Document ea9zvaQYwbZ5RgL0jRVv5Qoq

M2&-0236 Attachments to Letter to C. Auer dated May 18,2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds 6. N-EtFOSA N-ethyl perfluorooctanesulfonamide Acute Toxicity 1) Final Report, Acute Ocular Irritation Test with T-3608 in Albino Rats, Riker Laboratories, Inc., 3M Reference FX-12, Study No. 0984EB0367, September 5, 1984 2) Final Report, Primary Skin Irritation Test with T-3608 in Albino Rats, Riker Laboratories, Inc., 3M Reference FX-12, Study No. 0984EB0368, August 13, 1984 3) Final Report, Acute Oral Toxicity Screen with T-3066CoC in Albino Rats, Riker Laboratories, Inc., 3M Ref. No. FX-12, Study No. 0981AR0146, July 13, 1981 Acute Toxicity Studies Not Submitted (Bibliography Only) 1) Final Report, Acute Oral Toxicity Study of T-6684 in Rats (OECD Guidelines), Coming Hazelton Inc., 3M Ref. No. L-14394 (slurry), Study No. CHW 61101149, January 31, 1997 2) Final Report, Primary Dermal Irritation/Corrosion Study of T-6684 in Rats (OECD Guidelines), Coming Hazelton Inc., 3M Ref. No. L-14394 (slurry), Study No. CHW 61101150, January 31, 1997 3) Final Report, Primary Eye Irritation/Corrosion Study of T-6684 in Rats (OECD Guidelines), Coming Hazelton Inc., 3M Ref. No. L-14394 (slurry), Study No. CHW 61101151, January 31, 1997 Genotoxicity 1) Final Report, Protocol and two amendments, Mutagenicity Test on T-6294 in an In Vivo Mouse Micronucleus Assay, Coming Hazelton, Inc., Study No. 1785-0-455, May 10, 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 -9- 000337 Attachments to Letter to C. Auer dated May 18,2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds Mechanistic 1) T. J. Cross and R. G. Schnellmann, Mechanism of Toxicity of a Unique Pesticide N-Ethylperfluorooctane Sulfanomide (NEPFOS), and its metabolite perfluorooctane Sulfonamide (PFOS) to Isolated Rabbit Renal Cortical Mitochondria (RCM), Abstract from 1989 Society of Toxicology Meeting 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 Analytical 1) Analytical and Research Properties - 3M Industrial Hygiene Laboratory, January 1993 - 10- 0 0 0 9 3 8 Attachments to Letter to C. Auer dated May 18,2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds 6. N-EtFOSA N-ethyl perfluorooctanesulfonamide Bibliography Showing Studies in 3M's Possession Believed To Be In FIFRA Docket. REDACTED - 11 - 000339 Experiment No.: Conducted At: Dates Conducted: Conducted By: Acute Ocular Irritation Test with T-3608 in Albino Rabbits 0984EB0367 Pathology and Toxicology Riker Laboratories, Inc. St. Paul, Minnesota July 23, 1984 to July 30, 1984 G. H. Hart ijj/Laboratory Technician Acute Toxicology k.'D. O'Malley, Bs Senior Toxicologist Study Director dc t f K. L. Ebbens ^P. D. Griffith x N. C. McCormick G0340 1. Summary The results of the acute ocular Irritation test conducted from July 23, 1984 to July 30, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota indicate that T-3608 is minimally irritating (10.3/110.0) to the eye of the female albino rabbit. Slight conjunctivitis was noted at the one hour evaluation and subsided by the three day evaluation. Neither corneal opacity nor iritis were noted during the seven day test period. Introduction The objective of this study was to determine the acute ocular irritation properties of T-3608 when instilled into the eye of female albino rabbits. This study was conducted for research and development purposes and is, therefore, not regulated by the Food and Drug Administrations's Good Laboratory Practice Regulation of 1978, although the standard operating f procedures of this laboratory adhere to the general principles of this regulation. The raw data generated by.the Study Director and the final report are stored in the conducting laboratory's archives. 000341 2. Method and Results a Young albino rabbits of the New Zealand breed-- were used to evaluate the ocular irritating properties of the test article. b modeled after that of Draize et al-- . She test method was The test article was instilled into the conjunctival sac of the right eye of each rabbit according to the treatment procedure presented in Table 1 with the left eye of each animal serving as a control. At each scoring interval, the cornea, iris and palpebral conjunctiva were examined and graded for irritation and injury according to a standard scoring system^-. She maximum possible score at any one examination and scoring period 110 points, which indicates maximal irritation and damage to all three ocular tissues (cornea, iris, conjunctiva) while a score of zero indicates no irritation (Table 2). In this scoring system, special emphasis is placed upon irritation or damage to the cornea, while less emphasis is placed upon damage to the iris and conjunctiva. After completion of the test, the scores were analyzed, and a descriptive eye irritation rating was assigned to the test article. The criteria used for assignment of the descriptive rating were the frequency, the extent and the persistence of irritation or damage which occurred to thp three ocular tissues (Table 3). The individual results are presented in Table 4. a g Hazleton Dutchland, Inc., Denver, PA -- Draize: Appraisal of the Safety of Chemicals in Poods, Drugs and Cosmetics (1965). 