Document wgRzkkQN952X9b5kDVdM0OqjB

/""A for release IMMEDIATELY U l .1 SUBJECT TO PROTECTIVE ORDER. lonsanto D. R. Bishop (314) 694-2891 PUBLIC RELATIONS DEPARTMENT M onimto Company 0 0 N. L i n d b a r o h Aoui mvard St. low*. Mitaovrl 63 1 6 6 STUDY FAILS TO LINK AGENT ORANGE TO DEATHS OF INDUSTRIAL WORKERS ST. LOUIS, Oct. 9 -- Monsanto Company today reported dhat no apparent relationship exists" between TCDD, the toxic dioxin contaminant in "Agent Orange," and the cause of death of S8 employees potentially exposed to it during 2,4,5-T herbicide production at the company's Nitro, W. Va., plant. This finding was among those reached in a new study, o-authored by Monsanto epidemiologist Judith A. Zack and Raymond R. Suskind, M.D., of the University of Cincinnati Medical Center. Their investigation examined the cause of death of all hourly workers who had been active employees of the plant for one or more years between19S5 and 1977 and have since died from any and all causes. The entire group was successfully traced and all deaths verified by death certificate. Monsanto produced 2,4,5-T at its Nitro plant from 1948 until 1969. It is currently the subject of widespread controversy centering on its use in the defoliant Agent Orange during the Vietnam War. j This is the second major effort undertaken to examine i the mortality (cause of death) of Nitrojplant workers, either . exposed or potentially exposed to TCDD.[Mrs. Zack and Dr. Suskind earlier this year co-authored a separate but related study of employees who had experienced high peak exposure 41 2- - ay* to TCDO during an industrial accident at the plant in 1949. The results of that investigation, published in the January, I960 issue of The Journal of Occupational Medicine, indicated no excess in total deaths or in deaths from cancer or cardiovascular disease. in this larger, follow-up effort, the mortality experience of the total Nitro plant workforce was analyzed by the modified life-table method using the U.S. population as the standard. Of the 884 men identified for study, 721 (82t) were verified as still alive and 163 (18%) were confirmed dead by death certificates. The study found no statistically significant excess in total deaths or deaths due to cancer -- ot^--disease of the nervous system, circulatory system, respiratory system or digestive system. The study did confirm and quantify an apparent excess in bladder cancer among Nitro Plant workers (nine observed vs 0.91 expected) which has been known for many years. This finding reflects the established and previously documented association between exposure to Para-aminobyphenyl (PAB) and cancer in man. PAB was used at Nitro from 1941 through 1952, for use as a rubber antioxidant and dye intermediate. Its use was discontinued when its cancer-causing potential was confirmed. The authors pointed out that an intensive screening program was instituted by the company about 19SS to examine, on a continuing basis, all workers exposed to this chemical. -more- CONFIDENTIAL. ' O 1 O r-- .4 fI ^ f r<nh vonrTM I7fc00 4 0 3- - Seven PAB-reiated deaths from bladder cancer have occurred among Nitro Plant employees enrolled in this program over these 25 years. These seven deaths are included in this study. A review of the work history records of the 163 decedents further revealed that S8' (3S.6I) had been exposed to 2,4,5-T and potentially to TCDD. One hundred four (63.8$) were considered non-exposed and the exposure of one decedent was not determined. The mortality experiences of these two subgroups were then compared using the proportional mortality method. This was done to test whether any relationship existed between potential TCDD exposure and proportional mortality. No such relationship was observed nor were any unusual patterns -- of mortality found in this exercise other than the PAB-related deaths described earlier. The expected number of deaths in the 2,4,5-T subgroup was calculated on the basis of the percentage of deaths from various causes in the U.S. general population. Specifically, cancer deaths among 2,4,5-T workers (nine observed versus 10.94 expected) were found to be lower than in the non-exposed group (25 observed versus 20.43 expected). Deaths due to disease of the nervous system, respiratory system and digestive system were also found to be lower than one would expect to find in a group of this size. While not statistically significant, deaths due to disease of the circulatory system (largely arteriosclerotic heart disease) were elevated at 31 versus 26.48 expected. 