Document O1JrK8Ezm43qzkq5xNEJ8Grxp

ASFDuco20252027022 Table 3 DbiesntzroiibcutaicoindoofnrasdoiiolaLctUiFviAty2.a4ftaenrdapipnlciucbaattiioonnofun"dCe4r{raeirfolbuiocrcoomnedtihtoixoyns) [% TAR] ACNMO ATClNiMeO Totalexe O=D Acc1t2one tracted w81z7 Tnrra 503 T0o0 nawa. 2p3x) T1o0r2s2 si1s 112s5 979s4 0705 n0a00. 2169.2 1a0b2s0 ssass 112265 7124 a7r8 000%0 119910 558833 14402 aiss 15880 3o500o0w 1a0408 s50i 2248 171)s s2027 0o0ot0 50 2or7a 2250 i2)2 a3rs 221 oooott aa74 s5u3s8 77 0078 o0s2 1130 6i1r 00000 || aatts sors. mean| 0057 o0a4 i11 5s9a ooom | | aasd 5s8s5s o0s5 0044 10s0 s5i5a1 o0o0 || aas2d || t1o0o1os 0055 o0a4 0099 st5a93000%00 3037.92 5575.34 o0s3 0043 a0ss 6sss 0o0m sa2s [s0603s 0034 0033 a0ss 66ss o0om asrsa | i59z8 0022 0023 0044 s8y900om [[00 02 02 os sr om 856 TwNAEaRRsnraolsnatcaecadinatdeorecshces 100% = 07ma) aoesaoorowwamth5bporess aaac adpinngofcCOubanand rndoy afer rca B. Characterization and identification of extractable radioactive residues (ERR) "tThhee i"dCelntaibteyolfetdhetepstareinttemsuabnsdtanadcdeitwiaosnalconmfaisrsmedspbeyctcroommpeatrriicsonanwailtyhsitsheofretreenptrieosnenttiamteivoef samples. Results are shown in Table 4to Table 6. -Du1r0i2n.g7t%heTcAoRurastedoafyt0hetostvuadyl,uetshe a2m.o0u%ntTAofRpaatre1n4tDcAoTmp(osuoinldLiqu1i0c).kl6y dDeAcTre(assoleldLfUrFomA927..24) daentdec7teDd,ATbu(tsoalll bLeUlFoAw l2e.v4e)l.sBoefs0i.d2e%thTeARpa.rent compound, a few unknown metaboltes were Page 20123 soma vp applicationof *C-4trifluoromethoxy)benzoic acid and incubation under aerobic conditions [% TAR] =5 [wim] v21| 261 |"26s J2s02e3]707500]515516[382s3e5s7|] Te2r rr ra er [--omean roar| eer| oe er [mean es I er[ea |. Teas [ TE Ee [mean mer1 er ECE [Smean 7s | 1.1-1 Tre [-] Ee reeEE [omean "sa101 et[00[ez | oa[ot| 48[oir | Ere rr rE [H4mean1201 1.1. 20 C : eeee eaE [28mean143 1na "na |na |na |na|na |na |na | FEE EE EE Eng [S7mean|os |na |na|na |na|na |na |na |na| m Pi EEil stirmemmm------------ Crate _-- ASFDuco20252027022 Table 5 Capopmlpiocsaititoinoonfo"fCr-a4d-i{oraicftlivueorroemseitdhuoexsyo)fbeenxztoraicctascoifdsaonildLiUncFuAba2t.i2oanfter under aerobic conditions [% TAR] EE PPS ee FeTm 1Tmt Tout ftreratemednt [mm | a[ow [owe[ow] |7w3we] 268265| m1 |sersar| sr | [Come1 s | e7r28a |. e7n2a8 -| [mean me To mea eR [ZF mean zeaT Et N = T e6e2ese er[X} [mean | s262 |.02 | | ss | 00 | Foo[onPa[l a[m 0 [oP meiaann aTa a na TPhw a [w a na Ta ha [aEmeEn| aa a7 |vmnaas| mi a | nVaO |A na | EE tH [Smean | 0s | na | na | na | na | TAR oa ppdadc 100% = 07 ORG) aS=evennontianrrtsneed meaacneisn adforndysc.noehpesHtPLoCnagnaslyseoswfsh, pocld ol exactswrecredoksce ealoxrcied Page tacts wer m Tables Gompositonofradioactive rsiofecxtruactseofsollLUFAZaft applicationof "C-4-{triflucromethoxy)benzoic acid and incubation under aerobic conditions [% TAR] Dane onns ny a[ee | mo] 3ars34 | Fe a o T = ns |omean1 eea esa | [meanTr | a ma sa [2mean meme| su [mean a7 | ar | [7mean Ta aa oe [fomean en 0 | na | [tLamoeaan[|oe0=0| [onwa | a |28mean a 056| rn na | r arroms [Semean| 04| na | EERE I enc pentLbT ac :oars C. CHARACTERIZATION OF NON-EXTRACTABLE No further NERcharactrizawtaonscariod out. RESID UES (NER) 0. PROPOSED DEGRADATION PATHWAY aThne 0eosnlfy5atomreandosfrorsdmaotitrohneiOraeGnaFcvtiainroonouompfad-te{omfonuncsotfrromamteeothhvotryedboesnngzorwciihaschide.odbTosogeepravWdeoodhsowanemrooefuhnet cece, OCFrors ray' a lrg raised, wih na proces. of `eminaeraslaiizaTtioionn cncoonnTtainanuaminargcereavstesnyatarofnatebHr oitmehesth,readLOiooCaFc1tsiavniotdysdwaso2tpoarmtgdofoethpHeroosnknonih-neoxtsrotaocsttable oThneipornopsosedredegaramdeadtoonipathway of 4-fucromethoylbenzic acd in sol under aerobic ison anor onc asa . o 7 2 A You y Nonreescitduaebs le . co, Figure 1 sPorlolposed routeofdegradation for d<{rifluoromethoxy)benzoic acid in E. KINETIC EVALUATION 4Ki-n{ertiilcucervaolmueatthiooyn)oaenndzociaclcaucliadtiwoans opferDfeogrTmsexd faolnldowiDneggtThseorevcaolumemsen(dtaitgigoenrsoefntdhpeoiFnsO)CUfoSr dKeitnaeiilscssoweorTkagbrloeu7p-[TRaefb.le1]5..The Gblained DegT.o and DegTes values aro given below. For Trigger endpoints of -(riluoromethoxy)benzolc acid at 20 C [sor T winoticmodol| gomortxs | DogTwist | Dostwia| [ueTw T see T aw [ oe | [|waza| so | we | ws | am | [waza | ws | a0 [ we | 21 | QTuoodaepripvreoatcihggaercceonrddpionignttosaFO1C2USC,[Rtehfe.c1o]rrceocntsiiodnefroirngteSmpFeOraKtiunretiwcasforcoanldtuhcrteeed suoslisn.gTthhee rbeelsopwe.cive temperature correction factor (fr) and trigger endpoints at 12 C are summarized Estimationof tigger endpoints for 4<{rifluoromethoxy)benzoic acid at 12 C Dwoagee]|| Dwoagmee||C5e7e5r0" D|ogGe a)| DWoghon) [uo|so |ws |aor |ess|21|smo | wes | [weazz]soTwe| vis |ase|zie| 245 |ais| Jwraza]so | ze|ow |sz | zie |27|ear| "basedon 8 Qsconectionforo 258 Pron t6t20 SR [o EELE owm sr[[aRE vee T[eF [e0n] degradation of "C-trifluoromethoxybenzoic acid in soil Li 10 ccpiatie ka: 0.0129 nd (overall) (overall) EreTbeT ReV eA yETdk ea t represented by the SFO model; x" error is <15%; k is significantly different from zero (p-value T D Te T `estimated values for a and B are very large, indicating that degradation is close to first-order | BEE ERE IrRn HS model provideas visually good fit.thefitted initial concentration matches well and the overall decline pattern is well represented, with no systematic deviations; x* error is lower than for SFO Eo I er . NA = Not applicable. R BEIeE e nR c A: `approximately 1 2" i aan res ASFDuco20252027022 Tables dSteagtriastdiactailoannodfv"iCs-uralifalsusoersosmmeetnhotxoyfbdeinfzeoriecntackiidneitnicsomilodLeUlFsAt2e.s2ted for [sro Toc [ro[Koil[ge[ vo [om | We 103.1 WA FoMC | acceptable a M6e.:3180E3+.0103 B: W1o:.0160E3+.0104 NA K:08031| <0001 1.15 sacepiatie kz:g0:1..001053 NndA (overall) HS | acceptable WLKoi::i01.06d30.31 NnndAe [5 SFO Kinetic mode provides a visually accopta7b.i3o3f1i; althoughNtAhe residuals show somo systematic Kdeivsiastiigonn,iftihceanotvedriafllrednetcirnoempzaetrtoer(ips-wvaelluer<e0p.r0e0s1e)n.tedbythe SFO model; 2error is above 16%; [ iFsOnMotCimkipnreotivcedmosdienlceptrhoevid*eesraorvisisuailnlcyraecacseepdtcabolmepaire(vdertyo tshiemiSarFOtomSoFdeOl;fth:etheesgtoiomdanteesds-voafl-ufeist [ DfoFrOaPankdineBtiacremovdereyllaprrgoev,idiensdiacavtiisnugaltlhyatacdceegprtaadbalteiofint viserdyosseimtiolafrstto-oSrFdOerfki)i,nebtuitcsn.o improvement oavse1riSnFdiOcaatinndgFthOaMtCd;eghraeda2tieornoir icslohsieghteorftrhsatnorfdorerSkFiOnetaincds.FOMC; he parametor gs estimated J HovSerKSinFeOtamnoddF el prO ovTihdeeM spaavriC asumalelry;tacscepntoatbaldeeqfiuta(tveelryy isinmsiildaertthoe SobFsOervfia)t,ibountrnaongie.mprovement [> fCoorn"cClutsiifoonr:omSeFtOhomxoydbeelnzsoicocnasciidd:erDedethgebe=st1..f1i5t