Document oMooVe78Oj6Q7xp5NXYNEdJxX

-f y T -o r o o . n i l Attachments to Letter to C. Auer dated May 18,2000 ( g i O O O O O O O l O ) Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds dR lW rC tfH I 8. N-EtFOSE alcohol N-ethyl perfluorooctane sulfonamidoethanol Acute Toxicity 1) Corrected Final Report, Acute Inhalation Toxicity Study in Rats, 3M Reference No. T-2991IT, Hazelton Laboratories America, Inc., Study No. 154-157, February 2, 1981 Genotoxicitv 1) Final Report, Mutagenicity Test on T-5710 in an In Vivo Rat Micronucleus Assay, Hazelton Washington, Inc., Study No. 15516-0-454, April 23, 1993 2) Final Report, Genotoxicity Test on T-5710.1 in the In Vivo/In Vitro Unscheduled DNA Synthesis and Cell Proliferation in Rat Liver Cells, Hazelton Washington, Inc., Study No. 15516-0-494, September 14, 1993 3) Final Report, Mutagenicity Test on T-6292 in an In Vivo Mouse Micronucleus Assay, Hazelton Washington, Inc., Study No. 17384-0-455, May 2, 1996, with Protocol and Protocol amendments 4) Evaluation of the Mutagenic Activity of T-6906 in an In Vitro Mammalian Cell Gene Mutation Test with L5178Y Mouse Lymphoma Cells, NOTOX Study No. 223458, 3M Reference No. FM-3923 a) Final Report, December 22,1998 (see letter below) b) Letter from Steve R. Haworth, Ph.D., Covance Laboratories, reviewing the NOTOX study and concluding it was technically inadequate and should be repeated Note: 3M is repeating the study Repeated-Dose Toxicity 1) Final Report, Ninety Day Subacute Rat Toxicity Study on FM-3422, International Research and Development Corporation, Study No. 137-086, November 10, 1978 - 13 - 001247 Attachments to Letter to C. Auer dated May 18,2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds 2) Final Report, Ninety Day Subacute Rhesus Monkey Toxicity Study, on FM-3422, International Research and Development Corporation, Study No. 137-088, January 16, 1979 3) Two-Year Dietary Study a) Report, Volumes 1-5, Two Year Oral (Diet) Toxicity / Carcinogenicity Study of Fluorochemical FM-3924 in Rats, Riker Laboratories, Inc., Study No. 0281CR0012, August 29, 1987, Conducted during April 1981 - May 1983 b) Report Amendment No. 1, Two Year Oral (Diet) Toxicity / Carcinogenicity Study of Fluorochemical FM-3924 in Rats, Riker Laboratories, Inc., Study No. 0281CR0012, October 25, 1988 c) Xenos Letter dated May 24, 1991 with attachment: 3M Response to FDA Letter of December 10, 1990 [re 2 year cancer study], Food Additive Petition Nos. 0B4197 and 0B4206 d) Pathology Review of Reported Tumorigenesis in a Two Year Study of FM-3924 in Rats, Pathology Associates International, November 25, 1998 e) Analytical on retained sample f) Review by Dr. William H. Butler of Two Year (Diet) Toxicity / Carcinogenicity Study of Fluorochemical FM 3924 in Rats 4) Ongoing 2-Year Study a) Summary Report of Week 53,104-Week Dietary Carcinogenicity Study with Narrow Range (98.1%) N-Ethyl Perfluorooctanesulfanoamido Ethanol in Rats, 3M Reference No. T-6316.1, Covance Laboratories, 6329-212 and-228 (draft final report expected fall 2000) Pharmacokinetic Studies 1) Synthesis and Characterization of N-Ethyl FOSE 14C, Riker Laboratories, March 17, 1981 2) Final Report, Absorption and Biotransformation of N-Ethyl FOSE and Tissue Distribution and Elimination of Carbon-14 after Administration of N-Ethyl FOSE 14C in Feed, Riker Laboratories, Inc., January 19, 1983 - 14- 001248 Attachments to Letter to C. Auer dated May 18,2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds Previously submitted