Document 99nqqz0q4va3QK1LJR1MQNMJL

Attachments to Letter to C. Auer dated May 18,2000 Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds AfU&-03Q 11. N-EtFOSEMA N-ethyl perfluorooctane sulfonamido ethyl methacrylate Acute Toxicity 1) Acute Oral Toxicity Screen with T-3494 in Albino Rats, Safety Evaluation laboratory, Riker Laboratories, Inc., Project No. 0884AR0013, 3M Reference No. T3494 (L-1048, FX-14), March 13, 1984 2) Primary Skin Irritation Test with T-3494 in Albino Rabbits, Safety Evaluation laboratory, Riker Laboratories, Inc., Project No. 0884EB0012, 3M Reference No. T3494 (L-1048, FX-14), February 7, 1984 3) Acute Ocular Irritation Test with T-3494 in Albino Rabbits, Safety Evaluation laboratory, Riker Laboratories, Inc., Project No. 0884EB0011, 3M Reference No. T3494 (L-1048, FX-14), January 24, 1984 Immunotoxicitv 1) Guinea Pig Maximization, Hazleton Laboratories America, Inc., Project No. 40703985, 3M Reference No. T-3610 (NB No. 63601-32, FX-14), October 9, 1984 Genotoxicitv 1) In Vitro Microbiological Mutagenicity Assays of 3M Company's Compound T-3610, SRI International, Project No. LSC-3145, 3M Reference No. T-3610 (NB No. 6360132, FX-14), September, 1984 -21 - 005510 E xperim ent No.: Conducted At: D ates Conducted Conducted By: R eview ed By: Acute O ral T o x ic ity Screen w ith T-3494 in A lbino R ats $*L 0884AR0013 S afety E valuation L aboratory R iker L ab o rato ries, Inc. S t. P au l, M innesota Jan u ary 19, 1984 to F ebruary 2, 1984 D. M. M arkoe, J r . , BS' T oxicologis t Study D ire c to r D ate Ki D. O 'M a lle y , BS \ Senior T oxicologist Acute Toxicology D ate d e : M. T. Case K. L. Ebbens F . D. G r i f f i t h W. C. McCormick 005511 Summary The ac u te o r a l to x ic ity sc re e n w ith T-3494 was conducted from Jan u ary 19, 1984 to F eb ru ary 2 , 1984 a t R ik er L a b o ra to rie s , I n c ., S t. P a u l, M innesota u sin g male and fem ale a lb in o r a t s ran g in g in body w eig h t from 190-236 gram s. The t e s t a r t i c l e was a d m in is te 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 5,000 mg/kg body w eig h t w ith no m o r ta litie s noted 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 on day one and s u b s id e d by th e day fo u r o b se rv a tio n . T his resp o n se, however, would be ex p ected u s in g c o tto n s e e d o i l a s th e v e h ic le a t a c o n s ta n t volume o f 20 m l/k g . Body w eight g ains 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 le s io n s . Hie a p p ro x im a te o r a l LD50 o f T -3494 i s g r e a t e r th a n 5 ,0 0 0 m g/kg i n f a s t e d m ale and fem ale alb in o r a ts . In tro d u c tio n The o b j e c t i v e o f t h i s s tu d y was t o d e te rm in e th e a c u t e o r a l LD50 o f T-3494 in f a s te d 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 Food and Drug A d m in is tra tio n 's Good L a b o ra to ry P r a c ti c e R e g u la tio n o f 1978, a lth o u g h the 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 th e conducting la b o ra to ry 's a rc h iv e s . 005512 Method and R e s u lts Young a lb in o r a t s ^ w ere used in t h i s t e s t . A ll an im als w ere h e ld un d er 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 en d ed , w ire-m esh ca g e s i n tem p eratu re and hum id ity c o n tro lle d rooms and p e rm itte d a sta n d a rd la b o ra to ry diet^- p lu s w ater ad lib itu m ex cep t d u rin g a 16-20 hour p erio d im m ediately p r i o r to g a s tr i c 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 d o ses were a d m in is te re d a t a c o n s ta n t volume o f 20 m l/k g d i r e c t l y in t o th e stom achs of th e r a ts u sin g a hypodermic sy rin g e equipped 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 --c . A fte r g a s tr ic a d m in istra tio n of th e t e s t a r ti c le , th e r a ts were retu rn e d to t h e i r cag es and o b se rv e d f o r th e fo llo w in g 14 d a y s . I n i t i a l , sev en day and f i n a l body w e ig h ts, m o r t a li tie s (T ab le 1) and ad v erse r e a c tio n s (T ab le 2) were re c o rd e d . A n e c ro p sy was co n d u cted on a l l a n im a ls t h a t d ie d d u rin g th e s tu d y a s w e ll as th o s e e u th a n a tiz e d a t th e end o f th e 14 day o b s e rv a tio n p e rio d (T able 1 ). The p ro to c o l, p r in c i p a l p e rs o n n e l in v o lv e d in th e s tu d y , com position c h a ra c te ris tic s and Q uality A ssurance statem en t are contained in A ppendices I - IV. g j- 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 005513 TABLE 1 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS w ith T-3494 M o r ta l ity , N e cro p sy , A d v erse R e a c tio n s an d Body W eight D a ta Dose-- Animal (m g/kg) Sex Number I n d iv id u a l Body W eights (g) T e s t Day Number: 0 7 14 Number Dead Number T e ste d Percent Dead 4R411 4R412 4R413 4R414 4R415 4R432 4R433 4R434 4R435 4R436 231 285 317 234 297 339 216 263 288 213 268 303 236 285 323 207 251 265 191 216 232 190 224 218 205 241 255 199 234 251 0/5 0 0/5 0 The t e s t a r t i c l e was a d m in is te re d a s a su sp e n sio n in c o tto n s e 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 m g/kg i n f a s t e d m ale and fe m a le r a t s . N ecropsy N ecropsies performed upon term in atio n o f the study rev ealed no v is ib le le sio n s. Adverse R eactions D ia rrh e a was noted in a l l an im als on days one through th r e e , in c lu s iv e . 