Jm,odDeelgTapwpr=op3r6ia2t.etoderive trigger endpoints NndA==NNoottdaeptpelricmaibnleed. "Statistics may be missing because the covariance matrix could not be fully caaplpcruolxaitmead,teTlhyis1"may be because the higher-order model fd is lose o an SFO fi: @_Parentis Since a and B are no rate constants, est results were not roported. [Page 90123 J SR [o EE L om e[[aEr Twee ToeF|a T] degradation of "C-trifluoromethoxybenzoic acid in soil LUFA 2.4 sacepiatie ka: 0.0135. nd (overall) hs ka 1.72 20.1 R SShcEieI ahSNr nlTt m m 3Ea a n -r r5a amiE amds nT Sind `over SFO and FOtM he C *er; ror is higher than for SFOandFOMC; the parametegr is estimated i i -- TF ASFDoc020232027022 Il. CONCLUSION The model compound 4riflvoromethoxy)benzoic acid degraded quickly under aerobic `incoDnedigtTizonosvaanlduewsaosfl1a.s2t o0b3s.e1rvdeadyasfattt6ehre- 1t4emdpaeyrsaotfuirnecuabta2t0ionC..TNhoerkmianelliizceedvatlou1a2tioCn bryesuuslitendg the Quo temperature correction factor of 2.58, the DegTso values increased to 2.1 - 5.7 days. "The only transformation reactions observed were the formation of carbon dioxide (up to 61.8. a~7m2o.u7n%tsToAfRC)Oa;nfdoorfmendonf-reoxmtrtahcetaObCleF rgersoiduupesd(e2m2o.n9si- r3a1t.e1t%haTtAaRloantg swtiutdhytehnedd).egTrhadeathiiognh of the molecule, the OCF:-group is rapidly and largely mineralized, with the process of `rmeisniedruaelsi.zaTtihoen ccaornbtoinnumiinngereavlieznatiaofntefrrothmethreadOioCaFcst=ivgirtoyupwaiss anparitndiorfectthperonoofnt-heaxttraalcstoabthlee. organically bound fluorine atoms are fully mineralized in soil, ending up as inorganic fluoride. Overall, the experimental data show that the presence of an OCFx-group does not automatically leave a molecule persistent in the environment or lead to persistent degradation products. IV. REFERENCES [Ref.1] FDeOgCraUdSatio(n200K6in)eti"cGsuifdraonmceEnviDroocnummeenntatl oFanteESsttuidmiaetsinogn PPeersstiisctideenscein aEnUd RDeogciustmreantitonR"efReerpeonrcteoSfatnhceo/F1O0C05U8S/2W0o0r5kveGrrsoiuonp 1o.n1 D(eDgercaedmabteiron20K1i4n)et,i4cs4,0pEpC. Pogo 230123  , CropLife EE es A ) Experimental work on degradation of CFs-containing molecules Key messages, First results of an ongoing degradation study of triluoromethoxy benzoic acid in soil tushshiiosnwgsspaenccoiaoplmemrposoiiusentteydn,crecal,deidaoer-lslypaibstehellocewadrtr(h*ya`iCtn)gtdhaierCemFcotyllreycoauutlpte.heis CdFe-ggrraoduedp tvoerfyolflasotw itnhesofialteanodf + The results also show that the C-F bondofthis single CFs-group is not as stable as t ipsoloyfftleunorpionsattueldaatlekdylinsudbosctuamnecnests(PdFeAsSc)riibnitnhgetehnevicroonncmeernnts. around the behaviour of + Further resus will be presented as soon as they are available. Scopeofthe study Within the upcoming "ire-ightng foam" and "univarsal" REACH restcon processes for PFAS, a chanical ogTrofosiuppiaiconingvecwoiPnlFceAbpoStudiessfetidon,ibiueonnud,seAercdcwoiinrocdrihdnegcrototmotphroeeustncradilcstfoawllhopcvohldyefcnlaucrceryiaJnanutdedcauanrlekeynlCtFlsy-ubGasrvtaoatunapcbelasee(rPadFelAf,Si)netfdhael3lOinEgPCuFnDAdSePrFaAtnShd.e Consequently wil al wihinth rosiricion scope. `CTlhoeremvaejrorchaemnidcaclosn"s)i,stae5ntprcoovnecnerinn socfiePntFiAfiSc pausblaicgartoiuonpsifso thleoirngcalanidmemdednoinu-mdecghraadnabPiFliAtSy imnoltheecuelnevsi(roen.meCnAt and higher). Single CFgroups are often used to improve the efficiency of active ingredients (6g. in plant protection products or human or veterinary pharmaceuticals). Environmental as well as animal and plant metabolism `studies performed within the regulatory EU approvalprocessesclearly indicate that these single CFgroups. `are notthe chemical moieties which decide ontheoverall persistenocfy a molecule. There are CF-carrying pDleasnptitperootfehcteiowniadcet-isveprienagdreddoiecnttisnowhfitchhhvaevreyvsearbylsehaorntdhuanlfb-rleiaveksabinlesoCil-.F bond, scenic Reraure describes cbcoohtnehdmiitlchoanelsra,mnaOdlnbeaionslduogcyihcdarsloudbleslftlcauaonlrciyenaudtneisotnnatbrleeead.ctAfirsoonpsm,atrhsoofmseacieolnfatriwgfheiriccmehrocalatenucrtueaksiesupiclhfaucaoermuoonimdeeettryheafsnnvecixlrpo(encHmtOee-ndtCaF1l:l)byowrheulinecavhbalniets 10 8c35 termina metabolite,or `arrowhead substance'. ShiengtlaerCgeFt-ghruosupasllaorweinvgertyheuserfeudluccthieomnicoaflimhoejdeoisees Wrhailcehs hfeorlpactioievnesusrubeshtaantctehse.aTcheeeIxnpgerreidmieennttarleascthuedsy. pfrionsaelnfioerdmihnagrCiOnfoanndsloucinivdesLtei.galtey miinngolraeizGeF. Tgwrooumpsodceolucdomppootuenndtslywibthe ddfeegrreandtedbobnydidnogloofrinhaetConF, Group othe rest molecule (O-CFsnlC-CFs bonds) were chosen. =A p " 4Carfuoromethoxy benzoic acid A . 5 4Carfvoromethylphonct FranGcroopphoinoeEuSercotpoonaofitthe|9BuusisneGsusiGmoa1urt b|f10 60B64r30s1sS25es5l0]e7rFo|apxBHee3QgUTG28|R0BG3C1o250P84M04ea6L110o8p7e1.F0i|snteenrorfoLpoeleuPatrsoopndseu Tl: BRIZ2LORETS October 2022 t"hTahte fbirisotdmeogdreadlactoiomnpooufnda,l4a-rCge-rtfmlouloecruolmeetwhoouxlydbleenazdoitcoatcrdif(upo-rTomFeMtBhAa)nwolasfosremlaetcioine,d twohtiscthtbheechayupsoeiheitsiiss Athebremnalzloyicanadchdyddreorlvtaitciavley wunassiabulsee,dwoausldthiemmpeadraetnatlmyoluencduelreg,o asbiinocteictdheecsoempaorseitkinoonwtonffoormuCndOe;rgaondraHpFi.d biodegradation, and thus maximise the ime avalable within the studyfo folowing the metabolites forme. bTihoedegsreacdoanldionmoofdeblenczoemnpeosuunbds,ilu4l-e"dC-rtiilluuoorroommeetthhyyllpmhoieentoile,s dwoasnotseallewcatyesd lteoadtteostpetrhseistheynptomtehteasbioslltehsa.t depending on secondary substituents and their molecular positon. cInomoprdoeurndtso,gottheinnefocremsastairoyn 'a"bCo-uatbetlhetopobsesiubsieldtyiofthmeetraebsopleiccivdeefmueotranboaltiosnmrsetaucdtiieosnsneweidths 1O0-CbFe:torrodCu-cGeFds dHiGrFectilaybaelitehde fcloumorpionautnedd actartbhosn.stTahgee.synthesisofthis special radiclabel could only be achievedfo the OnFeuxrtth1erainrvienstgi-gCa-taitoonms aisrenopllaenanseydtoonacthhoieCv-eCeFxpceroimmpeonutnadly..UCnufrorretnutnlayt.layt,itehmepiisnraordeucotnigooninofgtthoof"inCdFf:easlaibbelle amentdasbaofleissmynitnhveessitsigraotuitoenssfowirlh(olo2,w3asanpder4fiosrommeedrsf.orItnhecaOs-eCthFemcoloemcpuoluendc.an be synthesized. the same soll Timelines TNhoevefminbalerre2s02u2s. fFoirmstthinteprrimesreentsuosladreegrpardeasteinotnesitnuhdyswibrhietfhinegOn-otCe.F-compound are expacied by end of 2In02c3a.se the synthesisofthe C-CFs model substance can bo achieved, fist resus can be expected in Qf Experimental outline In order to investigate the potential degradation of the O-CF:miely n sol, prifluoromethory benzoic acid (Wipt-hTFtMiBsAt)eswtacsomcphoousennd aasn aaemroobdieclsociolmdpeogurnadda,tiwiotnhstthuedy"wC-alsabceolndpulcacteedd aincctohrediOn-gCFtoOgEroCuDp (gAuipdpeelnidniex301)7 