Document NGn6DnzpbKY4a90mnMxaoLR2R

Bio)/dynamics Inc. Divisionof Biology and Safety Evaluation PROJECT NO, 78-7186 AN ACUTE INHALATION TOXICITY STUDY OF T-2307 CoC IN THE RAT Submitted to: Minnesota Mining and Manufacturing Company St. Paul, Minnesota 55101 Attention: James E. Long, Sc.D. Date: February 8, 1979 B0 /dynarnies Inc. 78-7186 I. GENERAL An experiment was performed to assess the acute inhalation toxicity of a dust of T-2307 CoC in Sprague-Dawley rats. The test material, received from the Minnesota Mining and Manufacturing Company, was labeled "3M Company, T2307CoC," and was in the form of a fine, yellow-orange powder. II. EXPERIMENTAL Two test material exposures were performed. For the first exposure, the test material was placed in a 500-milliliter, threeneck flask, fitted with a stir bar. For the second exposure, the test material was sieved through a 60-mesh sieve and placed in a 1000-milli- liter, three-neck flask, fitted with a stir bar. The flasks were placed on a magnetic stir plate to provide constant agitation of the test material during the exposure periods. Dry air, at the flow rate of 10 liters per minute, was passed through the test material, and the resulting dust-laden airstream was directed into a 26.5-liter glass exposure chamber containing the test animals. The exposures lasted for one hour. The flasks containing the test material were weighed before and after the respective exposure periods. The differences in weight were equal to the amounts of material consumed during the ex- posures. The nominal concentrations were calculated by dividing the weight lost by the total air flow through the chambers during the exposures. -2- B io/dynamics Inc. 78-7186 ii. EXPERIMENTAL (cont.) The test animals consisted of two groups of five male and five female Sprague-Dawley rats obtained from Charles River Breeding Laboratories, Wilmingtong Massachusetts. On the days of exposure (Day 0 - 10/4/78 and 10/12/78), the pre-exposure weights ranged from 200 to 297 grams. The basic health status of the test animals was established by a pre-exposure examination. The animals were observed for abnormalities at 15-minute intervals during the exposure period, upon removal from the chamber, hourly for four hours post-exposure, and daily thereafter for 14 days. Individual body weights were recorded prior to exposure on Day 0 and on Day 1, Day 2 (Group I only), Day 3 (Group II only), Day 4, Day 7 and Day 14 (terminus). On Day 14, all survivors were sacrificed (ethyl ether) and gross necropsy examinations were performed. All animals dying spontaneously were examined by gross necropsy as soon as possible after death. III. RESULTS AND DISCUSSION During the first exposure period (Group I), a total of 39.98 grams of the test material was delivered in a total volume of 600 liters of dry air, yielding a nominal exposure concentration of 66.63 milligrams per liter. During the second exposure period (Group 11), 13.33 grams of the test material was delivered in the same volume of dry air, yielding a nominal exposure concentration of 22.22 milligrams per liter. Bio/dynamics 78-7186 Inc. III. RESULTS AND DISCUSSION (cont.) After 32 minutes of the Group I exposure, the chamber atmosphere remained static for a short period of time (less than five minutes) while the delivery flask was refilled with test material. Abnormalities noted in the Group I animals throughout the exposure period were mucoid nasal discharge, excessive lacrimation, and excessive salivation. Squinting or closing of the eyes was observed from 30 minutes of exposure through exposure termination. Chromodacryorrhea was observed in one animal at exposure termination. Signs observed in the Group I animals upon their removal from the exposure chamber were excessive lacrimation (eight of ten rats), excessive salivation (one of ten rats), chromodacryorrhea (two of ten rats), mucoid nasal discharge (three of ten rats), and dry rales (one of ten rats). These signs were also observed sporadically during the four hourly post-exposure observation intervals. Seven of ten rats from Group I died during the 14-day observation period. Pre-death signs in these animals were mucoid nasal discharge (five of seven rats), red nasal discharge (five of seven rats), dry rales (one of seven rats), excessive lacrimation (one of seven rats), excessive salivation (one of seven rats), labored breathing (five of seven rats), yellow staining of the ano-genital fur (seven of seven rats), brown staining of the ano-genital fur (one of seven rats), reduced activity (seven of seven rats), poor general condition (seven of seven rats), spasms (one of seven rats), coldness of the body (two of seven rats), brown nasal discharge (one of seven rats), hair loss (one of seven rats), and rapid breathing (one of seven rats). Signs observed in the th,*-ee-su rv iv ing an imal s duri ng the 14-day in-1 ife period were red nasal discharge (two of three rats), mucoid nasal discharge (three of three rats)- -4- B lo/dynarnics Inc. 78-7186 III. RESULTS AND DISCUSSION (cont.) excessive lacrimation (two of three rats), dry rales (one of three rats), labored breathing (three of three rats), yellow staining of the ano-genital fur (three of three rats), brown staining of the anogenital fur (two of three rats), reduced activity (three of three rats), poor condition (three of three rats), spasms (one of three rats), loss of righting reflex (one of three rats), rapid breathing (one of three rats), and pilo erection (one of three rats). Individual body weights and necropsy observations of the Group I animals are presented in Table I. Animals dying during the study lost weight steadily prior to death. Two of three surviving rats also exhibited steady weight