Document XRqRx8eKXxKqZnxqb17rj1okJ

AfUlt-oiOG UNION C A R B ID E BUSHY RUN RESEARCH R. D. 4, Mellon Road, Export, Pennsylvania 15632 CENTER Telephone (412) 733-5200 TITLE: T-3607 Acute Inhalation Toxicity Test AUTHOR: Donald J. Nachreiner SPONSOR: 3M Company 3M Center 220-2E-02 St. Paul, MN 55144 INITIATOR: William C. McCormick DATE: December 19, 1984 000062 Bushy Run Research Center A Joint Mellon Institute-- Union Carbide Corporation Operation UNION C A R B ID E BUSHY RUN RESEARCH R. D. 4, Mellon Road, Export, Pennsylvania 15632 CENTER Telephone (412) 733-5200 Project Report 47-527 11 Pages December 19, 1984 T-3607 Acute Inhalation Toxicity Study Sponsor : 3M Company ***** Abstract Five male and five female Wistar albino rats were exposed for four hours to a vapor of T-3607. The actual chamber concentration was 3.74 mg/L (182 ppm). There were no mortalities or clinical signs of toxicity during the exposure or postexposure periods. Mean body weight gain was observed for both sexes during the postexposure period. There were no gross pathologic lesions. The results of this study indicate that the four-hour LC50 for T-3607 is greater than 3.74 mg/L. Objective This study was designed to determine the acute inhalation toxicity to rats resulting from a single, four-hour exposure to T-3607. Materials and Methods This study followed the specific protocol (BRRC Project 84-62-40122) and standard amendment to the protocol prepared by the Bushy Run Research Center. Test Article A two-quart bottle of T-3607 was received on August 9, 1984 from 3M Company (St. Paul, MN), assigned BRRC Sample Number 47-249, and stored In Rooms 109 and 118. Information received from the Sponsor stated the purity to be approximately 100% perfluorooctyl sulfonyl fluoride. An identificaton or CAS Registry Number was not available from the Sponsor. 000063 Bushy Run Research Center A Joint Mellon Institute-- Union Carbide Corporation Operation Report 47-527 Page 2 Animal Species, Source and Husbandry Male and female Hilltop-Wistar albino rats [200-300 g, HLA(WI)BR] (Hilltop Lab Animals, Inc., Scottdale, PA) were used. On the day of exposure the male and female rats were 45 and 59 days of age, respectively. They were received on September 19, 1984, and assigned unique identification numbers by toe-clipping. The rats were housed five per sex in 23.5 x 40.0 x 18.0 cm high stainless steel wire mesh cages on carriers in Room 109 and kept on a 12-hour photoperiod throughout the postexposure period. A layer of Deotized Animal Cage Board* (Shepherd Specialty Papers, Inc., Kalamazoo, MI) was placed under each row of cages. Pelleted feed (Agway Prolab RMH3000 Certified Rodent Chow, Agway Inc., Syracuse, NY) and tap water (Municipal Authority of Westmoreland County, Greensburg, PA) were available ad libitum except during exposure. Inhalation Chamber Design and Operational Characteristics The rats were individually housed in 16.5 x 9.5 x 15.0 cm wire mesh cages and exposed in a 120-liter (approximate volume) cuboidal Plexiglas* chamber in Room 118. Total airflow through the chamber was maintained at approximately 25 liters per minute. The inhalation chamber design and operation are summarized in Table 1. Exposure Regimen Five male and five female rats were exposed once for four hours on September 24, 1984, to a vapor atmosphere of T-3607. No control exposures were performed. Generation of the Test Material The T-3607 was metered with a piston pump (FMI Model RPG-6/Lab Pump Jr. Assembly) into a glass tube containing glass beads used to facilitate evaporation at ambient temperature. The fluid was metered at a rate that would provide a nominal concentration of approximately 5 mg/L. Dry, filtered, compressed air was used to vaporize the test material. The entire chamber airflow (approximately 25 liters per minute) was passed through the evaporation tube. Figure 1 presents a schematic diagram of the generation and exposure system. Air was removed from the chamber via a vacuum line. The exhaust air was filtered through three scrubbing devices each containing approximately two liters of water. Target Concentration The target concentration for this exposure was 5 mg/L, based on the guidelines for "limit" testing set forth by the Toxic Substances Control Act (TSCA). 