Aerobic and anaerobic transformation insoi (Apr 2002). "isTheeqeuxippepreidmetontrwouatisnepleyrpfeorrfmoerdmastitmhuelaftsitonfasctiluidtiyeosf(BeAgS.FO.EACgrDicu3l0t7u,raOlECeCnDter3,08L,imObEurCgDerh3o0f8,)Gwietrhmiannthy, wfhriacmhe of the requirements of EU directive 1107/2009 for placing plant protection chemicals on the market. AucncdoerrdcionngtrtoollOedEcCoDndgiutiidoenlsiantea30s7l,l msaoilsstuarmeplofe~s4w0e%roefttrehaetemdawxiitmhutmhewraaedriohloalbdeilnlgedcatpeasctittyemataantdemipnecruabtatuerde mof 2g0C(d(troymwaexiigmhitzeequmievtaalbeonlti)tetfooramlaltoiwonf)o,ruandreolridaabrlekacnoanldyistiisonsw.itThheratdeisot-dceotneccetnitornatmieotnhwoadss cwhiothsean Ialmi0..6o7f aqeuraanttifoincwataosnoufsaedtwlietahstan0.a1t%acohfetdhetrtaoptpailnagppslyisetdomrafdooratchteivdioy.miAnacltoisoend iofncvuoblaattilooncsoymsptoeumndwsi.thTchoentaiinruwoauss.. frst going through an ethylene glycole trap followed by two NaOH-soluon traps (Append 2) sTahmepliinncgusboavtieornas wpelraennpeedrpfeorrimoeddofin28thdraeyes.diTfheeresntolGperropmearntiessolase(sLiho1w0,n iLnUAFpApe2n.d2ixan3d. LUFA 2.4) with 8 bAty eLaScCh(salmpulisncgntdialtaet,ioenvcooluvnetdinagn).dFtorrapepaecdhvsooldataineds (sea.mgp.l"iCngOztmin.NwaoOHretprlaipcaptiensgwseolruotitona)kweneranedqeuxatnriaicfteedd {woithdealceemtmoinnierietlhwealaemromuinxttuorfestaentdsaucbesltoanne,ceanrdemtahieneixntgraicntsSwolelreanadnatlhyezendubmybLeSrCaanndd armaoduinot-HPoLfCpointeonrtdaelr cmeolmabbuoslttieosn. inTaon OcxoimdpilzeetreantdhesubrasdeiqoaucetnitvitLySCbamleaancseu,retmheentno(nA-pepxteancdt4aib)xl.e residuos were quantified by tInhceacsheemtihsetrcyhrboymasttrougcrtauprheieckcaindalaytsiiosnofmethtshoodls elixkteraHcPtsLrCe-veMaSleMdSdeogrrsaidmaitairo.n produc, tis planned to ident 2s Brz2L08s7S October 2022 First Results aFinsdtLrUeFsAus22fruopmt0he14stduadyyswaiftherthreeaOm-eCnFt3(DmAoTd)e.l compound are meanwhile avalable fromth sols Li 10 Teshpeecdiisatliyb.utAoln voafluaedsiaarceieixpyreisnstehdeatsw%oosfotlshatnodtalthaepplmiaeiderialdiobaacltainvcee(i%s dTiAsRp)lafyendotinsaTtaebdleosth1erwainsde.2, fA(ol<rt2e5r%7aT-nA5iR6noc%fubTpaAatRri.oennpeercioovdeorfe1d4indaaxyt,ratchte).paForentbtchomspoo,untdhewamasjaokrndoesgtracdoamtpiloeneplryodduecgtrawdaesdCiOnthaecwcoounoilnsg aInnyodoeerropcoloennftia (tshilal tuhreinraadtieoda)cvtilyaidn tthreanNsafOoFrmHartaiponpipnrgodsuocl,utwioonsdciofnesriesnttedmeitnhdoedesd woferCeOuzseadn.d(n1o)tAonf 8a3liCqOuo,twoifcihhetNhaenOcHantrbaepppirnegcsipoaioend bwyacsrtirfautgeadtwni,h lBeaaCvikn.g AnnoyorCiOnsiginniftihcoanNtarOacHeswiolfbaodoraacnisvfiolrymiondthteo sroalputpieodn.C(2)OAissreecloenadseadlaqnudoocfatnhboeNeaxOpaHlerdapfpoinmgtshleisiaonlits,relaelaevidnwgialghacionncn.ooHC,ollyeaidnisniggnliofitchaentafrfaecctetshoaft radactvty in the souon. wWais fborhmemdetdhuroidnsg,sthol riandciuobaacttiiovni,tyImndeiacsatuirnagmtohnaisthof rthaeckNlaaObeHletrdapcpairnbgonscalttoomnsinctlheaerlpyarsehnotwmeodletchautle"CwaOs:. completely delornated. Nalowaoytshe< l0.a0t5%i, degradate couk! be detected The radoaciiy nthe ethylene glycole tapping soon was Bmeasxiidmesummilnoovreaslzofat4o5n.5to% CTOA;R (foLrm1at0i6on DoAfTn)ona-nxdtr5a0c.i6a%blTArResi(dLuUeFsA(2N.E2R/)3waDsATo)bsbeefrovreedtwhheiycdhecrreeaacsheedd again olevels of 32% TAR and 35.6% TAR at 14 DAT, respectively. ToCfhOirasrlioonmvdaeitcsiac)teacslastrohbasohnpoayrwlt ohafctaihdhesiapsasdrebonestnzenosoittc tsatceoipd.twhaTshfebuotpuhrenordcedfeeodgtirhanedgahdtueimfoilncuoomfranFlaitilicuorninoamsneoldi,hmowixinyec-rhgarliioszuaapt,kionbnoutw(niJunscrtreeasaclstoiiwnogns it down 0a certain extn. HcoPmLpCouannadly"sCi-s po-fTtEhMeBAso(lsceoxtFriagcutrser1e)v,eLaol.edexrtahcatatbhlee emxetlraabctaeldtersawdeioraecinvoityfocromnesidsitnedapopnrloycioabtehaempoaurnetnst (posing peak 20.2% TAR in any sample). Conclusion Tcahrryfirnsgt areCsuFlgtrs ooufpt,hethsoeilendtergeramdoalteicounlestiusdvyerwyitqhuitclkuloyrdoemgerlahdoerdy-inbesnazloiacnadcindotcaetaratlystsahbolwe sasthpaotsdtelsaptielde fo1or'aalcoPmAplSetemoldeecfullueosr.naFtuornihoefrtmhoer,Cocamn awlistohbfoisnahofwornmahtiaontohfeCCO-:F.bNoondocthaenrbceibarloke(nigrhlaypp.ersliesatdeinntg) teacton products were detected. Outlook cFuarnthbeerarcohisosvewd,ihsithmesO-oxCpFarmmoedneilscwoimpbooupnedrwoirmbeeeswuimhmaariCz-eCdFasmosdoeolncaosmtphoeuynadr. avallabe. Ifsyntesis as Table 1: Distroifbraudiotacitiovinty and material balance in Li 10 soil treated with *`C-pTFMBA FECT ET [750 [206 |46| 14[02| 00[1027[04[00[ Tos] a [a TaleTaTel aTaae] |e70 |203 | s7 |13 |o6 [ 02[e62|ss[02|28 [ 1036| ESTEE EEE [sos[wea| 46|21 |o7|02|747[tea|03[toa tors| [sas[24|36 |21 | 04|02|52[264|04[175 tote| EAA IAEARAEACIEIRIE [a1 16 | os |12|02|01 |78[ass|os|a67|1007| [28 [11 | 04 | 08[ 02| 01| 54[411]03[513 eas| sRBeTE E cE ursors [orTos T 02 | 06 | 01 |00|16 |320 o1[se] 018| eizzL0nsaTs october2022 Tablo2: PDTFiMBsA tofrradiioabctivuitytanidmaoterinal balance nLUFA22 solltreatweitdh C- CC RGHSTOo| mAmCNer Som [ome| oar | 5 | exotraects 6a10 in76 o0s8 aare aWwo swaas [ot2[24s |77| 32 os[02 [ora[os[oo| Tors] rr [aas[tewss||665s | asToors[02[70m0o|[f1a5sa [oa[at[ous] Er [Ciwsr7 |[rze T|2a6 | 12 02[o0o0 [|26m74|[amso[05[22200| oeusso| a 2p0ri [6s |ou | p2r0[62| 0011 ||s460 [|sasrs[os[usssa||ootsas| [as |aos l|aop l| aos l| aoi |[eoo ls mais |aog l| atao| ]sso (el[TeooTloasl"0a2[[0a5[l0a1|l000e|l21e[al0a2m0024l[ma1]lnorasl| osTasTos[os 6010 || oooo [ 14[00[0s[ss|oa| ACN =[acTotoonairlTe 02 T01T02[ 00 [00 | 1[36]04[er2]sao] NEDART ==ndoany-osxatrfarciraebaletmreenstidues CC0O:==CCOO;;mwheiacshurveodlviedthedvuonlgtthae rraipnpigngsimokoifotnhseextractedsol residuebeforecombustion on RE rr = so g som [Fao yom EET aa Figur1e: RraedaitomoHnPtLC chromatoofAgGrNHaZOm (01) extrac 13of soil Lit0, 6 days aftr ss BRIZ2L0735973 Appendices Appendi1x: Test tem information Structure i 0 wo { ) { 7N\ " on Av1bUrPoAvCatNaemde:Name: 4p+--T{F(MTBorAometnorybenzoic acid, `LSapbecificradioaciity: {3i0f8u9o4r5odmeptmhoxy-C1d) Radochemical purty: Applied amount. 