Document reqgyBn11y4540pmNKVpwyjJ

O ff 3M 3\1 General Offices 3M Center ^ ' ^ 55IJ4-,00 * * 2 - 2 .1038 ftR 86H Q . -.& J O I - 0 5 1 3 September 5, 2001 Document Processing Center (7407) Office o f Toxic Substances U.S. Environmental Protection Agency 401 M Street, SW Washington, DC 20460 Attn: TSCA Section 8(e) Coordinator 3? ^ & e > 0 * b (f ^ 3 5 Dear Section 8(e) Docket Coordinator: Re: TSCA 8(e) Supplemental Notice on Sulfonate-based Fluorochemicals With this letter, 3M is providing final reports and other supplemental information related to previous TSCA Section 8(e) notifications. Many o f the enclosed items are analytical reports providing blood serum and liver levels o f test materials for which the in-life report referring to administered doses has already been submitted to the 8(e) docket. In other cases where the 8(e) notification consisted o f preliminary data, we are submitting a final study report. All o f the enclosed items are already in EPA's possession and available in TSCA Docket AR-226. We believe, however, that placing these items in the 8(e) docket may allow for more convenient access to information directly related to previous 8(e) notifications by 3M. The table below lists the enclosed items and references the study or data which already has been the subject o f an 8(e) notification by 3M: Attached Submission Related Study/Data Already Filed Under 8(e) 1. Amended Analytical Study, 2(N-Ethylperfluorooctane Combined Oral (Gavage) Fertility, sulfonamido)-ethanol in Two Generation Rat Reproduction, Developmental and Perinatal/Postnatal Determination of the Presence and Concentration of PFOS, Reproduction Toxicity Study of N- M556, PFOSAA, and PFOSA in the Liver and PFOS, EtFOSE in Rats, 3M Reference No. T- M556, PFOSAA, PFOSA and EtFOSE-OH in the Sera of 6316.5, June 30, 1999, full report CrhCDBR VAF/Plus Rats Exposed to EtFOSE-OH, 3M submitted February 15, 2000 to Reference No. T-6316.5, Analytical Report TOX-013, supplement earlier filing LRN-U2095, June 11,2001. Contain NO CBl ro CSO cry m --o 1X5 cn 53 CO CO ro T) m ~a c i -- trn -.2 m OO TSCA Section 8(e) Docket Coordinator Page 2 . Attached Submission Related Study/Data Already Filed Under 8(e) 2. Analytical Laboratory Report, Determination of the Presence and Concentration of Potassium Perfluorooctanesulfonate (CAS Number: 2759-39-3) in the Serum and Liver of Sprague-Dawley Rats Exposed to PFOS via Gavage, Laboratory Report No. U2006, Requestor Project No. 3M TOX 6295.9, October 27, 1999. 3. Report Amendment 1, Combined Oral (Gavage) Fertility, Developmental and Perinatal/Postnatal Reproduction Toxicity Study of PFOS in Rats, Argus Research Laboratories, Inc., Protocol 418-008, Sponsor's Study No. 6295.9, April 13,2000. Combined Oral (Gavage) Fertility, Developmental and Perinatal/Postnatal Reproduction Toxicity Study of PFOS in Rats, Argus Research Laboratories, Inc., Sponsor's Study No. 6295.9, June 10, 1999, full report submitted February 15, 2000 supplementing earlier filing 4. Analytical Report, Determination of the Presence and Concentration of Perfluorooctanesulfonate, Perfluorooctanesulfonylamide, M556, and M570 in the Liver and Sera Samples, 3M Environmental Laboratory Ref. No. U2636, TOX-028, February 23, 2001 13-Week Dietary Study of N-Methyl Perfluorooctanesulfonamido Ethanol (N-MeFOSE) in Rats, 3M Ref. No. T6314.1, Covance Study No. 6329-225, dated June 30, 2000, Section 8(e) filing July 24, 2000 5. Analytical Laboratory Report, Determination of the Concentration of PFOS, PFOSA, PFOSAA, and EtFOSEOH in the