Document VRzobOqnKLok0a5Q9BOOJKgo

I world u.Ti .v:x:-' CPC/.N43A DOM : ON Ci A:wl LA PAN"' j``>i;-v.r./.'i:o tip .ip /://' '.;'i\ i9.::v.\;v: o.: :/,//: r.r- JO *v* V * i* - - . . - A. - W * . W - * a:.;) "c::;jL;::ooc;':-' woi/ibb 'ff. 1 01.0 n.'O'AOV ,_.4hmA12..:\.AulLc oJ"-70 FAb/il/VO, , (a) - 0__,JL aC,,, by Dr P. 3. s (Consultant) Acetone (CH.^CU.O.h.,) is rc-.Oi.i7 absorb;d by solution into the blood after inhalation (iaxix. 1924) a.vi proyr^snive accur.nlation in tin .roes has boon noted after 6 hours irhti on (begga-d et cl., 19//,). bain ab50rpti.cn cccuis cniy slowly in ar.ir?.l:j (Le'-'arcw ot at., 1931) rrd -probably rone through intact human skin (Ceearo and Pir-rolo, 1947). Largo oral dor-os are .neatly excreted un changed thvourr'' tho lungs (A0-70:1) e,ni the kidneys (l3-30;i) but smll amounts are metabolised slowly to for wo.to ruvl acetate '. ! Ini ir 14 hours (lillians, 1939). Dogs excrete in thoir urine sous 1-4,1 of acetone whan administered orally at rates of 0.2-1.6 g/kg. Seme 60,) in excreted through the lungs (behwara, 1893). Snail doses (1.7 ng/kg body weight) ars oxidised mainly to C0o (53,1) while some 7-14> is exhaled unchanged (Price and Aittehberg, 1950; Sakaisi and Lafaye, 1950). Sons 10/) of inhaled acetone is excreted through hucati skin (Pnmeggiani end S&ssi, 1954). Acetone labelled with in the methyl group was shown to b? converted by rats to liver glycogen, sorir.a, choline and methionine via formate and acetate (Sukarno. and Imfaye, 1950), while another metabolic pathway involved direct conversion to pyruvate in the liver (ock.nA and Lafayn, 1951). Acetone injected into dogs produced high hepatic level?, of .l-liylroxytutyric acid (Valdiguie. 1935). Cf 1 g. adninistewed to ran seme 24t acx; excreted through the lungs (Aothxopf. 1936). I.v. injection into rabbits ra-..v c:.ily .increased ac2toe.c0M r- - M A and* The bsud of Vhia Cccerv'i.Mt dooa not cor.&ctuta formal publication, It tiiouid no*, bo r-jviL-vvad, ab,,tuict;d or e.uaLcd vitheut !:-n ogroen-ont of ti'u World hf2.1th Or'tsnv'tioc. Author 0 Ciloivj era ro.pO.Kt.'iji'P for viw.ve c.orwncd In fi jnr.d titlelo ASI 00004237 C" document no co-",ntit,JO D&"* une puuirjuuu'i. II nc doit fairo I'objci. d'aucun ccvptp rendu ou rdsuntiS ni d'eucuno Citation .w.ns l'aut'j..s:it.on ds I'Oracni:.'.',10.1 i.'oeriUie do Ir. Santo L*,.': oj.'.-niors oir-dmirc Cons Ion tirt.olcc ijn;S ont .corn ci' o k'cic iiutuurs, ' _ A/r 1,7 () 1 `1 2 t-ouy.n.pt - "hi and yJneaue le/rls in their ticca (>-.cc'. j. Yyyf). .b'tev i.v, i.yin - at .nabcu: rate o f 10 y acovaio into *ji rear 2 hours <;.: c it) ug r -1 r. cut th -1 ul: r. (1 noi- D - di aba ii r1 .r. i. , ; :-c Cotal .i;a' ' y no tone i-. ti.aU . L/l Itj * ; _ 0 .jVV. ' fa a i- J1 2 - y'y) at \tz e: i: y; V;;; in Cl h'n'i.'U by #* * * . > Tr-d : t;h ...-.a- 1 -. .v rf LJ i.n 7 1,1.: r 4 V- L ' Y.` 1 \ro-.' j 1 r.ai: a 1 sunj-'or--, 19 r.vanal sub a r tyl. a ad an baa V, t, r;or.,e z , ,oy 1 j t'n 1h" ` ; ' c . r`.>. i': ;>o,: * /' , 1 *. 