4- - The analysis of the total Nitro plant population found a similar excess in deaths from arteriosclerosis. In the discussion section, the authors pointed out that these excesses most likely reflect the higher mortality from heart disease which has been observed for Charleston and Kanawha County, W. Va. A third study, based on health information gathered from extensive physical examinations of over 400 present and former Nitro plant employees is currently being conducted solely by Dr. Suskind and his medical team from the University of Cincinnati's Institute of Environmental Health. Included in this ongoing study are both those workers exposed during the 1949 accident as well as those exposed during normal 2,4,5-T operations between 1948 and 1969 when the unit was shut down. A control group of employees who worked in other areas of the plant during that time frame is also being studied for comparative purposes. The results of this study are expected later this year and will be submitted for publication in an appropriate medical journal. 100980 -oOo- I -;: - r - ;:':. -- Human and Enviromnenial Risks ol Chlorinated Dioxins and Related compounds Edited by Richard E. Tucker Dynamac Corp Enviro Control Division Rockville. Maryland Alvin L. Young U.S. Veterans Administration Washington. D.C. and Allan P. Gray Dynamac Corp Enviro Control Division Rockville. Maryland PLENUM PRESS NEW YORK AND LONDON s * fc - s y < ,77- Library of Congress Cataloging in Publication Data Main entry under title: Human and environmental risks of chlorinated dioxins and related compounds. (Environmental scien ce research; v. 26) Proceedings of an international symposium on Chlonnated Dioxins and Related Com pounds, held October 25--29, 1981 in Arlington. Va. Includes bibliographical references and index. 1.Tetrachiorodibenzodioxin-- Environmental aspects-- Congresses. 2. Tetrachloro* dibenzodioxin-- Toxicology--C o n g re sse s. I. Tucker, Richard E. II. Young, Alvin L. Ill Gray, Allan P. IV. Series. QH545.P4H 85 1982 6 6 V .8915 82-18121 ISBN 0 -3 0 6 -4 1 1 7 0 -9 Proceedings of an international symposium on Chlorinated Dioxins and Related Compounds, held October 25--29. 1 98 1, in Arlington, Virginia 198 3 Plenum Press, New York A Oivision of Plenum Publishing Corporation 2 3 3 Spring Street, New York, N.Y. 1 0 0 1 3 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Pnnted in the United States of America ENVIRONMENTAL SCIENCE RESEARCH Editorial Board AAWlsaseosxhcaiinangtedtodenrU. nDHivo.Celr.lsiatieens.dIenrc. CRMoaamnsabsarlciddhguesF.e.tMtsParIsnossbatsictthuuetesienottfsTechnology aBEBTnanhrdleuvtiicJrmooeohnrnmLes..eHnMWtoaupelrkvlBcitainhonsmdUedniicvienresitRyeSsecahrocohl.oInf cM. edicine Recent Volumes in this Series PEOdiLteLdUbTyETDaftRYA.ITNoribara, Morton W. Miller, and Paul E. Morrow EEdNiVteIdRbOyNTMrilEocNhTaAnLS.EBDaUksChAi aTnIdOZNe:vPNrainvceihples, Methods, and Applications PERdiItMedAbRyYPaPuRl GO.DFUaClkToIwVsIkTiY IN THE SEA Volume 20 TEHdiEtedWbAyTWEaRynEeNWV.IRCOarNmMicEhaNeTl : Algal Toxins and Health MEdEitAedSUbyRGEeMorEgNeTGO. BFerRgISaKndS H. David Maillie SEELHaNdriOVtreyRIdRCTbOl-yaTNxMEtMoRicnEMh,NaaeBTnldAIDOLS.AtWeMSpSahIAXteenYTrsUSN, RSeIshNEnaSohTwbHIIeEg ANALYSIS OF COMPLEX S. Sandhu, Joellen Lewtas Huisingh, BEdIOiteSdAbLyINAEntRhoEnSyESAaRnCPHie:trAo Look to the Future Volume 24 ECdOitMedPbAyRFAreTdIeVriEckCJH. EdeMSIeCrrAesLaMndUMTAichGaEelNDE.SSIShelby GEdEiNteOd TbOy XRIaCymEoFnFdECR.TTSicOeF, DAaIRniBelOLR.NCEosAtaG, EaNndTSKaren Schaich DEHdIUOitMeXdAINbNySARANiNcDhDarEdRNEEVL.IARTTuOcENkDeMr,CEAONlMTviAnPLOLU.RNYISDoKuSSngO, FanCdHALllOanRIPN.AGTrEayD 0 J n -'- l MORTALITY STUDY OF WORKERS EMPLOYED AT THE IONSANTO COMPANY PLANT IN NITRO, WEST VIRGINIA Judith A. Zack and William R. Gaffey Monsanto Company St. Louis, Missouri USA BACKGROUND , The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a I'b -y toxic impurity that is formed in trace quantities during the roduction of 2 ,4,5-trichlorophenoxyacetic acid (2,4,5-T). Exposure o TCDD can cause chloracne, a skin disorder characterized by omedones, cysts, and abscesses.1 Outbreaks of chloracne have been eported among workers associated with the production of 2,4,5-T and ,4,5-T based products. Such incidents resulting from both accidental nd routine occupational exposures have been reported from several ountries.2 The first reported industrial accident involving exposure to CDD occurred in 1949 at the Monsanto Company plant in Nitro, West irginia. A total of 122 employees developed symptoms of chloracne ollowing a trichlorophenol (TCP) process accident. An undetermined umber of other employees developed symptoms of chloracne resulting rom exposure to the regular operations concerned with 2,4,5-T prouction over the period 1948-1969. Between 1949 and 1953, Ashe and Suskind3 '1* examined thirty^ight Nitro p.lant employees with chloracne. Twelve of these had eveloped symptoms of chloracne directly following the 1949 TCP accient; twenty-six other chloracne cases had resulted from exposure to he regular 2,4,5-T production operations. In addition to chloracne, ther signs and symptoms were observed in this group. These included evere aches in the lower extremities, fatigue, nervousness and rritability, loss or decrease of libido, dvspnia, and vertigo, hese findings are consistent with those that have been reported in ther industrial incidents.5 J r * jj ? 