Document 5DqqK6eze5kjyOjaGVLe47QD0

jb . U n g H id! (JJ\ Journal of Occupational Medicine January 7SS0 Vd. 22 No. 1 ''The M ortality Experience of Workers Exposed .to Tetrachlorodibenzodioxin in a TrichlorophencH Process Accident dh A. Zack. M.P-H, and Raymond R. Suiktnd, M.D.; A standardized mortality ara lysis was conducted on workers exposed to etrachlorodibenzodioxin in trichlorophenol process accident at trie Monsanto Company plant in Nitro. West Virginia. One hundred and twenty-one sorters who developed chloracne resulting from this acti- I on March 8. 1949, were selected for study. Follow-up " oi this group was 100% complete. The standardized mortalrty rath for all causes of death was shown to be 0.69, with 32 deaths observed and -*6.47 expected. For the categories of malignant neoplasms # and .circulatory . 'dhcases Ihe standardized mortalky ratios were 7.00 and .(''respectively. Because of the small size oi the cohort and the relatively small number of deaths observed, the results of this study cannot be considered conclusive. However, h is important that no apparent excess in total mortality or in deaths from malignant neoplasms or diseases of the circulatory system was observed in a group 0i.workers with a high peak exposure to tetrachlorodibery zodioxin who-were followed over a period of nearly 30 years. The results of this study will be incorporated with those oi a larger study which will include plant workers ex posed in the course of 2.4S4nchlorophenoxyacetic acid production during the period 7943 to 7969. A wide variety of acute and sub-acute health effects has been reported in workers involved in the manufacture of 2.4.5-inchlorophenoxyacetic acid 12,4.5-T) from 2.4.5-trichlorophenol [TCPJ. The most consistent clinical finding is chloracne. a skin disease characterized by com- v* W Ow-i'--I H >< **4 (i u**-**wt*l mW. I * L-xrtwth "4 IW a w . Si oi i f--t Wi. MO dim l*W Kr*lllv Z*U. 0ijb c ' * ,c r * - D"U-wil.orrlu n , oi C--< MM<|I Crf*. C*"< tt. OH ISJV edones, cysts, pustules, and abscesses. Hepatic d y sfu r ' lion, peripheral neuritis, disorders of fat metabolism, and porphyria cutanea tarda are other frequently reported findings in these workers.' Chloracne has been shown to be essentially due to 2.3,7.8-tetrachIorodibeniodiaxtn (TCDDU-a byproduct in the synthesis of 2.4,5-T. The subject of this paper is the chronic health effects of exposure to TCDD. as reflected in the mortality experience of a cohort of Monsanto Company workers who developed symptoms of-efclcWcnf Jtdlewwtg-^.qjchferbphenol-pro-. cess accident at the Nitro.'West Virginia, plant in 1949. Production of trichlorophenol began in the fall of 19*8 at the Nitro plant. In this process, the reactants 7.2.4.5-tetrachlorobenzene. sodium hydroxide, and methanol were all added to the autoclave. Heat was ap plied and, when the pressure reached the desired point, the autoclave was vented. On March 8,1949, about six months after production start-up. a violent reaction and decom position occurred when temperature and pressure within the autoclave became excessive. The relief valve opened and the fumes and tarry residues from the decomposed contents of the autoclave were discharged into the at mosphere and into the interior of the building. Employees who worked in the area of TCP production or were involved in the clean-up.began to develop sym p' toms immediately following exposure to the material which was discharged from the autoclave. Symptoms in cluded eye and respiratory tract irritation, headache, diz ziness and nausea, and a severe irritant reaction of the ex posed skin. After these initial symptoms subsided, the chloracne and other symptoms became evident. Ashe and Suskind*"* examined a total of 12 more severely affected workers on three occasions during the period of 1949 to 1953. Another 