90.96.79%mks (250 gna) cry sol cober 2022 Appendi2x: Test sotup wash tower! airinlt bottes 12 soil est vessel `Sequenceofvolaie trapping solutions: flfaassk4k3 t0 nyNloNn5 aeOgHale fask5: 2NN0 aOH pump 34 5 absorptiontraps on aznonsers ovetnrzz Appendix 3: Soil properties EGCoT yr4 ww 55 | ETwe5er |wmosza|| Ssaunraatl 741 Toiro pwAn [ellosursOT Signy les saa_| Todo amy snd_|sSiag nyo Clay [%] 85 [GSSioaltnm%a]e capone[vor[zmn17e6 au] oShS TTE sr[ams ra] (Mic9ro/bi1gal0drb0yiosmoials]s (SIR) PW Img C/10g0 dry soil] it cottocnount Appendix 4: Analytical methods rJ oss-- Gor 2910TR (Pain Er LioScincs,Garmary) Cs For combustion: Uhre Soeiy.PeSnonSthhrer Tri<Carb 4910TR (Perkin Elmer Life Sciences, Germany) Biological Oxidizer OX-501 (R.J. Harvey Instrument Corporation) Combusiod samo: Gaye Ch Zeer bic L$i 3S0C(aallmsaamplaesn)d:adzaton method wi a bulin Bradaton rcs was used for ha determination of 0 CGomobumstioon stoottssamwperle:absobos soeC00blanca oreorohe cm_--s--, E nme e a re ova oc a eae PEL RadioHPLC: [Tdoovranrog Reson" Mobile phase: m mene aE BR nSs 2GT5ookousmean A: HzO + HCOOH 10+02.05 (viv) B: Acetonitrile + HCOOH 1000 + 2.5 (viv) BRIZ20/35973 Gradient [ Timegmin) we] moso T To o1| wT 1 mT ww] Ce = T To o]| October2022 sis ~ CroplLife LET [Ere] Additional information on the Scope of the proposed restriction of Per- and polyfluoroalkyl substances (PFASS) in firefighting foams. Key Messages: + AcedrdtiatiinonaPlFAiSnfosrumbastitoannciess,prtohvuisdedimtpoacRtiAnCg otnhethdeeflianictkioonf sPecrospiesteofncethe(hapzraorpd)osfeodr + rTehsetrOicEtiCoDnodfePfeinri-tiaonndispoalylfiltueroarloacloknyvlesrusbisotnaonfce"spe(rP-FaAnSd) pinolfyifrleufoigrhotailnkgylfosaumbss.tances" iancttoiosntrtuhcetursaclocpheemsihsoturlydtebremsf.urTthheerOnEaCrDroawuetdhotros aclesaurblysesttamteattchhaitnfgortrheeguclraittiocrayl properties under consideration e.g. Persistence. It is thus a misuse of the OECD + Tdehfeinrietvioinewinofittshuensacbireintdigfeidc lfiotremraitfutrehipsrpersiennctipeldeIinstnhoetAanpnpleixedX.Vdossier is inadequate farnodmmtihsessecsiaentsiifgincilfiitcearnattubreodayndofrekgnuolawtnorcyhesmuibsmtirsys.iCohnesmsihcaolw ptrhoatpecretrytadiantsainagvlaeilCabFl,e fu-nNcCtFiso.nInalogurrovuipesw chisajusbntiefpineesrsaoimstotedntidfuiectaootcfihteohmneicdaelfirneiatcitoinvistcyowpieth(wgartoueprien.gg). fOoCr Fth,e + Trehsetrircetsitornicptiroonpopsraolp.osal should be amended to: Per- and polyfluoroalkyl substances (PFASs) defined as: any substance that contains at feast one fully fluorinated methyl `(eCxFc)ludoirngm-e0tChFy,le-nNeCF()CF) carbon atom (without any H/CUBr attached to it, and + Certain additional single -GF or -CF; functional groups cannot also be assumed to be imnehcehraenntilsymsp,erwsihsitcehntindouuer tvoiecwhjeumsiticfailesraeafcutritvihteyr "wsiatfhetwyatneetr" odrertoogaottihoenr,fdoergcraadsaet-iboyn+ cPlaasceinugstehwehaebroeveevsiudbesntcaenicseasvaoilaobu fles.cotpe, or potentially subtoajdeerogcatiton, does not in any way lower protection of human healthor the environment, because it remains irenscpuemcbteivnet RoEnAaCnHy rRegEiAstCrHatiroengsi,strants to demonstrate the lack of persistence in the 1. introduction CropLife Europe wishes to provide additional information to the Dossier Submitter on the dleafcikniotfioPneurssiesdteinnctehe(hAanznaredx) XfVor RceesrttraiicntiPonFARSeposrutbsftoarnacePsr,optohsuaslifmopraactRiensgtrtihcetisocnoopne Paenrd- and polyfluoroalkyl substances (PFASS) in firefighting foams (Version 2.0, dated 23 March 2022). While the definitions discussed here do not appear to be highly applicable to the chemistries used in firefighting foams, never-the-less the general claims being presented by the Dossier Submitter about PFAS substances are of more widespread applicability, including several specific references in the Restriction Report Annex to active substances, necessitating detailed comments from CropLife Europe. FraCnrcoophponEeurSaovpieoaniotfteRBuuesiGneusiTsmeGator3d|k31o0420BBr7ruu1s2s5set56l0s| 6A|FoBa3pexkfge4uo3m2u2t| 6Bp6Ea3G01r45o76p06H1e8e8u7r1oRsse| wgnoifTLeoogrpePoerusosnpsae poszaL03sisT 24082022 As has been noted on page 13 of the Restriction Report, the OECD definition isa literal conversion of "per- and polyfluoroalkyl substances into structural chemistry terms, not tclaekairnlgy sitnattoeatchcatoufonrtrheaguzlaartdoroyususperotpheerdteifeisnitoironrisshkosu.lTdhbeeafuutrhtohrers onfartrhoewOedECtoDmdaetfcinhittihoen jpursotpiefiretdi.es under consideration, and it is thus a misuse in its unabridged formif this is not If the unabridged OECD structural definition is used to define PFAS, the result is that the Restriction Report (page 1) incorrectly states "All PFASs are very persistent in the `environment. This is the key hazardous property common to all PASS". For this statement 10 remain correct, the OECD structural definition would need to be further refined for use in hthuismarenstrhiecatlitohn,oirnctlhuedienngvisruocnhmetnhtat" tahree rmeeqtu,irWeemenrtesquoefsAtrtsiculceh68s(i1m)pl"iusntaiccceapntdabilnecorirsrkectto statements are removed from the Restriction Report. The Dossier Submitter confirms this on page 54 of the Annexes to the Restriction Report: If there are specific PFASs for which sufficient evidence is provided that the `rpeesruflltuionrginaatedsbuobnstdainsceb/rsoukbesntaantcaesratwehwihcihchiis/nadriecatneostthaem to be not persistent, PFAS, then those saruebsktnaoncwens/togrtohuepdsossshioeurlsdubbmeitetxerc.luded from the scope. Currently, no such PFASs Chemical property data and degradation information from the scientific literature are psruebssetnatnecdeshaerreenotto cdheemmoincsaltlryatsetabtlhea,t,anadsfaurtmhienrimmoruem,cancenrottaibne O"aErCroDwhesatrdu"ctsuurablstPanFcAeSs for these moieties found in larger molecules. Examples are presented for CFa/CFa containing substances which clearly demonstrate that carbon fluorine bonds in certain substances can be, and in practice are, broken under environmentally relevant conditions. 2. Definitions and Scope The recently published OECD structural definition for the universe" of PFAS chemistry is (OECD 2021): "PFASs are defined as fluorinated substances that contain at least one fully fluorinated methyl or methylene carbon atom (without any H/CUBH/I atom attached to it), ie. with a few noted exceptions, any chemical with at least a PpeArfSl.uo"rinated methyl group (~CF:) or a perfluorinated methylene group (~CF=) is a The OECD definition goes on to clearly state (page 18) that perfluorinated methylidene cstaartbeosnosf(t=hCeFd2e)fisnihtoiuonl:d not be considered to be PFAS. Of particular note, the OECD report "This report does not make any recommendation on how working scopes should be set up, in terms of which factors to be considered (which depends highlyon specific local context), nor on PFAS grouping. However, when a working scope of PAS is used, this report highly recommends that users clearly provide the context and aravtoiiodnacloenffoursseilonecbtyinogthtehresi.r"PFAS working scope in order to provide transparency and 217 poszaL03sisT 2052022 The Annex XV restriction proposal (page 6, and Section 1.1.1.1) aligns with the full OECD structural definition without further refinement to align with the grouping justification (page 16, Section 1.1.2), thus constituting a misuse of the OECD structural definition: "To summarise, the grouping is based onstructuralsimilarity (common