576 J. A. ZACK AND W. R. GAFFEY To examine ehe chronic health effects of exposure to TCDD, a mortality study of the Nitro plant employees who had developed symptoms of chloracne following the 1949 TCP accident was conducted.6 The study cohort was comprised of 121 of the 122 chloracne cases; one female who was living as of the endpoint of the study was excluded from analysis. At the time of the incident, it was assumed that the symptoms were caused by exposure to unknown products of decomposition. From today's vantage point, these symptoms suggest exposure to TCDD. The 121-member study cohort, with a presumptive high-peak exposure to TCDD, was followed for mortality through 1978. The entire cohort was traced: thirty-two deaths were observed and eighty-nine persons were confirmed as living. Analysis indicated no excess in total mortality or in deaths from malignant neoplasms. The study presented here examines the mortality of Nitro plant workers who were assigned to an area of TCP or 2,4,5-T production, with potential for exposure to TCDD. The mortality of these workers is examined in the context of the mortality experience of the total Nitro plant worker population. The Monsanto Nitro plant began operations in 1922, when the Rubber Service Laboratories purchased the plant as war surplus and began production of chemicals and additives for the growing rubber industry. In 1929, Monsanto Company purchased the Nitro plant from the Rubber Service Laboratories and entered the rubber chemicals business. Over the years, the Nitro plant has diversified to where it now produces agricultural chemicals, paper chemicals, plasticizers, fine chemicals, and intermediates, in addition to rubber chemicals. The plant is situated in the Kanawha River Valley, an area containing one of the largest concentrations of chemical production facilities in the United States. Of the many chemicals used over the years at the Nitro plant, one has an established association with the occurrence of cancer in man. ?ara-aminooiphenyl (PA), used from 1941 through 1952 for use as a rubber antioxidant and dye intermediate, was shown in 1954 by Walpole et a-1.7 to induce bladder cancer in dogs. In 1955, Melick et al.9 confirmed the carcinogenicity of para-aminobiphenvl to man with the reporting of bladder tumors among workers exposed to this chemical at two Monsanto plants. Para-aminobiphenyl was produced at one plant and then transferred by tank car to the Nitro plant where additional processing was carried out. The minimum duration of exposure reported to have produced a bladder tumor is 133 days; the latent period has ranged from 15 to 35 years.9 An intensive screen ing program was instituted at Monsanto Company about 1955 to examine, on a continuing basis, all workers exposed to this chemical. Seven deaths from bladder cancer have occurred among Nitro plant employees enrolled in this program. These seven deaths are included in the present study. 10RTALITY STUDY OF WORKERS 577 Other chemicals with known health effects produced at the Nitro lant include methylparathion and carbon disulfide. The acute effects f exposure to each of these chemicals have been described310 while he chronic effects are less well understood. Besides p-aminobiphenvl, everal other rubber chemicals are of potential health concern. For 11 of these, there is insufficient evidence to evaluate their carcingenicity to man. Tetramethyl thiuram disulfide is considered an nimal carcinogen11 and there is some evidence, although not suffiient, that N-methyl-N,4-dinitrosaniline is also an animal carcingen.12 For several other rubber chemicals, there is insufficient vidence to evaluate the carcinogenicity to animals. Nowever, these hemicals have the potential for forming nitrosamines, certain of hich are known animal carcinogens.13 Zinc dimethyl dithiocarbamate, etramethyl thiuram disulfide and tetramethyl thiuram monosulfide ave the potential to form N-nitrosodimethylainine. N-Nitrosomorphoine has been found in product samples of 2-(morpholinothio) benothiazole and 4,4T-dithiodimorpholine (Frisone, G.J., The General ire and Rubber Company, unpublished data). Although several of the chemical compounds produced or used at he Nitro plant over the years have been associated with