Document 6R3OxRyNVE7Z5zm6oM4eNDbxE

bs Eas TTEECCHHNNIICCAALL RREEPPOORRTT SSUUMMMMAARRYY [FRp---------------- mest pr3mi Ss,o mdoomn TO: TECHNICAL COMMUNICATIONS CENTER - 201-2CM _-- Toei rommental Laboratory (EE & PO) TT feE FfaanottveeirfooofnfmrFFue1lnouutrooaorrloocccLhhh~eeebssmoiiireccanaatolltTsssy (EE & PC) BttEivoabluuamrtoionmnooffetthhmee BinosetncenrtraasionnFPootitmennsntiieald of PM 3422 Eva0.lua1tiosnacoofn the Bioconcentration Potential of FM 3422 D. L. Bacon ETETT AA.LNN.. Wweell~teerr I A Auug;uuss~t 1I6G. . ]19977F f -- ~t. S0e2o2a2s n : 029367 wars I cm Es |HER Teg [] 00~. ~ o~ Tm, [emer ere Ee a, KEYWORD$: mow EE 47C- Div. | 23.. TDDheeoctloeerrmniitnnieeeneupxatcnardke/etoorraynsdipssacutlshe:waaryancfeorrFaYtes342o2f PU 3423 in EE & PC - Divo Progress Report CURRENT OBJECTIVE: Progress Report i1.. EEvvaalluuaattee BBiiooccoonncceenmttrraattiioonn PPootteennttiiaall ooff FFMM 33442222.. 2. De~ermlne uptake and clearance rates of FM 3422 in whole ~lsh sad/or issue. 3. Determine excretory pathway for FM 3422. EE RE Ea FF ]uorOoU CcRheemmiT CcaaLlSs IG REPORT aeraACT AIISTRACT: (700 80 more I;IOO':~S0 wo~di] Thssormue Thil lintel mrmaters inforlPIll~-- a ouvoauindbyte +s dllt,lb~;ld by Ih, Tachncal T*chn~-*l CommuncanonsComer15 Cm'nmun~lt~Onl ~4nllr 10 (Aquatic) Sonscits Toxicity istic: (Bioconcen- tration i a. | uc; DLB isKLB iMaNTE | Wprokop-236-38 R.Prokop-236-2 jwe | SKW TV [-- CONFIDENTIAL 11118855..00000011 EE 1185 33MMAA1100006666661199 a-2- IINNTTRROODDUUCCTTIIOONR Living organisms possess the ability to concentrate and LivlnK orcanfsms possess the accumulate high concentrations of ability to lipophilic ocrognacneinctrcaotempoaundnds accumulate high esther directly cforonmcetnhteriartioennsviorfonleipntopohrilifcroom~tghaenitcr cfoom odposuonudrs ce, either directly ~rom their environment or fro~ their food source pheaonesoswhich is well docuseated (Burpstt, 1971; Gustafson, apheno~enonwhich is 1870). This ability well documented to bioconcentrate (~ seuermnientgtl, y 19no7n1-; t oxic sub- Gustafson, 1970). This ability to h~oconcentrate seemingly non-toxic s~h- stances might well pose & hazard for the ultimate predator species. stances might well pose This fovestigation a hazard for the was conducted to udelttiemrmaitene pwrheedtahteorr aspecies. Th~s investiga~ion fluorochestcal, FU322, wdoaes s cbolnodcuocntecdenttoratdeeteirn~ionreganwihsemtshear nda if fluoroche~lcal, F~3422~ does bloconcentrate in organisms an~ if 50, does the material depurate rapidly. Selective organ systems so, does the mater~al were analyzed for the depurate rapidly. Selective organ subject fluorochemical as potential uptake were analyzed for the subject fluorochemtcai a~ poten~la~ uptake ates. sites. Since the aquatic environment serves ss a primary mode of S~e the aquatic environment serves as a primary mode of entry for FNI422 into the enviroment, this stidy ves conducted entry for FW34~ into the environment,'this study was conducted using the channel catfish lotalams punctatu)s 4 the test species. The subject using the channel catfish ~!~a~s pur~ta~.~) fluorochemical, F3422 is a wansi1t3e~egtersatnuslpaerciemsa. ter- The subject fluorochemical, FM3422 is a w~ite granular mater- ial, molecular weignt-S7), possessing physico-chemical properties aZ, molecular ~eght-57~, possessing physlco-c~emlcal properties which suggest that this material may bioconcentrate. Thus, the which suggest that material was found this to be material may relatively boconcentrateo water insoluble andThpuoss, sethsesed m a ahitegrhiadl iswtarsibfouutnidontocobeeffirceileanttiv,eldyatawawtheirchinsiosluibnldeicaatndivepoosfsesased a high d~stribu~on coefficient, data which is ndicative of a highly lipophilic molecule. This profile is generally accepted highly lpophilic molecule. This profile ~s generally accepted as that of a substance which will tend to bioconcentrate as tha~ of a substance which w~1 tend to bioconcentrate. M~ETTHHOODDSS TThhee hhyyddrroopphhoobbiicciittyy ooff FF~3324222 precluded precluded a a sinplistic simplistic determin- determin- ation ooff iittss wwaalteerr s~oolluubbiillilt~yy.. Use of the Veith-Comstock technique Use o~ the Velth-Comstock technique 11118855..00000022 33MMAA1100006666662200 --3%- (1075) wherein water in a constant-level reservoir was continu- (1975) wherein water ously saturated with TinU34a22conbystacnitr-cluelvaetlingrestheervwoairterwasthrcooungthinu- ously a bed saturated of inert with F~3422 by circulating substrate impregnated with the water TM3A22. through Samples for a bed of Inert substrate impregnated analytical ssalysis were obtained vis w a isthampFlMi3n4g22p. ortS.ampRleesplifocarte analytical analysis were obtained via a sampling port. Replicate sstluud~iieess vweerree perforaed. performed. ~Thee ddiissttrri~bbuuttiloomn ccooeeffffiicciieenmtt ooff FFMM3342222 1ian mn--oocctZaannooll//w~aatteerr wwaass ddeetteerrnmlimneedd uussiinngE tthhee m~etthhood~s ddeesscerrilbbeedd bhyy CChhiioouu eett.. al. al. (1977) (1977) and FPuu~jiittea eett.. aall.. (1964) C Chhaannnneell ccaattffiisshh ((IIce~taaZlaarruuss ppuunncce~aat~uuss)) were were acclimated acclimated to to the following test conditions for a minimus of 14 days: the followinE temperature, test conditions 211C, 16-hour for Light a minimum of and 8-hour 14 dark phot days: o pe r i o d with temperature, 21~IC, 16-hour light and 8-hour dark phoSoperiod with a 30 minute transition period and were fed daily (Tetra Min). a 30 minute translt~on period a~d were fed daily (Tetra MID). Fu3422, previously impregnated on 3.5 ma Class beads was FM3422, previo~ly i~regnated on 3.5 ~ gl~s beads w~ Placed in & 114 1 aquarius, forming a layer approximstely 2 cm placed ~n a 114 I Rquarlum, ~orm~ng a layer approximately 2 cm above the gravel filter which was then covered by sand. The above the gravel filter ~hich was then covered b~ sand. The test tank was then filled with carbon-filtered well vater. This test r~nk was t~en filled with carbon-filtere~ well wa~er. This systen under continuous aerobic conditions generated a saturated system u~der continuous aerobic conditions generated a saturated water solution of FM3i22, having a final loading ratio of 0.55/ water solution of FM3422, havlng a final ]oading ratio of 0.5g/~. Based on a previous study (1977) which indicated rapid uptake Based on a previous study (1977) which indicated rapid uptake and depuration rates for T3422 in this species, the bioconcentration and depura~lon rates ~or FM3422 in this species, the bioconcentration test was modified so that the uptake and clearance periods were tesl was modified so that th~ upt~e and clearance periods were seven und five days respectively seven and five days respectively. FFoolllloowwiinngg tthhee iinnttrroodduuccttiioonn of o[ the the channel channel catfish catfish into into the the experimental and control aquaria samples of 4 channel catfish and ex~eri~ntal and control aquaria samples of 4 channel catfish and three water samples. top, middle and bottom layer. for PA322 t~ree water samples, lop, middle and bottom layer, for FM342~ uptake analysis were obtained at the following time periods: control uptake analysis were obzained a~ the ~ollowing time period~: control. 11118855..00000033 33MMAA1100006666662211 prior to introduction, 18 s-i4m-ites, one hour, tw hours. four hues. etgat prior hotours, twelve ho introduction,ur1s5, sixteen minutes, ohonuersh,outr.wentwtyo hours. hours, twenty- four ht~ur-~, four eighthohuorusr,s, antwd ealvtethweonutrys-, fsoiuxrteheonurhoinutresr, vetwlsenftyor a per hours, iod of twenty- sfovuernhdoauyrss.. ~nTdheact htawneenltyc-afotruirehhowuerreinttehervn arlsemofoverdtopecriloedaraonfce sCeavnekns dfoarys.two~heourcshisnaed1 fcinaatlfilsyh twraenresfethrerned to & fl removed otow-tchleraoruagnhcesystem wa~vkinsg foflrowtworatheosursthr~odughfintahellytestrtanchsfaemrcreerds otof afouflrowwa-ttherrouvgohlumseysstem phearvin2g h~o1u~rs.ra~Aessathmrpoluignhg ~rheesin~eenst idcehnat~iecrals ot~o tfohautr wofatethrevoulputmakees Phase per 24of this hours. stAudsy~pw~aisngSnrseedgiiaotnely~dfeani~ciicsatledtoaat~da~teromfin~aetedupa~ teer ph~e of th~s s~udy wgs five anIynsd.ividual (whole fve days. i~ed~tely fish, 5-2) i~itia~ed and pooled ~d te~nated tissue samples after (ae) wIenrdelvwlediugahled(,whotliessufeinsih,zedn,~)refarndigpeoraotleedd tsinsdsusetorseadmpliensethyl a(cn=e2t)atewerperiworeit~oedt,het~asnsauleymtiizceadl, derteefrrmiigneartaitoend afoodr sFtIoZrZe.d ole in ethyl ian wore blotced before the weighing procedure. The pooled Sfaimshplewserecobnlsoitstteedd bofefotrhee tfhoellwoewiiKnhgint~isspureo:cedburraen., Tghiellsp,oolLeidver. sfaamlplebsladcdoenrs,istKieddneoyf, ~bpuistfrooltlnotweisntEintsilssuter:actb,raisnk,in.Eilsluss,clelivaeard, aExao]lrerbelnadder, k~dney, E~rolnZest~nal tract, skin, muscle and see lemoTni.osue and water samples vere analyzed fer TX3A22 using 3 HoviotcT-iPssaucekar~dndmwodaetlerSs71~3l~gass ~cehrreomaatnoaglryazpehd efqoruipFpMe3d42~wituhs~n1a~ Hewlett-Pack~rd ~del 5713 K~ ~romato~r~ph e~uipped with an eelleeccttrroonn ccaappttuurree ddeetteeccttoorr ((5i'%i~73)).. SSppeecciiffiiccaattiioonnss a~nndd operating conditions were as follons: stainless sree columelength-s fost conditions vere as ~ollows: stainless s~eel colu~-lenE1h-6 x U/8", column packing snd suppors-10% Carbonsx 20 Kon Chromosors- x I/8"~ col~n packinK and suppor~-lO~ Carbowa~ 20 Mort Chromosorb- W aacciidd wwa~shheedd 6600//8800 m~essh'h.: ooppeerraa~tiinnEg tteemappeerraattuurree--iissootthheerrmmaall 118800CC,, was above 50% ddeet~eecct~oorr--330000CC;; ccaarrrriieerr g~a-s-55~% m~eathnanee iin~ aarrg~oon~.. RReeccoovveerryy rraattee was aboSvteati90s%t.ical treatment of the dats utilized the OM Trac system, MINITARS~a11%~spr~oIgcraaln.