perfluorinatod moieties) that triggers equivalent hazards and risks among the substances covered, primarily related to the verypersistent property of the substances." In light of these considerations, it is consistent with the OECD definition to "deselect" individual PFAS moieties which do not demonstrate Persistent properties, and that should not fall within scope of the proposed restriction. The following amendment to the restriction definition in Column 1 (page 6) is proposed on the basis of extensive chemical property and degradation information presented is subsequent sections: Por-andpolyfluoroalkyl substances (PFASs) defined as: any substance that contains at least one fully fluorinated methyl (CF3) or methylene (CF2) carbon atom (without any H/CUBr/ attachedto it, and excluding -OCFs, -NCFs) 3. Single CFs moieties which are unstable towards hydrolysis The -CFa moiety is the shortest alkyl group within scope of the proposed PFAS restriction definition. Data from the scientific literature are presented here for 5 trfluoromethoxy (CF20-) containing molecules, and thus shows that should the corresponding alcohol be formed as an "amowhead" substance, it will be rapidly hydrolysed. Similarly, data is presented 13 molecules which show simple trifluoromethylamino (CFaN<) groups wil directly hydrolyse. These molecules meet the proposed PFAS definition, and yet they are demonstrably not persistent (Table 1). Any persistence which precursor (parent) molecules may demonstrate cannot be linked to the presence of these moeties in those molecules. As a result, these functional groups should be placed outof scoofpthee PFAS restriction. Further details on these compounds substantiating the lack of persistent properties despite `meeting the PFAS definition are provided in the subsequent sections. It must be emphasized this is a cursory inspection of the literature, and there are very likely many CFa/CFs `compounds with similar properties which are not identified here. Tablet. Ldiesmtoonfst1r8astuebspterasnicsotsenwthipcrhopmeorteitestheatOtrEibCuDtasblteructtourtahledepfrionisteinocnewhoifc-hOdCoF3NOoTr >NCF3. [Substance_ TStucture [Moety | [[-Nmeetmheotsyn-yNN-m-ertfhylNo-o||{SSeiereefFFoiiuggurmuoer3reesotmnetyhly|[>>alNNGCjFnR,,ainiiinnee|| [Neethy:N-irilu|oSereFoigmwees thyl[5lNaChniine| air poszzOmsist wos02z [eNth-ylbenzyi-N-(irfluo|SreoeFmigeurtedhyljg[>iNyCEcinate| 34. Trifluoromethoxy groups Chemical stability of trfluoromethanol towards hydrolysis TofhethteripfrlsooproosmeedthoPxFyAmSoiertesytrfiecattiuonresdetfihneitsihoonr.teWshtettehremrinatlhealkiynlclgursioounp o(f-ClFasr)gewrithpirnecsucrospoer `dmeopleencudlsesonfetahteuruilntgitmhaitsegsrtoaubipltoynotfhtehbeaasirsroowfhienahedrsenutbsptearnsicsetteincleuoorfommeettahbaonloilt.es s justified xXFo "0% A9 a t F Figure 1. Model compounds: 1) trifluoromethanol (CF;OH), and 2) carbonyl difluoride (CF:0). Tbreihfalvsioorromiesthtahneolm(oFsitgurreel1e)vahnatscboenteenxtg.roHuopweedvewri,th stihnece"F-tgraisfelsu"o,romiemtphlaynionlg aistmnoostphietrsielcf commercially manufactured and ts thermal and hydrolytic stabilty precludes plausible future iussenso,t pitesrspirsitmeanrt,y arneldevaasnacen ainrrthoiwshdeiasdc,usfsoiromneids vaisa ahnyderoxlaymspisleanodfabiPoFdeAgSrasduabtsitoannrceeacwthiiocnhs ionfstolrlif(linucolruodmientghsaonilolpoarnedwaptrere)cuarnsdorinmaoqlueecouulsesmedisiam.oWree sauppgrgoepsrtiatthealtythpeladciesdcuisnsitohne general chemistry section, rather than with "F-gases'. Trifluoromethanol (CAS No. 1493-114) is an unstable substance which is a gas at room tseymnptehreastiusreed. iInt w1a97s7inuitnidalelry scpoemcpulleatteeldy tahnahtyidt rwoauss tcooondrietaicoinisveatto-e1x2is0t,Can(dRewdawsooodnly19f6i5rs;t eSleipmpienlatti1o9n7o7f).hyWdirtohgeanmefllutoirnigdepotiongti-v8e2caCr,biotnwylasdifdleusocrirdiebe(dEqans 1b)e,iwnigthutnhsetramballe dteogwraarddastitohne uesntdiemrataendhbyodirlionugspociontn)d.itIinoansmoarlereraedcyensttpaurtbilnigcatsiloonw,lCyhraitst2ie0ofCa/ ((c2o0r0r7e)sspiomnildairnlgy swtiatthe tthhaet aHlFcoehloilmsinpaotsiosne,ssainndg paefrlfuoorrimneedatthoemsoynntthheesias-cofartbroinflautoroommeatrheanuonlstuanbdleerasntdricutnlydearnghoydfracoiulse icnovnednittoiroiness.: TritfliusonrootmeathcanoomlmeirscnioatllRyEAreClHevarnetgisstuebrsetda,nncoer, aapnpdeargisvoenn atnhye galobboavlechtehmeircmaall instabilty, it cannot plausibly be considered a `regrettable substitution" candidate. Odsetceormsptorosme woifthala (f2ir0s1t9-)ordreerproartteedcoeaffisciimeinltarofskub=st(a1n.c6e8,xg1a0s9e)ou5s, dciofrlrueosrpoomnetdhianngolt,o afno atmospheric halflife of 6.9 minutes at room temperature. CVaFc1uOuHm ias nsdtrroinggolryouascliydiacnahnyddrsouosmecosnadlitti(oKn,s,Rbh,owCesv)erf,ortmhsesheavaelsobeiemnmesdyinattheelsyisheyddruonldyesre a posaaL03sisT 2u052022 o1n97c9o)ntact with water or moist air to give purely inorganic products (Redwood 1965; Kidter CF30H -- CF20 + HF (ean1) Redwood et al (1965) noted "The trifluoromethoxides are reactive compounds and are immediately hydrolyzed on contact with water", confirming this analytically for the K, Rb, and Cs salts with the stoichiometric presence of fluoride ions in hydrolyzed aqueous solution. Inspection of the synthetic method reported by Kidter et al (1979) reveals other inorganic. compounds featuring the CF1O moiety with high likelinood of being unstable towards hydrolysis, and thus potentially invalidating the current PFAS definition proposed e.g. trifluoromethyl hypochlorite (CFsOCI). We request these above examples are taken ahycdcrooulnytticoaf,llaynudnsatafbulretheexrasmepalrecsh. of the academic literature is likely to reveal more Schneider et al (1996) investigated the energetics of unimolecular and water-mediated decomposition of CFsOH into CF20 and HF. They concluded that the energy barrier to the unimolecular decomposition was large and that at room temperature the rate of the reaction is negligible; however, the presenceof water significantly lowers the energy pathway making dfiengdriandgastitohnatmohraevefavionudriacbaltee.d Tthheesenefeidndifnogrs aanrheydfurlolyuscocmomnednitsiuornastein wiotrhdeerxpteorimiseonltaatle trifluoromethanol. Given the potential occurrence of tifluoromethanol in the environment will not be under anhydrous conditions, decomposition into CF2O and HF is considered inevitable and rapid. The restriction report Annex (p107) incorrectly attributes a millon-year half-life below 40km for trifluoromethanol to Buszek and Francisco (2009). In fact, thiswas a theoretical estimate calculated by Schneider etal (1995), and is purely considering photolysis, and not the overall catamuossephdeergriacdahatliloinfew.aTshceal4c0ulkamteadrtiosebsebiencsuafufsiceieUntVinlitghhte