adverse ealth effects, no attempt has been made to relate chemical exposure o mortality with the exception of decedents exposed to the TCP or -T operations and potentially exposed to TCDD. As a result, the ni> specific hypothesis that can be tested is whether a relationhip exists between potential TCDD exposure and proportional mortalty, especially for malignant neoplasms. The mortality for this roup is examined in addition to that of the total Nitro plant worker pulation. DPULATION AND METHODS A study cohort was developed from the Nitro plant consisting of mployees active on or after January 1, 1955 with one or more years f employment on the hourly roll prior to December 31, 1977. Salaried ersonnel who had never worked on the hourly roll were excluded from tudy because many of these employees had no appreciable exposure to he plant environment and, for the most part, their exposure cannot e determined from plant records. Females and non-white males were Iso excluded because of their small numbers. The cohort was assembled using government earnings reports, cidependent of the plant work history records. Annual earnings eports were available on a computer file from 1951 through 1977. ames and social security numbers were identified from this source, ork history records were used to supplement the earnings records, nformation on race, sex, date of birth, date of hire, date of sepaation, ana,'if deceased, 2,4,5-T exposure was abstracted from these ecords. Ascertainment of 2,4,5-T exposure was confined to decedents aly because it was too tedious to do for the entire cohort. The J | \ \ r ' > ;i 578 J. A. ZACK AND W. R. GAFFEY information from the work history records was used to determine which names identified from the annual earnings records met the cohort entrance criteria. Employees identified from the earnings records who terminated prior to 1955 were not included in this study because work history records for all such employees were not retained prior to this date. Exposure to 2,4,5-T was determined by assignment to a 2,4,5-T operation based on the work history records. 2,4,5-T exposure was determined for all but one decedent. Employees holding a job having plant-wide responsibilities with the potential for exposure to 2,4,5-T were, for the purposes of this study, considered to be nonexposed. The vital status of each member of the study cohort was deter mined using standard follow-up techniques and ascertained as of December 31, 1977. Death certificates were coded by an independent nosologist for the underlying cause of death, according to the rules of the Eighth Revision of the International Classification of Diseases, Adapted.*1* Data for the total Nitro plant study population were analyzed by the modified life-table method using the U.S. population as the standard. With this method of analysis, the age-, race-, time-, and cause-specific mortality rates for the U.S. general population are applied to the person-years lived classified by age, race, and time. A standardized mortality ratio (SHR) was calculated for 23 selected cause of death categories. Cause-specific SMR's for 15 selected cancer sites were calculated for subgroups of the total Nitro plant study population defined by date of death, age at death, and year of hire. The statistical significance of the deviation in a SMR from 100 was tested using the formula: standard error of SMR * 100 vfio. observed deaths no. expected deaths If the observed SMR differed from, 100 by 1.96 standard errors, it was regarded as significant at the 5% level. A SMR was tested for significance only when the observed number of deaths was five or greater. Data for those deceased were also analyzed according to 2,4,5--T exposure using the proportional mortality method. In this case, the expected number of deaths is calculated on the basis of proportions of deaths observed in the U.S. general population. A proportional mortality ratio (PMR) was calculated for 23 selected cause-of-deavth categories. PMR's were calculated separately for those exposed to 2,4,5-T and for those not exposed. The statistical significance of the deviation of a PMR from 100 was tested by calculating the 95% MORTALITY STUDY OF WORKERS 579 confidence interval for the PMR for a given cause k according to the formula: confidence interval _ N(confidence limits for % of observed deaths) for PMR, X exp, K. where N * number of observed deaths for all causes Both the standardized^and proportional mortality analvses were conducted using the computer program developed by Monson.