000064 Report 47-527 Page 3 Chamber Concentration Analysis The concentration of T-3607 in the chamber was measured approximately every 30 minutes. A known volume of air was sampled from the breathing zone of the animals through evacuated flasks supplied by the 3M Company. The flasks containing the atmosphere samples of T-3607 were sent to the Sponsor for analysis of perflurooctyl sulfonyl fluoride. The nominal concentration was determined by dividing the total weight of the test material used by the total volume of air which passed through the chamber during the exposure period. Temperature and Relative Humidity The temperature and relative humidity in the animal housing room were recorded continuously with a seven-day recording hygrothermograph (Cole Parmer Instruments, Chicago, IL). During the exposure the temperature was monitored with a Series 400 A Digital Trendicator (Doric Scientific, San Diego, CA) and the humidity was monitored with a Model 8501 A Humidity Module (Hygrometrix Inc., Oakland, CA). Animal Observation All animals were observed during exposure, and for 14 days following exposure for signs of toxic effects. Body Weights The animals were weighed prior to exposure and on postexposure days seven and fourteen. The change in body weight was calculated by subtracting the pre-exposure values from each successive weight. Necropsy The animals were sacrificed on October 8, 1984. Following methoxyflurane anesthesia, the animals were exsanguinated by severing the brachial blood vessels. A complete necropsy was performed. No tissues were saved. Statistical Procedures The mean and standard deviations of the body weights, body weight changes, and exposure concentrations, were calculated. No statistical comparisons were made. Storage of Records The final report and all raw data are retained in the Archives of the Bushy Run Research Center. 000065 Report 47-527 Page 4 Results Chamber Concentration The mean ( standard deviation) measured concentration of perfluorooctyl sulfonyl fluoride (T-3607 is approximately 100% POSF) in the exposure chamber was 3.74 ( 0.26) mg/L. The individual data for the actual exposure concentrations received from the Sponsor are presented in Table 2. The nominal concentration was 5.2 mg/L. Humidity and Exposure Chamber Conditions The temperature and relative humidity in the animal housing room ranged between 21 and 22C and 43 and 57% respectively, throughout the study period. The mean ( standard deviation) temperature and humidity in the exposure chamber was 26 ( 0)C and 14 ( 5)%, respectively. Animal Observations There were no clinical signs of toxicity observed during the exposure or during the 14-day postexposure period. Mortality No rats died during exposure or during the 14-day postexposure period. Body Weights The individual body weights and body weight changes are summarized in Table 3. Mean body weight gains were observed for both sexes on postexposure days 7 and 14. Necropsy No gross pathologic lesions were found in any animals. Discussion A single four-hour exposure to an actual chamber concentration of 3.74 mg/L T-3607 produced no mortality. There were no clinical signs observed during exposure or during the 14-day postexposure period. Both sexes gained weight during the postexposure period. There were no gross pathologic lesions. The results of this study indicate that the LC50 for T-3607 vapor in Wistar albino rats is greater than 3.74 mg/L. 000066 Project Team D. J. Nachreiner, B.S. M. L. Steel D. R. Klonne, Ph.D. Reviewed and Approved by WPC/rkk/0630B-2 11-19-84 Report 47-527 Page 5 Study Director Senior Technologist Project Manager y flue Donald J. Nachreiner, B.S. Study Director Date L efV v '*---- Dennis R. Klonne, Ph.D. Project Manager I 2 - - l - _W li Date / * /CI . / ^ " 1 *--^ Frd R. Frank, Ph.D. Director Date 000067 Table 1 Inhalation Chamber Design and Operation T-3607 Acute Inhalation Toxicity Test Report 47-527 Page 6 CHAMBER Location: Room 118 Construction; The chamber was made of Plexiglas*. Shape: Cuboldal Dimensions: Height - 0.38 meter Length - 0.61 meter Width - 0.52 meter Total Volume - Approximately 120 liters Airflow Measurement: A Manostat flowmeter, calibrated with a Singer* dry test meter, was positioned in the air supply line to the evaporator tube. Test Article Generation: FMI Model RPG-6/Lab Pump Jr. Assembly; glass evaporator tube containing glass beads; ambient temperature. Chamber Atmosphere Conditions: Chamber Number Nominal Concentration (mg/L) Temperature* (C) Mean SD Relative Humidity** (%) Mean SD Air Flowrate (L/min) 120-1 5.2 26+0 14 5 25 * Determined using a Series 400 A Digital Trendicator. **Determined using a Model 8501 A Humidity Module. WPC/rkk/0630B-2 11-19-84 000068 Table 2 Exposure Concentration Measurements T-3607 Acute Inhalation Toxicity Test Report 47-527 Page 7 Actual Concentrations: Sample Number Time into Exposure (min) Sample Flowrate L/min) Sample Duration (min) POSF* Concentration (mg/L) (ppm) A 55 1 B 65 1 C 115 1 D 125 1 E 175 1 F 185 1 G 210 1 H 215 ' 1 5 3.45 168 5 3.47 169 5 3.65 178 5 3.48 169 5 3.94 192 5 3.87 188 5 3.99 194 5 4.11 200 Nominal Concentration: Target Concentration (mg/L) Exposure Duration (min) 5.0 240 Mean Standard Deviation 3.74 0.26 Chamber Airflow (L/min) 25 Total Mass of T-3607 Used (grams) 31** 182 13 Nominal Concentration (mg/L) 5.2 * The T-3607 samples were analyzed by the sponsor for the concentration of perfluorooctyl sulfonyl fluoride (T-3607 is approximately 100% POSF). ** A volume of 17.2 ml T-3607 was metered. At ambient temperature, 31 grams of T-3607 (17.2 ml*density of 1.8 gm/ml) was vaporized. The density was determined by weighing 10 ml of T-3607. WPC/rkk/0630B-2 11-19-84 000069 Report 47-527 Page 8 Animal Number 84-14763 84-14764 84-14765 84-14766 84-14767 Table 3 Individual Animal Data T-3607 Acute Inhalation Toxicity Test Weight At Day 0 7 14 Body Wt. Change 7 14 Gross Pathology at Necropsy MALES* 241 270 306 246 284 324 253 304 348 245 295 353 258 329 378 29 65 38 78 51 95 50 108 71 120 NGL NGL NGL NGL NGL Mean: Std. Dev.: 249 296 342 7 22 28 48 93 16 22 Mortality Ratio 0/5 Group Observations: No clinical signs were observed during the 4-hr vapor exposure or 14--day postexposure periods. 84-14828 84-14829 84-14830 84-14831 84-14832 FEMALES* 241 266 276 241 243 257 251 263 282 243 256 267 228 249 252 25 2 12 13 21 35 16 31 24 24 NGL NGL NGL NGL NGL Mean: Std. Dev.: 241 255 267 8 10 13 15 26 97 Mortality Ratio 0/5 Group Observations: No clinical signs were observed during the 4-hr vapor exposure or 14-day postexposure periods. NGL " No Gross Lesions Exposure Date : September 24, 1984 *Albino rats [HLA(WI)BR] Hilltop Lab Animals, Inc. , Scottdale, PA were used. WPC/rkk/0630B-3 12-10-84 000070 Figure 1. Vapor Generation and Exposure System T-3607 Acute Inhalation Toxicity Test Fluid Metering Pump &9 m Report 47-527 Page 9 000071 Scrubbing Bottles Report 47-527 Page 10 BUSHY RUN RESEARCH R. D. 4, Mellon Road, Export, Pennsylvania 15632 CENTER Telephone (412) 733-5200 Compliance with TSCA Good Laboratory Practices This study was conducted in accordance with current Toxic Substances Control Act (TSCA) Good Laboratory Practices with the following variation: 1. The Sponsor provided the purity of the test material and indicated that it would be stable for the duration of the study. However, the composition and other characteristics were not available for the testing facility. An identification or CAS Registry Number was not available from the Sponsor. It is the opinion of the study director that these factors did not influence the results or interpretation of this study. WPC/rkk/0500B-l 12-10-84 cPcthuU y yfuthASu- D. J. Nachreiner, B.S. Study Director Date 000072 Bushy Run Research Center A Joint Mellon Institute-- Union Carbide Corporation Operation Report 47-527 Page 11 UNION C A R B ID E BUSHY RUN RESEARCH R. D. 4, Mellon Road, Export, Pennsylvania 15632 CENTER Telephone 1412) 733-5200 Quality Assurance Unit Study Inspection Summary Test Substance: T-3607 Study: Acute Inhalation Toxicity Study Director: D. J. Nachreiner, B.S. The Quality Assurance Unit of BRRC conducted the inspections listed below and reported the results to the study director and to management on the dates indicated. It is the practice of this Quality Assurance Unit to report the results of each inspection to both the study director and management. Inspection Date Type 5-20-83 Standard Protocol 10-2-84 Standard Protocol Amendment 12-4 to 12-5-84 Final Data and Final Report Date QAU Report Issued To Study Director To Management 5-20-83 5-20-83 10-3-84 10-3-84 12-6-84 12-13-84 d* ^ j M // 7A V L. J. Calisti / 'Date Group Leader Good Laboratory Practices/Quality Assurance Bushy Run Research Center 000073 A Joint Mellon Institute -- Union Carbide Corporation Operation