with May 4, 2000 letter --Qualitative Investigation of the In Vitro Metabolism of T-6292 (n-ethyl FOSE), T-6293 (n-ethyl FOSE phosphate diammonium salt(ester)), T-6294 (n-ethyl perfluorooctane sulfonamide) and T-6295 (perflurooctane sulfonate) by Rat and Human Hepatocytes Using Ion Spray LC/MS and LC/MS/MS, Advanced Bioanalytical Services, Inc., [Preliminary] Analytical Report, Report 96ADEM01.3M, November 12, 1996 Previously submitted with May 4, 2000 letter - Advanced Bioanalytical Services, Inc., Analytical Report, Additional Characterization of Metabolites of T-6292, T-6293 and T6294 from Rat and Human Hepatocytes by TurboIonSpray LC/MS and LC/MS/MS. Semi-Quantitative Analysis of T-6295 in Rat and Human Hepatocytes Incubated with T6292, T-6293 and T-6294 by LC/MS/MS, January 28, 1998, Report 98AGKP01.3M Mechanistic 1) Final Report, Analysis of T-5877 in a Cell Proliferation Assay in Rat Liver Cells, Hazelton Washington, Inc., Study No. 154-208, 3M Reference T-5877 (wide range ethyl FOSE), FM-3924, Lot 547, L-13202, November 1, 1994, with Protocol and Protocol Addendum, Key to FC Alcohol Tox Samples (including 5877), and Analytical data Teratology 1) Oral (Gavage) Developmental Toxicity Study of N-EtFOSE in Rats a) Final Report, Oral (Gavage) Developmental Toxicity Study of N-EtFOSE in Rats, 3M Reference No. T-6316.7, December 17, 1998 b) Summary N-Etfose Rat Teratology, Oral (Gavage) Developmental Toxicity Study of N-EtFOSE in Rats, 3M Reference No. T-6316.7 2) Oral (Stomach Tube) Developmental Toxicity Study of N-EtFOSE in Rabbits a) Final Report, Oral (Stomach Tube) Developmental Toxicity Study of N-EtFOSE in Rabbits, 3M Reference No. T-6316.8, January 11, 1999 b) Summary N-EtFOSE Rabbit Teratology, Oral (Stomach Tube) Developmental Toxicity Study of N-EtFOSE in Rabbits, 3M Reference No. T-6316.8 3) Teratology Studies of T-2999 (FM-3924) in Rabbits - 15 - 001249 Attachments to Letter to C. Auer dated May 18,2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds a) Final Report, Oral Rangefinder Study of T-2999CoC in Pregnant Rabbits, Safety Evaluation Laboratory, Riker Laboratories, Inc., Study No. 0680RB0019, June 25,1981 b) Final Report and Protocol, Oral Teratology Study of T-2999CoC in Rabbits, Safety Evaluation Laboratory, Riker Laboratories, Inc., Study No. 0681TB0212, 3M Reference No. FM 3924 (88% ethyl FOSE), January 7, 1982 c) 3M Internal Correspondence re alcohols being used in Riker studies, from DR Ricker to WC McCormick, dated December 10, 1980 d) Analytical Analyses of Suspension of FM-3924, Internal Memo, from TR Mathisen to EG Gortner, dated April 8, 1981 e) 3M Internal Correspondence, Analytical Evaluation of FM-3924, dated June 22, 1982 4) Oral Teratology Study of FM-3422 in Rats a) Final Report, Oral Teratology Study of FM-3422 in Rats, Safety Evaluation Laboratory, Riker Laboratories, Inc., Study No. 0680TR0010, January 22,1981 b) 3M Internal Correspondence re alcohols being used in Riker studies, from DR Ricker to WC McCormick, dated December 10, 1980 5) Teratology Studies of T-2999CoC (FM-3924) in Rats a) Final Report, Special Lens Oral Teratology Study of T-2999CoC in Rats, Safety Evaluation Laboratory, Riker Laboratories, Inc., Study No. 0680TR0020, 3M Reference No. FM-3924, December 22,1981 b) Final Report and Protocol, Special Lens Oral Teratology Study of T-2999CoC in Two Strains of Rats, Safety Evaluation Laboratory, Riker Laboratories, Inc., Study No. 0681TR0362, July 20, 1982 c) 3M Internal Correspondence re alcohols