wliolwhersuaftfmicoisepnhteernee.rgSychtnoeididreerctelty al (1995) although concluding photolysis was not an important mechanism, never-the-less stated in their conclusion "Once in the loweratmosphere, CF:OH will be rapidly removed by incorporation into rainwater-seawater-cloudwater where hydrolysis will give COz and HF" The work of Buzek and Francisco in fact showed that the atmospheric behavior is more cmoomlpelceuxl,esacnadn cparteasleynzteeddecaomnpoeswitmieonchianntihesmatmwohseprheebrye.thteispirmepseonrcteantootf rweactoegrniazendthOesHe are not experimental studies, and there can be additional unrecognized processes in play. We request that this paragraph (bottom p107) in the Restriction Report Annex is corrected 50 as not to suggest that the true atmospheric half-life of trfluoromethanol is in the order of millions of years. Its also claimed by several of the above authors that rofifllounogreormecthhaainnolpeirnfltuhoeruocphpeemricaatlms.ospItheisreimipsoartpaontetnttioalresicnokgnfoirzethtehaotxitdahteivheypdeogtrhaedsaitzieond source of these CFs radicals are the longer perfluorinated molecules otherwise within scope of this restriction, and applying the restriction to CFsOH itself or potential OCF; precursor molecules, would be misdirected and have no effect. Carbonyl difluoride (eqn 1) does not meet the formal OECD PFAS definition because the cdoaurbbto,ntihsenOeiEtCheDr mdeeftihnyiltionnorexmpeiitihlyllyeneex,clbuudtesratthhiesramsebtehiynlgidteenreme(danad PfoArSt)h.e aAvlotihdoaugnhcenootf formally meeting the PFAS structural definition, once formed, carbonyl difluoridealso does sir posaaL03sisT 24082022 wnaotterd.emonstrate persistent properties. It is known to rapidly hydrolyse in the presence of CF:0 + HO --~ CFi(OH)2 = 2HF +CO; (ean 2) Although a gaseous substance, Uchimaru et al (2004) noted that carbonyl difluoride can rleeaacdttwoitpahrctiotnidoneinnsgetdo alitqmuoidspwhateerri.c Twahteerf,irsatnodrdtehre Hhyednrroyl'yssilsawrecaocntsitoannctosefafnidciheyndtrfoolrysciasrbroatneysl. difluoride has been experimentally determined in liquid water 10 be kno = 4.3 5, cdeosrcrreisbpeodndaisnga t1r0anasiehnatlFiinfteermoefdi1a.t6e sinectohendrsapi(dDereaBcrtuioynn of19c9a5r)b.onDyilfdliufolruoormiedtehawniethdiwoalteirs which ultimately releases HF and CO; as depicted in eqn 2. (Science of Synthesis, page 325). Figure B.41 (page 107) implies carbonyl difluoride is a PFAS, and provides an unattributed half-ife of 5 years. We request this is corrected c.f. De Bruyn 1995, with the relevant hydrolysis half-life, and the atmospheric half-life attributed or removed. Examples of trifluoromethoxy degradation from larger precursor molecules The following examples are larger molecules containing the trifluoromethoxy groups, which have been shown to undergo degradation in biotic systems. During this process trifluoromethanol is eliminated, and once formed undergoes hydrolysis as described above. Dinel et al (2009) describe the in vivo metabolism of a development pharmaceutical pwirtohcetehdeirnegsuvlitainCgYPfo-rmmeadtiioanteodf oCxFi>dOatHi,vewdhiiscphlraacpeimdelyntdeofgrthaedetsritfolufoorrommectahrobxoyngyrloduipfl(u-oOriCdFea)a,t room temperature (Eqn2). This demonstrates that in in-vivo biological systems the carbon fluorine bonds can be broken, Consistent with this, a survey conducted by Pfizer scientists published in 2015, found no consistent improvement in metabolic stabilty for trifluoroanisoles (Ar-OCFs) compared to anisoles (Ar-OCHs) acrossa seroife43s9 mixed matched pairs (Xing 2015; Johnson 2020) Complete biomineralization has been described for a model substance featuring a rifluoromethoxy group, 10-triluoromethoxy~decane-1-sulfonate (Peschka 2008; Fromel 2010). Analysis of fluoride ions over the course of the degradation process indicated a rapidly increasing concentration between 3 and 17 days, which slowed and then reached a plateau between 63 and 87 days. The favoured biotransformation pathway (90%) started with desulfonation and oxidation to a carboxylic acid. The alkyl carbon chain was then shortened by successive B-oxidation to finally yield trifluoromethanol, which was stated to be unstable in water, was also described and to which dpergorcaedeedeadbiotiincalcloym. paArisseocnondvelreyssslfoawvloyure(dunprealtahtwead y t(o10t%h)e trifluoromethoxy group), but stil ultimately led to trifluoromethanol, which once formed, underwent rapid mineralisation. As a resull virtually complete mineralization was claimed. While Peschka (2008) appears in the Restriction Report reference list, the results of this study do not appear to have been taken into account in the discussion. We request the mineralization of 10-trifluoromethoxy-decane-1-sulfonate be acknowledged in the Restriction Report. 6117 -- 32. Trifluoromethylamino groups Chemical stability of trifluoromethylamine towards hydrolysis -- The trifluoromethylamino moiety (Figure 2) features the shortest terminal alkyl group (-CFs) within scope of the proposed PFAS restriction definition. Whether the inclusion of larger precursor molecules featuring this group on the basis of inherent persistence of metabolites is justified, depends on the stability of the arrowhead substance trifluoromethylamine. Kidter et al (1977) synthesised the trifluoromethylamine using similar approaches to trifluoromethanol, under strictly anhydrous conditions, with spontaneous thermal E i" X\ C T a A. decomposition increasing above 21C to form a mixture of compounds (Kldter, 1979). Figure 2. Model compounds: 1) trifluoromethylamine (CFiNH:), 2) carbamoyl fluoride (AA'NCOF). Inspection of the synthetic method reported by Kidter et al (1979) reveals several other inorganic compounds featuring the CFsN moiety with high likelihood of being unstable towards hydrolysis, and thus potentially invalidating the current PFAS definition proposed e.g. trifluoromethyliminosulfur difluoride (CF3N=SF2), trifluoromethylamine dichloride (CF3NCE), trifluoromethylamine hydrochloride (CFsNHz.HCI). We request these above `examples are taken account of, and a further searchofthe academic literatureis likely to reveal more hydrolytically unstable examples. Examples of trifluoromethylamine degradation from larger molecules a a urls AG, Schiesser et al (2020) synthesised 12 model trifluoromethylamine derivatives (Figure 3) which very rapidly hydrolysed (within 72 hours) to give a carbamoyl fluoride, A,A-NCOF, precursor trifluoromethylamines for the purpose of the proposed restriction. We request that these examples demonstrating rapid hydrolysis of the trifluoromethylamine group are taken account ofthe Restriction Report. Unlike simpler amines, N-pyrazole and N-imidazole on the other hand, were more stable towards hydrolysis on the timescale of the experiment (72 hours). Never-the-less, further investigations in regulatory hydrolysis studies or studies on biodegradation in environmental media could also demonstrate consistent hydrolysis or degradation for these functional groups. See also H-pyrazole and H-imidazole in section 4.5 below. Poszanonsist : fr ` QwvJ OT . ae . mn . eX,r ; L 2uosauzz . GF/ on k Ea 5LhA. I F men FF I F "en . OL- EeF F F- I F "5 drso Le - Figure 3. 