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(~EIfIGU. ~ D~'O~Ld.TXON ~.OF~,.Z Subject: Di13,d=osat:ole l~epued b?: bma=ie A. Fs~s: C~kesictl E~fe©:s E~o=aa:to~ Caste: Oak lidle Hstiozml E, abo:ato~r Chemical ~aae : 1,3-bnzodLozole, ~-1~:o1~rl- (9 CI) (CAS Ko. 94-58-4) Date of hpo~c: MaT 17, 1984 [XEC~X'A'~E ~W Xa 1Sr77, ~he ]rmoA,Ae:Lon/i=pe:tatiom o5 dL]z~l:osat:ole yes in he :8JzIe 500,000 ~o $.000.000 pcru~s (USVA 1983b). T~e ~.S. Z,~te=aacLonal T:ada Coumissioa did act :e~o:: deaes:~c predzo~Lo: at Us conpou~S ~c: ~he ~es:s 1974-1981 (us'rzc, 197~-~982, as :epo:~e4 L=~I=A 1983t). ~'ae aos-eonfidentlal ~le o~ ~e ~SCA C~zenLcaZ S~bstances ~=veato:~r (~A 19831)) ILs:s ~cnz: ccmptaies rJzat p=o~ce~ ~L~=osa~:ole in ~Sr~; the osl~ c~v:en: 4ones:it p:od~ce: of 4ib~d:osa~:ole Listed b~ SR.X is ralama C~euLcal, Za~.. [~lana Spec~al~es, Zac., Beau~oct. SC (SRX 1983, as :epo~e4 ia ~SEI:A 1983a). Zad~st:ial monAco=inS data we:e not ~ou:zd ~o: ~acil£~Lee :a=u~actazia| the eo~o~z~d. ~o=ke=s nay be ez~ose~ ~o dLM~L:osa~=ole d:LCi~$ Lts w.se as • chemical ~atez:se~iate L: Use p=oA:e~Lc~ o~ p~pe:ozrFL b~ozi~e (CAS ~o. ~i- 03-6) an:l relate4 LKsec:icidal sTse:lists (T.J~C 197(. F~sMbe~ aa~ Foam 1949) o and in :he ~:oduetLon of t:zl:ances ~o: cosle:ic pxodnccs. Dit~d:o-. sa~=o[e ~as bee~ Lden~ied as sa imp~u:icT (to caace~c:a:~ons 0£ ~0.1~ b~ weiJh=) Ln pipe=on?~ bu:czide. Pipe:on~l butoz~de is p:oduced b~ :eact£nj ~Jze ohlo=ometh~1 ~e:iva~ve c~ ~L~d:osaf:oLe vi~ ~Me sc4~mm saL~ o~ b~1 :a:bi:ol [~,UiJ II (TD~) 1984b]. Mo evidence ~as ~ound :o La~ica~e vhe~e: ~ze cc~spo~n4 ~s p:o~uced b~ an enclosed o: open p:ocess. Dt~rd:osaf:ole is :epo:ced co be ~sed •s • F:t|~znce ~= deCe:|encs a~ in cosmetic prodvc:s suck as c:e•ns, lotions, pe=~mmes, soaps (~SEPA lPS3a). Opd~ke (1~74) =epo::s ~a: ~be ~.S. ase o~ 4i~7~rcsa~:o~e as • f:al:a~ce anouted ~o less ~tan ZOOO po=~s/~ea:. ~e compound ••so vas "-~ need douescic~11T as • ~IKVQ~Ln| aje~c i~ :oo~ beer. but yes p=obibLced ia 19~0 b~ ~e FDA ~or ~se in ~oods (2~ ~ IS~I80) Cc~sazuer ex~os~=e co~i~ O • CO O

. coo~ |Ja:o|lh ~* ue of products suck u OOSleCics. deter|eats, and so|ps co which di]zydzosaf=ole has been added. No ~sfozlstiom yes located on enTi:onmeutal release or biode|=ad&tio~ of dikydrosafrole. UnliY.o its ciose scr:at=u:si analog, saf=ols, d~ydro- ssf:ole Ls ~ot fou=d t= mature. B. Ksal C/z Effects Dthydrossfrole is • member of • class of compounds Senerally kzovs as uethylenadiozTpkeayl (NDP) derivatives (Do B=:il lg76). The p=imscT meta- bolic l~tUsvay of NI)P compounds ia mice tKYOITeS the mszyustic kyd:orylatioR of the umChylene j:o~p yield•hi fomte sad ¢02. WttkLm 48 ~o~rs •~ter ors1 •dmiaistrstio~ of 5 ~mole di]~drosafrole/k| body :silk'. Co mice, 655 of r.he dose was |1wen off •s C02° 18~ was detected i:t ~cize, 4qb i:L feces, and 10~ •oo=amis~ld l~ ~e body (Casid& st •1. 