Document 91JQVZJMdg559Mvz1Z9nZe86e

M FORDUPONT USE ONLY AR226-2934 Du Pont HLR 624-87 Study Title Inhalation Approximate Lethal Concentration of [ ] Author Rudolph Valentine Study Completed On November 10, 1987 Performing Laboratory E . I . du Pont de Nemours and Company, Inc . Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P . 0 . Box 50 Newark, Delaware 19714 Medical Research No . Laboratory Project ID Haskell Laboratory Report No . S24-87 Page 1 of 10 company Sanitized. Does not contain TSCA CBI t MaterialTested : GENERAL INFORMATION, Du Pont HLR 624.87 MedicalResearchNo . : Haskell No . : Physical Form : Synonyms : Purity : Composition : 16,758 C [SON -2- Company Sanitized. Does not contain TSCA CBI Composition (Cont'd): GENERAL INFORMATION (Cont'd) Du Font HLR 624.87 Contaminants: Other Code: Stability; Sponsor: i) Material Submitted By; The test material was assumed to be stable throughout the exposure phase of the study. Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Milmington, Delaware Inc. J. R. Alender Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Jackson Laboratory Deepwater, New Jersey Inc. In-Life Phase Initiated - Completed: Notebook: 10/15/87 - 11/3/87 There are 10 pages in this report. Distribution: - 3 - "o^a^rygaRTRze?.. foe? n^ ee^am TSC^ (m Du Font HLR 624-87 Inhalation Approximate ^Lethal Concentration (ALC) o SUMMARY GrouDSof male Cr1:CD*8R rats were exposed to aerosol/vapor atmospheres s t ^ ^ e ^ C T o''norrf^B ^lngje^^iou ^^^^^^^^^Lraacs r p 9211 eriods mag//mm"-. Under the conditions of this At an atmnocsnphoeHripc rcnonnrcoennttpraaltion of 230 ing/in ofael (spheric concentrations of acetone and f f ^ w e r R b U et^y-lene-oJ^col-lMi 3110 9.4 ppin. respectively. Ine cflncentratlons of these v8PW^erM(e11 below those associated with animal mortality. All deaths occurred either during exposure or within 24 hours of exposure. No common clinical signs of toxtclty were observed 1n surviving rats during the 14-day ^ -- * i s recovery period. Based on the atmospheric concentration of the aerosol, considered to be extremely toxic on an acute Inhalation basis. Work by: Ro^<J 1. 1/x/i/njtV- Robert T. Turner Technician H /?/^7 Study Director: Q.>Ly. ^.:. . n/>o/e^ Rudolph Valentine, Ph.D. Research Toxicologist Approved by: Section Supervisor, Acute and Developmental Toxicology Section RV: sink: HLR 71.8 - 4 - Company Sanitized. Does not contain TSCA CBB Ou Pont HLR 624-87 QUALITY ASSURANCDEOCUMENTATION STUDY ----^IBf Inhalation ApproxTmateLethal concentration Because snort-term studies are numerous and routine in nature, representative studies from this test type are audited quarterly to ensure the studies are designed and conducted in compliance with the Good Laboratory Practice Standards. -i^lh^f^ Reported by: -&LLL Kathlleen L. Reed Quality Assurance Auditor K-tO-^ Date I) Company Sanitized. Does not contain TSCA CBI Du Pont HLR 624-87 INTRODUCTION ^ ^ ^ T h--Tehp--eup--urnrn--ppsseinmoafl e t his rat s s * t u d T y h e was AL t C o w a d s etermine defined a 4-hour Inhalation ALC for as the lowest atmospheric conceSn^ffrfSi^Wronn tested that caused the death of 1 or more rats either on the day of exposure or within 14 days post exposure. Except as documented In the study records, this study was conducted according to the applicable Good Laboratory Practice Regulations. MATERIALASND METHODS A. Animal Husbandry Young adult male Crl:CD<BR rats were received from Charles River Breeding Laboratories, Kingston, New York. Each rat was assigned a unique 6-diglt identification number which corresponded to a numbered card affixed to the cage. Rats were quarantined for one week prior to testing, and were weighed and observed twice during the quarantine period. During the test, rats. were housed in pairs In 8" x 14" x 8" suspended, stainless steel, wire-mesh cages. The rat assigned the lower number in each cage was identified by a slash in the