~reaBtimoecnotnceonftrtahteiodna~afacuttoirlsizeadndtuhepta3kMeTrraatce sycsotnesm, MsItNaIntTsABweIIreprcoaglrcauml.atedBiboacsoendcenotnraftoiromnulsfeactporrosposaendd buyptaakne ASrTatKe ccoonnm-ittse~ean~dsevweelroepincgalcaulsattaenddarbd~semdethonod ffoo~rulc~oendupcrtoipnogsbediobsyoncentration steteudideesvewliocphinfissh s%1a8n7d7a)r~ method for conductin bioconcen~ration studies wi~h fish 11118855..00000044 33MMAA1100006666662222 --55-- RESULTS RESULTS The water solubility of Fi3422 was 50 ppb (Veith-Comstock techniqTuhee) wactoeurplesdolwuibtihlittyheofaddFeMd342o~bsewravsat5i0onppbtna(tVeitthihs-Cocmh~etmoi~ckal wtaeschnsilqiugeht)lycouvpolleadtilweith(Metnhedela,dde1d077o)b.servation t~a~ this chemical was slUiUsgshiitnnlggy tthhveeolammletithlhoeodd (ddMeeesnsdccerrlii,bbeedd19bb7yy7).CCh~iioouu,, eett.. aall.. (1977) (1977) tthhee aistribution coefficient for FM3422 was determined to be in excess odfist1r0%i,butiinonan cn~-fofcitcaineonlt/vaftoerrFMsy3s4t~e2m.w~Vadleuteesrmionfedthi~so obredeirn oefxcess om~agn1i0t5udeIn ~ are ni-nodci~caantiovle/waof~erthesyshtiegmh.ly Vlailpuoepshiloifc ~mhlasturoerdeorf of the t~egsntitsuudbestaanrcee indicative of the highly lipophl]ic nature of the zeal suIInbnstccaoonnncsseii.ddeerraattiioonn ooff tthhee sslliighhtzllyy vvoollaattiillee nnaattuurree ooff FH3422, FM3422, the test organises vere introduced into the newly filled experinen- the tal Zaeqsu%ariourmgaannids~samwpelriengi~orfodbuoctehd chianntnoelthecantefwilsyh afnidlleedxpoesxupreerimen- wtaalteraqbueagrainumfiafntdeesn~pmliin~ugtesof lbaotterh. channel catfish and exposure waEer beECh Table 1~aiftielelnusmtirnautteess thleatemre.an concentrations of FM3422 in Table la Various layers oifllutshetreaxtpeossutrhee mean water . concentrations The test su b sot~anFcMe342w2as iqn uite evvaerniloyus dilsatyerrisbutoefd thtehroeuxgphoosuutretwheatearq.uarTihuem atsestinsduibcsattaendcebywc~oncqeunit-e etvreantliyonsdiosftr0i.b4u9,ted0.~5h4r.ougahnodut0.5t2huet/a1quoafriuFmHAs2s2 lnindieth~etedtopb,y meiodndeleen- traZions ang lower of 0.49, 0.54. water layer of and the 0.s5qu2auri/um. of FSMi3n4c2e2 FMin342tZhewatsop,premsiedndtle aasnd a lsouwseprenwsai~oen.r leaxyceritaobfiltihtey Guarium. Since of the test org an~i3s4m~s2 was resu ltDirnegseni~n uasnusauaslusD@einsstiuornb,anceeac~oftabtihle~tbyottoofm tsheand~/eFstN31o2r2ganliasymesr wroeusludlticno~ntribute t~onustuhael vadriisatbuirlbiatnyceofofmetahen bcoon~coe~ntrsastnido/nFM3v4a~l2ueslayaser iwnoduilcdated by the mtoagn~ihteudvearoifabitlhietystaolnda~radnercroonrcen(tTraablteion1a)value~ as indicated by the magnlluUdpoen ofana~lheysissIKnofdartOheererxoporsu(rTeabwlaetelra).samples for FMD4Z2 evidencUeponwasanoabltyasiisnedof thtahte etxhipsosumraeterwiaatler samples was bein g forrapiFdMl~y422r,elease d evidence into solu twiaos n ob(tTaaiblneed tha~ 1b). Tthheiss e m~dalteariasluggwe~st bin~ that crosnplcde]nytrarteiloen~sse~ ianplporosaochliunYgioneq u(iTlaibblre iu]nb).v al uTehsesew erdeataatstuarirneeadl w itthah~in concentrtions 3 hour of esxDpporsou~rcehinK equilibrium values were a~laine$ w~hin ] hour exposure. 11118855..00000055 33MMAA1100006666662233 %- -6- TTaabbllee 1a la -- -- PMMeeearaninosCCoonncceenntrtraattiioonn of of FNM22 FM342~. Exposure Exposure Water: Water: Experimental Period Ssaumappliiinngg SSiittee n . ccoonncceennttrraattiloonnSu~i//tt Top ayer 15 15 492.08 Top layer usdare Taver 1 542.08 .49+_.06 ~lddle layer 15 .54+_.06 Lover ayer 1 522.00 Lower layer 15 .52+_.04 "Mean concentration of exposure period + 5.E. aMean concentration of exposure period ~ S.E. Table 1b = Concentration (ppm) during Initial 4 Hours of test' Table ib -- Concentration (ppm) during Initial 4 Hours of testa Sampling Site Sampling Site Top ayer Top layer Muiiddddllee Tlaayyeerr DLoowveerr llaayyeerr 15 win 15 rain. .a199 =.31 2 .23 3 hour 1 hour a.4s5 .14s9 54 .54 2 hour 2 hour a.43 a.47 a .47 PExpressed as s1/t 4 hour 4 hour 5.35 .a422 55 ,55 WWHHOOLLEE FFIISSHH UUPPTTAAKKEE AANYDD CCLLEEAARRAANNCCEE UUppttaakkee ooff the the fflluuoorroocchheemmiiccaall FTMH334Z222 bbyy cchhaannnneell ccaattffiisshh hhaass bbeeeenn ttaabbuullaatteedd ((TTaabbllee 22)) aanndd iilllluussttrraatteedd ((FFiiggss.. 21. , 22)).. DDuurriinngg the first 23 our exposure period, both Fish A and Fish 8 showed the first 24 hour exposure period, both Fish A and Flsh B showed 4a rapid r~pid uuppttaakkee ooff tthhee tteesstt ssuubbssttaannccee.. TThhiiss iinniittiiaall wuppttsakkee rraattee mmaayy bbee aattttrriibbuuttaabbllee ttoo mmoovveemmeenntt ooff FFM3344Z222 subsequent binding to lipophilic tissues. saeAcrroossslssowettrhhee rc aiitnnelteeggor uufmmeeFnnAt~MZww2iitthh subsequent btndin~ to lipophilic tissues. A slower rate of FM34~2 uptake was noted for both organisms which was possibly accounted for uptake was noted for bo%h or~nism,~ which wa.% possibly accounted for by a decressed water/organism concentration gradient. No uptake by a decreased water/organism concenlration ~rsd~ent. No uptake pP]laattee~a.uu iinnddiiccaattiivvee ooff aa sstteeaaddsy--ssttaattee waass oobbttaaiinneedd ffoolllloowwiinn~g cannaallyyssiiss 1118855..00000066 33MMAA1100006666662244 r= -7- Table Table hour 2 - FN3422 Uptake 2 rime -' FM3422 Uptske Time 28 min. 4 2481 2 nhhhoooowuuurrrrsss hhoouurrss 11121602268 nhhnhhoooooouuuuuurrrrrrssssss 42422B40488 rhnhhhooooouuuuuerrrrrsssss 199276602 hhhhoooouuuurrr~sss 111124460448 hhhhoooouuuurrrrssss. 