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ASI 00004260
Probably bt.-tm m 71-7-.^ of inhaled irila.r.e in ir-pm1' JAtrjC-`- In van moip; abaciption occurs within the first :. than Gccram.ea to an croiilbxin:.: V; twain air/bi nod con- . c.'.m ocnuv bainto, m skin and iron the ga si re-in ho a; (von ircblknycn.., 1953).
absorbed through the ibrutes of c,.p'V.u''C! ar.l
tiers. ib-.ii-r-nbe abm,': l mecm. ubrer ingschbc:
In Due rat, rabbit and dog absorbed trilonc is 'hast Vuiod ar.cn." ell organs and
tisruen tut concentrates r.-ootly in fat and brain and I - in skeletal
lung
and live;, also retain lo'..T levels (bsrreht et, al. , .1939; - : ybon C: Parkhcnsc, 19'o2>
von Gottingen, 1333). Gimilur organ concentrations '. or; -maud in guinonplgs tut r.ig
levels were also found in ovaries and adrenals (Fabre i ', eh..wt, 1952). In the rat
trilcne and trichloracetic acid my be selectively bonne' wo erythrocytes lienee given
high, spleen levels (Fabre & Trvlaut, 1952) but plasm pi' beins my also be involved
(Soucrk h Vlachova, I960). In ran trilcne is detectable in the blood within 30 none
of inhalation (Stewart et &1,, 1962).
Trilersc is metabolised slowly to chlomlhyjrate (vj..' or. cnoidde) and than ranid to 2; 2,.2-triu'ilerauetic acid <GC1 COCll) and 2,2,2 triob'i. u otherol (CGI bld^Cd), wrier, latt c,r two suits halites are exciv t'id r.s urinary flu curone.. .0 (e, r, triced 11 ethanol
gluey ciciurcnic acid) very little unchanged trilcne acp:vr ' ng in the urine (i cwcll,19 Butler, 1949; Bhl 1 brag, 1953; 'fillinns, 1939; Smith, l` d6). Dogs erc.rcro 5-c`;j of
absorbed trilcne as trichloracetic acid and li-GOb r.s ta'.-'hloretkmol up to /, dr's after c:.p:n: ere (Barrett at al., 1939; nameU 6 Johnston. 1930: vor. ueitiv.grn, 1355) The lung ard sole.on, less so the liver are probably the. i r'm altos of metabolism
Ilia b?,.c cf iiitc CccjMant
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Cc flocuciant a cr-itUiie O'lB uno puMicaticn. II r.r d-i! f..iic 1 :'r..t r't'.uc.n co;np'..j mriu ou fCi-vi!"* r; <i';.i o-iiatian tano I'; 'nerii-.'.lien do
I O'^ a '.w na . V mi flv !'i Uc-iiL j. o;;t,iv'is CNgi' J ol..-. 1 .1 '.'L.i.103 i.i its n'i;iu:'.(--n'.
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Calves
a.'.. .
A : : rib ' a.rfnici .-raa trilr go triehiorno,;tic acid (if)
and trice Vae/harel (13-15*') epp:r4-g in thv.:.. urine
bar with a twee of hrb; v.
The b'.larva
probably . via! or excreted in tin frecvs (Go Go 4 Gchulise, 1955).