26 persons with chloracne. apparently not related to the accident were also examined in 1958. The jcurnal ol Occupational M eiicine/Vol. 22. No. 1/January 198D 11 iW --i .. clinical ,ynptomS. in ord p of 131 f'Wuency, .ndudcd acneform lions: ,evert pains in muscles of upper and low eitremities. shoulders and thorax on exertion; fatigue nervousness and irritability decrease m libido: dyspnea; vertigo and intolerance to cold. On examination. accidental industrial intoxication. In 1976. a TCP process accident in Weda. Italy, resuliec n the contamination of a large and densely populates area.* A preliminary mortality study has been conducted in two of the 11 towns affected. The overall mortality rate 11 of the cases had chloracne. Several were severely hype* did not differ from that expected, but increases in deaths pigmented, especially on the face. Of the she workers ex- from liver cirrhosis and leukemia were suggested. mined In 19^9 2 nd 1950, four Kid liver enlargement and The chronic toxicity of TCDD exposure to animals h.*- one had sensory loss in one foot. Liver impairment as in been more extemivefy studied. TCDD toxicity has ber-n dicated by hepatomegaly, tenderness and soreness in the thoroughly reviewed.1 Chronic toxicity to TCDD h right upper quadrant and epigastrium and a delayed pro manifested by liver necrosis, thymic atrophy, and deple thrombin time, was observed.1** tion of the lymphoid organs. Two studies indicate ih.it In 1953. four of he su workers examined in 1949 and chronic administration of low levels of TCDD to rats h 1950 were re-examined and six additional workers involved associated with an increased incidence of neoplasia r. in the accident weie also examined. The findings in this one study, the oral administration of TCDD produced an later examination indicated a general regression of both increase in hepatocellular carcinomas and squamous cell the cutaneous and noncutaneoi^s symptoms which had carcinomas of the lung, hard palate/n2 sal turbinates, or been present earlier. All of the wckers showed a marked tongue.11 In another study, TCDD fed to rats produced improvement in their-skin lesions -- there were residua of tumors in 35% of the test animals.'* Neoplastic nodules the acne and a few active lesions. In a few cases, workers and cholangiocarcinomas of the liver were observed, ' continued to complain of aches and pains of the lower ex- - w- -The study reported here will examine the mortality t v trerr.ities and back, nervousness, excessive fatigue, and ''perience of a-cohort of 121 employees involved in the dyspnea. No clinical explanation for these complaints 1949 trichlorophenol process accident, with special em could be made based on the results of the physical ex phasis on cardiovascular disease-and on neoplasms, par amination.* ticularly of .the stomach, liver, lung, and skirt The findings of the examinations by Ashe and Suskind are consistent with those which have been reported in Population and Methods other industrial episodes which occurred subsequently.' In this study, the development of chloracne. a hallmark The acute health effects of TCDD exposure are described of TCDD exposure, was used to identify employees fox in the literature.' but little is known of the chronic effects. Several reports describe the occurrence of cancer and other deaths in workers exposed to TCDD which suggests an association between exposure and the subsequent development of a variety of noopl.ium.*" Ttx.