Sera and Liver of CrhCDBR VAF/Plus Rats Exposed to N-EtFOSE, 3M Environmental Laboratory Report No. TOX-098, Laboratory Request No. U2402, 3M Ref. No. T-6316.7, February 6, 2001. Final Report, Oral (Gavage) Developmental Toxicity Study of 2(NEthylperfluorooctanesulfonamido)ethanol in Rats, 3M Reference No. T6316.7, December 17, 1998, submitted to Section 8(e) docket per letter of August 21, 2000 6. Analytical Laboratory Report on the Determination of the Presence and Concentration of Potassium Perfluorooctanesulfonate (PFOS) or another metabolite of 2(N-ethylperfluorooctanesulfonamido)-ethanol (NEtFOSE) in Liver and Serum Specimens, 3M Environmental Laboratory Report No. TOX-097, Laboratory Request No. U2452, 3M Ref. No. T-6316.8, February 8, 2001 Final Report, Oral (Stomach Tube) Developmental Toxicity Study of NEtFOSE in Rabbits, 3M Reference No. T-6316.8, January 11, 1999, submitted to Section 8(e) docket per letter of August 21, 2000 7. Final Report, Alexander, B., Mortality Studies of Workers Employed at the 3M Decatur Facility, University of Minnesota, April 26, 2001. Preliminary data submitted to Section 8(e) docket in letter of December 15, 2000 TSCA Section 8(e) Docket Coordinator Page 3 . Attached Submission Related Study/Data Already Filed Under 8(e) 8. Final Report, Acute Oral Toxicity Screen with T-3290CoC Acute Oral Toxicity Screen with T- in Albino Rats, Safety Evaluation Laboratory, Riker 3290CoC in Albino Rats, Safety Laboratories, Inc., Project No. 0882AR0362, 3M Reference Evaluation Laboratory, Riker No. T-3290 (40 % K+PFOSAA in 3 % EtOH, 17 %IPA Laboratories, Inc., Project No. wa1n9ad8s24to0[Bb%ieblmHio2og0v,reaLdp-th6oy7T7e8Sn,CtrFAy-6i8n8(e7D)3od,coLkcoektteA5t]0R1-)2,2N6,ofvienmablreerp5o,rt 0882AR0362, 3M Reference No. T3290 (40 % K+PFOSAA in 3 % EtOH, 17 % IPA and 40 % H20, L-6778, F- 6873, Lot 501), November 5, 1982, submitted to Section 8(e) docket in August 21, 2000 self-audit letter (which erroneously refers to rabbits rather than rats) 9. Giesy, J.P., and K. Kannan, Accumulation of Perfluorooctanesulfonate and Related Fluorochemicals in Fish Tissue, Michigan State University, June 20, 2001. Preliminary data submitted to Section 8(e) docket May 26, 1999 10. Giesy, J.P., and K. Kannan, Accumulation of Perfluorooctanesulfonate and Related Fluorochemicals in Mink and River Otters, Michigan State University, June 20, 2001. 11. Giesy, J.P., and K. Kannan, Perfluorooctanesulfonate and Related Fluorochemicals in Oyster, Crassostrea Virginica, From the Gulf of Mexico and Chesapeake Bay, Michigan State University, June 20, 2001. 12. Giesy, J.P. and K. Kannan, Perfluorooctanesulfonate and Related Fluorochemicals in Fish-Eating Water Birds, Michigan State University, June 20,2001. 13. Giesy, J.P. and K. Kannan, Accumulation of Perfluorooctanesulfonate and Related Fluorochemicals in Marine Mammals, Michigan State University, June 20, 2001. If you have any questions about this submission, please contact me at (651)737-4795. Sincerely, Enclosures A Geoij&jn Adams Manager, 3M Corporate Product Responsibility 3 M 3 ` i t ' 7L( Acute O ral T o x ic ity Screen w ith T-3290COC in A lbino R ats & * 'B , R h . C b ! V c . D Experim ent No. Conducted At: 0882AR036 2 S afety E valuation L aboratory R iker L ab o rato ries, In c. S t. P au l, M innesota Dates Conducted: C o n d u cted By: b P J 'Q o - 3 7 J u ly 30, 1982 to August 27, 1982 H. S . Rhodes j r . L aboratory T echnician A cute T oxicology fC, k- D ate D. M. M ark o e, J r . , BS T oxicologis t Study D ire c to r Dat R eview ed By: K. D. O 'M a lle y , BS Senior T o x ico lo g ist A cute T oxicology 2_ (A D a Dtate d e : M. T. Case K. L. Ebbens F . D. G r i f f i t h W. C. McCormick s> j e p a - o t s 000811832N 0filia35IV N. V, ^ <3* v- Summary An a c u t e o r a l t o x i c i t y s c r e e n w ith T-3290COC was c o n d u c te d from J u ly 30, 1982 to A ugust 27, 1982 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 ts ran g in g in body w e ig h t from 209-269 g ra m s. The t e s t a r t i c l e was a d m in is te r e d by g a s t r i c i n t u b a t i o n a t a d o se le v e l e q u iv a le n t to 200 mg/kg and 1250 m g/kg body w e ig h t w ith 0 /1 0 m o r t a li ti e s n o ted a t th e 200 mg/kg d o se le v e l an d 9 /1 0 m o r t a l i t i e s n o te d a t th e 1250 mg/kg dose l e v e l . The untow ard b e h a v io r a l r e a c tio n s w hich o c c u rre d d u rin g th e 28 day o b s e rv a tio n p e rio d a t th e 200 m g/kg d ose le v e l c o n s is te d o f h y p o a c tiv ity from 60-120 m in u tes p o s t dose a d m in is tra tio n . The 1250 mg/kg dose l e v e l e x h ib ite d h y p o a c tiv ity , a t a x i a , d ia r r h e a a n d , i n th e fe m a le s, unkempt a p p e a ra n c e . R ecovery was g e n e ra lly p re c lu d e d by d e a th . Body w eig h t g a in s w ere n o te d i n a l l a n im a ls w hich s u rv iv e d th e stu d y . N ecropsies perform ed a t term in atio n of th e stu d y rev ealed no v is ib le le s io n s , how ever, a u to ly s is p reclu d ed e v a lu a tio n of th re e 1250 mg/kg dose le v e l a n im a ls w hich d ie d p r i o r to th e end o f th e s tu d y . The a p p ro x im a te o r a l LD50 o f T-3290CoC i s g r e a t e r t h a n 200 m g/kg a n d l e s s t h a n 1250 mg/kg in f a s te d m ale and fem ale a lb in o r a t s . 1. 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 t o a p p ro x im a te th e a c u te o r a l LD50 o f T-3290COC i n f a s t e d a lb i n o r a t s . T h is s tu d y was c o n d u c te d f o r r e s e a r c h and dev elo p m en t p u rp o se s and i s , t h e r e f o r e , n o t r e g u la te d by th e Food 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 1978, a lth o u g h th e standard operating procedures of th is lab o rato ry adhere to the g en eral p r in c i p le s of t h i s r e g u l a t i o n . The raw d a ta g e n e ra te d by th e stu d y D irecto r and the f in a l re p o rt are sto re d in th e cond u ctin g la b o ra to ry 's a rc h iv e s. 2. Method and R e s u lts young a l b i n o r a t s a- w ere u s e d i n t h i s t e s t . A ll anim als were 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 tin g w ith only anim als w hich ap p eared 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 it ia t io n of the s tu d y u s e d . The r a t s were h oused in su sp e n d e d , w ire-m esh c ag es in te m p e ra tu re and h u m id ity c o n tr o lle d rooms and p e rm itte d a s ta n d a rd la b o r a to r y d ie t-- p lu s w ater ad lib itu m ex cep t during th e 16-20 hour p erio d im m ediately p r i o r to g a s t r i c in tu b a tio n when food was w ith h e ld . Q The r a t s were a d m in is te r e d th e t e s t m a t e r i a l -- a t 200 m g/kg a n d 1250 mg/kg body w e ig h t. A ll d o ses were a d m in is te re d u n d ilu te d d i r e c t l y in to th e stom achs of th e r a ts u sin g a hypoderm ic sy rin g e equipped w ith a b a ll-tip p e d in tu b a tin g needle^. A fte r g a s tr ic a d m in is tra tio n of the t e s t a r t i c l e , th e r a ts were re tu rn e d to t h e i r cages and o b se rv e d fo r th