being used in Riker studies, from DR Ricker to WC McCormick, dated December 10, 1980 d) Analytical Analyses of Suspension of FM-3924, Internal Memo, from TR Mathisen to EG Gortner, dated April 8, 1981 e) 3M internal correspondence re analytical analysis of FM-3924, from EG Gortner to RM Payfer, dated June 22, 1982 - 16- 001250 Attachments to Letter to C. Auer dated May 18,2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds 6) Memo from EG Lambrecht to Riker Study Files re Fetal Lens Artifact -- Summary of Developments to Date, dated November 6, 1981 Previously submitted to TSCA 8e docket, Final Report, Combined Oral (Gavage) Fertility, Developmental and Perinatal/Postnatal Reproduction Toxicity Study of N-EtFOSE in Rats, 3M Reference No. T-6316.5, June 30, 1999 Note: weight gain effects in Fi generation currently being reanalyzed. Report may require amendment. Studies In Progress 1) Protocol, N-EtFOSE Bile Method Development in Rats, 3M Strategic Toxicology Laboratory, Study No. T-6316.15; ST-30, In-Life Start Date August 12, 1999, In-Life End Date August 20, 1999 2) Protocol, Feces Method Development Metabolism Study for Perfluorooctanesulfonate Derivatives [N-EtFOSE, PFOS, and FOSA], 3M Strategic Toxicology Laboratory, Study Nos., T-636.17; T-6295.21; T-7132.3; ST-41, In-Life Start Date November 22, 1999, In-Life End Date November 24, 1999 3) Protocol, Cell Proliferation Study with N-Ethyl Perfluorooctanesulfonamido Ethanol (N-EtFOSE; 3M T-6316.11), Perfluorooctane Sulfonic Acid Potassium Salt (PFOS; 3M T-6295.16), and N-Ethyl Perfluorooctanesulfonamide (PFOSA 3M T-7091.1) in Rats, Pathology Associates International, Study No. 1132-100 Pre-1976 Studies (bibliography only) 1) Final Report, Oral LD 50 (4 levels), 3M Reference No. T-961, WARF Institute, Inc., Study No. 4043911, June 12, 1974 2) Final Report, Acute Vapor Inhalation Toxicity Study in Rats, 3M Reference No. T1260, Industrial Bio-Test Laboratories, Inc., July 21, 1975 3) Final Report, Acute Vapor Inhalation Toxicity Study in Rats, 3M Reference No. T1259, Industrial Bio-Test Laboratories, Inc., July 21, 1975 4) Final Report, Skin and Eye Irritation Study, WARF Institute, Inc., Study No. 5060080, 3M Reference No. T-1260, June 17, 1975 5) Final Report, Skin and Eye Irritation Study, WARF Institute, Inc., Study No. 5060079, 3M Reference No. T-1259, June 17, 1975 - 17- 601251 CORRECTED ^ FINAL REPORT ACUTE INHALATION TOXICITY STUDY IN RATS T-2991IT Submltted to 3M COMPANY February 2, 1981 HAZLETON L A B O R A T O R IES A M ERICA . INC. 8 8 0 0 L E E S S U R G TURNPIKE. VIENNA. VIRGINIA 8 8 1 8 0 . U 9 A 001252 H A Z L E zT Q lM LABORATORIES AMERICA, INC. SPO N SO R : 3M COMPANY D A T E : February 2, 1981 M A T E R I A L : T-2991IT SU B JECT: FINAL REPORT Acute Inhalation Toxicity Study in Rats Project No. 154"157 I. SUMMARY The test material, T-2291IT, was evaluated for acute inhalation toxicity in rats. Exposure to the test material for four hours at a nominal concentration of 6.57 mg/liter caused sniffing and preening. After 60 minutes of pressure, all animals appeared normal and remained so until the end of the study. Most exposed animals lost weight by post-exposure Day 1, but subsequently recovered. All animals gained weight by the end of the study. Gross pathology findings at necropsy revealed a higher incidence of lung lesions in exposed males, but there were no consistent findings indicative of a compound-re lated effect. Microscopic examination of fixed lungs, livers, kidneys and all grossly