Concentration (ing/ liter BL Olefin) 45.8 204 433 D. Summary Fractional Mortality (^ deaths/ten animals) 0/10 0/10 0/10 Clinical Si^ns None None None The ALC 433 ing/liter for for ^S^ts exp_o_se^d^--fo--r" [Crude (H#9545) is greater than tions, 6his material is :our hours. Under our test coadiconsidered to be "relatively harmless" on an acute inhalation basis. IV. VfUH^Composite A. Generation Procedure In light of the problems experienced with syringe driving such mixtures; (reference ti^fjBl^fPomposifce discussion), the bubbler method of generation was enployea in this test. Chamber concentra tions were varied by adjusting the ratio of air bubbled through the telomer solution to the amount of dilution air or by altering the telomer solution temperature. This method of generation more closely aaplpirqouxiidm.ates the equilibrium1 vapor composition o'- 3 would expect over B. Analytical Procedure The procedure employed was identical to Chat used forl|B--------| Composite, The only variation was that the column oven waB-pTBgramnied from 50-80C at 4C/min. C. Results and Discussion Similar to fchey'^BlHm^o'^POSite bubbler exposures, high con centrations of low BBTling components were observed immediately upon - start up of exposure and gradually disappeared over the first hour of exposure (See I igurc 1). Test results are presented in the table below: - 5 - .Company Sanflfced. Does not contain TSCA CB8 Exposure 4 5 6 7 8 8a Analytical TWA Concentration (mg/liter of n = 3 component) 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 (# d&aths/lO rats) 0/10 0/10 2/10 0/10 2/10 0/10 2/10 (8/10) (0/10) Clinical Signs + t -f- * * * * * None All mortalities occurred during exposure and- wi-6hi-n tire time peri'o'd ttsat theT low boilers were present in highest concentrations, For illustration, during exposure #8 at 12,5 mg/liter, eight of ten rats died during the first 45 minutes of exposure. The two remaining rats, removed from the chamber at 45 minutes, started recovering from effects immediately and suffered only mild weight loss. Ten new rats, placed in the chamber (Exposure # 8a) at 45 minutes, were used to com plete the remainder of the four-hour exposure. No adverse clinical signs were noted in the new rats, suggesting that the early deaths of the other rats were due to the presence of the low boilers. The effect of solution temperature on exposed rats appeared to be minimal. At similar concentrations, comparable fractional mortalities were obtained at both temperature ranges - 50-70"C and 130-140C, D. Summary Under these experimental conditions,'' Composite (H^9543) has a four-hour ALC of about 6,0 mg/liter ^"S" = 3 c! iponent concentra- tion). This value is considered "moderately toxic" on an acute inhala- tion basis. f Mild to moderate salivation, early signs of labored respiration, hyperem_a, and red discharge around the nose and eyes. * Profuse salivation, lacrimation (and later, red discharge from the eyes), red nasal discharge, convulsions, and light to moderate yellow fur discoloration. .Company Sanitized;. Does not contain TSCA CpF IQoMttanv SmMvaif nB< s -"---->-.- - Appendix A Telomer Molecular Formula "/ ".eporEed by"^ ** See Appendix A Organic Chemicals Department ,e^n,p.any.Sa.nStis8d, Does not contain TSCA CB8