168 ho~rs by Chanae) Fie A by Ch&nne~ :1 1.249 16 se58 5&62 10a641 i2110332:422 a1189100 2s3352125z0102 Catfish Cstfish (lotalcma (rI iee n ~ 1:4 E1~2-d09 16sn170e04 212111150330 222055177 221207311998 158 putas! pu~eatus) a* EExxpprreesssseedd 1ass vals. ooff FF~M 33442222 ccoonntteenntt ooff tthhoossee ffiisshh ccoommpprriissiinngg tthhee ccoommppoossiittee oorrggaanniissmm AA ((FFiigguurree 11))., TThhee 1166S8--hnoouurr vvaalluuee ffoorr tthhee tteesstt fflluuoorroocch~eemmiiccaall mmaayy be a outlier us these values encompessiag the period from 72 = be an outlier a~ these values encompassing the period from 72 - 120 hours suggest a plateau (steady state) at TY 3422 concentra- 120 hours suggest a plateau (steady state) at FM 3422 concentra- ttiioonnss oo~f ~~220000 ~ugg//gg.. AA ppllautteeasuu eef~feecctt wwaass oobbsseerrvveedd ttoo ooccccuurr w wiitthh sample B, having an uptake value of approximately 220 ug/g PH 3422 sample B, having an uptake value of approximately 220 ~g/~ FM 3422 ((FFiigguurree 22)).. CCoonncceennttrraattiioonnss ooff PFMU 33442222 bbiiooasccccuummullaatteedd bbyy tthheessee tteesstt oorrgEaanniJssemss wweerree oobbsseerrvveedd ttoo vvaarryy Iinnddeeppeennddeenntt ooff wwhhoollee ffiisshh wweeiigghhtt.. CClleeaarraannccee oof~ FFiMM 33442222 bbyy tthhee cchhaaannneel) ccaattffiisshh rreeqquuiirreedd iinn eexxcceessss ooff 55 ddaayyss ((TTaabbllee 33)). 11118855..00000077 33MMAA1100006666662255 8 -8- Table 3 -- PU3422 Clearance of Tetalarus punciatas TTiimmee 11155 nommiutnrn.. 242I hhhnoooouuuurrrrsss 12848 hhnnoooouuuurrrrssss 21110662 hhhBoooouuuurrrrssss 24224480 hhhnoooouuuurrrrssss 6477822 hhhhoooouuuurrrrssss 11922600 hhhooouuurrrs~s o~hlolee FFiisshh AA 323060896 222256852902 25226663000 ~232358355. 22233-3778,b 212300-%00 101103866 WWhoolee FFiisshh BB 22311996 232310406929 222244042822 12Z175077567 2122009511050 222122297670 75226 78 a EExxpprreesssseedd aass ~vgg//gg-. b sSagmmppllee lloosstt TTIISSSSUUEE AANNAALLYYSSIISS:: YMUUSSCCLLEE OOff tthhee ttiissssuuee aannaallyyzzeedd ffoorr FFMN33442222,, tthhee mmuussccllee llaayyeerr ooff tthhee cchhaannnneell ccaattffiisshh vwaass ffoouunndd ttoo ppoosssseessss tthhee lleeaasstt pprrooppeennssiittyy ttoo bbiiooaaccccuummuullaattee tthhiiss fflluuoorroocchheemmitccaall (Table (Table 4, 4, Figure Figure 3). 3). A A pPllaatteeasuu eeffffeecctt wwaass oobbsseerrvveedd Ttoo OocCcCuUr iinn tthhee ccoonncceennttrraattiioonn rraannggee ooff 110000--220000 v~gg//gg ((TTaabbllee 44)).. TTiissssuuee wweeiigghhtt wwaass aann iinnddeeppeennddeenntt vvaarriiaabbllee,, nnoott ~affffeecct~iinngE tthhee bbiiooaaccccuummuullaattiioonn lleevveell ooff FFHM33442222.. DDeeppuurr~attliconn ooff tthhee ssuubbjjeecctt fflluuoorroocchheemmiiccaall,, FFMU334A2Z22., wwaass ddeellaayyeedd,, a&pppprrooxxiimmaattee]lyy 5500%% ooff tthhee mmaatteerriiaal~ hh&avvtinngE cclleeaarreedd wwi~tthhiinn ffoouurr ddaavyss ((FFiig~uurree 33 TTaabbllee 53)). TTIISSSSUUEE AAN~AALLYYSSIISS -- BBRRAAII~N0. GGAASSTTRROOIIN~TrEES~TTIIN~AALL TTRRAACCTT UUppttaakkee oof~ FFMM33442222 bbyy bbrraaii~n aanndd tthhee g~assttrrooinntteess1t~inn=all t~rra~cct~ wvaass eelleevvaatteedd dduuee ttoo tthhee 113~ppiidd nnaattuurree ooff tthheessee mmaatteerriiaallss (~TTaabbllee G6)). BBrra~iinn uuppttaakkee ooff FFNM33442222 Ccoonnttiinnuueedd tThRrToOuUgEhNoOuLtT tthhee eexxppeer?immeenntt ((FFiigguurree 44)) 11118855..00000088 33MMAA1100006666662266 -o- -9- TTaabbllee 44 --I--otFFaM Ula33r44u22s~2-PuUUrppctttaaakktuees bbMyyuscle Icta~a~ Pu~nrat~s ~cle CToTinim~teerol C11135ohnom mtuirlnron.,l 4221 hhhhoooouuuurrrrsss. 12488 hhhhoooouuuurrrrssss 21110266 hhhhoooouuuurrrrssss 22424480 hhhhoooouuuurrrrssss 94775822 hhhhoooouuuurrrrssss 19205 nhoouursrs. 111124460448 hh~hoooouuuurrsrrsss. 168 hours ~Muu0ss.cc1llee <0.1 3'1 <0.1 15035 221a220 333a8189 166141198 111112238775 111135595373 47197 147 * EExxpprreesssseedd ~ass u~agl/sg.. TTaabbllee 55 ---- TTiimmee 11155 nmomiuinnr.. ~421 hhhhoooouuuurrrrsss 12488 hhhhoooouuuurrrrssss 21110626 hhhnoooouuuurrrrssss 42224084 hhnhoooouuuurrrrssss 34776228 hhhhoooouuuurrrrssss 11292600 hhhooouuurrrsss FFUM33442222 CClleeaarraannccee ooff M Muussccllee 11112s87 111I20207888 111144427878 1u1184zm18? I15170752 16770772 677922 a? EExxpprreesssseedd aass ~ugg//cg.. IIoet~oollaar~uusa ppuunmtaattuuss mmuussccllee"a 11118855..00000099 33MMAA1100006666662277 "10 -10- TTaabbllee 66 ---- FF{MhU3e4422B~2a-sUtUprptotaiaknkteeosbbtyyinTIaoolta~ltaarma~sctppuunoncf~taa~Tt-ou~ssalbbmrruaaeiinnpttuiinsscsstuuaeetus~sandd CToTCfiniemmtnieetrtotell BB<<3r0rua.a1ii-nn GGaassttrrootianw8<tt0e1ae.s1sttiinnaall Trace Tract 2212I1 5hhhhnooosooiuuuuunrrrrr.sss 0252 8 28 i3<360, l 1112264&8 hhhhhhoooooouuuuuurrrrrrssssss 1111113015ss0050 12 41 554 1=0110 22210406 hhhhoooouuuurrrrssss 22214244809 4284 hhoouurrss 325225 222i210001%e1169 34778832 nhhhoooouuuurrrrssss 3233a528628 19260 hhoouurrss 6S0o66 ==si230 510 533 . 