abnormal tissues also failed to reveal com pound-related histomorphologic changes. II. OBJECTIVE The purpose of this study was to assess the acute inhalation toxicity in rats to a single 4-hour exposure to T-2991IT in conformance with proposed FIFRA guidelines (40 CFR Section 163-81-3 August 22, 1978). The study was initiated November 25, 1980, and terminated December 10, 1980. OOi^Sa 154-157 HAZLETON L A B O R A T O R IE S A M ERICA . INC. III. MATERIALS AND METHODS A. Test Material The test material, T-2991IT, a yellow liquid, was received November 19, 1980, and stored at room temperature. Information on the methods of synthesis, sta bility, as well as data on composition or other characteristics which define the test material are on file with, the sponsor. B. Animals and Animal Care* A total of 20 healthy appearing rats, equally divided by sex, of the Sprague-Dawley descended strain, obtained from Charles River Breeding Labora tories, Inc., Wilmington, Massachusetts, were selected from a stock pool of 2*. Animals not selected for study were returned to the stock pool. The animals ranged in weight from 228 to 335 grams when selected, and had been quarantined for at least 19 days prior to selection. Throughout the study, the animals were individually housed in stainless steel wire-mesh cages with food (Purina Lab Chow # 5 0 0 0 and water (via automatic lick valves) available ad 1ibiturn except during exposure. A 12/12-hour light/dark cycle (6:00 A.M. to 6:00 P.M.) was maintained by automatic timer throughout the study. The exposure was conducted during the light phase. Rats were used in this study because they have histori cally been used in safety evaluation studies and are required by FI FRA regulations C. Groups The selected 10 animals per sex were assigned to two equal-sized groups by use of a table of random permutations of 16 (Cochran, W.G., and Cox, G.M., Experimental Designs, 1957) as follows: * These animals were maintained in animal care facilities fully accredited by the American Association for Accreditation of Laboratory Animal Care. - 2- 001*254 154-157 HAZLETON L A B O R A T O R IE S A M ERICA , INC. Group No. Humber/Sex Treatment Target Nominal Concentration 1 5 Air Control 2 .5 5.0 - 5.5 mg/L 0. Exposure Conditions Group 2 was exposed to T-2991 IT aerosol in a 100-liter glass and stainless steel chamber operated dynamically at a constant airflow of 16 .7 1 iters/minute. Group 1 was "exposed11 In a chamber to air only. The compound was generated for 240 minutes as an aerosol by use of a Solo Sphere nebulizer at an aspirator setting of 100? and operated at an airflow of 3*5 1 iters/minute. The aerosol was introduced into the turret top of the chamber with make-up air at 13-2 1iters/minute. The exposure was 4.0 hours in duration (plus 30 minutes to allow for chamber purging). E. Exposure Monitoring 1 . Aerosol Concentration a. Nominal: The nominal concentration of the exposure was calculated by dividing the total weight of T-2991IT aerosolized by the total volume of air passing through the chamber during aerosol generation. b. Gravimetric: During exposure to T-2991IT, samples were collected on Gelman Hetricel DM-450 filters via a probe extended to the approximate breathing zone of the rats. A sampling rate of 10 1iters/minute was used. Four 15-minute samples were drawn, starting at 60, 115, 170, and 225 minutes after exposure initiation. Weight gain on each filter divided by total volume of air sampled (150 liters) was used to cal culate each gravimetric concentration. - 3- OOi-iSS 154-157 HAZLETON LABORATORIES A M ERICA IN C CORRECTED lV ?