^ The observed mortality was compared to that of the United States white male population for the time period of study. RESULTS A total of 884 men were identified for study and traced for deaths through 1977. The entire cohort was successfully traced. Death certificates were obtained for all deaths. Seven hundred twenty-one (82%) were verified as living and 163 (18%) were confirmed dead by death certificates. Tables 1-3 characterize the total Nitro plant study population bv age at hire, year of hire, and length of employment. The dis- bution of the study population by age at hire indicates that the workers were fairly young at first hire (Table 1). Seventy-two percent of the study cohort were hired by age 30. None were hired at age 50 or above. Table 2 shows the distribution of the study population by year of hire. The majority of workers (75.3%) were hired during the period 1940-1959, while smaller percentages of workers were hired prior to 1940 (10.8%) and after 1960 (13.9%). An examination of the study population by length of employment indicates a fairly even distribution over the intervals less than 10 years, 10-19 years, 20-29 years, and greater than 30 years (Table 3). Observed and expected deaths occurring during 1955-1977 among the total Nitro plant study population are shown by cause in Table 4. The SMR for all causes of death was 103 with 163 deaths observed and 158.10 expected. There were 35 deaths from malignant neoplasms with 30.92 e'xpected, yielding a SMR of 113. inga.ficantly elevated SMRfs were seen for the categories of malignanF"`neoplasms of the genitourinary organs and of the bladder. The SMR for bladder cancer was 989 with 9 deaths observed and 0.91 expected. This excess in t^L^dder cancer deaths is reflected in the elevated SMR for malignant liqfrlasms of the genitourinary organs. A significantly elevated SMR is also seen for arteriosclerotic heart disease. There were 79 deaths from this cause with 59.40 expected (SMR - 133). The SMR for 580 J. A. ZACK AND W. R. GAFFEY Table 1. Distribution of Total Nitro Plant Study Population by Age at Hire Age at Hire Number _______ Percent <20 20-29 30-39 40-49 50+ Total 122 513 191 53 0 884 13.8 58.6 21.6 6.0 0.0 100.0 Table 2. Distribution of Total Nitro Plant Study Population by Year of Hire Year of Hire Number Percent Prior to 1930 1930-1939 1940-1949 1950-1959 1960-1976 Total 21 74 361 305 123 884 2.4 8.4 40.8 34.5 13.9 100.0 Table 3. Distribution of Total Nitro Plant Study Population by Length of Employment Length of Employment (yrs.) Number Percent <10 10-19 20-29 30+ Total 225 213 204 242 884 25.5 24.1 23.1 27.4 100.1 Table 4. Observed and Expected Number of Dea Standardized Mortality Ratios (SMR*S) Cause of Death All causes of death All malignant neoplasms Buccal cavity and pharynx Digestive organs and peritoneum Stomach Liver All other digestive organs Respiratory system Lung All other respiratory organs Skin Genitourinary organs Bladder All other genitourinary organs Lymphatic and hematopoietic tissue Other sites _r Diseases of the nervous system and sense organs Diseases of the circulatory system Arteriosclerotic heart disease, including CHD All other diseases of the circulatory system Diseases of the respiratory dystem Diseases of the digestive system All other diseases External causes of death_______________________ Number at risk: 884 Person-years at risk: 13968.7 *p < .05 During 1955-1977 by Cause Showing for Total Nitro Plant Study Populat ion ICDA Codes 8th Rev. Observed Expected 140-209 140-149 150-159 151 155-156 -- 160-163 162-163 -- 172-173 185-189 188 -- 200-209 -- 320-389 390-458 410-413 -- 460-519 520-577 -- 800-998 163 158.10 35 30.92 0 1.03 4 8.65 1 1.63 0 0.60 3 6.42 14 10.51 14 9.91 0 0.60 0 0.58 12 3.75 9 0.91 3 2.84 1 3.15 4 3.25 0 1.28 92 82.59 79 59.40 13 23.19 6 9.13 5 8.03 5 10.46 20 15.69 SMR 103 113 0 46 6i 0 47 133 141 0 0 320* 989* 106 32 123 0 111 133* 56* 66 62 48* 127 2 LH33J > n H -< (H/> C O -< T) o3$3 7^ m33 (Si O 00 582 J. A. ZACK AND W. R. GArFEY ocher circulatory diseases was significaacly low ac 56. A significant deficit was also seen for the category of all other diseases where the SMR was 48 with 5 deaths observed and 10.46 expected. Trends for malignant neoplasm deaths with calendar time are shown in Table 5. SMR's which increased consistently over the period 19551977 are seen for the categories of all malignant neoplasms and malig nant neoplasms of the respiratory system. The SMR for all malignant neoplasms rose from 32 to 131. The SMR for malignant neoplasms of the respiratory system rose from 0 to 172 reflecting a SMR for lung cancer which increased from 0 to 181. Although based on very small numbers, the SMR for malignant neoplasms of the digestive organs and peritoneum consistently decreased over time from 99 to 24. The SMR for malignant neoplasms of the genitourinary organs peaked during the period 19601969. This is reflected in the SMR for