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FOR DU POST USE ONLY AR226-2928 Approximate Lethal Concentration by Inhalation (ALC) of Haskell Laboratory Report No. 279-85 Haskell E. I. du Pont de Nemours and Company Laboratory for Toxicology and Industrial P. 0. Box 50, Elkton Road Newark* Delaware 19714 Medicine Date Issued: May 23, 1985 eoTOpany Sanitized. Does not contain TSCA CBI HLR 279-85 Approxfny:*- Lctlio^ Concentration by Inhalation (ALC) of Sumnary (^.^^BR Groups of 6 male rats were exposed to aerosol atmospheres of W----Pfor asTngTe.4-hour period. Under the conditions of this test, the ALC for ^f----was greater than 1200 mg/m , the highest concentration that could be generated. This material Is considered no worse than slightly toxic by Inhalation. Work by: Study Director: Jig^i^ ft kL^^ Laura A. Kinney Chenilst 57 at/ iS Approved by: hl^^^Q^W^.. Nancy W. Chromey, P|y?D. Section Supervisor Acute Investigations -s-w/rs- LAK:HLR9.7 - 2'- ffp'nipany^ <s,aa"n"i^eS. 15053 no? conta-n '^CA Cl^ Haskell Laboratory Report No. 279-85 Haskell No. 15,590 Material Tested: Sponsor: Textile Fibers Department E. I. du Pont de Nemours and Company Mflmlngton, Del aware Material Submitted by Textile Fibers Department E. I. du Pont de Kemours and Company Kingston, North Carolina Test Facility: E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine P. 0. Box 50, Elkton Road Newark, Delaware 19714 Study Initiated/Completed: 10/18/84 - 11/7/84 There are 7 pages In this report. Distribution; - 3 - '^fflpany Sanitized. Does not contain TSCA C8f INTRODUCTION HLR 279-85 purpose of this study was to determine a 4-hour inhalation ALC for In male rats. The ALC was defined as the lowest atmospheric concentration 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. HATERIALS AND METHODS A. Animal Husbandry Young adult male Cri:CD*(SD)BR rats were received from Charles River Breeding Laboratories, Kingston, New York. Each rat was assigned a unique 6-digit 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 aar. Rats' tails and cage cards were color-coded with water-insoluble markers so that individual rats could be identified after exposure. Except during exposure, Purina Certified Rodent Chow i?5002 and water were available a;d libitum. B. Exposure Protocol Groups of 6 rats, 8 weeks old and weighing between 237 and 268 grams. were restrained in perforated, stainless steel cylinders with conical f f k nose pieces. Each group wa? exposed nose-only for a single, 4-hour period to an aerosol atmosphere in air. Rats were weighed prior to exposure, and were observed for clinical signs during exposure. Surviving rats were weighed and observed daily for 14 days post exposure, weekends and holidays excluded except when deemed necessary by the rats* condition. C. Test Material Physical Form: Purity: Composition: ICofflpanySani"^-Does "ol conla'" w ^ Synonyms; HLR 279-85 Stability: The test material was assumed to be stable throughout the test. D. Atmosphere Generation Aerosol atmospheres of------I------were generated by pumping liquid test material into a Spraying Systems nebulizer. Air introduced at the nebulizer aerosol!zed the test material, and swept the aerosol stream through a cyclone elutnator. The cyclone removed large particles by inertia! impaction, while aerodynamic particles passed through the cyclone and into the exposure chamber. After one exposure, the cyclone was removed in an effort to generate higher atmospheric concentrations. E. Analytical The atmospheric concentration of ^------tf^was determined at approximately 30-minute intervals by drawing calibrated volumes of chamber atmosphere through prewaighed, glass fiber filters. Filters were dried overnight in a desiccator containing Drierite* to remove any residual water from the filters. Filters were weighed on a Cahn model 28 Automatic Electrobalance. The atmospheric concentration of particulate was calculated from the dried filter weight differential before and after sampling. Particle size (mass median aerodynamic diameter and percent respirable) were determined with a Sierra cascade impactor during exposure. During each exposure, chamber temperature was measured mercury thermometer, relative humidity was measured with a Bendix* 566 psychrometer, and chamber oxygen content was measured with a BioMarine Model 225 oxygen analyzer. each with a Model F. Records Retention All raw data and the final report will be stored in the archives of Haskell Laboratory for Toxi alogy and Industrial Medicine, Newark. Delaware, or in the DuPont Hall of Records, E. I. du Font de Nemours and Company, Wilnnngton, Delaware. 5 - Company SanHFzed'. Does not contain TSCA CBt RESULTS HLR 279-85 A. Exposure Conditions and Associated Mortality A mist was visible In the chamber during each exposure. Chamber temperature ranged between 16-23C, relative humidity ranged from 51-861, and chamber oxygen content was 21%. Atmospheric characterization and mortality data are summarized below. Characterization of <_ and Associated ^Atmospheres )rtal1ty Parti cut ate3 Concentration (nig/in'3) Mean S.D. Range 27 650 1200 17 0 - 58 210 300 - 1000 180 1000 - 1500 Respirable' 96 94 96 HHD(um)- 1.2 2.0 2.0 Mortality (# deaths/^ exposed) 0/6 0/6 0/6 Represents the concentration of the active Ingredient only (excluding . water). Percent by weight of particles with aerodynamic diameter less than 10 urn. Mass median aerodynamic diameter. One additional exposure was attempted but not completed because a higher concentration could not be generated. B. Clinical Observations During or immediately following exposure, rats in all groups had red facial discharges, wet perineum and diarrhea. Rats exposed to 650 nig/in and rats exposed to 1200 mg/m had no startle response when the chamber was tapped and had faces stained by the test material. At 1200 rng/m , rats were gasping, lethargic, and limp. During the postexposure period, rats exposed to 27 mg/m and rats exposed to 650 mg/m had minimal weight loss (0-31) one day after exposure. At 1200 mg/m , most rats lost approximately 151 of initial body weight one day after exposure, and 1 rat continued to lose weight for 1 more,day. No adverse clinical signs were observed in rats exposed to 27 mg/m . Rats exposed to 650 mg/m and rats exposed to 1200 mg/n had lung noise lasting up to 2 days post exposure, and hair loss feom the head and nose from the 5th to 14th day post exposure. At 650 mg/m , 1 ^wipariy l^an^ss, "D'-Ses ny? cWain 'fSCA '""' HLR ?79-85 rat had red ocular discharge for 2 days after exposure, and 1 rat had brown nasal discharge during the second week post exposure. At 1200 mg/m , additional clinical signs included gasping, diarrhea, wet or stained perineum, dry red nasal discharge, and stained or discolored fur. The majority of'these signs were observed 1-2 days post exposure. CONCLUSION JUBBR No rats died following exposure to 1200 mc/m of Under the. conditions of this study, the ALC for fHHBUf^as greater than 1200 mg/m' Th's material is considered no worse than slightly toxic by inhalation (ALC bff-.ween 800 and 2000 mg/m ). Calculation described in Sierra Instruments, Inc., Bulletin 7-79-219IM, Instruction Manual: Series ?10 Ambient Cascade Impactors and Cyclone Preseparators. 7- ^^ySan.ffzed.Does '^^^rsc^