*so reports, however, arc generally of small groups of workers with relatively short periods of follow-up and are considered to Study. The study population consists of all persons with chloracne which could be attributed to the 1949 TCP pro cess accident. One hundred and twenty-two employee-' who developed chloracne following this incident wrnidentified from plant safety records dating to the time lh the accident and from workmen's compensation ant: plant ijpdical jecord^ One husdred and twenty-one be preliminary in_nature. In a 25-year feflow-up study..17 deaths were observed among a "cohort, of 75 German -.workers who had been involved in a 1953 TCP process accident* Of the 17 deaths observed (11-2S expected white mates were.included'in this study -- one'female who was living as of the endpoint of the study was not in eluded in this mortality analysis. It is assumed that all ot the skin disorders recorded in the plant records represent depending on the choice of a control population! six ' true cases of chloracne and not other types of occupa were from cancer (four or fewer expected! five from car tional or nonoccupational dermatitis. An analysis of the diovascular disease (as expected! two from suicide (fewer chloracne cases and exposures not associated with this than one expected! one from liver cirrhosis, one from a accident but rather with the normal TCP/2.4.5-T produc urogenital tract disease, and two from external causes. Of tion processes will be the subject of a future paper. the six cancer deaths, three were from stomach cancer in The data were analyzed by the modified life-table the age group 60-69, a number significantly higher than method using the updated Monson program.1* In this expected. Two other cancer deaths were from oat-cell method of analysis, the age-, race-, time- and cause- carcinoma of the lung and one was from' adenocar specific mortality rates for a standard population (in this cinoma of the colon. case, the population of the United States) are applied to A similar accident occurred in the Netherlands in 1963 the person-years lived classified by age. race, and time: A in a factory producing 2.4,5-T.1 Eight deaths have been standardized mortality ratio was calculated as the ratio of observed arrtong 93 exposed workers. Five or six of these the observed deaths to the expected deaths for 22 deaths were from cardiovascular disease. Tbe proportion selected causes of death. The statistical significance of of deaths due to myocardial infarction was noted to be differences between observed and expected numbers was high. based on the Poisson distribution and statistical signifi Jirasek et aP ** and Pazderova". followed 55 of the 78 cance was determined at the 5% level of significance. Czechoslovakian workers who were affected by chlor- For the purpose of analysis, each member of the study acne resulting from occupational'exposure to 2,4.5-T and cohort was assumed to have entered the study on March pemachlofophenol. In this study, five deaths were o k 8.1949. the date of the accident The vital status of each included two deaths from bronchiogenic member was determined using standard foilow-up tech carcinoma (Jess than one expected! one from cardiovas niques and ascertained as of December 31,1978. For each cular disease, one from liver cirrhosis, and one from an person found to be deceased, a death certificate was o k 12 Mortality Experience ol Workers Exposed to Tetrachlorodiben2odioxin/2ack and Suskind. Ci if** AHcausa d cura AJl frullini ncoQtiPRS BifCiil cavity and pharynx Oipcslnrt organs >"d pntenev* SlorruO L'rver ADstiver difcslnre organ* Respiratory system Lung AS oihe respiraiory organs Skm Genitourinary organs Lymphatic and herrjipp^eiic liilut Otrxf sues Diseases Ql me nervous jysitm and sense organs Diseases ol me cncutatory system AncriesderoiiC hurt disease, including ^ coronary nean disease AD otner disease el the circulatory system Disuses et the respiratory system Disuses d tne digestive systsn Alt other d is u s a External causes d DUth ICO Xa. [Eighth Srrituw) 140-209 140-149 150-159 151 155*156 -- 160-163 162,163 _ 172.173 185-189 200-209 -- 320-389 390-451 410-413 460-519 520-577 -- 800*99 Obierttd 32 9 0 -0 0 0 0 5 5 0 1 0 3 0 0. 