bladder cancer which increased from 0 in 1955-1959 to a peak of 1471 in 1960-1969 and decreased to 833 in 1970-1977. The analysis of observed and expected deaths from malignant neo plasms by age at death revealed little in terms of consistent trends with age (Table 6). For most of the cause-of-death categories, the SMR peaked at age 45-64 rather than continuing to rise with increasing age. Bladder cancer is one category where the SMR remained high at age 65 and over. The distribution of deaths from malignant neoplasms by year of hire is shown in Table 7. No deaths from malignant neoplasms were observed among workers hired after 1960. The SMR for all malignant neoplasms was similar for those hired prior to 1945 and for those hired in the period 1945-1959. The greatest difference in SMR's be tween those hired prior to 1945 and those hired from 1945-1959 occurs with bladder cancer. The SMR for bladder cancer is highest for those hired prior to 1945 with a SMR of 1111. A subset of deaths identified from the total Nitro plant study population was studied separately. Table 8 characterizes the deced ents according to 2,4,5-T exposure. Of the 163 decedents, 58 (35.6%) were considered to be exposed to 2,4,5-T based on their work history records, while 104 (63.8%) were considered to be non-exposed. The exposure of one decedent was unkown. The results of the proportional mortality analysis by 2,4,5-T exposure classification are presented in Table 9. The proportion of cancer deaths among 2,4,5-T workers is lower than in the non-exposed group (PMR: 82 vs. 122). The PMR for lung cancer deaths is slightly higher in the exposed group (PMR: 159 vs. 117). The proportion of deaths due to bladder cancer is higher among the decedents not ex posed to 2,4,5-T. There were 7 deaths from bladder cancer among these workers with 0.65 expected (PMR = 1077). The PMR for bladder cancer among decedents exposed to 2,4,5-T was 909 with 2 deaths observed and Table 5. Observed and Expected Deaths from Malignant Neoplasms During 1955-1977 by Calendar Time Showing Standardized Mortality Ratios (SMR'S) for Total Nitro Plant Study Population Cause of Death Calendar Time 1955-1959 1960-1969 1970-1977 Observed Expected SMR Observed Expected SMR Observed Expected SMR All malignant neoplasms 1 Buccal cavity and pharynx 0 Digestive organs and peritoneum 1 Stomach 0 Liver 0 All other digestive organs 1 Respiratory system 0 Lung 0 All other respiratory organs 0 Skin 0 Genitourinary organs 0 Bladder 0 All other genitourinary organs 0 Lymphatic and hematopoietic 0 tissue Other sites 0 *p < .05 3.13 32 13 0.11 00 1.01 99 2 0.25 00 0.09 00 0.67 149 2 0.87 04 0.80 04 0.07 00 0.07 00 0.33 05 0.09 05 0.24 00 0.40 00 0.34 02 11.81 110 0.41 0 3.48 57 0.70 0 0.28 0 2.50 80 3.83 104 3.59 111 0.24 0 0.23 0 1.37 365 0.34 1471* 1.03 0 1.24 0 1.25 160 21 0 1 1 0 0 10 10 0 0 7 4 3 1 2 15.98 0.50 4.16 0.69 0.23 3.24 5.81 5.52 0.29 0.28 2.05 0.48 1.57 1.50 131 0 24 145 0 0 172 181 0 0 341 833 191 67 1.68 119 583 MORTALITY STUDY OF WORKERS k\ I Table 6. Observed and Expected Deaths from Malignant Neoplasms During 1955-1977 by Age at Death Showing Standardized Mortality Ratios (SMK'S) for Total Nitro Plant Study Population Cause of Death Age at Death <45 45-64 65+ Observed Expected SMR Observed1 Expected SMR Observed Expected SMR All malignant neoplasms 2 Buccal cavity and pharynx 0 Digestive organs and peritoneum 0 Stomach 0 Liver 0 All other digestive organs 0 Respiratory system 0 Lung 0 All other respiratory organs 0 Skin 0 Genitourinary organs 1 Bladder 1 All other genitourinary organs 0 Lymphatic and hematopoietic 0 tissue Other sites 1 *p < .05 2.39 0.06 0.51 0.10 0.03 0.38 0.54 0.51 0.03 0.13 0.20 0.02 0.18 0.55 0.40 84 0 0 0 0 0 0 0 0 0 500 5000 0 0 250 21 0 4 1 0 3 11 11 0 0 3 2 1 1 2 16.85 125 0.67 0 4.58- 87 0.85 118 0.32 0 3.41 88 6.36 173 5.99 184 0.37 0 0.31 0 1.43 210 0.39 513 1.04 96 1.60 63 12 0 0 0 0 0 3 3 0 0 8 6 2 0 1.90 105 . 1 11.69 0.31 3.57 0.68 0.24 2.65 3.61 3.42 0.19 0.14 2.12 0.50 1.62 1.00 103 0 0 0 0 0 83 88 0 0 377* 1200* 12 3 0 0.94 106 J. A. ZACK AND W. R. GAFFEY MORTALITY STUDY OF WORKERS iaoie /. observed and Expected Deaths from Malip ~ t Neoplasms During 1955-1977 by Year of Hire Showing Standardized Mortality Ratios U .<'S) for Total Nitro Plant Study Population Cause of Death Observed Expected SMR Observed Expected SMR Observed Expected SMR All malignant neoplasms 25 Buccal cavity and pharynx 0 Digestive organs and peritoneum 2 Stomach 0 Liver 0 All other digestive organs 2 Respiratory system 10 Lung 10 All other respiratory organs 0 Skin 0 Genitourinary organs 9 Bladder 8 All other genitourinary organs 1 Lymphatic and hematopoietic 1 tissue Other sites 3 * P < .05 21.30 0.70 6.27 1.21 0.45 4.61 7.14 6.73 0.41 0.31 2.90 0.72 2.18 1.95 117 0 32 0 0 43 140 149 0 0 310* 1111* 46 51 2.03 148 10 0 2 1 0 1 4 4 0 0 3 1 2 0 1 8.63 0.31 2.19 0.39 0.14 1.66 3.09 2.93 0.16 0.22 0.76 0.18 0.58 1.00 116 0 91 256 0 60 129 137 0 0 395 556 345 0 1.06 94 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.99 0.03 0.19 0.03 0.01 0.15 0.27 0.26 0.01 0.05 0.09 0.01 0.08 0.20 0.16 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Table 8. 