Hen ever r es 6i"--l6f ol inholoi trilen" as trichloracetic acid (Ahlvarb and
Forsevin, IvM); oti:er:.' 'ovivd 75-171 ot retained ty-Mcn.a bain;; e;:cretod as tri.ctl1 or-
acetic acid (bv-all, 19/5: Coueeh -./o a!),, 195'*') -an '..'.-ll as t -ic'iloroL'-.ar.nl, nonochloracetic: acid :.' d cbiorcC: '(ivea: ot al.19"1; :7c:."al,'"ie, 1165 ). Cvnll amounts of tricllorscotic acid may cOill:^ to b? e::cr'l.c : in the rri' a ter up to 12 c:yo after
inyle exr:osavr (vc;i Oet'/.njen, 1955). 5 human anbiects e::poc-~d for 5 houar to trilene e::c'--et.-:d 4> of tno rc;toi..ad done an r.:-o.:aoc!:lorac-.-tic ac'c, 19t as trichlor acetic acid rr.d 5'1'- ; s t;f ei-lcrothvrol c;v-.v thf- re::t 17. days (douce! 1 vlaciiova, Ive'J; Def'iyje, 19-1). In rViOth'jr enperi-or.t 6 sub;oats inhaled trilmc for 5 bourn. 51-641 of the i.uh:5.;.d t: _'' auo van retained the rapt i,y e>di;l! ed uuchajipod. Of Mo retained triione pd-pOl ran cncrctod as urinary triohl'vcbr.uol ar:i 17-365 as u>l''iry trich?.oracctio acid. C.4`'' cf trichi oiacetic acid and trichlor'et'irjyol aas ease t: a in the faeces, Svoni and saliva contained also both neintoli Mr (bartonice:', Uhl). In all species most of the trichloracetic and trichlorsth-u.ol is cmere tod in the first
2 days after empesure b. t excretion may f~o on up Go 53 days, borne 2-4 hours elapse after
single exposure before trichlor,acetic acid ap mars in the blood ranching a maximum in 20-50 hours (Ablmarh 4 Fcrss.man, 1951; Oefalges, 19ol). Trichloretlianol appears to be the main metabolite and is much more toxic (bartouicei: 4 Teisirper, 1962). Jisulfirmn de creases the excretion of trichloracetic acid and trichlorcthar.ol by acting either on converting enzymes or on trilens release from fat depots (Bartonicek 4 Teisinger, 1962) while glucose and insulin increase production (Boucek 4 Vlochova, I960).
Chronic exposure may cause disturbance of protein metabolism by an increase in
the p-globulir. to 165--216 (normal 5 0;t-l/,6) and in fat v.etobolicm by an increase jn
unsaturated fatty acids (Guyot-Jeannir. 4 Van otconkisle, 1956). Bepeatei inhalation
or oral ingestion by rats causes transitory elevation of SCOT levels for 24 hours
after the last errposure, the SG?T levels remaining normal. 6G0T levels return to
normal within 9 days after exposure, bo such transitory effects are seen in rabbits
(folor et al., I'/Ao; Via!liar 4 Casanova, 1965). Previous ingestion of ethanol
potent lutes ir.lleue toxicity in rots as shown by a rice
an fdrT and biOij (isocitric
dehyirogcr/ase) and i.-ide-nporoad deyei'erauive lipid infiltration s,s '.:ell as early
cenlrilobular necrosis of the liver (Cornish 4 udefuin, 1966).
Single e'vrasure of mice to tire initiation ID of trilano shorred some hepatotordcity as evidenced by a rise in BGbT (Ccr.rang, '3 9c3).
ASI 00004261
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Reference
Mouse
Eat Guine-nri G Rabbit
Dog
inhalation Or Ct
i.p. oral inhale Lion inuaiaraon s.c. fob ml a Lion percutaneous i.v. i. p.
11.0 2.2 4.92 *
-
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7300 pa- (2 has) ~ p-
20000 37000 r-. 5\0..ia) 18O0 , .
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von OeiGingsn.1955 Flan et al., 1550 Elucssen i- Flus-lTiu Saych et sL.,lc`tl A'i'-v'-- ot al,, 19"1
von C. Ltj.i.ren, 1555 Earsa-a. -*1 Sued .15 54 B err a: d i ct al. JL Smyth ot al,, l'>7Bar- cvr ci Sae,d, 15*.5' Klee seen U Fisa,15i
Mice, rits, guinearigs end rabbits dying acutely from in::. 1 tion, show no toxic effects c;n the tissues, liver or kidney no:- after s.c, or . ,v. edminisi'ration (Brown: ng, 1965). I.p. injection of Z, 5 ml/Vg trilc-re in . :.foc had no e ffect on PSP excretion and produced no proteinuria or glyco.-v-in ".or histological renal changes (Flaa a Larson, 1965). Oral dopes of >f rf. eg bod;,-weight vere fatal to rats, mice and guineapign with signs of gastro-ir .stiunl irritation (von Gottingen, 1955). Chronic oral poisoning has caused -.ne liver and renal damage in dogs arid rabbits (con Oettingon, 1955).