111124630484 hnhhoooouuuurrrrsss 59650985558 6a5580s384 168 hours 905 533 2 EExxpprraesssseedd aass vis Table Table 7 7 -- -- oFFfM U334T4e22t22atCCanllieesaarrpaaunnnccseetaootffBBraraiinn and and the the Gastrointnstinal Gastrointestinal Tract Tract of I~a~azu8 pun~z~z'#u~a Tee Brain Br~n GGaassttrrooiinntteessttiinnaall TTrraRcctt 21111 55hhhomoomuiuuinnrrr..sss 11617m86512212 $25523038210015 1228482 hhhhhhoooooouuuuuurrrrrrssssss s6GS75i0081112222 525333006200257273 222i11004~26 nhhhnhoooooouuuuuurrrrrrssssss 582 si~18 35529559 1155228200600455355 24 1848 97272 hnhhhhoooooouuuuuurrrrrrssssss 523 35586 i35z0450 2523530~5539444330 19260 hhoouurrss i423 nz390 120 hours 417 712 a EExxpprreesssseedd aass uwg//eg. 1118855..00001100 33MMAA1100006666662288 ue -11- TTaabbllee 88 ---- FFt~uhe3344C22h22annUUepplttaukkCeeatfbbiyyshLL~ivveerr,, Kidaey, Kidney, and ~nd Gall Gall Bladder Bladder of the Channel Cgtfish TTiimmee LiLivveerr 11551 mmhiionnu..r <100..1i 2241 hhhhoooouuuurrrrsss 311I1IZ 12848 hhhhoooouuuurrrrssss &633171 21110266 hhhhoooouuuurrrrssss 16998199 32224344083 hhhnnnoooooouuuuuurrrrrrssssss 121431364622911993 192796026 hhhhoooouuuurrrrssss 4s42866t119 111124460448 hhnhoooouuuurrrrssss. 345836680941 168 hours 561 a EExxpprreesssseedd aass ~ugg//g.. KKiiddaneeyy <00..11I E<<A00,,'I1I F735E779] 149970733 118499999 2a210s080e09 333345110953 413554229 GGaallll BBllaaddddeerr 0<<001.,I1 <<pw00e.l.tI1 15o<<800l..Ii 221214541585 1232244872213 1111553587885335 2231882577673153 11333882006851 TTaabbllee 9 8 ---- ToFfHM T33e44t222a2taCCrllueesaarraapmnuccneectabb}ty,usLLi~vveerr,, Kidasy, Klchuey, and and Gall Gall Bladder Bladder TiTimmee 1155211 nnhm hioooinuunurr.rs 122483 hhhhoooouuuurrrrssss hhoouurrss 21110266 nnhhoooouuuurrrrssss 232247404828 hhnhhhoooooouuuuuurrrrrrssssss 199276620 hhhhoooouuuurrrrssss 120 hours Laver Liver 656575050504408 77575079879 445744028678 447a2223008 534751475635 031777666 507 Kidney Kidney 22517641 54433637979 354395490970 s3i55561s935 232385561995 210328502313 221888525 Gall Blaader Gall Bladder 131559440338 4511902208836868 353307725111008 244232442497517 823349919110522 2111824212121101 s61444991717 EExxpprreesssseedd 1ass uugg//8g.. 11118855..00001111 33MMAA1100006666662299 : -12- -12- With no apparent plateau effect. At 198 h the concentration of with no apparent plateau effect, At 16g h the concentration of M3422 1n this organ was equivalent to 905ug/g tissue. The brain FM3422 in this organ was equivalent ~o 905~g/g tLseue. The brain tissue levels of FN3422 remained elevated upon completion of the tissue levels of FM3422 remained elevated upon completion of the Clearance phase of this test; 417ug/g (Table 7, Figure 4) clearance phase of this test; 417,g/g (Table 7, Figure 4). TThhee ggaassttrrooiinn% teessttiinnaall ttrraacctt uuppttaakkee ooff FFM~33442222 iiddeennttiiffiieedd three three pphhaasseess:: rr~appildd ~anndd aslloo~w uupptta~kee c~oom~ponneennttss w wiitthh aa ddeem~onnssttrraabbllee ppllaatteeasuu ((TTaabbllee 66,, PFiigguurree 55)).. T~hhee ffiirrsstt ttwwoo pphhaasseess ppeerresiissZteedd ffoorr 2244 aanndd 48 nours respectively while the platesu effect was minimally of 96 48 hours respectively ~hlle the plateau effect hhoouur~dduurraattiioonn.. AAss mmaayy bbee nnootteedd ((TTaabbllee 77 aanndd FFi~gguurree 55))., tthhiiss oorrggaann 4~4ld4 nnoott cclleeaarr ~FU3S442222 rreeaadailllyy,, rr~atthheerr aann ilnneexxppll~iccaabbllee rriissee in oorrggaann ccoonntteenn%t ooff M~33442222oOccccuurrr~edd dduurriln~ggtthhee llaaZtt~eerr ssttaaggeess ooff ddee-- ppuurraaZtiioonn.. TTIISSSSUUEE A~NY ALSYSIISS -- G Ga~llllbbllaaddddeerr TThaiiss oorrggaann ddeemmoonnststrraatteedd aa ddeellaayyeedd ""uuppttgakkee"" ooff FFi~313442222,, ddeetteeccttaabbllee lleevveellss bbeeiinngg iinniittiiaallllyy nnootteedd aatt 1122 hhoouurrss eexxppoossuurree ((TTaabbllee 88).). TThhee ""uupptta~kee"" ppaatttteerrnn ddiiffffeerreedd ffrroomm tthhoossee ooff ootthheerr oorrggaann ssyysstteem~s bbeeiinngg ~anaallyyzzeedd iinn tthhaatt tthhee ccoonncceennttrraattiioonn ooff fflluuoorrooccbheemmiiccaa~l iinnccrreeaasseedd tthhrroouugghhoouutt tthhee eexxppoossuurree ppeerriioodd.. TThhiiss oorrggaann sshheowweedd aanne~rrraattiicc cclleeaarr-- aannccee ppaatttteerrnn,, aann iinniittiiaall ddeeppuurtaattiioonn ffoolllloowweedd bbyy iinnccrreea~seedd lleovveellss ooff f~lluuoorroocch~eemmicicaall,, aa pphneennoommeennconn w~hnilcc~h ~ vas oobVs~eerrvvee~d ttahrroouugg~hoouutt tthhee rreemmaaiinnddeerr ooff tthhee eexxppeerriimmeenntt ((TTaabbllee 99 FFiigguurree 6) The remaining tissues tested exhibited similar levels of T~e remaining tissues tested e~ibited similar levels 0f FFM H33442222 uuppttaakkee.. IInn aallll ccaasseess ~a sstteeaaddyy--ssttaattee ccoonncceennttrraattiioonn could could bbee ccaallccuullaatteedd uussiinngg tthhee ppllaatteeaauu mmeeththood.d. D Deeppuurtaaitiioonn ddaattaa ddiidd not establish definitive evidence for the clearance of FM3422 by these establish definitive evidence tot the clearance of FM3422 by t~ese ttiissssuueess:: g giillllss,, sskkeelleettoonn aanndd sskkiinn.. TTh~ee l]~ivveerr ddiidd eexxhhiibbiitt pronounced pronounced ddeeppuurtaattiioonn ooff tthhee ttee~stt cchheemmiiccaall ffoolllloowwee~d bbyy rraappiidd uuppttaakkee., a phena phen- oommeennoon~ aassssoocciiaatteedd w wittlhh ddeeppuurtaattiioonn ddaa~tva oobbtI.a~iinaee~d ffoorr Zthbee g~assttroro- BLEstinal tract and the gal) Miadder 11118855..00001122 33MMAA1100006666663300 1 -13- Te TAble 1I00 -- Comp~latolnonFaocftaWrhsoluerFiinsgh Ean rOrgpantooSyFvsitseaumzzrliSe Sample centra~ion Factors rege DurinsioEcxpoonscuernetratcoioFnM3422 Sample yetgbtc 8ioccncentr.