Document N8N5EE4NOkGXr4nQJa61QqVQ

FOR DU FONT USE ONLY AR226-2942 Du Pont HLR 466-89 Study Title Inhalation Approximate Lethal Concentration (ALC) of\ Author Rudolph Valentine Study Completed On September 6, 1989 Performing Laboratory E. I. du Pont de Nemours and Company, Inc. Haskell Laboratory for Toxicology and Industrial Elkton Road. P. 0. Box 50 Newark, Delaware 19714 Medicine Laboratory Project ID Haskell Laboratory Report No. 466-89 Page 1 of 9 Company Sanitized. Does not contain TSCA CBI I Material Tested: Medical Research No. Haskell Ho.: Physical Form; Other Code: Synonyms; GENERAL INFORMATION Du Font HLR 466-89 17.869 White aqueous dispersion Purity: Composition: Stability: Sponsor: 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, Uilmington, Delaware Inc. Cnemicais and Pigments Department E. I. du Pont de Nemours and Company, Jackson Laboratory Deepwater, New Jersey Inc. - 2 - Company Sanitized. Does not contain TSCA CB! Du Font HLR 466-89 GENERALINFORMATION (Cont'd) In-Life Phase Initiated - Completed; 7/13/89 - 8/1/89 Notebook; There are 9 pages in this report. Distrlbutioni 3 - - Company Sanitized. Do&s not conlam T5CA CB1 Du Pont HLR 466-89 Inhalation Approximate Lethal Concentration (ALC) ofj SUMMARY Groups to aerosols atomization Atmospheric of 6nia]eCr1:CDBR rats were exposed for a single, 4-hour of^----B^tn air. Test atmospheres were generated by of the liquid tjst material In a high pressure air stream. concentrations ofU------^were determined by gravimetric period analysis. After exposure, rats were observed for clinical signs of toxiclty during a 14-day recovery period. Deaths occurred following exposure to--------I at atmospheric concentrat+ons^ of590 mg/m or greater; all deaths were post exposure and occurred within 24 hours of exposure. Clinical signs observed iminedic.tely after exposure Included red nasal and ocular discharges, lethargy, and compound-covered faces. During the 14-day recovery period, rats exhibited lethargy, hunched posture, labored breathing, red nasal discharge and wet, yellow stained perineum; these clinical signs had resolved by day 3 post exposure. Although slight to severe weight losses were noted in surviving rats 1 day after exposure, these rats began to regain body weight by day 3 post exposure. flHMI15 Under the conditions of this study, moderately toxic on an acute inhalation basis. considered to be ^^^^^fc^ Work by: C. W. Hutt Technician Study Director: Acute-and Rudolph Valentine, Ph.D. Research Toxicologist Developmental Toxicology Division Reviewed and Approved for Issue: RV:a1r:HLR121.2 V^, \, K. ^ ^ ^ ^/^fey Rudolph Valentine, Ph.D. 4 - Company Sanitized. Does not contain TSCA CB^ Du Font HLR 466-89 QUALITY ASSURANCE DOCUMENTATION B B B H V STUDY: H# 17.869 Inhalation Approximate Lethal Concentration (ALC) AUDITS: Items Audited Protocol, conduct Records, final raport Audit Dates 7/13/89 8/24-25/89 SHORT-TERM AUDIT REPORT NUMBER: ------H DATE FINDINGS REPORTED TO MANAGEMENT AND STUDY DIRECTOR: 8/25/89 Reported by: ^^Wt^-jf.^^^ William J. Lynan Quality Assurance Auditor ^A/f? Date 5. - Company Sanitized. Does nol contain TSCA CB1 INTRODUCTION Du Pont HLR 466.89 m^frtin _____jrpose of this male rats. study was to The ALC was determine a 4-hour Inhalation ALC for 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. -AnimaT Husbandry Young adult male Crl:CD*BR rats were received from Charles River Breeding Laboratories, Raleigh, North Carolina. Each rat was assigned a unique 6-digit 1dent 1 ft elation number which corresponded to a numbered card affixed to the eager Rats were quarantined for approximately one week prior to testing, and were weighed and observed three times 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 jy a slash In the right ear. Prior to exposure, rats' tails and cage cards were color-coded with water-Insoluble markers so that Individual rats could be Identified after exposure. Except during exposure, Purlna Certified Rodent Chow i?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 j_ 2C and relative humidity of 50 + 101. Excursions outside these ranges were judged to have been oT insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Exposure Protocol Groups of 6 rats, approximately 7-8 weeks old and weighing between 242 and 271 grams, were restrained in perforated, stainless steel cylinders with conical nose pieces. The restrainers were inserted into a face plate on the exposure chamber such that only the nose of each rat ofHU^In protruded into the chamber. The ratsj?ere exposed nose-only for a single, 4-hour period to aerosols air. Rats were weighed prior to exposure, and were observed for clinical signs of toxicity during and immediately after exposure. Surviving rats were observed