1966). ~ race. the con- poud is rtpor:ed Co made:IS essentially :sapiens metabolism within 72 ko~=s o5 •1 bstrs|sstrio dose of 1 :sole/ks wick the re:nation 05 16 idea- tifie4 metabolites. Tke primary mmcaboLtte fo~ned was 1,2-byd:ozT-4-(1- p=opyl)bonzene (t~1~lSOOyr ud Sckelile 1982). By comps:ison, female boise flies ()hsscs domestics) injected wick 170 ~mole :adiolabeled dth~sosatrole/]cS metabolized the compou:d more slowly. 0sly I~ of c/re dose v~s :eoowe:ed wit~l~ 24 ko~=s. A majo~ portion (6~) of eke dose is rope:ted to be los~: for metabolic processes dns to direcc yolaCiIizacio= f:on t~, flies (Casids ,t el. lP6~). Di~yd=osaf:ols is :eaolnized •s • cz:cinoae= i~ ezpe:iaental ~:~nnls by t~e ~l~tO~ltiOKA1 A|e~Oy for ~Jsea=ck 0m C&uce= (~C) sz~ t~le ~[&~ion&l Canoe= T~stit=tc Bloc/say P=o|:sn. Dui~| eke con=so of • ck=o~io o=11 toxicity study, p=im~=7 esopks|eal t=mo~s ve=e indued i~ cats fed 2,~00, $,000, o: 10,000 p~m i~ C~oi: diet re: two 7st:s (Halt: st •1. I96S). ~,t • no•be: st~iy, chert v~s • si|nificamt i~c=~ase of hTpe=~iasis snxi ca:time- us of eke forestomsck iz female mice iniesti:$ 1,400 ppm dikyd:osafcoLe for 82 ~eeks, wkile male mice deyeloped s si|nlficanc ins:ease of Iiyer cs=ciamnss (Re,be: I979). Non-mecastasizin| kepstomss indnced in male mice was the l~imsz7 Cumo:i|enio effect coted ~ • :elated st=dy, wken mice yore |iyen 1,400 ppm d~yd=osaf:olc o=•ILy re= I8 mo~tks (Isles st al. i~69). A~so obse:ved ve=e pKlmon~=y rumors, consist•n| p:;incipallT of ademomas, .in male s:zd female 8:zimais. ~opic•I application of dikyd=osaf:ole co mice resnlCed in 1~ i~cidenocs of skin pspi11~ts not si|nifican:ly diffe=ent f:om Cl, ose of cent=elm (Bo=cke=~ ec el. 1973). A:z epideuiolo|ical sc~dy of escpksfeai cancer ~icCims amen| eke black pop, lit•on of Soutk Ca:oli:a llnXs cJze disease Co eke in|escion of a variety o~ folk remedies end Co occupational ezpos~=~s (gotten 1973, •s reported in NZOSKTEC 1984). Sasst~cs__~s~So contain•uS c~e ~novu ca:cinosen ssf=ol, was one of the folk medicines mentioned ~n this scuds. Cants= o~ the esophalU• yam :he most common pc•ms=7 an=o: amens males in a 8:sup of 894 patients ac Ck~ee institutions. The only |enocoxiciC~ sc~dy f~und lave as|sOlve results :ick and ~icko¢C me~aboli~ activation in Salzouells cp,=kimu:ium sc~sins TA~3~ and TA100 (~lslooki etal. 1977). .._..a. O O Lkn Px.)