Acute human poisoning cases have recovered without hex tic or renal sequelae. After ingestion tntre is come burning of the oral mucosa, jo tor nausea and vomiting with vertigo, ataxia, somnolence, confusion, delirium mud u;-s (Browning, 1965). Excessive inhalation has been blamed for hepato-nephritis Lut the incidence is very low and ix is possible that liver and renal involvement ar-. ihe result of underlying previous disease (Roche et al., 195S). Untoward effects o'- the circulation, cardiac irreyolaritics and excessive capillary owsirw; with Inchy.,: -a tut no ndvew'o renatre effects huve been \epo?"ed after anacstnotic use (von uutJ: -.yen, 1955). Ingestion of 60 ml appeal's to be fatal in man (Fcbay-fKryroula et al., lyS6). At elevated tempera tuxes trileno reacts with aorta lime to form dichlor: , aiylcre ,and this reacts lurlhcr to generate phosgene carbonylehloiudo and various , ids which are all toxic (Dr.frlyre, 1961). The present fLV is ICO ppm, in Sweden '< ppm, in USE?. 6 ryem (Browning, 1965). Spies oleoresins my contain a nuxi.r.u-.'. of 30 pum,decaife'i::atcd ground coffee 15 ppm and doonf fcine.led soluble coffee ^Ivoct 10' rum (fjA, 96.3).
A=;T 0 0 0 0 4 2 6 2
L .1'* n
" jr:-;.;. ': '' 3
(I.1;-.;;; ,j.ou vita uioc-m.'vf' v. ji. rat
caU v ' ;c-
...era in non and
"roe avai"1 :'nlo
b'V' f
Kone avow j
Obrcrvaib
in v Is ( , Of S Aor v'.v" ir A ; ;:v_r V. up to ion r/nits . sh-a/
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...1 `J,, v . u C-J.OC.VC 00 liver or Array or
if . : :-A:.
. C. V
and gaugi
cr\'.l dure; or:,tier
(;; cr;v
o'1"' 'capvg : r: io oI roan-
rabbit . r.A d -ye vers c.xpcKid 0
to 3..:.A
fm 6 VC :n i-fliiciv
i Vic: !. oiv; ,e c i i g 0 .<' . d>.~. rmr to 189 m.g/i.:''
for 90 day a do jv/v-led aa si/nj Alcant p-.thoJ.og'. al ctnng
['u c c. l,, J
1967;. Groups of A j mice -.-"'e i-.:;'; ? r-i. for 1-3 vr.v rh to 2Cj or Ivei V';/..1 daily for
4 hours. Only r.-i.J.. '"i tr'rcic-:' t Tatty hepatic day1 aeration on.I no renal effects were
been (bylin ot al., 1995).
Guincani-s vo"'? crossed to van err of trilene fee 2v - /, month:' vit'^rui adverse
effects on bodyvoight, hoe. .'vtoiogical findings or eririiysis m-su;;..:. but there /as sit rh i eviferco of hepatic parenchymal deroaoraiiar ml non;?. alone: .i. .r end
tubular deferer.vol.co (l.-inio ct al., 193;). babbits fiver, for 1 - 3 ::.o:n 0.C74 G/--G
trilene shoved livtle sdv:
effect or oof yvoi riot,
nioic"icnl finding. urinary
analysis but see. h V.,t;
ror.d. lesions were sc Amis eh a';., 1939). fa;
were o.vr mod be- 139-750 pen d: ^: for 2-3 weeks. hepatic injury as ovidone-'d by
EUP excretion, glycogen da; lotion and carercny; '1 defacer'.tier as veil as weight
loss, lethargy and diu'-rioro. occurred cut cleared or stonnir-j c::u:a;c (boillcr,
1944).
