Document rp7JnEa7G8x3NKqQg9grEwx4G

Attachments to Letter to C. Auer dated May 18, 2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds AM&-0304 10. N-EtFOSEA N-ethylperfluorooctane sulfonamidoethyl acrylate Acute Toxicity 1) Acute Oral Toxicity Screen with T-3493 in Albino Rats, Safety Evaluation Laboratory, Riker Laboratories, Inc., Project No. 0884AR0010, 3M Reference No. T3943, February 7, 1984 2) Primary Skin Irritation Test with T-3493 in Albino Rabbits, Safety Evaluation Laboratory, Riker Laboratories, Inc., Project No. 0884EB0009, 3M Reference No. T3943, February 7, 1984 3) Acute Ocular Irritation Test with T-3493 in Albino Rabbits, Safety Evaluation Laboratory, Riker Laboratories, Inc., Project No. 0884EB0008, 3M Reference No. T3943, January 24, 1984 Immunotoxicitv 1) Guinea Pig Maximization - Method, Summary, and Raw Data Appendix, Hazleton Laboratories America, Inc., Project No. 40703984, 3M Reference No. T-3609, October 5, 1984 (plus May 13, 1985 report amendment) Genotoxicitv 1) Chromosomal Aberration Study of Sample D-l in Cultured Mammalian Cells, Mitsubishi Chemical Safety Institute, Ltd., Study No. 2L162, 3M Reference No. T6322.3 (FX-13), October 23, 1995 2) Mutagenicity Testing of 2-[N-ethyl-N-perfluoroalkyl (C=l~8)sulfonylamino]ethyl acrylate in Bacterial Reverse Mutation Assays, BML, Inc., Study No. 2862, 3M Reference No. T-6322.5 (FX-13), April 24, 1996 3) In Vitro Microbiological Mutagenicity Assays of 3M Company's Compound T-3609, SRI International, Project No. LSC-3145, September, 1984 Repeated-Dose Toxicity 1) Twenty-Eight-Day Repeated Dose Oral Toxicity Study of Sample D-l in Rats, BioMedical Research Laboratories Co., Ltd., Study No. BMR143C, 3M Reference No. T-6322 (FX-13), February 16, 1993 -ail- 005188 E xperim ent No.: Conducted At: Dates Conducted: C onducted By: R eview ed By: Acute Oral Toxicity Screen w ith T-3493 in A lbino R ats 0884AR0010 S afety E valuation L aboratory R iker L ab o rato ries, Inc. S t. P aul, M innesota December 3 0 , 1983 to Jan u ary 1 3 , 1984 D. M. M arkoe, J r . , BS T oxicologist Study D ire c to r tM fr D ate K. D. O 'M a lle y , BS Senior T oxicologist Acute T oxicology 1 D ate de: M. T. Case K. L. Ebbens F . D. G r i f f i t h W. C. McCormick 005189 1 Summary The ac u te o ra l to x ic ity sc re e n w ith T -3493 was conducted from December 3 0 , 1983 to Jan u ary 1 3 , 1984 a t R iker L a b o ra to rie s, I n c ., S t. P au l, M innesota u sing male and fem ale a lb in o r a ts ranging in body w eight from 2 2 7 -2 7 2 gram s. The t e s t a r t i c l e was a d m in iste re d by g a s t r i c in tu b a tio n a t a dosage le v e l o f 5 ,0 0 0 mg/kg body w eight w ith no m o r ta litie s n o te d d u rin g th e 14 day o b s e r v a tio n p e r io d . D ia rrh e a was n o te d i n two m ales on day one and had su b sid ed by day th re e and a lo p e c ia was n o te d in one fem ale on days f iv e th ro u g h n in e , i n c lu s iv e . Body w e ig h t g a in s were noted in a l l anim als a t th e end of th e stu d y . N ecropsies perform ed a t te rm in a tio n of th e stu d y re v e a le d no v is ib l e l e s i o n s . The approxim ate o r a l LD50 o f T -3493 i s g r e a t e r th a n 5 ,0 0 0 mg/kg in f a s te d m ale and fem ale a lb in o ra ts . In tro d u c tio n The o b je c tiv e o f t h i s s tu d y was to d e te rm in e th e a c u te o r a l LD50 o f T -3493 in a lb in o r a t s . T his stu d y i s n o t re g u la te d by th e Pood and Drug A d m in is tr a tio n 's Good L a b o ra to ry P r a c t i c e R e g u la tio n o f 1 9 7 8 , a lth o u g h th e standard operating procedures of th is lab o rato ry adhere to the general p r in c ip le s o f th i s re g u la tio n . The raw d a ta g en era ted by th e Study D irecto r and the fin a l re p o rt are sto re d in the conducting la b o ra to ry 's a rc h iv e s . 