~ion Whole Tish 01 10.8g245 575 Factor mote Whole TFllsahn ##12 11.5024 lO.S+_~.5 06575 Skeleton Whole Fish #2 1.82.3 11.5~2.4 11.8+2.3 so406 501 SSkeenleton 2.909 53 GSkiins s12.2 ~.9~.9 534 saz GLiilvelrs Ev .64+.2 an542 GKLKiuiidsdvnnteeerryyosstestioal ES .51+. 1 1..3462!..4i 474 700 1700890 GGaasltroBilnatdedsertinal 10.341+..042 261506048% BGraaliln Bladder 191.03 ,03+ .02 .19+ .03 1044 26548d 1344 MBurszcinle 7.082.0 m1 Muscle 7.0+~.0 ~81 "Sa3aBCvCFeFr-a-geccaalwlcacutulelaratteecddoncuuessniitnnrggatppilloaantteeaaouuf mmFee3tt2hh2oo.dd C.52 ppm b"C"AhDsvaaetevtaeran~gee,xxdpparywreaestsBsesCereFddvcaosalssnuceemm.enewtannrsabt=!aieonS3ns..D0e..ofof FMp3l4a2t2e,au ~.e5f2fecptp.m Seven day BCF value, absense of piateau effect. 1185.0013 1185.0013 33MMAA1100006666663311 --1u4-- Table 11 -- (UCphtaannkeel sSaammppilee wile Fish A ~hole Fish A mole Fish B Br~ahoilne Fish B GGGBiarnlsalteinsrointestinal Gastro"iTnrtaecst tinal Tract LiLvievrer Gall Bladder Kidney Gall Bladder MKuisdcnleey Muscle skin SkSekilneton Skeleton CRaactteisCn)onstant of FX32: ia U cUpoptntasaktkeaentrraatcteeomposite Rapid R~pid co3n.s2t0a0n3t composite 5.7 63..24+31..03 5 .? 5.6 67..47+023..14 8.6 9.3 57..740+32..34 9.3 7.3 56..40+:32..43 7.3 7.3 6.0+2.4 7.3 44.550+22..33 66..33 82a? - 48.2.010a.8 5.-4 41..08~:01..46 -5.4 6.73.2 1.8+0.6b 5.-9 63..72+031.20 3s8.9 3.1+1.0 3.5 fotalams PPhhaassee punotati: SSllooww PPhhaassee 22..77 33..99 55.,11 22..77 14..44 33.66 3.- 0 3.0 3- 6 3.6 2.4 2.4 2a UVUpaptltauakkeese rsraaittmeeilaccroonnsastttaannatltl aattt is11e6688 phheorouiurorssds b Values simS, far a~ all time periods 1185.0014 1185.0014 33MMAA1100006666663322 5 -15- A ttaabbuullaattiloonn ooff tthhee bbilooccoonncceennttrraatliioonn factors ~actors (ECF) (~CF) determined determined at an approximate steady state, using the platesu method provided eatvidaen ncaepprdoexmiomnastteratsitnegadythestaltiep,ophuisliincgittyheofplaFtMe3a4u22 me(tThaoblde,pr1o0v) ided evidence Although dtheemognasltlratbilnagddetrhe polsispeopshsleldlctihtey hoi~gheFsMt342B2CP(Tfaobrlecomi0p)a.rative Although purposes the gall bladder these data can be ignored possessed the for highest ressous BCF to be for dis cussed. Of comparative purposes these data can be ignored ~or reasons to be discussed. Of the remaining organ systems the propensity to bioaccumulate FM3422 the was remaining organ systems the mast prominent in the braln panrod pgeansstirtyointotesbtioiancaclum truaclta.te FM Th3e422edible was ~z~ prominent n the braln and gastrointestlnal tract. The edible portion, muscle, minimally bioconcentrated F3422 portion, muscle, minlmally bloconcentrated F~3422. AA ttaabbuullaattiioonn oo~f u upptta~kee rate rate constants constanls for ~r whole whole fish fish and and organ systens provides further evidence that the lipophilic nature of organ syste~ provldes ~urther evidence that ~he lipophilic nature o~ Fu3422 does influence uptake rate (Table 11). Both brain and the FM3422 does influence uplake rate (Table 11). Bo~h brain and gastrointestinal tract had high uptake rate constants. A second gastroinlestlual tract had high up1~e rate constants. A second premise may be established that being the greater the surface ares premise may be es~abllsbed that benE the greater the surface area exposed to the material the greater the uptake rate, hence elevated e~osed ~o the material the greater the up1~e rate, hence elevated uup~tta~kee rraattee ccoonnssttaannttss ffoorr bbootthh sskkiinn and and ills. gills. The former instance The for~r i~stance provides a physiological basis for uptake while in the latter case provides a p~ysiological basis ~or uptake while in the latter case bbootthh mmeecchhaanniiccaall aancdd physiological physiological mechanisms ~chansms were were operative operative. Clearance rate constants could not be calculated due to data Clearance rate constacts could nol be calculated due ~o data vvaarriiaabbiilliittyy. DpIrSsCcuUsSsSiIoOnN IInn tthheessee ssttuuddiieess tthhee pprriinncciippaall mmeecchhaan~isse~ss ffoorr inniitti~aal~ uupptta~kee of FU3422 were the gills and integument. Substantisting evidence consist FM3422 were the gill~ and integument. Substantiating evidence consist- ing of uptake rate constants which exceeded all cther organ systems ex- in of upt~e raze constant~ which exceeded R~I ether orgR~ syste~ copting brain. gastrointestinal tract and the gall bladder. The gl) eir- cepting brain, gastrointestinal tracl an~ abe gall bladder. T~e gill clr- ccuullasttiioonn ffuunnccttiioonnss aass a~ ttrraannssppoorrtt ssyysstteemm ddiissppeerrssiinngg tthhee fflluuoorroocchheemmiiccaall to various sites in the bods. The importance of this