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THE LANCET Vol338 Saturday 26 October 1991 NO a774 Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols Epidemiological studies have revealw an seem to be spec:f:cally associated wlth those increased risk of cancer, notablysoft-tisuesarcomas herbicides probably contaminatedby TCOO. and non-Hodgkin's lymphomas, in people Lancer 1991,338: 1027-32 occupationally exposed to chlorophenoxy herbicides, including those contaminated by 2. 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCOO). We repm here a historical cohort study of monaliw in an international register of 18 910 production workers or sprayers from ten countries Ehoostire 'was reconstructed through questionnaires. factory or spraying records. and job Cacje-jpec:fic n ~ t ~ ' 3dola!h ' x e s 'ne'? ">ea d s reference. No excess '&as obsened :n 31I-c~usernonalin, for all neoplasms. ior t r e most Introduction Qllomphcnoxy herbicides have becn used atensively sine the mid-1950r for oonml of w e d and for m w g unuantcd brush on non-crup land.' In the 1960s an equal m r r of 2,Cdichlom and 2,4,5-mchlom phmoxyaatlc a d s agent orange' was h c a d p usedin South Viemm and Cunhdu far .!c!,!:x!;m h? m e CS .irmed fcrrcn. Since 1969 rn cm.cralmdusmalised iuunmes. pnducnon m d u x PC \ c m p ampun,!.. mif q w v . a l ! v t>f 2.1.5:?;hlon,Fh~n,.u\.~ceris and 2.4.3- I' dnd 11s &m-aWe!, h a i r t x c n icLIuLcJ dr t.micd Chlc.niard FhcnOk 3re comnion epithelial cancers, or for lymphomas. 4 Statistially non-significant two-fold excess risk. based on 4 observed deaths, was noted for soft- tisue sarcoma with a standardised mortality ratio I (SMR) of 196 and 95% confidence interval (CI) 53-502; this was concentrated as a six-fold statkticclllv significant excess. occumng 10-1 9 vears f:rst exposuve In the cohort as a whole iSMR=606 [165-15521) and. for the same time r-*+ ?c 3 w y - f ~ ) I dPICPFF amonc sov,'ers i>.,:,n -00,' ,25;:;,. u;pt--,-;j lu Lc Inwased for cancers of the testicle. thyroid. other .i,i,i:, ,ir,di:ss'v 3::3 rJ..dlc.1- *, based * on m a i l numbPrs ot oe,?tns The excess of soft-tissue sarcomas among sPWefS is compatible with a causal role oi chlwophenoxy herbicides but the excess does not Cohon I.A u r r r h :. .+"Slr-I 3177 s ;59 , PC 1: / m ;s ?a43 P ! 616 , 61 ' 325 4; 110;!Ji I 'ii P P P T P ? P VOL 338: OCT 26,1991 THE LA?U'CET 1U29 TABLE ICMORTALITY BY DETAILED CAUSE AND EXWSURE TO CHLOROPHENOXY HERBICIDES AND/OR CHLOROPUENOLS. B o w SEXES SMR 195% CI) In0 01 0- doale) *D 0 0 ) ! 1 1030 i ! THEMCET VOL 338: OCT 26,1991 .. ... -.48 1 I I I f ..-_.-.. /2 ,, ! w 0 I4 ') 52 3 L, I , I 0% I I ,U I7 76.16 'I5 60-113' 97'761221 230.54 Io?'BeII5' i) I 5 029 089 1 I 3 -:*.