losses. One male rat (#14), however, was gaining weight by termination of the study. Necropsy observations of the Group I animals were liver discoloration (nine of ten rats), lung discoloration (six of ten rats), adrenal discoloration (one of ten rats), adrenal enlargement (two of ten rats), gaseous distention of the stomach (three of ten rats), gaseous distention of the intestines (one of ten rats), stomach discoloration (one of ten rats), and intestinal discoloration (two of ten rats). Abnormalities noted in the Group 11 (22.22 mg/1) rats during the exposure period were excessive lacrimation, excessive salivation, squinting or closing of the eyes, mucoid or red nasal discharge, and/or labored breathing. Upon removal of the animals from the exposure chamber, dry rales (three of ten rats), mucoid nasal discharge (two of ten rats), excessive salivation (one of ten rats), excessive lacrimation (two of ten rats), and yellow staining of the ano-genit.al.-fu(.nri--h-oef ten rats) were observed. These signs were also observed in-the rats B0 i /dynamics Inc. 78-7186 III. RESULTS AND DISCUSSION (cont.) during the four hourly post-exposure intervals. Other signs observed sporadically during those intervals were labored breathing and reduced activity. Observations made during the 14-day in-life period were dry rales (seven of ten rats), mucoid nasal discharge (seven of ten rats), rapid breathing (two of ten rats), yellow staining of the ano-genital fur (eight of ten rats), brown staining of the ano-genital fur (two of ten rats), orange staining of the ano-genital fur (two of ten rats), reduced activity (two of ten rats), pilo erection (one of ten rats), hair loss (one of ten rats), coldness of the body (two of ten rats), and generally poor condition (ten of ten rats). Individual body weights and necropsy observations of the Group II animals are presented in Table II. All Group II rats experienced weight loss following exposure to the test material. Though weight gains were retarded, all male rats exceeded their Day 0 body weights by termination of the study. None of the female rats recovered their original weights by Day 14, though three of five females were gaining weight by the end of the study. Necropsy observations of these animals revealed lung discoloration in eight of ten rats. -6- Bio/dynamics 78-7186 Inc. IV. CONCLUSION A pair of exposures were performed on Sprague'-Dawley rats to determine the acute inhalation toxicity of different concentrations of a dust of T-2307 CoC. The first exposure (Group I) yielded a nominal test material exposure concentration of 66.63 milligrams per I.iter. Seven of ten animals of this group were dead by Day 10 of the study. The second exposure (Group II) yielded a nominal exposure test material concentration of 22.22 milligrams.per liter. There was no mortality in the second group.. However, all animals exposed to the test material in this study displayed a definite response to their exposure to the dust of T-2307 CoC. In-life observations showed the animals to be in.poor condition following the exposure and post-exposure weight gains were markedly depressed. Necropsy examination of the Group I animals revealed liver discoloration in nine of ten rats, marked lung discoloration in six of ten rats and adrenal enlargement in two of ten rats. The main findings on necropsy of Group II animals after 14 days was lung discoloration in eight of ten rats. These findings, especially in Group 1, would appear to be indicative of a residual effect of the test material exposure. George M. Rusch, Ph.D. Dirqttor, Inhalation Technology Written by: Ilona R. Jupina William E. Rinehart, Sc.D. Vice President, Science - Table I An Acute InhalationToxicity Study of T-2307 CoC in the Rat IndividualBody Weights and Necropsy Observations Group I - 66.63 mg/l Animal Number Sex Day 0 Bodv Weights (q) 1 Day 2 Day 4 Day 7-Day 14 10 m 248 221 207 195 Deadb 11 m 270 242 226 209 Dead a 12 m 297 273 260 241 245 216 c 13 m 269 251 247 228 197 Dead 14 m 297 271 267 257 202 236 20 F 208 198 194 173 149 Dead c 21 F 206 194 187 185 183 179 22 F 234 207 199 184 172 Dead d 23 F 228 215 208 183 163 Dead e 24 F 238 220 205 194 175 Deade N.O.A. no observed abnormalities. Key:i R right;L = left;B = bilateral. Spontadeous death Day 6. Spontaneous death Day 7. c Spontaneous death Day 8. d Spontaneous death Day 9. e Spontaneous death Day 10. Necropsy Obse B. lungsred in color. Li red. Stomach distendedv B. lungsred in color. Li red. All lobesof livermottle B. lungs red in color. Al mottled red and grey. All lobesof livermottle B. lungs red in color. Al red with tan and grey pa larged in appearance and N.O.A. R. lobe of liver mottled adrenalsenlarged (1.5 x appearance. B. lungsred in color. A normallydark red in col with gas. Smallintesti distendedwith gas. B. lungsred in color. A normallydark red in col yellow in color,distend intestinesyellow in col Table 11 An Acute InhalationToxicityStudy of T-2307 CoC in the Rat Individual Body Weights and Necropsy Observations Group II - 22.22 mg/l Animal Body Weights (g) Number Sex Day 0 -Day I Day 3 Day 4 Day 7 Day 4 Necropsy Obs 30 m 281 253 265 256 250 291 Scatteredred foci on B. 31 m 288 266 255 258 272 301 B. lungs mottled pink and grey foci. 32 m 266 238 234 237 246 272 B. lungs mottled tan and grey foci. 33 m 276 267 262 260 265 282 B. lungs mottled pink and grey foci. 34 m 282 275 277 274 284 314 Scattered red and grey fo 40 F 214 207 200 194 189 202 Scatteredred foci on B. 41 F 206 179 175 175 177 169 B. lungs mottled pink and 42 F 200 196 196 188 188 187 N.O.A. 43 F 224 219 222 210 220 220 N.O.A. 44 F 207 182 179 175 164 195 B. lungs mottled pink and N.O.A. no observed abnormalities. Key: R right;L left;B bilateral.