000342 3. The rating is arrived at by selecting the maximum mean irritation score at one hour, one, two or three days after instillation. If the rate of dissipation of injury does not meet the requirements defined for the descriptive rating appropriate for a particular numerical score, the descriptive rating is raised by one or more levels. The rating system is presented in Table 3. The protocol, principal personnel involved in the study, composition characteristics and Quality Assurance statement are contained in Appendices I - IV. f 000343 Table 1 Eye Irritation Test - Albino Rabbits Treatment Procedure Test Article Number of Animals Evaluated Form Administered Quantity of Test Article Administered Contact Period (seconds) Volume Evaluation Time of Hash Post Dose (tap water) Administration T-3608 6 powder 0.1 gm unlimited none 1 Hour, 1, 2, 3 and 7 Days Table 2 5. Eye irritation Test - Albino Rabbits Scale of Weighted Scores for Grading the Severity of Ocular Lesions Ocular Draize Tissues______________________________Description______________________________ Grade Conjunctiva Redness (A) Redness (refers to palpebral conjunctiva only). 1 Vessels definitely injected above normal. More diffuse, deeper crimson red, individual 2 vessels not easily discernible. Diffuse beefy red. 3 Chemosis (B) Any swelling above normal (included nictitating membrane). 1 Obvious swelling with partial eversion of the lids. 2 Swelling with lids about half-closed. 3 Swelling with lids about half-closed tocompletely closed. 4 Discharge (C) Any amount different from normal (Does not include small 1 amount observed in inner canthus of normal animals). Discharge with moistening of the lids and hairs just 2 adjacent to the lids. Discharge with moistening of the lids and hairs and 3 considerable area around eye. Score (A + B + C) x 2 Total maximum 20 Cornea f Opacity (A) Opacity - Degree of density (area which is most dense is taken for reading). Scattered or diffuse area, details of iris clearly visible. Easily discernible translucent areas, details of iris slightly obscured. Opalescent areas, no details of iris visible, size of pupil barely discernible. Opaque, iris invisible. Area of Cornea Involved (B) One quarter (or less) but not zero. Greater than one-quarter, but less than one-half. Greater than one-half, but less than three-quarters. Greater than three-quarters, up to whole area. 1 2 3 4 1 2 3 4 Score equals A x B x 5 Total maximum > 80 Iris Values (A) Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive). No reaction to light, hemorrhage, gross destruction (any or all of these). 1 2 Score equals A x 5 Total maximum > 1 0 Note: T he maximum total score is the sum of all scores obtained for the cornea, iris and conjunctiva. 000345 Table 3 Eye Irritation Test - Albino Rabbits Classification of Test Materials Based on Eye Irritation Properties 6. Rating Non-Irritating Practically Non-Irritating Minimally Irritating Mildly Irritating Moderately Irritating Severely Irritating f Extremely Irritating Range 0.0 - 0.5 >0.5 - 2.5 >2.5 - 15.0 >15.0 - 25.0 >25.0 - 50.0 >50.0 - 80.0 >80.0 - 110.0 Definition To maintain this rating, all scores by the one day reading must be zero; otherwise, increase rating one level. To maintain this rating, all scores by the one day reading must be zero; otherwise, increase rating one level. To maintain this rating, all scores by the three day reading must be zero; otherwise, increase rating one level. To maintain this rating, all scores by the seven day reading must be zero; otherwise, increase rating one level. To maintain this rating, scores by seven days must be 10 for 60% or more of the animals. Also, mean seven day score must be <_ 20. If seven day mean score is _< 20 but < 60% of animals show scores <10, then no animal among those showing scores > 1 0 can exceed a score of 30 if rating is to be maintained; otherwise, raise rating one level. To maintain this rating, scores by seven days must be <_ 30 for 60% or more of the animals. Also, mean seven day score must be _< 40. If seven day mean score is _< 40 but < 60% of the animals show scores jC 30, then no animal among those showing scores > 30 can exceed a score of 60 if rating is to be maintained; otherwise, raise rating one level. 