* / c. Analytical: The above Gelman DM-450 filters were shipped in sealed glass vials, packed on dry ice in air-tight packages, to the sponsor for determination of the weights of active material collected. 2. Particle Size Distribution: Prior to and twice during exposure, samples were collected with Andersen 4-stage Mini-Sampler cascade impactors in order to determine the aerodynamic particle size (mass) distribution of the nonvolatile component of the aerosol in the chamber at the rat's breathing zone. Samples were obtained starting at 60 and 170 minutes after exposure initiation for 15-minute durations. A sampling rate of 1.4 11ters/minute was used. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (eg) of the mass distribution was obtained graphically after converting the dry weight gains on each stage and backup filter to cumulative percentages of total weight collected and plotting these against the stage cutoffs (in microns) on log-normal (probit) paper. Values at the 50th and 84/50th (or 50/l6th) percentile were taken as the mass median aerodynamic diameter and geometric standard deviation, respectively. 3. Temperature and Relative Humidity (R.H.); Temperature and R.H. in the con trol chamber were measured with an Abbeon Model M2A4B temperature and R.H. gauge and recorded every 30 minutes. Temperature and R.H. in the chamber varied from 69F to 75F and 45? to 53? respectively. F. Biological Observations 1. Toxic Signs: Continuously during exposure and twice daily for 14 days post exposure, all animals were observed for signs of toxicity, abnormal behavior, or unusual appearance. Noteworthy changes were recorded. 2. Body Weight; All animals were weighed and body weights recorded prior to exposure and on Days 1, 2, 3 4, 7 and 14 post-exposure and prior to necropsy. - 4- 001256 HAZLETON LA B O R A TO R IES A M ERICA . INC. 154-157 CORRECTED G. Necropsy All animals were killed on Day 15 post-exposure by exsanguination under pentobarbital sodium anesthesia. Complete necropsies were performed and gross pathology recorded. Special attention was paid to the lungs and upper respira tory tract. Lungs, liver, kidneys, and all grossly abnormal tissues were fixed in 10$ neutral buffered formalin. H. Histopathology Preserved tissues were embedded In Parap last, sectioned at 5~6 microns, slide mounted, stained with hematoxylin and eosin, and examined microscopically by a board-certified veterinary pathologist for Indications of compound-induced changes. I. Data Storage Ail raw data, specimens, and the final report will be stored in the archives of Hazleton Laboratories America upon acceptance of this final report. A. Aerosol Concentration H i . RESULTS 1. Nominal Concentration: A total of 26.33 grams of T-2991IT aerosol were dispersed into the inhalation chamber with a total air volume of 4008 liters. The nominal concentration was, thus, calculated to be 6.57 mg/liter of air of T-2991IT. 2. Gravimetric Concentration: Results of the dry weight gravimetric concentra tion determinations are shown below in Table 1. - 5- 001257 HAZLETON LABORATORIES A M ER IC A IN C 15<-157 CORRECTED Table 1 - Gravimetric Chamber Concentrations of T-2991IT Aerosol(dry weight). Sample 1n it ia 1 1 on (min.) 60 115 170 225 Weight Collected (m g ) 8.89 9.13 10. 