2,4,5-T Exposure Classification for Decendents During 1955-1977 Among Total Nitro Plant Study Population 2,4,5-T Exposure Classification Number of Deaths Percent Exposed Non-exposed Unknown Total 58 35.6 104 63.8 1___________________________ 0.6 163 100.0 585 586 J. A. ZACK AND W. R. GAFFEY Table 9. Observed and Expected Number of Deaths During 1955-1977 by Cause and 2,4,5-T Exposure Category Showing Proportional Mortality Ratios (PMR'S) Cause of Death 2,4,5-T Exposure Category Exposed Non -exposed Observed Expected PMR Observed Expected PMR All malignant neoplasms Buccal cavity and pharynx Digestive organs and peritoneum Stomach Liver All other digestive organs Respiratory system Lung All other respiratory organs Skin Cenitourinary organs Bladder All other genitourinary organs Lymphatic and hematopoietic tissue Other sites Diseases of the nervous system and sense organs Diseases of the circulatory system Arteriosclerotic heart disease, including CUD All other diseases of the circulatory system Diseases of the respiratory system Diseases of the digestive system All other diseases External causes of death Total number of deaths: *p < .05 9 0 0 0 0 0 6 6 0 0 2 2 0 0 1 0 31 27 4 2 1 3 12 58 10.94 0.38 2.80 0.52 0.19 2.09 3.78 3.57 0.21 0.29 0.96 0.22 0.74 1.35 1.38 0.61 26.48 19.72 6.76 2.67 3.70 4.31 9.29 58.00 82 0 0 0 0 0 159 168 0 0 208 909 0 0 72 0 117 137 59 75 27 70 129 25 0 3 0 0 3 8 8 0 0 10 7 3 1 3 0 61 52 9 4 4 .2 8 104 20.43 122 0.64 0 5.74 52 1.06 0 0.39 0 4.29 70 6.81 117 6.42 125 0.39 0 0.35 0 2.70 370* 0.65 1077* 2.05 146 2.07 48 2.12 142 0.83 0 55. 34 110 39.68 131* 15.66 57 6.49 62 4.93 81 6.70 30 9.28 86 104.00 MORTALITY STUDY OF WORKERS 587 0.22 expected. PMRTs for both exposure groups are quite similar for diseases of circulatory and respiratory system. Slight differences appear in the PMR's between the two groups for diseases of the diges tive system and all other diseases. However, the PMR's for both groups are quite low. The PMR for external causes of death is slightl} higher in the exposed group (PMR: 129 vs. 86). A listing of the cancer deaths among the 2,4,5-T exposed is given Ln Table 10. Table 11 listed the cancer deaths among the non-exposed roup. )ISCUSSION The observation made many years ago of an apparent excess in ladder cancer among Nitro plant workers was confirmed and quantified .n the mortality analysis of the total Nitro plant population presented tere. The SMR for bladder cancer was 989 and was the only statistially significant SMR among those for malignant neoplasms. The excess n mortality is not seen until 1960. The SMR peaked in the 1960's nd declined somewhat in the 1970's. The excess also appeared to be lustered in those decedents aged 65 years and older at death and in hose hired prior to 1945. This would suggest that we should see a urther decline in the SMR for bladder cancer over time. Although not statistically significant, the SMR for lung cancer ppears to be elevated. The SMR increased with calendar time and was ighest in those hired prior to 1945. The elevation appears to be lustered in those aged 45-64 years of age at death (SMR = 184) and oes not show a gradient with age. Further analyses to evaluate rends in lung cancer deaths as they relate to occupation cannot be arried out due to limitations in the data collected in this study. The SMR for diseases of the circulatory system was elevated at LI. This is most likely a reflection of the higher mortality from iart disease which has been observed for Charleston, West Virginia id Kanawha County, West Virginia (unpublished data, Neas LM, 1979 and iterline PE, 1979). For the total Nitro plant study population, lere was a statistically significant excess in deaths from arterio:lerotic heart disease and a deficit in deaths from other circulatory Lseases. This variation in the distribution of deaths from that of \e U.S. may be due to risk factor or medical care differences in the .ant population and the local area. These may include differences l smoking habits, the availability and use of medical services and te specificity of diagnoses. The proportional mortality analysis of decedents by 2,4,5-T iposure classification indicated no unusual patterns of mortality the 2,4,5-T exposed. The proportional mortality ratio (PMR for lignant neoplasms was low (PMR =82) in the exposed group. Lung ncer was the only site among the malignant neoplasms which was mewhat higher in the exposed group. 