e fo llo w in g 28 d a y s . I n i t i a l , 14 day and f i n a l body w e ig h ts , m o r t a l i t i e s (T a b le 1) and a d v e rs e r e a c ti o n s (T a b le 1) w ere r e c o r d e d . A n e c ro p sy was c o n d u c te d 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 as w e ll as th o se e u th a n a tiz e d and th e end of th e 28 day o b se rv a tio n p e rio d (T a b le 1 ) . The p r o t o c o l , p r i n c i p a l p e r s 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 co n tain ed in A ppendices I - IV. -- K ing L a b s , O regon, WI -- R a l s t o n P u r in a L a b o r a t o r y Chow, R a l s to n P u r i n a , S t . L o u i s , MO -- The t e s t a r t i c l e i s 40% s o l i d s a n d was d o s e d a t 200 m g A g an d 1250 m g /kg o f s o lid s which is e q u iv a le n t to an u n d ilu te d dose o f 500 m gAg and 3125 mgAg "as is " , resp ectiv ely . -- P o p p e r and S o n s , New Hyde P a r k , NY 6 TABLE 1 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS w ith T-3290COC M o r ta lity , N ecropsy, A dverse R e a c tio n s and Body W eight D ata 3. a Dose -- (mg/kg) Sex 200 M A nim al Number 2R3587 2R3588 2R3589 2R3590 2R3591 200 F 2R3607 2R3608 2R3609 2R3610 2R3611 1250 M 2R3592 2R3593 2R3594 2R3595 2R3596 1250 F 2R3612 2R3613 2R3614 2R3615 2R3616 I n d iv id u a l 3ody W eights (g) T e s t Day Num ber: 0 14 28 253 293 251 306 268 328 263 309 262 310 328 351 369 346 369 Number Dead Number T ested 0/5 225 263 269 216 263 260 219 236 252 222 241 257 219 235 249 0/5 265 (Day 7) 260 (Day 6) 263 (Day 5) 269 303 367 262 (Day 6) 4/5 217 (Day 5) 222 (Day 4) 216 (Day 5) 214 (Day 5) 209 (Day 3) 5/5 P ercent Dead 0 0 80 100 a -- The t e s t a r t i c l e was a d m in is te r e d u n d ilu te d * h o w ev er, t h e d o se r e p r e s e n t s mgs o f s o l i d s , o f w h ic h t h e t e s t a r t i c l e c o n s i s t s o f 40% s o l i d s . The a c u te o r a l LD50 i s g r e a t e r th a n 200 m g/kg an d l e s s th a n 1250 m g/kg i n f a s t e d m ale and fem ale r a t s . Note.- F ig u r e s i n p a r e n t h e s i s i n d i c a t e tim e o f d e a t h . N ecropsy N ecro p sies perform ed upon te rm in a tio n re v e a lo d no v ia ib lo lo o io n s a t th e 200 m g/kg dose le v e l. The 1250 m g/kg d o se le v e l p ro d u ced no v i s i b l e le s io n s upon n e c ro p sy , how ever, a u to ly sis precluded e v alu atio n of th re e anim als. 7 TABLE 2 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS w ith T-3290CoC Summary o f R e a c tio n s R eactions Dose mg/kg Sex 200 200 1250 1250 M H ypoactivity F H ypoactivity M H ypoactivity A taxia D iarrhea F H ypoactivity A taxia D iarrhea Unkempt M inutes 1--30 60 120 5/5 5/5 5/5 5/5 5/5 0/5 5/5 5/5 0/5 5/5 1/5 O bservation P eriods Number A ffected/N um ber Dosed Days 1234 5 0/5 0/5 5/5 5/5 5/5 5/5 4/4 0/5 1/3 0/1 4/5 2/5 0/5 5/5 5/5 4/4 3/3 0/0 0/5 5/5 2/5 4/4 2/3 0/0 4/4 3/3 0/0 10 11 12 13 14 *O b s e r v a tio n s c o n ti n u e d t o d ay 2 8 , h o w e v e r, no s i g n i f i c a n t r e a c t i o n s w ere n o te d beyond d ay 1 1 . A blank space in d ic a te s no s ig n ific a n t re a c tio n s. Riker Experiment N o .:__ 02o2^~'G3r 2 APPENDIX I PROTOCOL 5. j S j : A c u te O r a l T o x i c i t y __________________________________________________________________ SPONSOR: 3M CorenuTcial C h e m icals________________________________________________________Division CONDUCTED BY: Safety Evaluation Laboratory, Riker Laboratories, Inc., St. Paul, Minnesota TEST ARTICLE: . T-329pCo,,C----------------------------------------------------------------------------------------------------------------------------------- CONTROL ARTICLE: ^ ------------------------------------------------------------------------------------------------------------------------------------- PROPOSED STARTING/COMPLETION DATE OF TEST: 4 __ ' l h ' L ^___________________________________ TEST SYSTEM: f U ;T , 5 S STfcArAi SOURCE: K lf o G LAct C , l*-1I Sex: M,F Number: 5 /5 Weight Range: 2 0 0 -" 0 0 g ra n s OBJECTIVE: The objective of this test will be to characterize the acu te_____ a r a i______________ toxicity of the test article in albino r a t s __________ ____ E 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 food 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 o f ______ i 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 actions for the fo llo w in g ^ d ay# Initial and final body weights will be recorded. A gross necropsy which will include, but not be limited to; heart, lungs, liver, kidneys and general gastrointestinal tract will be conducted on all animals which die during the conduct of the test as well as the animals surviving the test period. Any gross abnormalities which are observed during the conduct of the necropsy will be re corded with specific mention to the organ and/or site observed. All raw data generated by the study director and the final report will be stored in the Riker Laboratories' Archive, St. Paul, Minnesota. . Purina Laboratory Chow, Ralston Purina, St. Louis, Missouri ti2^-d-"vys- F-c& d w t*- P f ok A. i t to F'Ei- '(.>1 > i -= close a t two l e v e l s : 1250 nvp/kf 5 200 nff/kp (as s o lid s ) s o lu t io n - v i s 5' soli f./'; /.< Sponsor Ia L _____ L I M j ZZ' O. L O Date Study Director 1 > 7/jo/fr Riker Experim ent No. : 0882AR0362 APPENDIX I ( c o n c lu d e d ) D e v ia tio n s a n d /o r Amendments to P ro to c o l 1. Thp te s t- a r t i c l e was s u p p l i e d a s a s o l u t i o n w i t h 40% s o l i d s n o t 50%. 6. . . Study D ire c to r L J, 7 / 3 0 /8 2 ^ Date 2. Study D ire c to r D ate 3. Study D ire c to r D ate 4. Study D ire c to r D ate 5. Study D ire c to r 10 D ate APPENDIX I I p r in c ip a l p a r tic ip a tin g P ersonnel Involved in the Study N a m e _____________________________________________________ F u n c tio n H. S ..R h o d e s J r. Laboratory Technician Acute T oxicology D. M. M arkoe, J r . , BS T oxicologist Study D irecto r K. L. EbJbens, BS S u p e r v iso r T oxicology T esting K. D. O 'M a lle y , BS Senior T o x ico lo g ist Acute T oxicology G. C. P eco re S u p e r v iso r Animal L aboratory APPENDIX I I I C om position C h a r a c te ris tic s 8. T h is s tu d y i s n o t r e g u l a 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 in fo rm atio n p e rta in in g to com position c h a r a c te r is tic s is not a p p lic a b le fo r in c lu sio n in th is study. I 9. APPENDIX IV Q uality 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 sig n ed and p rep ared by the C om pliance A udit d ep artm en t i s n o t a p p lic a b le . The s ta 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 r a to r y 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 C om pliance A u d it d e p a rtm e n 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 underw ay in th e A cute 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 m onth s c h e d u le . In a d d itio n a s e l e c t num ber o f R esearch & D evelopm 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 rch iv es by th e Com pliance A udit departm ent fo r review . 1}