12 model tiluoromethylamine compounds demonstrating hydrolysis within 72 `hours (Schiesser et al (2020). 4. Single CF; / CF; moieties which demonstrate variable degradation in biotic systems Data from the scientific literature are presented here which shows that at least the functional groups difluorodioxo (O-CF2-0), trifluoromethylphenyl (Ar-CFs), difluoroethoxy (-OCF2CHs), and difluoromethylene (C-CF2-C) groups degrade, or have the potential to degrade, depending on the details of the chemistry, without forming persistent PFAS metabolites. This should not be seen as an exhaustive list, but rather support the need for a "safety net" derogation for those molecules which have been, or could potentially be, demonstrated to be not persistent, nor form persistent metabolites. 41. Difluoromethanediol Diluoromethanedol meets the OECD structural defnion of a PFAS and features the sWphehorersttihessettrenatclhekeyolifngclrmuoesulipaobn(ooOlf-laCerFsg2e-trsO)pJuawsriietinhetidnm,osldceeocppueelneodsfsfteohanetufptirhneogp(soitsseadbglrPyouFpoAfSonthrteehsetmrboiacdtseiilosnosdfueifbinsnhlieatrineocnne.t dSiufblsutoarnocmee.thanediol (Figure 4, CAS No. 491379-14-5), and whether it forms an "arowhead" wn :, WX There is very little scientific literature for this compound, with only 6 references reported by `Chemical Abstracts, all of which are theoretical studies performing ab initio calculations. It `appears to have never been synthesized nor isolated, nor to be commercially available - Difluoromethanediol is the gem-diol form of carbonyl difluoride, and reversible equilibrium between gem-diols and ketones is very well established. Given that carbonyl difluoride is known to rapidly hydrolyse in water, and it has been stated that difluoromethanediol is a transient intermediate in the hydrolysis of carbonyl difluoride (eqn 2), it is equally expected that difluoromethanediol behaves similarly in condensed environmental media with `decomposition to HF and CO; (Science of Synthesis, page 325). Despite meeting the OECD structural PFAS definition as a CF containing molecule, account of in the Restriction Report. Examplesofdifluorodioxo degradation from larger molecules `metabolism of difluorodioxo groups. However, there are some examples of environmental `and mammalian metabolism leading to defluorination via carbonyl difluoride. Minor biotransformation in humans of fluorinated benzodioxoles has been reported for the pharmaceutical Lumacaftor (FDA 2014). The biotransformation was not elaborated on in the: regulatory document, but potential degradation pathways were recently proposed, both relying on arene oxidation followed by extrusion of carbonyl difluoride (Johnson 2020, see scheme 39). In juxtaposition, the same group appears to be conserved in the available parent molecule is dependent on far more than the simplistic presence or absence of a single functional group. This is further exemplified by Alexandrino et al (2020), who demonstrated that environmental microbial communities enriched from estuarine and agriculture ecosystems were capable of completely removing and deflucrinating Fludioxonil at concentrations up to 10 mg LTM', in a period of 21 days, under the experimental conditions of the study. Although difluoromethanediol is clearly unlikely to be stable, the available data indicates that generalizations about the O-CF-O moiety depend on the details of the chemical posaanomsiet awosznzz 42. Trifluoromethylpghreonuypls Chemical stability of trifluoromethylphenyl groups. No data on the chemical sabiolftthye model compound (iifluoromethylbenzene has been e.r v fr identified in the literature (Figure 5). 8 . 2P Figure 5. Model compound: 1) (trifluoromethyl)benzene, 2) (trifluoromethyl)pyrimidine In related aromatic heterocyclic rings, it has been reported by Fischer (1993) that ortho substituted trifluoromethylpyrimidines undergo hydrolysis of the trifluoromethyl group under alkaline conditions. The hydrolyzability of the trifluoromethyl group was indicated to be influenced by additional substituents, and location on the aromatic ring. cEaxrabmopnlse,saa3roeppproesseednt1e0dablkeyllocwaorfboobnscehraviensd.biotic degradation of -CF3 groups bonded to aryl Examplesoftrifluoromethyl degradation from larger molecules `Sakai & Santi (1971, 1973) describe the mechanism of elimination of single fluoride ions influenced by a conjugated Ti-system (Figure 6). This reaction was demonstrated among. others for o- and p-trifluoromethylphenol, finally ending up ino- or p-hydroxybenzoic acid. Ara thmSoargin Y=F ~-Y2% 11 Prt oman ea rarn re te rs: ToIho dTye, I ane TR 1 tel dopa a ihn ton font he Rsesgenton Le Ao xX =X. ReN S co gue Figure 6. Schematic reaction mechanism as described by Sakai & Santi (1973). Especially dervates. wor reaction c) is described for enzymatic degradation in trifluoromethyl uracil posaaL03sisT 2u052022 Avdidniytlioognaolulsy,haitlohfaorsm-bteypeen rreeapcotritoend tthhaatt lteraidfslutooroemleinmaidniaotnieon(FoifguCrFes 7)(Lacnafnranucnhdier2g0o12,a Johnson 2020). F o CU -- C0) on 1 2 Figure 7. 1) trifluoromenadione, 2) lawsone. `The mechanisms described above can explain why some triluoromethylphenyl- containing substances (U-"*C-labeled in the phenyl ring)did not show the high stability often assumed for classical PFAS and, in addition, do not always show formation of the metabolite trifluoroacetic acid (Figure 8). eos d -- Shim Figure. SCoyifllumdeetgorfaednat(idoanta obfase2d-{tornifpluubolriocmevtehryls)iboennzooficCyfalcuimdeto(fmeentabroelnietwealBd-o1s)sieorf 2021). Range of metabolite B-1 soil DT50s = 6.3 - 36.3 days (n=). From soil metabolism data with specifically "C-labelled substances (Figure 9) it can be shown that rather than the formation of trifluoroacetic acid, the "C-labelled C-atom next to the CFs group was mineralized to "CO2. This is only possibleif the stepwise loss of fluoride took place or if the CFs group was lost by forming trfluoromethanol. As described above, rifluoromethanol would then be mineralized (Peschka et al 2008). / oN \ cron Coy Figure 9. SFoliolnidceagmriaddarteinoenwaolf dionssseicetirc2i0d2e0)F.loRnaincgameidof(Fdlaotnaicbaamsieddsooinl DpuTbSl0isc =ve0r.s3io--n1o.9f days (n=4). wir Posaz0sist 2unszoz These findings show that (1) it is not the single CFs-group which defines the