7* 10.86 Sample Al rflow ~ rrr~ 150 150 150 150 Gravimetric Concentration (m g /L ) *059 .061 .072 CM 0r * . # 0i0n Particle Size Di strlbution: Results of the particle size determinations are shown in Table 2. The majority of the mass collected was In the res pirable size range (i.e.t less than 5.0 microns). Table 2 - Particle Size Distribution Data. Stage No. 1 2 3 k F Z MMAD (y) og Cutoff Size P >4.7 <4.7 <3.3 <2 .1 <0.65 PrelImlnary Weight Collected mg .18 .11 .25 .26 03 .83 2.6 2.00 Mortali ty No animals died during this study. Sample No. 12 Weight Weight Collected Collected mg mg 03 .05 .05 .07 .35 .52 .15 32 .00 .02 .98 2 .1 2.35 1.33 l.l7 6 - 001258 154-157 HAZLETON L A B O R A T O R IES A M E R IC A INC. C. Toxic Signs 1 . Group 1 (Air Control): All animals in this group exhibited normal appearance and behavior throughout the study. 2. Group 2 (6.5 mg/L): After one minute of exposure, all animals were observed to be sniffing the air, and after five minutes, all animals were preening. All animals appeared calm and normal after 30 minutes, and all animals ap peared normal after 60 minutes and throughout the remainder of the exposure. All animals exhibited normal appearance and behavior throughout the 14-day post-exposure observation period. D. Body Weights Individual body weights with group means (S.D.) are presented in Table 3. Most Group 2 animals lost weight after exposure, but subsequently recovered. All animals gained weight by the end of the study. E. Gross Pathology Gross pathology findings at necropsy are presented in Table 4. There was a higher incidence of lesions in the lungs of Group 2 males, but there were no consistent findings indicative of a compound-related effect. F. Hi stopatholoqy Microscopic evaluation revealed lesions of chronic respiratory disease consisting of peribronchial and perivascular lymphoid hyperplasia and focal pneumonitis characterized by focally thickened alveolar walls and a pleocellular inflammatory infiltrate, including alveolar macrophages. These lesions were essentially comparable in incidence and severity between control and treated rats with the exception of the control females, in which lesions were slightly less prominent. Histopathologic incidences are presented in Table 5- - 7- 001259 154-157 ^ HAZLETON ^ 5 ^ L A B O R A T O R IES A M ER IC A . INC. Microgranulomas and minimal nonsuppurative pericholangitis were noted in liver sections. Kidney sections revealed minimal to slight focal interstitial nephritis. Hydrometra was present in uterine sections from three females. Lymphoreticular cell hyperplasia was present in the various lymph nodes examined and was accompanied by congestion and pigment-1 aden macrophages in the mediastinal lymph node of one control female. Foci of agonal hemorrhage were noted in thymic sections of three rats. In conclusion, microscopic evaluation of hematoxylin and eosin stained sections of lung, liver, kidney and unusual lesions from control and treated rats from an acute inhalation study with T--19911T failed to reveal compoundrelated tissue alteration. Spontaneous disease lesions were essentially com parable in incidence and severity between control and treated rats. Submitted by: WILLIAM B. COATE, Ph.D. Di rector Inhalation Toxicology Department - 8- G 012G 0 154-157 Table 3 " Body Weights (grams). Animal No./Sex 47931 </ 47932/ 47933d* 47924/ 47935/ Mean +S.D. Pre 321 341 2-0 322 323 325 8.8 Day 1 319 341 325 324 323 326 8.5 Day 2 Day 3 GROUP 1 324 331 343 348 323 328 328 334 329 338 329 8.0 336 7-8 Day 4 324 348 331 335 340 336 9.1 Day 7 344 369 244 352 357 353 10.4 Day 14 382 408 381 86 395 390 11.3 <7936 2 47337? 