Soyabean real crime ird with trileno but not vith hevara or carbon tetrachloride has caused fatal refractory haer.orrharic apl'-stic are avia in. cavtlc (Pi ebon et al., 1953). Tha toxic factor was shomi to be associated vith t!io protv ir. fraction (Soto et al., 1953). Similar effects were produced by tui.lone-extracted moat scrap (P.ahfeld et al., 1953).. hov/cver, chicks fed trileno~e::tro.cted mat scraps shoved improved growth (Ballcun, et al., 1955). The toxic factor has been identified as S-trans-(dicliloicvlnyl)-L-cystoine, a reaction product of triler.e and protein v/hich becomes freed on protein hydrolysis (bcbinr.ey et al., 1957).
Groups of 20 male and female rats were fed instant decaffeinated coffee solid extracted uibh t.ri3ene for 2 years at Op or 5/) of their diet (ocvivalent to a' residue of 0.5 ppii* trilcva in tt;e diet) without deleterious effects on survival, hehaviour, growth, food consumption, urinalysis, haematology, organ weights and histopatr.ol.vfical findings (Zcitlin, 1963).
3 males and 16 female rats wore fed on a diet containing f;' or 5b of instant decaffeinated coffee solids extracted vith trilcnc (onnivalm: l > a residue of ` B 5 ppm trileno in the diet). 2 generations v/ere studied as regards paternal and filial mortality, conception rate, resorption, litter sire, grewth and survival of litter. Organ 'eights, blood chemistry, urinalysis and histopaihology of the f0 generation were nor..ml (Zoitl:`n, 1967).
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apparent car'-.v.ac . .irym
Vva:<' ..livial p;J sies and ootde r ^rve involvcMc:;'-!.
my !o io>n rl: = to any :ritioe`. iut havu rot boon ro-n vji:h p.wa matr-rial.
oA .1'...:'r:t; o-vl ('jOnotro-'inteotl ur 1 ry. ;oto'.:'.n havo boon rooortod all:r
inauryr: '.1 o-"o-v._.y-.r'.r''.?. nilIcl.io'.i .bar Icon reported (bar:A`.` j A Vyekocil, 1956;
Brouairy. ]Ao5; rrloy. 1913j ,rA.-.A:-,l.TJe; 3.961;
ivlt; Kit.'hull 1 Parri0r3-.-Sr.iah
1969). iY.y-ly. ,'tov parformr-co J n not a{Tcct-:,3 by r: rosurn to 190 ppn but there
is a doolj no in porj-omancc at higher iniialanion level:: (Itop.j u lIchAughlinj .1.967)
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)?clv:.'L;
' .V-ytcr.
(195") ?. ', IZU 763
bar." on ! I;., uni i c-
(jA;.:-A)
^_yy_.-___ ' . . 'yc;! -, ,7,- 6.75
da; .. O''1. i3r.r: ord
. v (,* 1 if ^y..r
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, 7, :r.G Pyy'r.ynv J. Lyla, A'-Allv... a-_ddl2- -y.d. ; "9. 37-6
Bc::.:r,7. P., Pyuan.,
and La.'ori, P. (19:4) Ipy ... .'.'.It.
7;2 669
Uxc.