005514 mmmmum Riker Experiment No.: APPENDIX I PROTOCOL 4. JEST: A c u te O ra l T o x ic it y _________ _________________________________________ __________ _ SPONSOR: m Cftiiunrci ' 1 C h em icals --------------------------------------------------------------------------- -------------- Division CONDUCTED BY: Safety Evaluation Laboratory, R iker Laboratories, Inc., St. Paul, M innesota TEST ARTICLE: ..... J - 5 4 94------------------ _ _ _ _ _ ----------------------------------------------------------------------------_____----- -------------- CONTROL ARTICLE: JS/.U-------- -------- ---------------------------------------------------------------------------------------- ---------------------- PROPOSED STARTING/COM PLETION DATE O F TEST: -- ~ ------------------------------------------------ TEST SYSTEM: f i L Q i j F f \ V ' , C O SOURCE: C H A f-L S -E fS tV ^ A IV l ' 'bTc'K j f M A . Sex: K ,F Number: 3 ,5 Weight Range: 2 0 0 -3 0 0 g ran s OBJECTIVE: The objective of this test will be to characterize the acute -- o r a i---------------------------- toxicity of the tes article In albino Rats------------------- ----------E a ts ------------were selected as a test system for reprc ducibitity 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 humidi controlled rooms during both the quarantine and test periods, with food! and water offered ad libitum Each animal will be identified by color coding, according to the laboratory's standard operating pr cedure, which will correspond to the animal numbers on a card affixed to the outside of the cage. A sin< dosage of 5000 mg/kg will be administered each animal, however, if this dosage level does i adequately characterize the toxicity of the test article, additional animals will be administered the t article at supplemental dosage levels. Any additional dosage levels will be documented and filed v this protocol. The test article will be administered to the animals in the form received from the spon after which the animals will be returned to their cages and observed for any untoward behavioral actions for the following 14 days. Initial and final body weights will be recorded. A gross necropsy w will include, but not be limited to; heart, lungs, liver, kidneys and general gastrointestinal tract wi conducted on all animals which die during the conduct of the test as well as the animals survivin; test period. Any gross abnormalities which are observed during the conduct of the necropsy will b corded with specific mention to the organ and/or site observed. All raw data generated by the director and the final report will be stored in the Riker Laboratories' Archive, St. Paul, Minnesota. a Purina Laboratory Chow, Ralston Purina, St. Louis, Missouri b Fbox> nj-iLi- (3 e lAj ` T V U J 6 l o A 't - Pt \ fH> f(>. i aft- To Qo$\ A'r _ f deczy Sponsor L i^ u .oc -,04 . Study Director 005515 H ik er E x p erim en t No. : 0884AR0013 APPENDIX X (c o n c lu d e d ) D e v ia tio n s a n d /o r Amendments t o P ro to c o l 1 . The w e ig h t r a n g e i s e x te n d e d t o 1 9 0 -3 0 0 gm t o e x p i d i t e th e s tu d y . 5 *p.***-* Study D ire c to r _________ 1 / 1 9 / 3 4 D ate 2. Study D ire c to r Date 3. Study D ire c to r D ate 4. Study D ire c to r Date 5. Study D ire c to r 005516 Date APPENDIX I I p rin c ip a l p a rtic ip a tin g p erso n n el involved in th e Study Name D. M. M arkoe, 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 Toxicology S u p e rv iso r Animal L ab o rato ry 00SS17 APPENDIX I I I C om position C h a x a c te ristic s T h is stu 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 tic e A ct o f 1978 and th e re fo re in fo rm atio n p e r ta in in g to com position c h a r a c te r is tic s is n o t applicable fo r in c lu sio n in th is study. 005518 8. APPENDIX IV Q u ality Assurance Statem ent T h is stu 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 o f 1978, and th e re fo re a statem en t signed and p rep ared by th e Compliance A udit departm ent i s n o t a p p lic a b le . The sta n d a rd o p e ra tin g p ro c e d u re s o f t h i s la b o ra to ry does ad h ere to th e g e n e ra l p r in c i p le s o f t h i s r e g u la tio n . The Compliance 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 f o r s tu d ie s underway in th e Acute T oxicology L aboratory on a re c u rrin 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 r o u tin e ly p ic k ed a t random from th e A rchives by th e Com pliance A udit departm ent fo r review . 005519