- AeeotdAal to ~be se&Le o~ GosselLn et IL. (1977). 4ih?dzosstrole slrpea~s to be 8uode~teLy ~c~tslT toxic ~btn sdministe~e4 o~&lIT to cats u~L aioe. hSam st al. (1965) =e~o~e4 EDSO v~es of ~2S0 sS/kg tad 3,700 It|/b| in rats as4 siee, tespeetLYsIT (•avis uul Tstken 2982). ~'Ae at•i~ tozie nanifes~ations of saute and subaents oral e=posu:es to di~,dzos•f~olo ia 1•boil•or7 ani:•is veto ch•alOS Lz the live=, s~:~ •s pronouceK fat•7 de|oasis•ion in xice (G:•even~tz. 1924), ~11ov disaolo~stion, fatty •ppo•=- • nee. Loss of normal tezt~e an4 enl•t|eue~t ~n =s~s (Ta~lo= et aZ. 1964). • :td ez~L•zlemest. ~e:•~. fattT Mtamo=~Eos~s, bile d~ot ptoILfo:•tLem, end atch~teet~sL i==el~Aa=~ties in :st• (KSl•n st a~. I5~$). The eoupo:n~ • lag is :spogted to ezez~ • stimu/ato~ elf e©• ~a live= tissue to|eaten•ion ~n ps=~ially h~patectmtized ~ats (Ge=s~be~ 1977). AX~bOUlk ~be flyer appea=s to be tke ua~o~ =at|st on|a-, re= ~be toz£~ offeets of 41)a?d=osa~ole, other adverse offsets have been =epo~s~ tad i~o~ude chronic meph=itis sad ad=enal enAs:|euent in :sis (Hesse st el. 19~$)o aode~ate ~oELLenAa= •t::opl~y o~ the spleen and |=ov~ =stands•ion in :ate (Halts et el. 196~), p:oio~ie4 i~e=eased :s~ezes i~ nice (Gtseve~i:z 1924), and ni~d i::i:atio~ on ~abb.it ski~ (S~sltaski tad ~oL~ova~ 1~73, as =epot~ed i= 0p~yke 19~4). Oih?d~esaf=ole produced no skin i==itatio~ o= sesaitLzatle~ ia veldt•e=• tested v~t~ • p=spa=at~on o~ ~ di~A=osaf=ole ~a pe~zolat~m (Eli|san 1973, as ~e~o~ed La 0p~Tke L974). C. ~v~=onnental E~feots O~hTdresaf:ole, i= ¢omn~m v~t~ other HDP ¢om~o~sds ae~s •Tat:lie•i- sally is ¢onbLaatio~ vi~J~ • aerobe= of ~secticides s~cM •s p~tstM=mn a~t on=boasts•. The no~e o+ •+~ioa of ~e MDP sy:e=liSts seems to be :he slow- Lnl dm o~ tke utaboIic btc~ivstion o~ inseezicides t)azo¢ i:.bibi:ion of a~c~osomsl ~rd=oxTLation secba~isas. ~e MDP de=ira•ires essentisllT se~ri:g •• •lts~sz:e sKbst=atss ~o: ~e :ized .~o:ioK ozid~ses (De B:ain L~7~). This 8e~an~sm o~ •ctio~ :sT also be ~es~onsible ~o= ~e=sesia| t]:e potency o~ certain ~=~Js by ~he iaJaibitio~ of ~o~mal decozA~icat~o~ :ec~sa- isms (Ca•ida st aA. 196~, [amienski and ~zsida 1970). iii 0 0 n-... C~D