1 he nr V '* b C i--v l ^ :* UI- rv; 1' 1 , U 0 4-; a ad a in a: r-*! ov: t. / i -b.Y t'i a ' a: ` Jjaunt 's' . mj'*.o r-'-i. 1 "', .. j*' 't b*: ^ci ; v'1 * * * I; .1 !L 1 1 yt-L.": ' * , j ; y (C ri r t.v, iron ? .Ill did not a fee. h ,, :< ; a.'.etc.- 1.-- La "a 7 nr .-..a fast iny uub.i acta. 1. .v. ;.njc-ct ` r:. 1 of Varc. ton 0 in,;. J_;` .'Cal' '.at; rn .a : ui. -1 i.: 1 ic voir '-.y :1 19 ::oj r ; 1 rubj-act.c- ha- nee no i.v 'imvu 1` 1*1 ability bjT,.l*0/ !ty,\ 'i CCf.U `/j: n di d'e,-!1^ s. Che r:t;; of bn;/.; . c *n in ;;o ilau, ua; t. r, a a to r..:,clu 'rclb. at 4 i'; char: a racll 't nswl Cat a ;a.C, 1 iz ?iO'/ r, i 'Uroouli an r-Cl tone sta ;'0 (a ochior ut fll. , It', 1). tent; Ari-ca.l Route LD_,, ng/k* iDe5auyv.-r.uayi,t ... References weight Rouse Rut inhat.c.tion oral i.v. inheir. tier Rabbit intrayasbric i.v. percutaneous Dog intragastric 1 10700 9700 - 5340 - ^ 20 nilf`s\S - 4,(3000 nprj -- 6-8 r.l/kr, 320C0 pp:-/ 4 hrs 5-10.72/kg 6-3 ral/kg 3 sAs Schultze, 1932 (byyth et al.,1962' (Shall Chemical Sc., 1963 Sector, 1956 Walton et ai.,19 (Anyth et al.,19 (Shell Chemical ( Co., 1963 Spcv-toi*, 1996 Walton et ?,l,;l`b'-3 Walton ctul./ORb (Smyth et a.i. .1962 (Shell Cb.enic-l ( Co., 1969 Albertcni, 1354 O ' fo The acute effects of acetone ore essentially that of a fairly strong anaesthetic (Elkins, ). It also causes moderate inhibition of cholinesterase in rino and in cats in vivo as shorn by increased chemical action potentials in the carotid body ncnF3 after ir.tra--arterial adrdrietrntion l(Landaren et al., 1953). Repeated jntra-- gastric administration of C i.J. to rabbits for 5-22 days or 3-10 ni to dogs for S-05 days produced albuminuria and epithelial necrosis of convoluted renal tubules (Altertori and Rincnti, 1857). Daily .administration of 1-2.5 g/kg acetone intra- racirlcally to 5 dogs for 9-19 days produced nephritis with tubular destruction (Poliak, 1925). Intragastnc administration to cats caused local irritation of the digestive tract (Taylor and Erodshan, 1943). ASI 00004238 FrJ/-7-./70.7 b) pH;:-: 3 Derm at.itis fr -.a ii rci'^-rt rust;: -iced skin veer. tv-cl at' 1 invite tic... of , as and the nn 'J, iw vs been ob-c rvc-1 in -in ( "rv,:ul'' a JO'.'i). ole renal ef uc "S in rv a im ve lif'ii rco i-i-xd r.\ <\ 'it J-k' /> '..a 177, a . ChO (Sax, ). 15-20 given orally dr. 1 ly to run over s.-v a sal days ; cod onlv slight drew sir: car but r.c other iil offc 'l 0 Ch (site -tor. j , 16:5/). .-.c. he massive injury ( iAt <' oxication IvdO; 2 i: i man has can ib mud h.vy-v sad 1 co'i la uso TJ,*i -/'1.. i; r and p''s:i: hi-: liver '-J. r.hi and J-; c-.-'-on, 19*';. .J.bri.it absnrpt.i on occurs threw mil the skin alto r c-.`" \J . >. U with lie "jxd acetcr.e Acciona vis ' paint-, i or: the dapped dorsal o'-in of CO female- mice t-hrce tinas o. \;;vk Per AiV dry.