system in terms to various s~es in t~e body. The importance of this syslem in term~ of both uptake and transport of foreign chemicals has been the of bomb uptake and transportS, of foreigu c~emlca~s has been the 11118855..00001155 33MMAA1100006666663333 --1166-- subject of recent papers by Granmo and Kolberg (1975) and Bass saunbdjeHcetathof (1r9e7c7e)n.t papers by Granmo and Kollberg (:97q) and Bass and Movement Heath (1977). of PU3422 across the integument also contributes to the body Movement of FM3422 across burden of FHIAZ2 based on UthpetakienteTgautmeenctonsatlasnots.contrDiebfuitneistiotno otfhe thbeodyextbeunrtdenofofthiFsM34c2o2ntbraisbeudtioonn ucpatnnaokte breazedetcoeirtm~iznaendts.as Dtehefineixtaicotn tor~antshpeoretxtepnatthwoa~y thhaiss ncootntrbeiebnutieosntabclainsnohtedbe determined as the exact transportOupratphrwaeyviohuass sntotudybee(n1977) did demonstrate the existence of a highly Our 1'psd plraeyveirouusndesr~luydying(19th7e7)Skdiind Wdheimocnhs~trhaeto,rrettihcealelxyistbeansecde of on a htihgehllyipo1p~hpiildicIiatyyer o funFdYe3r4l2y2lngshotuheld skin which serve as a Zshteoor~aegtetca(lbliyndibnags)ed siotn e the for tlhipsophcihZemiiccatly. o~VaFsMc3u4l2a2r spheorufludsisoenrveof asthiasstaorreaagecou(lbdinsdeirngv)e site to ~or tra nstphoirst chtehemicfallu.orocVhaesmciuclaalr pteor~outshleron soiftesthiisn tahreea bocdoyu,ldhosveervveer,to tthreansmpaogrntitutdhee o~fuopreorcfhuesmiocnalis to an outshkenrowsni.tesSi miin l atrhl~ y .bodiyf, onheowevvieerw,s the the magnitude 1ipid laye of r asper&~ubsiinodningis an site unfkonrowFnU.32S2i,miltahrelyn,atuir~e one of views the b~ihendilnigpidbecloanyeesr ss of res lebvianndcieng isnitdeete~romrinFiM3n4g22t,he the nature eae with wohlicthhematerial binding may be crbaencsop~osrtoed reellseevwahnecre e in determining the e~;e with whic~ may more behig~hrla~Iyttnswwplaaoissrptiedddd-eecm~ooennnlstsstaetriwrahna~eitreneegdd. previously in oprrgeavnisoustleyndeidn our latoratory that the otuorbiloacboonrcaetnotrryat~ehatthethe smuobrje e chtighfllyuorlaicphiedm-iccoanltamionrieng roeragdailnys. tended This tfoindbion<g~ohnacsenbtereante the sssauunubdbbjssettgcaaatnnstttiri~aoaltituneeotddreoscbbtyy~ienmttaihhlceea]pptrrreaemcssoteernnettbyresstnttuudhddeiyy~..yc.ircTTrruTahalninassstppooorfrryittndsiyoonffsgt;eFFmhMMa33s4Eo2f222betehttneoo the brain the fish seems saenldf-geavsitdreonitnteasstitnhaelse troarcgta, nsby the are hicgihrlcyulavatsocruylarsy.s~.eEmvio~dentchee o~bisthainseede~in stheilsf-estvutddyen~sugasgestthsesethaotrgatnhse saurbejehcitghlcyhemviacsacluRairs. houEnvdidetnicgehtloybtaasineidt this oes snottudydepsuurgagteestsapptrheactiantlhye. sub~Beyctimpclhiecmaitcialon is a btoiumnidlartisgihttulyatiaosn may does not exist at depurate the oil laapyperre/ciinatbe]g~u.e ntBy iinmtpelr~fcaactei,on thaer~einmyilarredusciitnugatitohne may oevxeisrtallat cotnhetriobilutiloanyeofr/tihnetein~tnetgumeinntterafsacae,soutrhceereboyf rfelduuorcoicnhgemtihceal for ootvheerrallorgcaonnstriibn uttihoen boodfy the inlegu~nt as a sourc~= of fluorochemica] for other organs in Organs cthoentrboidbyu.ting to the digestive process of lstalsme runstatus Organs contributin to the di~es~.ive pro~:ess of I~,t~=~r 1185.0016 1185.0016 33MMAA1100006666663344 --1177-- presented an interesting profile. The gall bladde-, serving as a preresseernvoteidr fanor inbiteleremsitinnugfacptrucrfei3deb.y The the gliavlelr,blapdodses:e-s, sesedrvthneggraesataest rceosnecervntoriartifoonr boft~eflm uoarnoucfhaecmtiucreadl boybsethrevedlivienr,thepsoessesstsueddiesth.e When greatest concentration Samples were obotf aifnlueodrofcohrem FNi3c4a2l 2 oabnsaelrvyesdis ,in d ithsetseen tisotundoief~t. he ~geanll samples bladder were obtained was observed, ifonrdicFa~t3i4n2g2 athnaatlysaits,ourdisstaemnptl~iLnong of the gal~ time we were bladder was in reality anoablsyerzviendg, a icnodnicceanttirnagtetdha~s a~ amp our le of sampl.~ng bile. time It is we were also pirnobraeballeitythaatnalthyizsingorggancopnacretnitcriaptaetdessamipnletheofebxiclree,sionIt of~s FMa3l4s2o2 from probable the body. that The tchiosmpoosrigtainonparoftlbeitlpeateiss in the sxcre~lon of such that given the FlMi~p4o2p2hilfircoimty the body. The composition of FU 3422, binding sites, of bile complex atisio nsucahnd/~hoar~ cgoinvjeungattiheo n lipophilXcity of this fol~uoFrMoc3h4e2m~i,cablindtoinbgi si~es, liary cocmopmopnleenxtastioins aanddi/sotrinocotn.