Document oDDQKKkQOOw7m0ej3NX4m6Xo7

" v -\ i : 2618. 0800-373 FA<R-1/226-7009964 ORIGINAL oo Sell 2 ne EB) Bio/dynamics Inc. Division of Biology and Safety Evaluation PROJECT NO, 78-7186 mn & EPA-OTS AN ACUTE INHALATION TOXICITY STUDY OF T-2307 CoC IN THE RAT Submitted to: Attention: Date: Minnesota Company St. Paul, Mining and Minnesota Manufacturing] 55101 James E. Long, Sc.D. February 8, 1979 00190 -1- - Mayremiesw : 78-7186 1. 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 2 500-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 plac 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 exposures. The nominal concentrations were calculated by dividing the weight lost by the total air flow through the chambers during the exposures. 000191 -2- ' fweemian 78-7186 11. EXPERIMENTAL (cont.) The test animals consisted of two groups of five male and five female Sprague-Dawley rats obtained from Charles River Breeding Laboratories, Wilmington, 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. 111. RESULTS AND DISCUSSION During the first exposure period (Group 1), a total of 39.98 grams of the test material was delivered in a total volume of 600 1iters 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. 000192 -3- Bay namics 1n . 78-7186 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 1 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 three surviving animals during the 14-day in-1ife period were red nasal discharge (two of three rats), mucoid nasal discharge (three of three rats 00193 a PYaynamies tn 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 ano- genital 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 1 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 intestine: (one of ten rats), stomach discoloration (one of ten rats), and intestinal discoloration (two of ten rats). Abnormalities noted in the Group II (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 lacrimatio (two of ten rats), and yellow staining of the ano-genital fur (nine of ten rats) were observed. These signs were also observed in the rats 600194 - : "ge OOO OO aymamicem 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. 00195 -6- . 78-7186 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 1) yielded a nominal test material exposure concentration of 66.63 milligrams per liter. 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-exposu 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 I, would appear to be indicative of a residual effect of the test material exposure. V2or yp A cecikens George M. Rusch, Ph.D. Director, Inhalation Technology Written by: Ilona R. 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