1 (1915) 1;7-1'1' J'LyJ-A-!' 373'' TYA 93 .; 4;7bi:di.;Ajy4A'dlr;:; -J sy.Lnr, Ansi. .'dun
Butler, 110. (1949; .by.2 yy: -Ah i . .y. . A y Byiuyteu,. K,H. ana .yi'yy. .'..7. (IdOt) yyny.-, I, 2.(7
Clay -iii; J.l. and PnrAvuay J. (1362) 4n:l L. 6 -_y ?:-' ., 4a, 1/1
Corn!eh, 1.14 and 11-44.;. .1. (7.946) 2:y7-,22'.U, t(yyi,..2.., 17 Daniel. j,;-.'. (l957n) yrayiy.iy/y In. ill./ a77
Bandy, J.VI. (19371)
'-'VP
danicl, 6.9. (1963) 14 y^' 4 ' a
?_9, 795
0
Defalruo._ R.J. (1961) (A iyJy:AAVyiL_.yAy A-, 2, 665
Derviliey 1., ''ur<, Ch. and Oasis,
(1930) 7191 jyt.Oonrr, Undallyd
labre, ii. and Trukau t, It. (1956)
4,,_La.'l4lli.r.i.-41-? 9, 39
Pood an! 7t.'.G Adulnistyation (d'X:A) .111:_111, i'4'7.
Gahyny, P,,J. (i960) T or: - a1 . a--.;-? . rr -. me a -l.. 1?, yyy
Guyon-i cur.nin, G. rend Van StoenkiL'tc, J. (ivi'd) ,-.rch. ) a! a-'. Prof-an., IQ. 439
Helllvel], P.J. and Hutton. A.A. (1950) AyoidiTy 5, 4
Johnson, M.K. (1965) Ivoohe:-. ?hn--ypl, V, 1303 lClar;cron, C.D. and Plan, Gy. (19690 Toricri. r. .nl. ?har-ncol. . 2; -99
Klaaasen, C.D. and rlaa, G.L. (1967) Tori cdl, rn~U. lna:::anrl.i Tip, 119
Kylin, B., Suneyi, I. and YUner, 6. (1965) Aci-' "-ham-'cl.
22, 379
Landc, P., Dei-villc-e, ?. and ihn:, Ch: (1939) Inch.
ioToss. , 7, 454
Uchinncy, L.L., '.Jeahloy, P.B., lldrldye, A.C., Canpbell, 7.1., Govan, J.C.,
Pickon, J.C. Jr. and Bieoter, II.1. (957) J. Aner. O-en. Soc. 72, 3932
i-S.lby, T.H. (1962) J. Occud. i-led.. 10, 252
i-dtchcll, A.3.S. and Farsonc-G.dl,n, 13.G. (1969) B.M.J. 11, 422
iiococ.hlin, 6. (1956) hl.inik_-l Tls^-nle agr 7or~j.p unmn. Th
, Stuttgart
Patty, l\k.. (195S) Industrial. hy"\c-ne and To;n.colo'4. Vol.II. 13C9
Pcbny-Poyroula, F., LeGall, J.P.., I'rl j-ville, J.P., PoscnOi'.al, 9. Ci Gaultier, K. (1966) lull. Soc. i.ed. };ar. laris. 117, 1137
Ficken, J.C. Jr., Jaconsen, b.L., .alien, P.S., Eicstcr, H.I., Bennett, P.C.,
McKirj'.ey, L b. and Covan, j.0. (1955) -rri.c. Food 01c---. .
420
Plan, G.L,, Ivans, 1. A. and line, O.H. (1950) J. ~r. / col. l~:nt. lhen-r>., 123., 224Plea, G.L. and 'narson, 3.2. (I3c5) Toxicol. .'.n-4, lnr.--:c.ol.. 7, 57
Prenderynsn, J.A., J one.., 3.A., Jen,.ins, L.J. Jr. au.d ^ieyel, J, (196?)
Toa-iooi . An-,],. Ph"rr a col., IT), 270
hehfeld, G.d., Pei.nan, V. , Buutler, .T.H. and achultao, .0. (1953)
A arig. Food. Chon., 6, 227
Roche, L.. Lejeune, a. and Hi Pi at, J. (1953) .-'.nr. lied LoVnle Crird.tr'l. Police Hci.
Tonlcrdl., a' 336
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