right ear. Prior to exposure, rats' tails and cage cards were color-coded with waterinsoluble markers so that individual rats could be identified after exposure. Except during exposure, Purina Certified Rodent Chow* if>5002 and water were available ad libitum. Animal rooms were maintained on a timer-controlled, 12 hour/12 hour light/dark cycle. Environmental conditions of the rooms were targeted for a temperature of 23 ^ 2C and relative humidity of 501 ^ 101. excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Exposure Protocol Groups of 6 rats, 8 weeks old and weighing between 230 and 277 grams, were restrained in perforated, stainless steel cylinders with conical nose pieces. Each group was exposed nose^onT^or^^single, 4-hour period to an aerosol/vapor atmosphere of[II^^Hf^min air. Rats were weighed prior to exposure, uid were observearorcTTnical signs of toxicity during exposure. Surviving rats were weighed and observed daily for 14 days post exposure, weekends included when warranted by the rats' condition. ^ GeBipany Sanitized. Does r,w coniah T5C.< '":?:? Du Pont HLR 624-87 C. Atmosphere Generation oWlffflfyere Mixed aerosol/vapor atmospheres generated with a Spraying Systems air atoning nozzle wTng^iTgn'^ressure air stream. The test material was nel^ered Into the spray nozzle with a Harvard Model 975 compact Infusion pump and atomized with high pressure air (approximately 24 L/min). The spray nozzle was connected directly to a cylindrical, glass 38-L exposure chamber that was fitted wtfh a baffle,to enhance aerosol dispersion. Atmospheric concentrations G^HBT""'""* were controlled by varying the test material feed rate. Cnamoer atmospheres were exhausted through a dry Ice cold trap and a MSA cartridge filter prior 10 discharge Into a fume hood, D. Analytical IIIUBUBB"^ S1ncetheorocessjf atmosphere generation produced aerosols of ^P0^ of acetone and ethylene glcol, two rerentanaTytTcaTp'ro^edures were used. The atmospheric concentration of aerosol 1zed polymer w^s determined by gravimetric analysis. A gas chromatographic method w^s used to monitor the atmospheric concentration of acetone and ethylene glycol. The atmospheric concentrations of aerosol 1zed polymer were determined at approximately 30-minute intervals by gravimetric analysis during each exposure. Known volumes of chamber atmospheres were drawn through preweighed Gelman glass fiber filters. Filters were weighed on a Cahn pmatic Electrobalance*. Atmospheric concentrations of pere calculated from the filter weight gain, determined from post-sampling filter weights. The atmospheric concentrations of acetone and ethylene glycol were determined at approximately 60-min intervals during some exposures. Samples were collected by bubbling known volumes of chamber atmospheres through tandem midget impingers containing water. Aliquots from both impingers were analyzed with a Hewlett Packard 5790A gas chromatograph equipped a with a flame ionization detector. Samples were chromatographed isothermally at l25C on a 3' x 2 inn i.d. glass column packed with 80/100 mesh Porapak* Q. The atmospheric concentrations of acetone and ethylene glycol were determined by comparing the detector response of the samples with standard curves* Acetone and ethylene glycol standards were prepared as needed by the quantitative dilution of acetone and ethylene glycol in water. Particle size (mass median aerodynamic diameter and percent particles less than 10 urn) was determined with a Sierra Series 210 cascade impactor during each exposure.1 During each exposure, chamber temperature was measured with a mercury thermometer, relative humidity was measured with a Bendix Model 566 psychrometer, and chamber oxygen concentration was measured with a Biosystems, Inc., Model 3100 oxygen analyzer. l) Company Sanitized. Does not conlasn TSCA CBI Du Pont HLR 624-87 E. Records Retention All raw data and the final report will be stored In the archives of Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware, or In the Du Pont Records Management Center, E. I. du Pont de Nemours and Company, Inc., Wllmlngton, Delaware* RESULTS A. Exposure Conditions and Associated Mortality Chamber temperatures ranged from 22-24C, relative humidity varied from 34-46X, and chamber oxygen concentration was 21%. Atmospheric characterization and associated rat mortality data are summarized in Table I* Atmospheric Concentrations of acetone and ethylene glycol are presented In Tables 2 and 3, respectively. Table 1 Characteri zation ofM^JUBfttmospheres and Associated Rat Mortality Concentration (mg/m3)8 Me^n S.D. Range n 11 10 0.34 - 24 5 21 17 63 39 230 17 0-42 6 1.4 - 96 5 210 - 260 5 I Particles. < 10 urn AD" MMDfumr 95 2.3 94 2.8 99 1.6 97 1.8 Mortality if deaths/1' exposed) 0/6 1/6 4/6 6/6 a Values shown represent the mean, standard deviation (S.D.), range and number L of observations (n) for each exposure. Percent by weight of particles with aerodynamic diameter less than 10 urn. c Mass median aerodynamic diameter. ^ 1^ - 8 "CDl^pgny 'Ssiiitizad.. ^ses r;'-^ '-ort^n T5CA CNI Aerosol Concentration 11 mg/mj 21 mg/m~ 63 mg/m" 230 mg/nr Du Pont HLR 624-87 Table 2 Atmospheric Concentrations of Acetone Mean NM NM 66 150 Acetone Concentration (ppm)J S.P. Range n NM W NM NM NM NM 31 27 - 100 4 19 120 - 160 5 a Values shown represent the mean, standard deviation (S.D.), range and number of observations (n) for each exposure. Table 3 Atmospheric Concentrations of Ethylene GTycol Aerosol Concentration 11 mg/m3 21 mg/m63 mg/m'230 mg/m Ethylene. Glycol Mean S.O. NM NM NM NM NM NM 9.4 5.0 Concentration (ppfl^ ___Range___ n NM NM NM NM NM NM 5.0 - 18 5 a Values shown represent the mean, standard deviation (S.D.), range and number of observations (n) for each exposure. B. Clinical Observations toHiUmat Deaths occurred following exposure tf^^^^^^^S) concentrations of 21, 63 or 230 mg/m . Clinical signs oftoxicity observed either during exposure or upon release from the animal restrainers among rats from these groups included diminished acoustic startle response, compound-covered faces, red nasal or ocular discharges, and labored or rapid breathing. AH deaths occurred within 24 hours of exposure. Rats exposed to 11 mg/m exhibited red nasal and ocular discharges during or immediately after v 9 - Gompany Sanitized. Does not contain TSCA CB( Du Pont HLR 624-87 exposure. With the exception of slight to severe (up to 9% of Initial body weight) weight losses within 24 hours of exposure In some rats, no clinical signs of toxicity were observed during the 14-day recovery period. DISCUSSION AND CONCLUSION Under the conditions of this study, the ALC for ------Jfwas 21 nig/in3. The amounts, of acetane- -and ethylene. glycol detected, uHne^xposure chamber at an aerosol concentration of 230 mg/nr were 150 and 9.4 ppm, respectively. Although extensive Inhalation toxicity data for acetone and ethylene glycol are not available In the literature for comparison, rat deaths have been reported after a 4-hour exposure to 16,000 pom acetone ; no deaths were reported in rats after repeated exposure to ethxiene glycol vapors at approximately 150 ppm for 8 hr/day for 16 weeks . The concentrations of these solvents observed In this study were considerably less than those flIBHHI19 associated with lethality or adverse effects in rats^. Based on the atmospheric concentration of the aerosol, considered to be extremely toxic on an acute Inhalation basi^ALCTess than 80 mg/m ). Calculation described in Sierra Instruments, Inc., Bulletin 7-79-219IM, Instruction Manual; Series 210 Ambient Cascade Impactors and Cyclone Preseparators. y Smyth, H.F., Carpenter, C.P., Meil, C.S., Pozzani, U.C., and Striegel, B.S. Amer. Ind. Hyg. Assoc. J.. 23. 95, 1962. Wiley, F.J., Heuper, W.C., and von Oettlnger, W.F. J. Ind. Hyg. Tox., 18, 123, 1936. - 10 - 'SQlrSBSRySsoWzefr. Ooes :-<oi eon^n TSCA C'31'