daily; rats were also weighed daily for 14 days post exposure, weekends excluded when warranted by the rats' condition. Company Sanitized. Does not contain TSCA CB1 Du Pont HLR 466-89 C. Atmosphere Generation Aerosol atmospheres of ^----R were generated by atomiration. The test material was metered Into a Spraying Systems nebulizer with a Harvard Model 22 Compact Infusion Pump. Conditioned, filtered houseline air introduced at the nebulizer (approximately 40 L/min) atomized the test material and discharged the resulting aerosol directly Into a 38-L cylindrical glass exposure chamber. Test atmospheres were dispersed with a conical baffle within the chamber to promote uniform distribution. Chamber atmospheres were exhausted through a dry-ice coid trap and a MSA activated charcoal/HEPA cartridge filter prior to discharge into a fume hood. D. Analytical The atmospheric concentration of ^HBB3^050^ was determined by gravimetric analysis during each exposure. Known volumes of chamber atmospheres were drawn through preweighed, Gelman glass fiber (Type A/E) filters at approximately 30-minute intervals. on a Cahn Model 26 Automatic Electrobalance. The filters were weighed The atmospheric concentration of aerosol was calculated from the difference In the pre- and post-sampling filter weights. Since the test material was supplied as an aqueous dispersion, filters were placed in a desiccator after sampling to remove residual water; the aerosol concentrations reported herein are based on the dry filter weights. Particle size (mass median aerodynamic diameter and percent less than 3 and 10 urn) was determined with a Sierra Series 210 cascade impactor during each exposure . Chamber temperature was measured twice per exposure with a mercury thermometer. Chamber oxygen concentration was determined with a Blosystems Model 3100R oxygen monitor once per exposure. Exposure chamber relative humidity was measured once per exposure with a Bel fort Model 566 psychrometer. 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, I-nc., Wilmington, Delaware. Company Sanitized. Does not contain TSCA CB1 RESULTS Du Pont HLR 466-89 A. Exposure Conditions andAssodated Mortality An aerosol of^BJ^Hlwas readily observed during the exposures; during trial runs, the aerosol coated the sides of the exposure chamber, preventing visual observation of the rats. Atmospheric concentrations of f----knd rat mortality data for each exposure are summarized in the Following table. Characterization ofi^l^^^Atmospheres Concentration (ing/m3^_ Mean S.D. Range n 440 130 280 - 660 8 590 220 330 - 940 9 920 210 660 - 1300 7 % Particles11 <3 urn <10 urn 78 96 76 95 79 97 MMD0 (urn) 1.2 1.2 1.2 Mortality (# deaths/fexposed) 0/6 1/6 3/6 a Values shown represent the mean, standard deviation (S.D.), range and number of observations (n) for each exposure. Particle concentrations were based on dry filter weights. Atmospheric concentrations based on wet filter weights obtained immediately after sampling were approximately 3-151 L greater. Percent by weight of particles with aerodynamic diameter less than 3 and 10 urn. Mass median aerodynamic diameter. B, Clinical Observations ofHimon The coating the chamber walls prevented visual observation of the raTsdurTng exposure. Upon release from the restralners Immediately after exposure, rats exhibi-ted lethargy, compound-covered faces, and red nasal and ocular discharges. No rats died during exposure. toff^^ffat Deaths occurred among cats exposed atmospheric concentrations of 590 mg/m or greater; aiTdeathswere post exposure and occurred within 24 hours of exposure. Clinical signs of toxicity observed in surviving rats during the recovery period included lethargy, hunched posture, labored breathing, red nasal discharge, and wet yellow-stained perineum; these clinical signs were transient and had resolved by day 3 post exposure. Surviving rats also had slight to severe weight losses (up to approximately 16% of initial body weight) 1 day after exposure; these rats began to regain weight by day 3 post exposure. Transient, sporadic weight losses were also noted in some rats from the 440 and 590 mg/m groups during the second week of recovery. " 8" Company Sanitized. Does nol contain TSCA CB1 Du Pont HLR 466-89 DISCUSSION AND CONCLUSION Underlhe conditions of this study, the approximate lethal concentration forJHI^^Is 590 mg/m . Based on the measured atmospheric concentration of th test material Is considered to be-moderately toxic on an m^Sv* acute Inhalation basis (ALC between 200 and 800 mg/iii ). Calculation described in Sierra Instruments, Inc., Bulletin 7-79-219IM, Instruction Manual; Serte^ 210 Ambient Cascade Impactors and Cyclone Preseparators.'' 9 - Company Sanffized. Does nol certain TSCACB1