potential tpreirfsliusortoeancceeticofacaid.parent compound and (2) not every -CF3 group results in formation of Trifluoromethylphenyl substituents have also been shown to undergo photochemical degradation to acyl fluorides and carboxylic acids. As an example, the pharmaceutical fluoxetine was found reactive in sunlight surface waters and proved to degrade to the corresponding carboxylic acid with a half-ife of 55.2 h under simulated conditions. (Lam 2005) While some precursor molecules are known to degrade to form stable. metabolites ceoxnatmapilniensgcltehaertycosnhsoewrvtehdat etrxicfelputoiroomnesthoyclcurm,oiaentdy t(hee.gs.e sthroifulludornooactebtiec inaccildu)d,edthweithaibnotvhee scope of the proposed REACH restriction. The conclusions in the Restriction Report Annex regarding the degradation of precursors (page 105) appear to rely heavily on justifications. previously made and accepted for PFOA. However, we wish to point out that the chemistry and environmental fate of single CF2/CF; groups is quite different from perfluorinated alkyl Cs chains, and requires more detailed discussion than reference to previous reports. 43. Difluoroethoxy groups Rodil et al (2019) describe the metabolism of a difluoromethoxy ether, proceeding via hydrolysisof -OCF2CHj with the resulting formationof an acetoxy-phenol as main metabolite at 28C by c. elegans (Figure 10). YK come " Win om ro Cp SOY " ptr me 3 " Grr es Figure 10. Metabolismof a difluoromethoxy ether (Rodil et al (2019). Degradationof asimilar ethoxy functional group but with ahigher degree of fluorination, has: been observed in Tetraconazole (Figure 11). The soil metabolism under natural sunlight conditions of Tetraconazole showed a stepwise attack at the tetrafluoroethoxy- group (see the proposed degradation pathway of tetraconazole in soil in the public version of dTeettercatceodnamzeotlaeborleinteewsalM1do4s3s6i0er-D2F01A9)a.ndThMe1m4o3s6t0 pallacuoshioblleisresahctoiwonn pinatFhiwguaryele12a.diTnghetofitnhael adceigdradation product of the tetrafluoroethoxy-group after having lost all fluoride ions is oxalic C Lo a +H ` CO fr Figure 11. Structureof Tetraconazole wa Posaanoasiet 2wosznzz a, Ws WN ONE Tf, wis ml 7%, Figure 12. Reaction. mechanisms. at the _toiralluroetionygroup leading fo. the TPehtortaocloynaezcoolnedimteitoanbsolites M14360-DFA and M14360 alcohol in soil under The fluoride-free metabolite M14360 alcohol is oxidized to the M14360 acid (not shown here), which then undergoes further transformation. This shows that also fluoride containing moieties like tetrafluoroethoxy-groups are in principle degradable and do not qualify for being classified as a "forever chemical". 44. Difluoromethylene groups Wangetal (2015) descar metiabboleic displacemoefnat difluoro-methylene group adjacent to methylene groups by cytochrome peroxidases. The fluorine atoms are eliminated and replaced to yield non fluorinated metabolites. ro ILd i 5 a fora - rn yam oe J at ym nSgr y" ge lum CFYe ome oOYr CS ly Birt Ko Xn ge ipa eles Figure 13. Metabolic displacemoefnat difluoromethylene group (Wang et al (2015)) wir posaonsist 45. (Trifluoromethyl)imidgarzoouplse aunsaozz Hayakawa et al (1998) describe the synthesis and subsequent hydrolysis of (trifluoromethyl)pyrazoles (Figure 14). [ a 2 1. Ow " 2 F 3. 27 Figure 14. Model structures 1) 2-{trifluoromethyl)-1H-imidazole, 2) 4-{trifluoromethyl)-1H- imidazole, 3) 5-(trifluoromethyl)-1H-pyrazole Tflhueor2id-eanudnd4e-rsumbsitdituatlekdaliimnieda(zpoHles=ar8e.9r)eploarbtoerdattooruyndceorngdoilroanpsid (eFliigmuirneati1o5n).ofAhdycdirioogneanl electronegative substituents can influence therateofelimination of fluoride ion. We request . - v ek on . o that this information is accounted for in the Restriction Report. Jo on Cm pre NZ NH N N_+H20 NZ NH__HF Ome NZ NH. +H NZ NH .F Fe oH o 0 N[ 1 ANa ENN L i oL o A a Hwe N NA NNa NaTezENTN ; Figure 15. iHumynidddreaorzloyalsleiksahloiafnse2 ahlnabdao4rl-attorioirffyfl8u0Ceohor,nodamienttdihoy4nl-sii.mfilAdulazoorploHem-eaDtchc(yo3lr0diimCni)gda2Hz4aofyllaeukoharawlotamefettehayollf()21-09T09Hh8..) oHbydsreorlvyesdisbyofEm(ovilfelnikoroomotetahly)(-20H1-2p)y,raaznodlewsaswitshubseeliqmuiennattlioyn opotfimhiyzderdogfoernyifelludorbiydeuswiansg much more aggressive laboratory condiions. uNnodedrataenovnirtohnemcehnetamlicaclonstdaibilloitny oofrthseusFicgeuprbei1i4yiwmiadrazdosle obriopdyergarzaodlaetimoondehlascoymeptoubnedesn identified in the literature. win poszaL03sisT 2052022 5. Conclusion The Dossier Submitter states on page 54 of the Annexes to the Restriction Report If there are specific PFASs for which sufficient evidence is provided that the preersfulluionrginaatedsbuobnstdainsceb/rsoukbesntaantcaesratwehwihcihchiis/nadriecatneostthear tPoFAbSe,notthpeenrsisttheonst,e substances/groups should be excluded from the scope. Currently, no such PFASs are known to the dossier submitter. We believe we have provided adequate evidence for specific functional groups that are not persistent, and cannot be "arrowhead" substances, despite meeting the OECD structural definition of PFAS. We request that these substances be removed from the scope of the restriction by amending the grouping definition. We believe we have also adequately shown that there are also functional groups meeting tthhee OmoElCecDulset,rumctauyralordemfianyitinoontoffoPrFmApSewrshiiscthen,td"eaprernodwihneagdo"n(tmheetasbpoelciitfei)c scuhbesmtiacnacledse.taBielsinogf unatobprlediect the full chemical behaviofotuhirs chemical space,we suggest introduction of a conditional derogation for those substances as a "safety net'. Placing the above substances out of scope, or potentially subject to a derogation, does not in any way lower protection of human health or the environment, because it rseumbasitnasnceisnciunmtbheenrtespoenctaivneyRREEAACCHHregriesgtirsattriaonntsdostsoieardse.quately risk assess the 6. References Alexandrino, DAM et al. (2020) Microbial degradation of two highly persistent fluorinated fungicides epoxiconazole and fludioxonil. J. Haz. Mat.; 394: 122545. hitos/doi.orq/10,1016/,jhazmat,2020,122545 Buszek, R. J. & Francisco, J. S. (2009): The Gas-Phase Decomposition of CF30H with Water: A Radical-Catalyzed Mechanism. Jounal of Physical Chemistry A, 113, 5333-5337. Christe, K.O. et al. (2007) Convenient Access to Trifluoromethanol. Angewandte Chemie; 46(32): 6155-6158. https /lonlinelibrary.wiley.com/doiffull10.1002/anie.200701823 De Bruyn, W.J. et al. (1995) Uptake of haloacetyl and carbonyl halides by water surfaces. Environ. Sci. Technol.; 29: 1179-1185.hoitrpas/:/duobsi,/apcsd.f/10,1021/e5000052007 Dinel, L. et a. (2009) Oxidative metabolism of the tifluoromethoxy moiety of OSI-930. Drug Metab. 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