TA2LZ OF O0~ C~e,,icsl Hazszd ~Iato~'mati.o~ P=of:LLe l).ib?d.~o saf~Z • wJrwo~'Z'yl ~lalAILZ .................................................... i I. SUrf' OF &VAII.~[,E 13.aTA ...................................... 1 A. ChexicaL ZdLen~L~y .............................................. i B, Physical a~ Chemical P~o~e~:ies ............................... 1_ C, r~rpo suzt ....................................................... 2 I. Vo~ke~ Ezpas~ce Cmasideraciou ............................. 2 2. Coast: I.zpoez=e .......................................... S 3. Envizoumensal Y~pos=ze ..................................... 5 D, HeaZth F~feats ................................................. 5 1. Xetabolisu ......... $ 3. Ca:c inojs~Loi t'7 ............................................ 8 . Gmzo~oz~it7 ............................................... 10 5. Te~lto |CLIO i Cy/~J~OdZuz~ ~ve F.ff oct8 ........................ lO 5, Other P.~feacs .............................................. 10 I. NecabolLsm ................................................. i3 2. L4thaiit'T ........ ~ ........................................ 14 3, R~p:od~cc/o~ ............................................... 1~ 5, ~ovck and OeveLo~enC ..................................... 14 7 Ab~o~£o £f~eoCS . 14 eee~ee~oe~oeoeleemomm~o~ eeem~eeoomo~oeoeee 8. Otha~ l~feocs .............................................. L+ F. 15 16 a. 2I C. 22 22 2. ~aca,Rases ................................................. 28 3. Search $e~ace|y ............................................ 29 D. CheuicaL SpectfL: Secoadax~ $oK:ces Seasched ................... 29 ~zis~:tn! Sts~sda, bl~Ztt/ozLs tad gocoumond~cLoas ............ Or, he: ~levxaZ I~fot-aacLon ..................................... iefeftnces ..................................................... I,i:efa c=ura Cited ............................................... $t~ptexencaZ rn~o~ut eiozt ....................................... Secoada~ Sources Seazche~ ..................................... i. Seeks ...................................................... O cJ~ C~3

~. SI~ 0~ &Ts£1~bL, Ds:: Ao C]tsm£u&1 Ids~:i~ 1. CJ.5 bIiSt~'T ~mbe=: 94-~8-~ e~ 2. ChJm£otl ~huse: 1.3-kazodLozole. 5-"p:o~I- (9 C~) , Sy~o:yus: Beueszo. 1.2-(met~leu4/ozT)--4-propyl (8 CZ); 0L~Td:ostt:ole" 2' .3'-9~zyd.vossf:ole: 1.2-( Me :~y lo=o 4£oz~) -4-pro ~ L~ enz ,=e-; $-P=,lffL-2.3-beazo4iozoLe []iR3)LJL5 TT (C]][Xl.~ 1.984]; 4--P::O~1--1.2-1etkylezLedio]~qJe~o:Le (Lewis a~d. Tac~:ea 1982); $.4-~n~lea44~ozTp:,pT11:ou.ze~ (w-wLeT 1981) 4. S~:a--zl FQ~nula: S. XoSeozZs= Pomu.Ls: ¢10B1202 i B. l~zysiaai &rid C~esi=:l P=ope:=ies 1. XoleavJ.Lv TeiShc: 164.22 (L,vis ,J~L TA~..~n 1982) 3. KolC~.