005190 2 Method and R e s u lts Young a lb in o r a t - w ere used in t h i s t e s t . A ll an im als w ere h e ld under q u a ra n tin e fo r s e v e ra l days p r io r to te s t in g w ith only anim als which appeared to be in good h e a lth and s u ita b le as t e s t anim als a t th e i n i t i a t i o n o f th e s tu d y u s e d . The r a t s w ere housed i n su sp e n d ed , w ire-m esh cag e s i n tem p eratu re and hum idity c o n tro lle d roans and p erm itted a stan d ard la b o ra to ry d iet^- p lu s w ater ad lib itu m except during a 16-20 hour p erio d im m ediately p r io r to g a s tr ic in tu b a tio n when food was w ith h e ld . The r a t s were a d m in is te re d th e t e s t m a te r ia l a t a s in g le dosag e l e v e l . A ll doses were ad m in istered d ir e c tly in to th e stom achs o f th e r a ts u sin g a hypoderm ic s y r in g e e q u ip p e d w ith a b a l l - t i p p e d i n t u b a t i n g n e e d le --. A fter g a s tr ic a d m in istra tio n o f th e t e s t a r t i c l e , th e r a ts were re tu rn e d to th e ir cages and observed fo r the follow ing 14 days. I n it ia l , seven day and f in a l body w eights, m o r ta litie s (T ab le 1) and adverse re a c tio n s (T ab le 2) were re c o rd e d . A n ecro p sy was co n d u cted on a l l an im als t h a t d ie d d u rin g th e study as w ell as those eu th an atized a t th e end o f th e 14 day o b serv atio n p e rio d (T a b le 1 ) . The p r o to c o l, p r i n c i p a l p e rs o n n e l in v o lv e d i n th e s tu d y , com position c h a ra c te ris tic s and Q u ality A ssurance statem en t are contained in A ppendices I - IV. -- C h a r le s R iv e r B re e d in g L a b o r a t o r i e s , I n c . , W ilm in g to n , MA -- R a ls to n P u r in a L a b o ra to ry Chow, R a ls to n P u r in a , S t . L o u is , MO -- p o p p e r and S o n s, I n c . , New Hyde P a r k , NY 00S191 3. TABLE 1 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS w ith T-3493 M o r t a l i t y , N e c ro p sy , an d Body W eight D a ta Dose^- Animal (m g/kg) Sex Number I n d i v i d u a l Body W eights (g ) T e s t Day Number: 0 7 14 Number Dead Number T e ste d P e rcen t Dead 5 ,000 M 3R7970 246 289 302 3R7971 256 302 322 3R7972 254 299 323 3R7973 272 312 350 3R7974 240 262 279 5 ,0 0 0 F 3R7896 238 252 266 3R7897 254 263 278 3R7898 227 245 257 . 3R7899 243 267 282 3R7900 251 288 303 0/5 0 0/5 0 -- The t e s t a r t i c l e was a d m in iste re d a s a su sp e n sio n in c o tto n se e d o i l . The a c u te o r a l LD50 i s g r e a t e r th a n 5 ,0 0 0 mg/kg in f a s te d male and fem ale r a t s . N ecropsy N ecro p sies perform ed upon te rm in a tio n o f th e study rev ea led no v is ib le le s io n s . 005192 R eactions Dmocjs,,/ekg 5 ,0 0 0 Sex M D iarrhea 5 ,0 0 0 F A lopecia TABLE 2 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS w ith T-3493 Summary o f R e a c tio n s M inutes 1-30 60 120 O bservation Periods Number A ffected/N um ber Dosed Days 1 2 3 4 5 6 7 8 9 10 11 12 13 14 2/5 1/5 0/5 1/5 1/5 1/5 1/5 1/5 0/5 Riker Experiment No.: 0834ARGC10 APPENDIX I PROTOCOL TEST:. Acute Oral Toxicity SPONSOR: 3M Commercial Cheniails CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, Inc., St. Paul, Minnesota TEST ARTICLE:____ T-3495 ____ ___________________________________________________ CONTROL ARTICLE. AJoK> PROPOSED STARTING/COMPLETION DATE OF TEST: J l j . ! TEST SYSTEM: AU & V ^O tvVf f CJ ) SOURCE: C Y w fE K ' Sex: M.F Number: 5,5 Weight Range: 200-300 grans Division OBJECTIVE: The objective of this test will be to characterize the acute--------o ra l----------------------toxicity of the test article in albino ra ts __________ ______'^a ts_____ were selected as a test system for repro ducibility of response, historical use, ease in handling and general availability. METHOD: The animals will be housed in stainless steel suspended wire mesh cages in temperature and humidity controlled rooms during both the quarantine and test periods, with foodi and water offered ad libitum. Each animal will be identified by color coding, according to the laboratory's standard operating pro cedure, which will correspond to the animal numbers on a card affixed to the outside of the cage. A single dosage of 5000 mg/kg will be administered each animal, however, If this dosage level does not adequately characterize the toxicity of the test article, additional animals will be administered the test article at supplemental dosage levels. Any additional dosage levels will be documented and filed with this protocol. The test article will be administered to the animals in the form received from the sponsor, after which the animals will be returned to their cages and observed for any untoward behavioral re waciltlioinncslufodret,hbeuftolnloowt ibneg l1im4idteadysto. ;Inhiteiaalrat,nldunfignsa,l lbivoedry, wkidenigehytss wanilldbgeerneecroarldgeda.stAroginrtoessstinnaelcrtroapcstywwilhl icbhe conducted on all animals which die during the conduct of the test as well as the animals surviving the tceosrdt epderiwodith. Asnpyecgirfoicssmaebnntioonrmtoalittihees owrhgiacnh aarnedo/obrsseirteveodbdsuerrivnegdt.hAellcoranwdudcat toaf gtheenenreacterodpsbyy wthilel bseturdey director and the final report will be stored in the Riker Laboratories' Archive, St. Paul, Minnesota. 5 Purina Laboratory Chow, Ralston Purina, St. Louis, Missouri F o o p t-o ii-L- S B A \io~Z-0 . Sponsor 10171.A . o w n \J) . . CA----__________________ (?- f t ~ Dat Study Director ` Date 005194 APPENDIX I I P rin c ip a l p a rtic ip a tin g personnel involved in th e Study Name D. M. Marfcoe, J r . , BS K. L. E bbens, BS K. D. O 'M a lle y , BS G. C . p e c o re F u n c tio n T oxicologist Study D ire c to r S u p e rv iso r Toxicology T esting Senior T o x ico lo g ist Acute T oxicology S u p e rv iso r Animal L a b o ra to ry 6 005195 APPENDIX III Com position C h a ra c te ris tic s T h is s tu d y i s n o t r e g u la te d by th e Good L a b o ra to ry P r a c t i c e A ct o f 1978 and th e re fo re inform ation p e rta in in g to com position c h a ra c te ris tic s is not ap p licab le fo r in c lu sio n in th is study. 05X9S 8. APPENDIX IV Quality Assurance Statement T h is s tu d y i s n o t o f f i c i a l l y r e g u la te d by th e Good L a b o ra to ry P r a c tic e R egulation of 1978, and th e re fo re a statem en t signed and prepared by th e Compliance A udit departm ent i s n o t a p p lic a b le . The s ta n d a rd o p e r a tin g p ro c e d u re s o f t h i s la b o ra to r y does ad h e re to th e g e n e ra l p r in c ip le s o f t h i s r e g u la tio n . The Com pliance A u d it d ep artm en t does in s p e c t d if f e r e n t s ig n if ic a n t p h ases fo r s tu d ie s underway in th e Acute T o x ico lo g y L a b o ra to ry on a r e c u r r i n g c y c le , and th e f a c i l i t i e s a re exam ined on a th re e month sc h e d u le . In a d d itio n a s e le c t number o f R esearch & Developm ent s tu d ie s a re ro u tin e ly p ic k e d a t random from th e A rchives by th e Compliance A udit departm ent fo r review . 005197