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FOR DU POST USE ONLY AR226-2928 Approximate Lethal Concentration by Inhalation (ALC) of Haskell Laboratory Report No. 279-85 E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine P. 0. Box 50, Elkton Road Newark, Delaware 19714 Date Issued: May 23, 1985 Company Sanitized. Does noi contain TSCA CBI Hl 279-85 Approxfm/:^, Utno' Concentration by Inhalation (ALO of Sunna ry Groups of 6 male Crl :CD*{SD)BR rats were exposed to aerosol atmospheres of for a single, 4-hour period. Under the conditions of this test, the ALC for ^ P P M B w a s greater than 1200 mg/m, the highest concentration that could be generated. This material is considered no worse than slightly toxic by inhalation. Technician Study Director: ft i\L Laura A. Kinney ' Chemist S/S/ S Approved Section Supervisor Acute Investigations LAK:HLR9.7 -2 ioi contain TSCA. Haskell Laboratory Report No. 279-85 Haskell No. 15.590 Material Tested: Sponsor: Textile Fibers Department E. I. du Pont d Nemours and Company Wilmington, Delaware Material Submitted by: Textile Fibers Department E. I. du Pont de Nemours 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 Distribution: > 3 Company Sanitized. Does not contain TSCA C8i '` INTRODUCTION HLR 279-85 ^ T h ^ u r p o s e of this study was to determine a 4-hour inhalation ALC for i H i 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. MATERIALS AND METHODS A. Animal Husbandry Young adult male Crl: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 ear. 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 #5002 and water were available ad 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 nose pieces. Each group wap 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: ICernpanySanitized. Does noi contain --4 Synonyms ; HLR 279-85 CAS Registry No.: Stability: The test material was assumed to be stable throughout the test. D. Atmosphere Generation Aerosol atmospheres of V H I w e r e generated by pumping liquid test material into a Spraying Systems nebulizer. Air introduced at the nebulizer aerosolized the test material, and swept the aerosol stream through a cyclone elutriator. The cyclone removed large particles by inertial 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 ^ ^ H l B R w a s determined at approximately 30-minute intervals by drawing calibrated volumes of chamber atmosphere through preweighed, 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 respirablj) were determined with a Sierra* cascade impactor during each exposure. During each exposure, chamber temperature was measured with a mercury thermometer, relative humidity was measured with a Bendix* Model 566 psychrometer, and chamber oxygen content was measured with a BioMarine Model 225 oxygen analyzer. . Records Retention ' All raw data and the final report will be stored in the archives of Haskell Laboratory for Toxi ology and Industrial Medicine, Newark, Delaware, or in the DuPont Hall of Records, E. I. du Pont de Nemours and Company, Wilmington, Delaware. " 5 - CWpny Saniffzetf. Does not conialo TSeA eB t RESULTS HLR 279-85 A. Exposure Conditions and Associated Mortality A mist was visible 1n the chamber during each exposure. Chamber temperature ranged between 16-23C, relative humidity ranged from 51-86%, and chamber oxygen content was 21%. Atmospheric characterization and mortality data are summarized below. Characterization of< < M M M | | Atmospheres and Associated Ra^MortaTity Particulate3*6 - Concentration (mg/m3 ) Mean S.D. Range % Respirable^ 27 650 1200 17 0 - 58 210 300 - 1000 180 1000 - 1500 96 94 96 MMD(um)c 1.2 2.0 2.0 Mortality (# deaths/# exposed) 0/6 0/6 0/6 3 Represents the concentration of the active ingredient only (excluding water). c 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 mg/m3 and rats exposed to 1200 mg/m3 had no startle response when the chamber was tapped and had faces stained by the test material. At 1200 mg/m3, 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 (0-3%) one day after exposure. At 1200 mg/m , most rats lost approximately 15% 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 550 mg/m3 and rats exposed to 1200 mg/m3 had lung noise lasting up to 2 days post exposure, and hair loss fnom the head and nose from the 5th to 14th day post exposure. At 650 mg/m , 1 6Kaftiihaii, 'Does ny? contain T;y'A C 1?' HLR 279-85 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 No rats died following exposure to 1200 mg/m of Under the~ conditions of this study, the ALC for greater than 1200 mg/m . This material is considered no worse than slightly toxic by inhalation (ALC between 800 and 2000 mg/m ). Calculation described in Sierra Instruments, Inc., Bulletin 7-79-219IM, Instruction Manual: Series 210 Ambient Cascade Impactors and Cyclone Preseparators. rriS\ I | j 1 e ij 5 i !i li I S S 2