-A l55bE IOB 92-1261 059 6 I 029 2 0I5 1 0 16 1 I -015 0 &IO541 ! aposure sums had high all-auw morrahw tablc I I , io bc incrmsed amcng S~I-~VCI-S ' 3 dclths. S M R - 3 7 m p ~ i a i l ?!or acoitmtr. piwnmg, md vwlcncc mcludmg i b l 4 S l : . .Udmrhs ocnvred 10-19 ?cars after fmr suiode S M R = 319 j182-518]j. aponue,@vtng nsc, for this m e m t m a l . to a ru-fold 1 Table 11 @ v aS . W b :and 95% CIS)and o b m e d deaths for rmpr ouvs of des* and for mlignant neaplvmt by site and aposurc for borh sua combmed s m a only 10 mccss risk in the cohon as a whole (oble 111) and an even grater accss among exposed s p n y m (3 deaths, S M R = 8 8 2 [I82-2579]). N o difknmtiaaon in risk was .Y -. dcarhs frcm cmm wm ivailablc lor WJ!:.TIS m o n g observed m rehnon to duntion ,afcxpnurc ur prubiblc m p w d ~CITU!CS. S i p . i l f i m t c x i e s s f i UCIC , b w n e dm o n g TCDD expuswe. 5 ddd1tiomIc1x5of wn-tissue sarcoma XIICC for m k r x : 3 y a : J id b : ~id .,i>pot:.;d 'xerc :Kordcd fi iohorl rncmbcrs ivho ucrc & I & ? dl h e cnd n m p h nrhe ex-powd category, malignant neophms of of follow-up or who had d~edwth a ccmfied QUX of death uachea, bronchus and lung UI rhc probably ccposed o r h a than ICD 171. Thew mduded I ncm-fatalcase m the ategory, and malignant n o o p h of unspecltieddigerove non-upxcd group. Detvls of all 9 QVS are given UI !I organs and bcmgn and unspcafied neoplasm m the nonarpoudatcgury; ngmf~andrcfiats were obvrved for able IV. rmlignanr neoplasms of nhn and of b m . j Expcvdurorktn had SMRS above Mo for n m p h of Mn/tgnant lymphoma unsprnfied digesove organs, neoplasms of rhc nose m d !4 h r h s from non-Hod* I lvmphoma I C D 200, Nul cant?., soti-nssue w m m . brcasi anm ,,ind c s i m,&hand 9rh mirwn)were obvrved among men and I and for neoplasms of rhe resns. other rndrrrnr glmd5 and mane unmcn I I d r d v -err n m w r d w+m- dl r e i 21)r o l l . Table 111 lpva combmed ShlRs for expmcd and probably c r p s d .sorkm of both *xes. for 111 ncuplurm. roti-tissuc WCOIWmd non-Hdgkm'r Imphornas. T h e panern of nsk for all neoplasms bv tune first cxposurc dld MoNLltv for exposed protably ccpoxd worken mas close IO crprned S W R = 95 \wth produrnon uurkm havlng a >mail > U t l , C I d . ~ nnslgnlfiwt m i r c a x n rnomirn s deaths, S.W? = 149 table 111 IOour 01 I 1 deaths occurred more rhvr IO \cars afrer B n r expcsurc o d a b s wcurrd 1 not i n h a t e a strong halthv worker effect. and mortal~t?h.d 001 vu), rubsuntully bnwecn rhe group cummed. amongworken crpovd for rhyla v a r , and no & m c c UI nsk muld bc seen m rclaoon to exposure to TCDD or type RF of chmal produced T h e hghat SMR amongprodurnon 7 Son tisue sarconw workm wm for those m "other lobs * trvlspon storage, hbntorv wrkm, p h t SUpcMvJrs 4 d a h s h 4 deaths were oburved, all among exposed male workm non-Hiodgluns lvmphoma were o b x n e d unong non- 'table I I I , So rncraxd nsk was obscrvcd among crpowd w r k m UI one Dmsh f a n o n oDhon 4' Monaiity produrnon workm !Ideath,, whcras m o d i n . appercd for n o n a p o v d w r k m was hgha than that ot all otpowd uuAers. and SVrUfar to that 01 pmiucnon wvrkcn uhlc IIJ. The M uox m ~ ~ cocunmncr Sot mcluded m abk~llarelausmcohonmanbaswhowcrcahveatthe end of follow-up or whow canficd underlvmg WUY of death was n a 1CD -XM or 202 Momlit\. imm H~rlglim'ds1-x u as k l o % bcxpauoon 11 I t ; I 1032 i I 1 :I ?f 'II TWE LLSWT VOL 338: 01726,1991