000346 Tissue Examination Period 4B1141 Cornea(D-A) Iris Conjunctiva (RSD) 1 Hour Total 0 0 8(2-2-0) 8 Cornea(D-A) Iris Conj unctiva (RSD). 1 Day Total 0 0 6(2-1-0) 6 Cornea(D-A) Iris Conj unctiva (RSD) 2 Days Total 0 0 4(1-1-0) 4 Cornea(D-A) Iris Conjunctiva (RSD) 3 Days Total 0 0 0 0 Cornea(D-A) Iris Conjunctiva (RSD) 7 Days Total 0 0 0 0 Table 4 Eye Irritation Test - Albino Rabbits with T-3608 4B1144 RESULTS ANIMAL NUMBERS 4B1136 4B1139 0 0 10(2-2-1) 0 0 12(3-2-1 ) 0 0 14(3-2-2) 10 0 0 4(2-0-0) 4 0 0 2(1-0-0) 2 0 0 0 0 12 0 0 8(2-2-0) 8 0 0 2(1-0-0) 2 0 0 0 0 14 0 0 8(2-1-1) 8 0 0 4O-1-0) 4 0 0 0 0 000 000 000 000 4B1142 0 0 8(2-1-1) 8 0 0 4(2-0-0) 4 0 0 0 0 0 0 0 0 0 0 0 0 4B1145 0 0 10(2-2-1 ) 10 0 0 6( 2-1-0) 6 0 0 2O-0-0) 2 0 0 0 0 0 0 0 0 Means 0.0 0.0 10.3 10.3 0.0 0.0 6.0 6.0 0.0 0.0 2.3 2.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 000347 Key: Cornea: D=Density A=Area Conjunctiva: R=Redness SSwelling -J Riker Experiment No.: APPENDIX I PROTOCOL 0984EB0367 TEST: Acute Ocular Irritation Test SPONSOR: 3M . Commercial Chemicals C O NDUCTED BY: S afety E valuation Laboratory, R iker Lab o rato riea, Inc., S t. Paul, M innesota TE S T A R TIC LE:____ ]___I= 3 6 o8------------------------------------------------------------------------------------------------------CONTRO L ARTICLE: N ifi PRO PO SED STA R TING /CO M PLETIO N DATE O F T E S T :. [ < M ' l0 / v f TEST SYSTEM : Fem ale New Zealand W hite Albino Rabbits SOURCE: D ivision O B J E C T IV E : The objective of this test will be to determ ine the irritation potential of the test article to the ocular tissues (cornea, iris and conjunctiva) o f __ 6------- albino rabbits. Rabbits were selected as the test system for their sensitivity to irritants, historical use, ease of handling and general availability. METHOD: The animals will be housed in standard wire-m esh cages in tem perature and humidity controlled rooms with foodS and water offered a d libitum. Each animal will be assigned a numbered ear tag which will correspond to a card affixed to the outside of the cage. The test article will be instilled into , ,the conjunctival sac of the right eye at a dose o f . Q . l e____ with the contralateral eye of each animal serving as a control. A t ----------------i -------------------------- hours and 1 2 3 and 7________ days (additional scoring intervals may be added to further characterize the ocular reactions), the fissues will be examined and graded for irritation and injury according to a standard scoring system of Draize et a/fe. After completion of the test, the scores will be analyzed, and a descriptive eye irritation rating assigned to the test article. Eye examinations may be carried out with the aid of sodium fluorescein. If deem ed necessary by the study director, washed eye procedures entailing a 5 and 30 second contact period with a __ 5 _____wash over a ___ 5 m in u te period will be conducted using 3 animals per procedure. All raw data generated by the study director and the final report will be stored in the Riker Laboratories' Archive, St. Paul, Minnesota. _____ ...-- f Purina Rabbit Chow, Ralston-Purina, St. Louis, Missouri | Draise: Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics (1965) Published by the Editorial Committee of The Association of Food anil Drug Officials of the United States. nsor orm WI71-7.A-PWO 00G948 APPENDIX II Principal Participating Personnel Involved in the Study Name Function G. E. Hart Sr. Laboratory Technician Acute Toxicology K. D. O'Malley, BS Senior Toxicologist Study Director K. L. Ebbens, BS Supervisor Toxicology Testing G. C. Pecore Supervisor Animal Laboratory 9. f 00034^ APPENDIX III Composition Characteristics This study is not regulated by the Good Laboratory Practice Act of 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study. f 000950 11. APPENDIX IV Quality Assurance Statement This study is not officially regulated by the Good Laboratory Practice Regulation of 1978, and therefore a statement signed and prepared by the Compliance Audit department is not applicable. The standard operating procedures of this laboratory does adhere to the general principles of this regulation. The Compliance Audit department does inspect different significant phases for studies underway in the Acute Toxicology Laboratory on a recurring cycle, and the facilities are examined on a three month schedule. In addition a select number of Research & Development studies are routinely picked at random from the Archives by the Compliance Audit department for review. f 000351