~| PoLio: ~(oc s~rz~.i&ble 4. ~ili=~ Point: 228"C [~I.;R3 1~ (T~B) lPS4s] 112"C zc 1~ ms HI (P=:is ~ BeLlanc& 1~71) SoL=bLli~ies L~s b. Non--tqueo=.5 soLyencs: Xiscibl, ~LCh ,c/~szoL. echo=, scocic acid. and benzene [XEDLAR3 ZZ (TDB) ].984~]. Somewhat soLc~bIe i~ zlco~ol (Hsvle~ ~g81); so2zb~e 1:9 L= 80% &1cobol, ~:2 ~ 90~ alcohol (¥~iz an~ Beli&~cz i~71) ~. Diss~cisCion consc=a:: ~oC zppliczbLe ! T. P==titioa coefficient (log P): ,qoc found 8, Densi:'7: 1.069~ ,so ~.00~ [,~I~DLA2$ I1 ('rDB) 198~t] 0 0 9. YoI:cilLc'F: qoc ~ou:d

~Jaa~i,r itS: a, b. C. L-ponze Combustible (Kawley 1981) bf:LcCiTe I:uLez: 1.$18"r a: 25e [~L,kU IZ (TDB) i984t] FtssJz Poiz:: 202"F ii cbe'Tss closed ::p (¥~::it Lmd BelZ~ua 197I) Odo=: RmsizLscent of s~8ssf:ls (~=:ix 8~d Bellsnot 1771) 1. Work,= F~pos~ve ¢onsidecm~ons I. hodnotioz/Zzgo:sscLos No i~[ozlA~ion~t8 ~muui :eSszdiA| ~kt a=z:sl: p:od=ccio~ volume of isqpo::/oxpo:: o£ di~Lvoss~:ole. T~e U.8. Into:ztcioui Tnds ¢omtission did not :epo:: domestic p:o- du:ioz o~ ~ke ¢amVoznd re: r~ze yeses 1974-1981 (USI"I~, 1~76-1982, as :sgozts4 ~US]r~k 1983s), bl~ did :spo:: l~Odmat/ou by one comptzry in 1971 Jmd 197~ (USTC 19)'3, 1974, as :e~o::e4 i~ USZPA 1983s). P:od~e:ioa volmne £o: ~koao yes:s vss no: ~o::s~. :e~e: o~ ~s p:od~atLon :s:|o (iaalud~s ~m~por:z~ioz ~oluaee) s~sCist~cs to: ddhTdxos,~zole (CJ~ No. 94-58-~), wbLa~ is l~sCsd t~ the ~:~CL,I pzdslLa (non-CBZ) TSC~ ~.:Tezco:7 (US]~A 1983b), hsa shorn CJzzc be~ee: 500.000 sad ~.OOO.QO0 pouds o~ C/sis chemiazl ve=s :epo:~sd ss prod=ascL/Lmpoz:sd in 1~. b:osJuimm st ~:oduocion by ind/T~dul compznies con ~, ~ound i~ sec- tion C.l.b P:oducs:s. • T~is lnrodza:iou csnZe ~do~-ssciou does zoc ipclude any p:odstatio~/inrpor:acion hcs cla~med as con~idsu:£sl by eke pc:sou(s) cope:sin| foe c/st TSC~ ~nTezcoz~', so: does it include an~r infoz:scto~ ---.- wb~ 'nm~zld co11~::om~se Costj~de:~c£sl B~s~ztsss Zn~o~-mac~o~. T~ze 4~ca submic~:ed "f~o: t~e TSC~ T,,TeZCoZ'T, inclo.din| p:oducc~ou cerise i~o=msCion, a:e szbjeec Co CJze ~J:~Cac~ons conca~na~ ~.: the ZnTenco:7 ~ RaporcLnl RsSUlacious (40 ~ 710). c_~'~

- b. P=od~ce=s T~, ~LT c~ent domestic pzoduce~ of dikT~lzoslfzole listed by SP.~ is z'tlaat C~l.emiczl, Inc., lalama Specialties. Inc., Btszfo~t. $C (SR.~ I983o a• reported In ~SEPA lg83s). Campsnies ckat reported production o-~ dihTdzo•sfzole iXL 1977o a• li•tod in the I, zblio noz-con~idontisl file of the TSCA Ckemic&l Sub•canes• I=vcnszoz7 (USEPK 1983b~ vere a• follows: Ve|no sub•imitzT. [sluts Chemian2, I~o. Betq.t[or~, SC 29902 1977 Pro~u©~to~ of 100,000-1,000,000 pound• FMC Corporacio~ Baltiao=8 Plant Bsitino:e. MD 21226 1977 Prodnotion of 100.000-I.000.000 pound• Pzodnaed site liaitmd Es=dwloko C~emiasl Corporatio~ Eljin, SC 29045 1977 P=od~otio~ of 100.000-1.000.000 ~c~nds P=od~oed site liaited &. ~o•# and Cmrpsz7 Hays=k, ~ 0710~ 1977 P=odact~on of 200,000-2,000,000 pound• The U.