17 O 4 1 0 2 3 Expected 46.41 9.04 0.30 2.59 0.50 O .lt 1.51 3.02 2.85 0.17 0.15 1.16 0.51 0.94 0.36 25 01 17.74 ,, 7.Z7 2.71 2.26 3 .It 3.71 SMI - 0.69* 1.00 t t t t t 1.66 1.75 t r t t r ! 0 68 0 73 T t T T t -p < 0.05 TL s than S observed fleams tained. The underlying cause of death was coded to the 6th Revision of the International Classification of Diseases. Adapted'* by an experienced nosologist. Results *n of the 121 members of the study cohort were Eighty-nine were verified living and 32 were <n.-d deceased by death certificate. ' The results of the standardized mortality analysis of the 121-member study cohort are shown in Table 1 The 5t>ndardir<*d mnrTalirv rafin (pr all deaths b shown to be, ~0.fe9,-*nft'32 observed deaths and 46.41 expected. I hb-b7 the only, statistically significant difference shown in this* table: There were nine deaths from malignant neoplasms with 9a>4 expected. There were no deaths from stomach' or liver cancer. There were five lung cancer deaths versus 3D2 expected and one skin cancer death with 0.15 ea* peered. The 'malignant tumor was a fibrous histiocytoma presumably of' dermal origirv which b rare. There were three deaths from neoplasms of lymphatic and hematopoietic tissue with 0.B8 expected. There were 17 observed from circulatory diseases with 25.01 expected. The standardized mortality ratio for circulatory diseases was low at 0.68. Case summaries for the cancer deaths are given in Table 2. Dbeuuion Because the study cohort was small and only 32 deaths were observed, the results cannot b e .considered con clusive. Nevenhfiiess.-the analysb_of. the -monaKry ex perience of these workers indicated no apparent excess of total mortality or of deaths due to malignant neoplasms or circulatory diseases. The TCDD-exposed workers in the present study repre sent the largest, group ever investigated after long-term follow-up. The criteria for inclusion [presence of the workers at the 1949 accident and the subsequent occur rence of chloracne) limit the group to those with a signifi cant exposure at that time. .The latency period of 29 yean Table 2. -- Cancar Deaths Among a Cohort ri 121 Maks Exposed ta Trtrachiervd&tazodiexm ta a Trichiprophonal Proeaxx AcddonL Tarai ima - Tor ri Tor ri Dun Cartrfial Stator** - Kw ---------- ---- ------ --- ri Can* ri Oath - 1909 1943 1962 1910 1927 1970 1911 1939 1964 1922 1945 1973 1915 1939 1970 1920 1946 1971 * 1919 1943 1973 1907 1943 1971 1910 1939 ISTI Lung carter {162.11 Pulmonary carcinoma (162.1) renattfgenc carcinoma (162.1) EUencruogtnc earpmema (162.1) Lung carter (162.1) Uafcgnam1prowl tatiocyioma ri soli su* origm (173.9) Hogkm's Otsusi (201.0) lyrrfi*ic leukemia (204.9) Acute myelogenous teukemj (205.0) `Smoking history 41 asumes by m tm nri wiift lamer eo-worktrs at the OecoOrus Journal ol Occupational Medcine/Voi. 22. No. 1/January 1980 - SMitf Hairy*" " Cigarettes Cigaretus Cigarenes Nonsmokr Clrens Cigarenes Cigarm a *P* Dgarcfm 13 f is longer thin that of any previous study, and the toiiovup is complete. Therefore, although [he cohort is small, it represents the best opportunity so far to study the longlerTT- effects of TCDD on mortality. By augmenting these data with the results of comparable mortality studies, the long-term effects of; TCDD may be more definitely evaluated. TS* iu rK n ---n>i 10 tkank m v >'1 Mr n*rMri Zonr la iKvtitAU><t wk ?Nr tfiu F<pl*t. J"d Mpi R eferences 1 Imrr national Agency fo R rw arcb on C a n te r lARC M ono^'apbt on itw Evaluation of Ih r Caftmoye-nic R*k of Chemical* to M i Vol. 15 Some Fumigant*. th Hrf+<<Srv 2.*-0 and 2.4.5-T, Chlorinated Dibentod*on and M u c tU m ro u i Induiinal Chemical*. Iro n lARC. 1977 2. Ctm m i| ) And S tS u li KH' OcCupiRpnal acne (*0-Clld chteracnc} due lo the chlorinated Afomafi?