- ('3/ weeks) ac, pari ci' orouher cup:-- vent. *fo local papillomata cr enreino" ' a were seen (von Dunren ci ul., ir,'6y). Hit The single inject on of 0.1 rl, ns peri of another experiment, into one or both snliv: ry glands of 35 male and 7 female rstc produced local necrosis and complete rogenerative repair after 3 weeks. Animals cbaervsd for 3 months showed no lm.r-,1 or distent humour formation either m.a c r0 3 c 0pi c ully or histo logically (Ch.,rry and Cliekaumn, 19-65). SMpJlh Injection o.f acetone into the yolk sac of fresh fertile chicken eggs tad little adverse effect on hutsuability (fOe of norm?!} ana produced no teratogenic lesions (l'.'c3*nur.hlLn et al., 1964). In another experiment only 37;3 of embryos survived, the remainder being killed by coagulation cue to acetone. Surviving embryos developed rormally (Walker, 1967). Obspivr.tior.s in ran Widespread industrial use over cany years (e.g. 2000 ppm inhaled for 15 years) only yielded a few cases of mild intoxication but no raports of permanent baavatological or organ damage (Brooming, 1965; Rowe and Wolf,) 1963; Ralsett, 1963)". ASI 00004239 I n\`. ) /,, PdF' 4 -\ A3.borteni * A.lbor bod. > T4.9 . ?* ( .1.' ,> j ) Ir"; p i: '1 ,* J \ -A t ' Am,1.* i . (1Z37 a IHol,, -A.X '.. r-b D '*7" **L Hxr b-! f r*-.r J Hd. <A y Browning, (\1-- ioxici1/ 7,..-i i : iC tabol;a 3.71 of rial iicjj-Vc 17 7: y -il ,,'i i,2?''U cln) O'?i 393 LI; '* i vier. "occur:, V-' * Ceoa.no, ,, 1 Ch'-'io v, G P (19 52) "f 3.n (' ... r;- iro:.3; ^ c:i -'i `J._Ik-:.. -nn; o L^.Vi.r.1 * M * . (1947 /) *' '' A. (3; 65) - J '* 1 ?.L> 163 B- : ,-,A4.1J^-/7...vJon, T".C,r an.*7,-y^ce.7 - 3\ 3n44.J ^^1 Bikins, II . u ( ) The CL, ddry of Tr.f.Ivor r.i ,1 I i ew Fassctt, 10 lj * rfVV r, u.d L 'don ( 196.; ) in P.A. ratty, Indu:; tri al Taxi cole,ji/ y e an<I Toxlcdcgy > (l963) voi.n Ragged, A.U., Greenberg, L.A, and Turner. J.K. (1944) J. Ind. Hyg. Toxicol., ?6> 133 Harris, L.C.-and Jackson, (195?) B.M.J., 2, 10.24 Kagan, A. (192/,) / rcl?. Hyg. Berlin, 22, Zl ^Coehler, A.B.; divisor, 2. and Hill, 2. (1941) J. bid. Cher1., I/O, Sll yF mdgren, G., Liljesirnnd, G. and Zottemann, I. (195.3) Arch. Bxpil. Pathol. Fharradiol., 21^., IS5 McLaughlin, J., Marline, J.-P., Verrett, M.J., Hutehlcr, i-'.K. and Pita Hugh, O.G. (196.-;) drier. Tr.d. Hyg. As*. J., M3, ?32 Pairnieggiani, Itj. and Gr.ysi, C. (1954) Mod. Lavo.ro, 45, 431, Poliak, 3. (1975) Arch. Gxptl. Path, rhsr:-r.kol., 2CM, 220 Price, T.O. ar.d hitLonborg, 9. (.1950) J. Did. Chem,, 335. 449 Rothkopf, H. (1936) Z. ges. exp.' Mod., 22* 4&4 Rowe, V.k. and Half, K.A. (1963) in ?. A. Patty, Industrial Hygiene and Toxicology (1963), Voi.ll, Sack, G. (1940) Arch. Gcverbepa.thol, Geverbehyg,, 10, 30 Saknmi, and Lafayc, J.H. (1930), J) Biol. Chem., .137, 369 Sakaai, U. and Lafaye,' JMi. (1951) -J. Biol. Chen!., 193, 199 Sax, II.I. ( ) Dangerous Properties oil Industrial Materials, Hew York and London Schultse, D. (1932) Dissertation, Univ. Wlrzburg Schwarz, L. (1898) Arch. Mxptl. Pathol. Pharnakol., /), 163 Shell Chemicals Co. (l9t>9) Industr. Hyg. Bull., I.G. 69-10 Smith, A.R. and Mayers, i-i.R. (1944) Ind. Bull. Hew York, State Dept. Labor.> 2ji, 174 Smyth, H.F. Jr., Carpenter, C.F., '..'eil, C.S., Pozzani, U.C. and Striegel; J.A. (1962) ; Ind. Hyg. J., 23. 95 Spector, VI.S. (1956) Handbook of Toxicology, Vol.l. ASI 00004240