47338? 47939? 7940S Mean S. 0. 271 23-5 256 283 275 264 18.6 271 238 256 290 280 267 20.5 276 240 256 291 275 268 19.8 273 240 260 291 283 269 20.1 268 236 257 278 279 264 . 17.8 280 236 260 291 275 268 21.3 286 243 266 286 284 273 18.8 47941/ 47942/ 47943/ 47944/ 47945/ Mean S.D. 47946? 47947? 47948 ? 47949 ? 47950? Mean S.D. 336 350 345 350 340 344 6.2 319 336 319 345 328 329 11.2 GROUP 2 329 337 347 353 333 342 350 358 337 346 339 9.0 347 8.4 338 354 343 357 342 347 8.2 355 376 362 383 363 368 11.4 382 414 401 423 405 405 15.4 248 239 242 249 278 251 15.5 237 233 241 256 265 246 13.6 237 239 242 258 278 251 17.3 241 239 242 256 282 252 18.1 243 238 241 254 270 249 13.1 246 239 244 260 279 254 16.2 254 242 259 270 289 263 17.8 - 9- 001261 154-157 Table k - Gross Pathology Findings OBSERVATIONS GROUPS 1 <f $ 2 % NO GROSS LESIONS 2/5 2/5 1/5 1/5 LYMPH NODES T rachea1 bronch1a 1: appear enlarged Cervical: left appears enlarged Mediastinal: left appears reddened left appears enlarged and granular left appears enlarged right side appears enlarged THYMUS purple foci right side reddened left side reddened 1/5 1/5 1/5 1/5 1/5 1/5 2/5 1/5 1/5 1/5 LUNGS Al 1 Lobes: numerous pale areas scattered white foci on surfaces scattered red areas patchy appearance Right Diaphragmatic Lobe: dorsal surface has two black foci consolidated linear area that did not perfuse Right Apical Lobe: did not perfuse Left Lobe: 1/5 1/5 1/5 1/5 1/5 1/5 1/5 anterior tip has dark reddened area surrounded by a pale area Intermediate and Left Lateral Lobes: scattered red areas on ventral surfaces CECUM Red area, probable injection site KIDNEYS Darkeortico - medullary area Dark zone in cortico - medullary area UTERINE HORNS Appear distended with clear fluid Appear thickened i i>v - 10 - 1/5 1/5 1/5 1/5 1/5 1/5 1/5 1/5 1/5 1/5 Table 5 H 1 H O P A TH OL OG Y I N C I D E N C E GROUP 1 Hales Females I ABL E GROUP 2 Males Females LS p Pratanl, 1 Minimal, 5 N No Socllon. 2 - Sllfhl. o - Absent A A ulolyili, 3 M odarata, X * Not Hamaikabla. 4 * M odtralaly savata/Hlyh, Table 5 H IST0PATH0L06Y INCIDENCE GROUP 1 Males Females TABLE GROUP 2 Males Females 1t9 ? T 0 0 LSl-*iSl Kayi P * N * N o Sacllon, I M inim al. i - SNt>l, s sevaic/Miyti o mAbsent A A utulyll, 3 M o d tra 'a , X Not Itin ltililllll, 4 M odaralaly Sasra/H lfh, HAZLETON L A B O R A T O R IE S A M ER IC A . INC. PERSONNEL STUDY DIRECTOR WILLIAM B. COATE, Ph.D. 154-157 PATHOLOGI ST: V /; ^ 4. * ^ ,, j. DEBORAH BANAS, D.V.M., M.S. Diplornate, American College of Veterinary Pathologists TECHNICIANS: ALLMAN, D. TRAMMEL, HENRY, GRIFFEY, REDDEN, HAND, KIMBLE, K. TRAMMEL, BOWERS, UDY - 13 OOi*ibb> HAZLETON LABORATORIES AMERICA. IN C OFFICE OF QUALITY ASSURANCE Project Title: Acute Inhalation Toxicity Study in Rats Project No.: 154-157 Quality Assurance Inspections of the study and review of the final report of the above referenced project were conducted according to the standard operating procedures of the Office of Quality Assurance and according to the general requirements of the Good Laboratory Practice regulations that were Issued on December 22, 1978, by the Food and Drug Administration for compliance on and after June 20, 1979. Findings from the Inspections and final report review were reported to management and to the study director on the following dates : Insoectlons/Rev1ew Findings Reported Inspector/Revlewer Study - 12/10/80 Final Report - 1/26/81 12/11/80 2/2/81 E. Prins K. Hogan Manager ______ J Office of Quality Assurance 00126