$. T&ztff Commission (USTC, 1973, 1974, e• =ape=cad in USEPA 1983&) repo::ed dome•tic prodnction of dikTdro•afrole Lu 1971 anal 1972 b7 CkmsFl,~:. In~., Nave:k, NZ. a. P=odnec~on Methods DtkTd~o•nf=ole is p=odnned bY tyd=olonscion of ssfroLe or isosafrole ~ttls s ::Lake1 et~slT•t, or b7 hydzo|esuttion of 3.4-uetkyLenm~oz7 e~:mzaLc aldekyde []~]~.~ES IZ (TDB) 19~4a, Opdyk8 1974, ZA]tC I976]. F~:ia ~d 8el- • mien (1~71) EeVoEC th.st dihTdro•afrole is also ST:Chesiz•d b7 the kydEose- erie: of •~froIe ~n Use pre•ence of palladium o= •eZiv~ted c~bo= eatalTSt•. 14C-l&beled d~hTdzo•&fzole vi~h • sl~eoif~e •etivit~ of 1.0 m~lllenz~e/mmoLe ~ts prepared by :oect~n8 methTlone 14C-~oaide rich p:op~l • atoo~ol (Kzvttszk: and C:•id8 I9~). P~pe=oWl b:tozid,, the p:incLptl end In~OdnCt of dihTd:osaf:ole, is produced I=7 :esecin| USe cblocomechTL derivative of ~lkTdrostf=ole v~th eke sodium sale of buCTi ca:b~CoL [NED~.~RS II (TDB) 1984b]. No evidence was found Co ~ndicaCe whacks: ke compound is p=oduced by an enclosed oc open process. C', i~|~iedpi__ ~I__~ ..... ;|__-- |LiiIi| i~A lill______L dllli, AA

& d. ~III (1) Zztousediate Uses I~dC (1976) :ape:as that dihTd:osafzole Ls p:odnctd aS U inca:radiate ta ~JLo pzod~ottoi at pipe•anTI b+toz£do (C~5 No. 51-03-6), t s3-nO:liSt fen FetJLToid ~Ioottoides. Raz~ieJ:s C~et4ot] Cox-pc:arian :ape]aCid ~IL ~e p~bl~ao now-~onfidoatisl T3CA T-venCo~v that Lt produced 100,000 to 1,000,000 pounds du:~n~1977 (p:od~eod site Lbtitsd) (USEPA 1983b). No Lz,formatios yes faunal ca c~r:eat p~odu~a=s of pipe•anTi bncox£de. FLshbeia lad Mslk (196g] ~epo:~ t~e eoupomsd's use in the rrsrJLosis of :eL&ted pes- tiaids£ syua:Sis=s, piperouTl s~Ifozide nut :-p=opT~ Lsoue. (2] End Uses T~o c~rreut end use of dih~d:ost~:oLo is no~ cle~:. T~o conpound yes rimed ~I ~Le U.S, uJ~I ~0 &I • ~t~O:~I &IOnC iJ$ ~OO~ bee= (~C 1~.'~), but ~8s then prohibited by :ha Food tad D:n8 ~inisc~•tLon [E'EI)~ REGIS- ~D~ (21 ~ 121.106), as :epo:~od in Opdyke ~9~]. inwLe~ (~981] :apexes tJ~st dihTdrosaf:olc is ~sed Lu oJseD~ial oil compositions. &oeo:dinl to 01~dTke (1974), dJ.hTd:osaf:oLe is used in fral:ancts, and has boon iJz publLc e•e LI ~.he U.