~puogsastiiboinliotfy.thisCon- tfrlaucotrioocnhemoif~atlhe togalblilibalrayddecromwpiotnhenttshe isrossuldtiasnttincetmptpyoisnsgibiolfitiyt.s Con- ctoranctteinotns oifntothethegalglasbtlroaidndteerstwi~ntahl thteracrtesmualy~anatccoeumnpttyifnogr of th e its sp o ra d i c contents into nature of the ctlhee ar@aanscteroicnutrevestifnoarl t~ae~ may this organ. account for the sporadic nature of the clearance One may view the curve ~or this organ. sequence of events occuring in the depuration One may view the sequence of events oocurin~: in the deputation pphhaassee ooff tthhiiss ssttuuddyy sass ii~t rreellaatteess ttoo tthhee ddi~ggeessttiivvee ssyysstteemm iinn tthhee following manner: FH3422 is cleared at a measurabe rate by Vfaorliloouwsin~orgmaannsn,er:beinFgM34t2r2ansispor~tleedaretdo tathe a lmievearsurbyable`heractiercubylatory various system. organs, Io the being ~ranspor~ed to liver. F322 either b%ihendsl,ivecrombpylex~.ehse circulatory and/or becomes system. In a conjugate the of nelwilvyer,manFuMf34a2c2tureeidthebirleb.indsT,he ~omplexes bile -& and/or then st o becomes red in a conjugate o~ newly manufactured bile. The bile :s then stored in tthhee ggaallll bbllaaddddeerr bbeeiinngg eexxpprreesssseedd iinnttoo tthhee dduuooddeennaall aarreeaa ooff tthhee intestine. This material may-then be either excreted within fecal matter inles~ine. and/or some TFhMi3s422matmeayriaulndemraygo,.r~ee-nupbteakeeitfhoerr beoxdcirlerteddiswtirtihbiuntifoencal matter and/or some FM342~ may undergo re-uptake for bodil~' distribution. EExccrreett~ioo.n ooff FFMM33442222 1Iss nnoott Ssoolleellyy vviiaa ffeecca~ mmaatttteerr aass za similar scenario can be described for renal clearance wherein elevated similar scenario levels of FN3422 can are bmeaindteasicnreidbedthrfoourghrentahle clearance wherein first "2 hours of deelpeuvra-ted levels of FM3422 are maintained through the first "'2 hours of depur- 11118855..00001177 33MMAA1100006666663355 --1188-- 41d TThhee eeddiibbllee ppoorrttiioonn ooff not bioaccumulate FN3422 the channel catf.sh, the the to anchaanppnreel cicaabtfl:e.shex, the tent muscle fillet, smuubssctlae ntfi~altlientg, did our pnroetviboiuosacocbusmeurlvaatteioFnM34f2o2r tthoisan tiaspspuree.ciable extent Substantiating our prevIinougseneorbasle,rvantoioandvefrosretshiisgnstiwsseuree. observed during the duration of the eIxn pegreinmereanlt, atnotesatdivnegrseto signs the nwoenr-etoxobisce)n-avteudreduorfingthitshe cdhuermiactailon oufndetrhe theexpecroinmdeinttionastteemstpilnogyedto inthethinson-ttesotx.ic nature of this chemical under t~e condizions employed in r~Is rest. concLUSIONS CONCLUS IONS This study of the ability of the chanawl catfish (foalarus punctatTuhtsio)s bsituodcyoncoofnttrhaeteabitlhietyfloufortohcehemcihcaanlnelFU3c4a2t2fishhas led to tho pfuo,l~laotwui=n)gtoco~nciloucsoinocnesn:tra~e ~he fluo~oa~emi~Rl FM3422 h~ l~d to 1. followin~ cBoontchluslliopnosp:hilic organs and organs possessing a large I. Both surface area at tlhiepowpa~tielri/corogragnansintanedrfaocreganpsosspeossssestsheinghigahelsatrgeuptake sruartfeacceonsatraenatsa.t the water/organ interface possess the hi.eat uptake ra~e constants. 2. Tne brain and gastrointestinal tract have BCF's in excess of 2. 10% due The to thberailnipoapnhdilgiacstrnoaitunrteestofinatlhe tra,~t have subject f lBuCoFr'osch emn i ceaxlcess of ~03 due zo the l~pophilic nature o~ the sub~ec~ fluoroch~mical. 3. The gall bladder duo to its storagn function shoved the highest 3,conc~eentrgaatlilonblaodfdeFrN34d2u2e to on its ~torag~ function a ug/g bass. showed the hghes~ concentration of FM3422 on a ~g/g 4. Whole fish or organ weight was an .ndependent variable, not a de4,termWihnoalnet fish in or the boirogcaonncweenitgrhtatiwoans an of _ndependent 322. variable, not a d5e.termEixncarnettioInn otfheFbMi34o2c2oncceonn~srisat~sionof obfoth urinary and fecal Excretion of FM3422 consists of bo~:h urinary and ppaatthhwwaayyss. 6. Clearance of FM3422 by components of the digestive system contribu6t, es Clearance of FM3422 by to the erratic nature ocfomptohenendtespuroaftitohne digestive curves system contributes 7. to the Fu3422 aterrtaheticexpnoastuurree ocfonctehentrdaetpiuntnatidoind curves. not elicit signs of toxic7.ity.~3t4h2e2refao~ret,he unedxeprosutrhee ccoonndcietnitornastioonf did this noetxpeerliimceintt,sigtnhsi s offluotrooxcihceitmyi,calthecraenfobree,conusniddeerretdhe ncono-ntdoixtiico.ns of this experiment, this fluorochemical can be considered non-toxic. A ier AN feo ANW!vm~ 11118855..00001188 33MMAA1100006666663366 | --1199-- sB iIsBLLiIoOcGRRaAPPRHYY 1. I. BBTuassass,, nWMiicchhhaaeeell L. L. sad and Alan Alan G. G. Meath. Heath. Water Research 11: Wat,.*r Rese&rch I--I: 2. 4B9u7r-s5e0t2e,, B1.977.Science 174:608, 1971. 2. Burnett, R. Science 174:606, 1971. 33. Chioonu,CC. TT., TFhreaed:, SVe. tH., eSchic mendd4h lnvgs, lB).or~.y, and 4. EKaochonne,rt,JonR.n -L.ConEtnrvm.snS,ci.ASTTeHchD.arIe--1:G4u7i5,de.1i9n7e7s., 1977. 5.4. lnabarawy, Eaton, John U-. T. Techaical Chairman, ASTN Report, 1977. Draft GuideLines, 1877, 65.. fPuagdica, T., Elnabarawy, Fuji~a, T., Imssa, M. T. lwas~, J., Hasech, C. J. An Chem. Technical Report, 197"~. J., Hansch, C. J. Am Chem. Soc. Soc. 88:5175. 8__6:5175, 7. G1r9a6s4m,o, A. and 5. Kollbers. Water Research 10:189, 1976. 5. GGurasntmaof, sAo.nC,a.ndG.S. KEnovl.lbeSrcKi.. TeTcha.ter4R:e8s4e,aJ-1c9h70I.0:189, 1976. 98.. MGeunsdtearf,sonn,. C.TeGch. nicEanvl. ReSpclo.rt,Tec1h9.77.~:814, 1970. 19.. goi8n,t.a0 Comtock . Mendel, A. Technical Report, 4. 3. 1977. Fi Ren. Bord Ca. Vei~h, G. D. and Comstock, V. M. J, Fish Res. Board Can. 10. weiter, 32: 1849, A. N.1975. Technical Report, 1977. 11. Welter, A. 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