- cyclic w ien . Cr+nviroJofica 113:540-5*. 1957. 2 A*Ne w f And 5u*kmd RR: Repeati on cMorAChc c i t n . Mon U nto Chemical Com pa fry. Nitfo. W n i VfijiniA. Reports oi the RrUcrmg Lbcv*rory, Decem ber 1949 And April 1950. 4. Su*kio<i RR; A climca! and errvironmental Uji~*ry. M om anio Chemical Com pany. Nitto. W est Virginia. Report, of the R enerm t Laboraiorf. fuly 1953. 5 Swskmd RR* Chlo<ACne And assocw ird problems Report ip t>w Conference of the NaiiooaJ Im utuie of Environmental Health Sciences on C hlorinated D<betuodioJim and D ibenicJuraro. Aprs] 3 1973. m anufacture of 2.4,5-T. Report to the Joutt Conference." Naw J In ilituie of Environmental Health S<>encei International A rm ey for Research on Cancer. Iron. France, lanuary 11,1971. 7. Young AL C alcajni JA. T hifkrn CE. rt a t The roeicofofr. w ironm enul fate. and hum an risk associated with herb*cde o rjn y r and >u atvociated dioam. U.S. Air Force O ccupatonal and try virenm ental Health Laboratory. Report OEHL TR-7&-92. Brooks A* Force Base. T rras, 1978. 8. International Agency for Research on Cancer Lcnj-tcnm hazards of polychlorinited d ib eruodioiiol and polychlcKmated dibenloforani. IARC Internal Technical Report >*o. 75001. Lyon. 1971 9. flrasek-L Ralen*ky 1. and Rubec R: Acne chlorina and porphm a cutan tarda during the m anufacture of herbodeS C r Dermale! 41.306-317. 1973. 1 10, firavek L Ralentky I, Rubec R. r t ah Acnr cW oni. porphyru Cutan tarda, and Other m anifestations of (enera) po*onmg (Jyime "the m anufacture of herbicides. It Cetk Derma ro! 41 145-157. 1974 11. F arderovi I. Lukas E. Nemcov M. et L Ch*o"< poiionurj k*chlorinated hydrocarbon* form ed n the product<on of so d ^ m 2.4.5-trighlorophe n o ty a c e tat. Ptac Lek 24;332-J39. 1974 T2. Roctba R |. Reyes DC. Beyer IE. et al: Results of i h^o-year chronic toaietty and oncogenicrrr Study of 2 J .7.3-letraCNorodiberuoi p-diorn m m Tencof Appf Ffurm aco/ 44.Z79. 30J. 1978 U ^ V a r Mler JF. L*l<h It. and Allen |R: Increased nc<m ct of neoplasm s m rats exposed to lo levels of 2_3_7.5*teuchJorodiberuop-dexm. Chemosphere 6537-5M. 1977. -14. Memson RR. Anairsts of relative survival and proportional m es tality. Comput d o m e d Re 7 J2 5 -3 3 2 ,1974. . IS. Eifth Revirn. International Classification of Diseaws. Adapted for Use in the Uned States. U.S. D-cpa rimer* of Health. E ducaiort and W elfare. FuWic H ealth Service. FHS FubfcaUon No. 1V9J W ashington: U.5. Co*em m eru Frintm f Office. 1977. . - ^ 1` ' ` Future Risk ' : := `- - r ~.*]r In rhe industrial coumries.we hive grown rich during the age of hierarchical business corporations, in which each executive arranges what the man below him will do with his hands, all the way down to the man turning a screw on the assembly line. Now, two rather fundamental things have happened. First, we have begun to realize that workers in rich countries don't like working in such places. Secondly, the rich countries are moving out of the postmanufacturing age. but they still have great hierarchical cor porations in which executives sit behind their desks trying to arrange what the man below will do with his imagination. This no longer works. New forms of business organization will have to be found, probably changing big corporations into confeder^ tions of entrepreneurs. The firms and counpies that will go bust in these circumstances ar* those that try to replace hierarchical corporations by even more ossified forms of hierarchy -- say. by deciding that you mustn't have a boss trying to arrange what free men.do w iththeij imaginations, but can have a trade union committee doing so in stead. ---------------- -- fv n > 1*4 Siam Ca* Kit* CiO----e --A*vl trad --If Whe~ by Mvitua *4*0 . a 14 Mortality Experience of Workers Exposed to Tetrachlorodiberuodiotift/Zack and Suskind