$. sL~ee c~e Lg~O°s. The done•tie ~le L~ ~=a|=an©es, p=esuI- tbl~ Llt the ea=Zy 19";O's, utonnced ~o less ~ta~ 2000 lbs/Tt'. ~TPL¢•Z pro- d~eCs vit~ d~lTd:osa~:ole s:e lis~ed is TabLe 1 (USEP~ 1983a). TabLe 1. Typical Fo~tn£atiou.s ContaLn.L~ OL~T.d:osaf:oLe ¢once~LC:ation i= Final P=oduet (%) ~ C~:eaII. Y otions PI :~e Usual 0.03 0.003 0.005 0.1 |(azinu: 0.3 O. 03 O. O~ I. Sou:©e: USEP~ 1983~ Dt~Td:osa~:ole sccs syne:|~s~ctlly vi~k • nuabe: of insecticides; hcmerYe~, no data ve:e [ound to i~dLcate that ~he compound ~s ~sed ss an L~see~ieLde. e. Detection Xet~ods k so•hod fen ~ke ItS-liquid clcsacoj:aphic decez'/BLnlC~on of d£hTd:o- s&~:oLe Lu non-alcohoLic bcve:•$es ~s :epozted by L~::~, (19~L). Bo~ntan a~d Be:oza (196;, 1968) deso:ibe t method ~mtbi:i~l Ins eh=oueCOl:tphT v~tk spoe:rofluo:~ec.'T applicable Co the 8~slTs£s of aothTIened£ozT~henTL cam- pOtl~I. ~Kn~JeS i~ ~he ~IloI:II :tn|e &:e :epocced Co be possible, ~ith load sonsitiyitT. The smallest detectabie quant~CT oF dihTd:osaf:o~e is :spa:ted to be 0.2 hi. OHM'/~ADS (I984) lists the ~oilcmin$ detection l~:iCs ~or the compound: (I) in waste race: - 0.0~ ppm; (2) in surface race: - 0.001 ppm (I ppb); (33 Ln d:i~kinl ware: - 0.0001 ppm (0.1 ppb). O

- f. Vo=ke~ Ezposu~e S. Dispose I Dtsposc2 of 4ilzTd:oscf:ole is :el=laCed undo= 2CILA sad GDLCLA (EPACA5~ 1982. ss :epoz:od L1 USEPA 19831). The aompoznd's hszz:doms ruts mmbc: is 0090 (OHN~A/)S 1984). GHNTADS (2.984) cecosmmsds psoksJin8 of prod•toe :esiducs ud so:be•to cedis Lz e~pory-IiucL 4:~ms 8zcL dLspas-,l tc t: F~A- tpp:oved sits. The compound may be dcst:oTed by pc=ms, Is•uses ozid-c/cl. kizh Cempe:#c~o JJZCinO:stLoz vi~k sczzbbin| 0qaipmout, o= zLc~owzye plssms ~JS ~C81~. 2. Consumer Ezposzre No L~orms:io: yam fomui ca consume: e~pot~e Co 4Lkyd:Os:Lf:o~e. Hey-- oyez, ~te pot•otis1 fa: aoms~me: e~pos~:e ezists ~LTO~Ch ~ez38sl couctct oz inhaler/co if the oomgou:L4 Is :tsecL ss • f::sl::tsLce in cosmetic pteptz,,tions. sosp•, 4ctez$cl:s, ozezms &~L lo~icns (U~.,P& ZgB3s). 3. E~visonmsntzl Ezposuze s. Eayixonnezcsl Release No data" were tmu~L. Severe:. d/h?d:ossf:ole has been identified as an isqmz~CT (sO ca~ce~c:scioms of (0.1% b? ve~8l~) is~ p~o:a~?], b~Coz~.de. • syz:hctic pesticidaZ sTno:|isC (Alb:o ec cA. 1972). Usa of r.his pesticide oo~LT.d z~s~It 41 iazdve::tsnc =e].esse of dihTd:os~f:ol.e i~ Yez'F re•s11 s~o~zCs ~:Zo Lko e~o~meA:. b. F~vizonme=t•2 FzCe No d~c• ve:s found. o. ~.zT~zomte=cz20cc~cmce No dLa, tz raze ~ozuzK om C/so satuzsl or tath:opolenic