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Bio/dynamics Inc. Division of Biology and Safety Evaluation PROJECT NO. 78-7184 AN ACUTE INHALATION TOXICITY STUDY OF T-2305 coc IN THE RAT Submitted to: 3M Company St. Paul, Minnesota 55101 Attention: Frank Griffith,Ph.D. Date: May 3, 1979 B0 i /dynarnies Inc. 78-7184 1. GENERAL An experiment was performed to investigate the acute inhalation toxicity of a dust of T-2305CoC in rats. The test material, received from 3M Company, was labeled "3M Company; T-2305CoC" and was in the form of a fine white powder. II. EXPERIMENTAL The test material was sieved through a 60-mesh sieve and hand packed into the large diametercylinderof a Wright dust-feedmechanism (gear ratio 1:6). Dry air, at a flow rate of 16.0 litersper minute,was passed throughthe dustfeed mechanism to generate the desired concentration. The resultant dust-laden air was passed, undiluted,into the 32.2-literglass exposurechamberhousing the test animals. The exposurelastedfor 1.0 hour. The packed cylinder,cutting blade, and nozzle were weighed before and after the exposure. The weight loss was equal to the amount of material consumed during the exposure. The nominal concentrationwas determined by dividingthis weight loss by the total air flow throughthe chamberduring the exposure. The test animals consistedof five male and five female SpragueDawley rats obtained from Charles River Breeding Laboratories,Wilmington, Massachusetts. On the day of exposure (Day O-January23, 1979) the preexposure weights ranged from 211 to 264 grams. The animals were observed prior to exposure to insurethat they were free from abnonnalities. Observationsfor abnormal signs were made at 15-minuteintervalsduring the exposure, upon removal from the chamber, hourly for four hours post-exposure, and daily thereafterfor 14 days, -2- B /dynamics Inc 78-7184 Il. EXPERIMENTAL (cont.) Individualbody weightswere recordedon Day 0 (priorto exposure), Day 1, Day 2. Day 4, Day 7, and Day 14 (terminus). On Day 14, all animals were sacrificed (ethlyether)and blood sampleswere drawn from the dorsal aorta of all animals. These sampleswere spun for serum, pooled accordingto sex, and sent to the sponsorpacked in dry ice for analysis. Gross necropsyexaminationswere also perfomed at this time. III. RESULTS AND DISCUSSION During the exposure,a total of 17.90 grams of test materialwas deliveredin a total volumeof 960 litersof dry air, yieldinga nominal exposureconcentrationof 18.6 milligramsper liter. The chamberatmosphere appeared cloudy for the duration-ofthe exposure and the chamberwalls became coatedwith the test material. A second exit tube was added to the exposure chamberafter the first half-hourof the exposure,when the first tube became obstructedwith the test material. Five minutes afterthe exposurewas initiated,all the rats that could be observed through the dust cloud exhibitedexcessive lacrimationand salivation,decreasedactivity,laboredbreathing,and gasping. At ten minutes into the exposure,most of the rats also had their eyes closed. At 20 minutes, some rats exhibited mucoid nasal dischargeand at 30 minutes, some rats exhibited irregularbreathingin additionto all the abnormalitiespreviouslymentioned. Upon removal from the chamber,red nasal discharge(ten of ten), yellow staining of the ano-genitalfur (nineof ten),dry rales (sixof ten),red material aroundthe eyes (fiveof ten),excessivesalivation(fourof ten),excessive lacrimation(.oneof ten),and body tremors(oneof ten)were observedin the rats. Excessivesalivationand lacrimationand body tremorshad abated by the -3- B lo/dynamics Inc 78-7184 III. RESULTS AND DISCUSSION (cont.) one hour post-exposureobservationand the rats did not exhibit red material around the eyes after the two hour post-exposureobservation. Red nasal discharge(tenof ten),yellowstainingof the ano-genitalfur (sixof ten), and dry rales (fiveof ten) were still seen at the four hour post-exposure obs-ervation. During the 14-day observationperiod,excessivelacrimation (sixof ten, one observationeach),excessivesalivation(threeof ten). mucoid nasal discharge(ten of ten),yellowstainingof the ano-genitalfur (fourof ten),dry rales (eightof ten),dry red materialaround'thenose (two of ten), and moist rales (one of ten) were observedin the rats. These observationswere generally scatteredin appearance. Individualbody weights and necropsy observationsare presented in Table 1. Weight gains appearednomal. Necropsy examinationsrevealed lung discolorationin eightof ten rats,which is a higherthan normal incidencethan that which is normallyobserved in Sprague-Dawleyrats in this type of exposure. -4- Blo/dy namics Inc 78-7184 IV. CONCLUSION A one-hour inhalation exposure to a dust of T-2305CoC, at a nominal exposure concentrationof 18.6 milligrams per liter, did not produce mortality in Sprague-Dawley rats. Immediate effects of the test material were excessive lacrimation and salivation, decreased activity, labored breathing, gasping, closing of the eyes, mucoid nasal discharge,irregular breathing,yellow stainingof the ano-genitalfur, and dry rales. The incidenceof the lung discolorationat necropsy indicated a possible residual effect of the material at 14 days post-exposure. George"W- Rusch, Ph.D. Director, Inhalation Technology William E. Rinehart, Sc.D. Vice President, Science Report Preparation: Sandra J. Duckworth, B.A. Table I An Acute InhalationToxicityStudy of T-2305 CoC in the Rat IndividualBody Weights and Necropsy Observations Animal Number Sex Day 0 Bo!k Weights(g) Day z uay 4 Day 7. 10 m 234 210 201 208 222 264 11 m 246 215 205 229 254 303 12 m 248 224 212 233 253 306 13 m 241 205 196 207 236 315 14 m 264 242 234 244 281 328 20 F 232 201 199 233 242 257 21 F 216 204 208 217 229 255 22 F 234 205 199 223 240 240 23 F. 216 201 206 210 223 234 24 F 211 192 196 212 226 237 Necropsy Ob B. lungsmottled red and pi focion all lobes. B. lungsmottled pink and t on all lobes. B. lungs mottled orange and B. lungs mottled orange and B. lungs mottled tan and da and brown foci on all lobes B. lungsmottled pink and t N.O.A. B. lungs mottled orange and B. lungs mottled brown, day N.O.A. N.O.A. - no observed abnomalities Key: R - right;L = left;B = bilateral.