occ:::e~cc of 4ihT~:oss~:o~e i~ Clze e~vizonme~t. D. Kezlc~ Effects 1. ~e~sboLisn ¢ssida st sI. (~6~) :epoFc ou the se~tbolim o! six methylene-14C- diOZTPhe~r| tom, cuds, Lacked/n| dihTd:OS•f:ole, in mice. The ~•beled com-- pouds vc:e sdmizisce:ed ocz11~ Co mile slbino mice zC t dose o£ 5 ~:noLe/kl of body wei|hc. TiChin 48 hon:s &fee: sdmLnLsc:stion of dLhTd:ossfro~e. ~q~ of the :~dioce:bon wzs liVe~ of~ is ~4C02. 18% yes deCe~ced Ln u:ine (I5% vale: soluble sn~ 3% toluene soluble), ¢% in feces, end 10% tcc:mn- laced in eke bodT. ~n ~n vic=o sc~dLss, eke labeled compound •as incubated 0

t • at a aomoeKtzatiom of I X 10-5 M wick mouse Iiye= homoaost&te$, with and vitkolt ~Jze addition of ~e cotzetof NADPH2. T~e sotabolie accivit7 of the Itia~J~t&l STatel f¢018 mo~ae liver vls ez~aJseed when NADPH2 ~as added: tke major motaboLito in th~s system waa ~o=uate. The =sdiooazbon £acovored (as vstez soluble mot•be•iCes) ia mouse ILver nit=cacaos was 2Pl and 15 wish ~ wL~o~ NADPH2, £espeetLvelT: Koveva~, ~he eve=all metabolic aotlvLt?" lz ~mL|kC to be no=e ez~ensive, because considerable 8stoics o~ eke com- pond t~o not &vaiXable ~o~ netabotiam d~e to voLa~i~Lz&¢ion 2oases d~in| L~c~bttL on. ~ Z= ¥L8 1., as stated by Cza~da e~ ai. (19L6), She matabolio pzth~•T Lavolves eU~nL~AC kydroz~L~AOa of ~lze Rot~L,~c-14C Sro~p. T~is p~c~TaT aeeo~s ~o~ ~ko to,ease o~ fo=maCe-A4C on soisaLo~ o~ r~e kyd=oz~- me~h~Leum-14C-~ioz~pheay~ SrO=p; the ~o~ma~e-~dC is 8etaboZLzed ~a v~vo Co ~eld 14C02. Tho ~vo L~¢oz~edia¢ot t~ b::acY~cs have act bee~ ~soLaced Lad s~e p~obsbly ve~-~ ~stab~e. T~c other ptthvsT - Pz~/ITs~ B - ~nToives modi~iCsCiou o~ eke :i~| sabstit~a~c(s) o= i= Lnc:odzccio~ 0£ 8=s zd~icion~ $=o~p into c~e pken~ :/al. In mace and in. C~e mouse Live= aAc:osama~ rys- Gem. pathva~ B :epresents• m4~o~ d~|=Ldation co~ce. F~au:e 1. Proposed pcckwsy ~o= metabolism o~ mechTLene-Z4C-dLoz~phczFL compouds. Adapted f:on C~sid=t et •~.. 196L More neontlyo •dditLoual cruz sczdLes c8=:icd oz: vi~h mLLe Swiss- Vobste= mace b~ ~lmienski and Caaida (IP70) con~i=med the ma~o= metaboAic ps~ltvey p=oposcd b~ C~stda eCal. (I966) vhicls is~o~ves the cle&vz|e o~ the • uothyloned~o~kc~l moLe~ and e~pi=ztioz of eke =etk~leze ¢•:bou as ¢ac- b~a diozido. T'ai=-laye¢ ch~:ouaCOlr:phAc aaalysis o~ er.her ezt:ac¢s of aecuuAzced 0-3.2 h~" ~i~e samples o~ nice $ivea $ ~noLes/k$ I4C-LabeLed dth~rosaf=oLc otaA~ co-tailed six mac•holLies, one of which cock=ousto- $raphed wick pipe:onyl~c acid: O O /