588 J. A. ZACK AND W. R. GAFFEY Table 10. Deaths Due to Malignant Neoplasms Among Nitro Plant Workers Exposed to 2,4,5-T Year pf Birth Year of Hire Year of 1st Year of Exposure Term. ear of Smoking Cause of Death as Given on Death History* Death Certificate 1917 1946 1951 1972 1972 Cigarettes Carcinoma left lung with mtastass (162.1) 1911 1948 1955 1972 1972 Cigarettes Metastatic carcinoma of the lung (162.1) 1916 1946 1959 1968 1968 Cigarettes Bronchiogenic carcinoma of right upper lobe (162.1) 1901 1944 1956 1963 1973 Cigarettes Carcinoma lung with mtastass (162.1) 1911 1941 1948 1971 1975 Cigarettes Bronchiogenic carcinoma with cerebral mtastass (162.1) 1922 1945 1948 1972 1973 Non-smoker Bronchiogenic carcinoma with mtastass (162.1) 1923 1946 1950 1972 1972 Cigarettes Generalized liposarcoma (171.9) 1902 1922 1948 1966 1966 Non-smoker Metastatic carcinoma urinary bladder (188.0)** 1910 1944 1948 1968 1968 Non-smoker * Obtained by interview with former coworkers of decedents. ** Included on the Nitro plant PAB roster. Carcinoma of the urinary bladder (188.0)** MORTALITY STUDY OF WORKERS Table 11. Deaths Due to M ^nant Neoplasms Among Nltro Plant Workers Not Exposed to 2,4,5-T Year of Year of Year of Year of Smoking Birth Hire Termin. Death History* Cause of Death as Given on __________ Death Certificate______________ 1911 1945 1966 1968 Cigarettes Carcinoma of colon (153.8) 1904 1935 1957 1957 Cigarettes Carcinoma of liver (157.9) ^ 1899 1929 1959 1960 Pipe Intraperitoneal carcinoma (158.9) 1905 1944 1970 1972 Cigarettes Carcinoma of lung (162.1) 1909 1943 1962 1962 Cigarettes Carcinoma of left lung (162.1) 1910 1927 1966 1970 Cigarettes Pulmonary carcinoma (162.1) 1912 1944 1965 1965 Cigarettes Carcinoma of apex of right lung (162.1) 1915 1937 1977 1977 Cigarettes Carcinoma of lung (162.1) 1915 1939 1969 1970 Cigarettes Carcinoma of lungs (162.1) 1894 1944 1960 1964 Non-smoker Carcinoma of lung (162.1) 1912 1937 1973 1974 Cigarettes Carcinoma of lung (162.1) 1919 1946 1963 1964 Cigarettes Carcinoma of urinary bladder (188.0)** 1901 1933 1962 1977 Cigarettes Carcinoma of bladder (188.0)** 189 7 1941 1962 1965 Cigarettes Carcinoma of urinary bladder (188.0)** 1898 1933 1962 1965 Smoked years , Carcinoma of urinary bladder (188.0)** 1905 1943 1971 1975 Cigarettes Carcinoma of bladder (188.0) 1898 1943 1963 1970 Cigarettes Bladder tumor (188.0)** 1888 1944 1956 1970 Unknown Carcinoma of bladder (188.0) 1905 1933 1969 1977 Cigars Prostatic carcinoma (185.0) 1906 1946 1968 1977 Cigarettes Carcinoma of prostate (185.0) 1925 1945 1973 1974 Smoked years < Carcinoma of prostate (185.0) 1919 1943 1972 1973 Cigarettes Hodgkin's Disease (201.0) 1901 1941 1964 1965 Cigars Osteosarcoma arising from left arm (170.4) 1901 1943 1966 1977 Cigarettes Carcinoma of liver & pancreas (197.8) 1922 1944 1964 1964 Cigarettes Adenocarcinoma (199.0) * Obtained by interview with former coworkers of decedents. ** Included on the Nltro plant PAB roster. 589 590 J. A. ZACK AND W. R. GAFFEY The PMR analysis is limited in that an assessment of the total force of mortality cannot be made. The cause-specific PMR's only approximate what an SMR analysis would have produced.16 The PMR analysis presented here estimates the cause-specific risks associated with 2,4,5-T exposure and potential TCDD exposure. It is interesting to compare the results of this study of Nitro plant workers potentially exposed to TCDD with the results of the study of Nitro workers involved in the 1949 TCP accident. The workers involved in that incident had presumed TCDD exposure as evidenced by chloracne. The results of the two studies are similar in that neither shows an excess in deaths from any site among malignant neoplasms. A recent study of Ott et al.17 found no excess in total mortality or in deaths from malignant neoplasms among workers exposed to 2,3,5-T. These workers were probably exposed to very low levels of TCDD since no cases of chloracne were observed. Other studies of workers who developed chloracne resulting from TCDD exposure have been conducted and have been reviewed.^ At the present time, data from these various studies do not constitute corroborative evidence of a cancer risk to man for any particular cancer site. REFERENCES 1. Greig, J.B.: The toxicology of 2,3,7,8-tetrachlorodibenzo-pdioxin and its structural analogues. Ann. Qccup. Hyg. 22: 411-420, 1979. 2. International Agency for Research on Cancer: Long-term hazards of polychlorinated dibenzodioxins and polychlorinated dibenzofurans. IARC Internal Technical Report No. 78/001. Lyon: IARC, 1978. 3. Ashe, W.F. and Suskind, R.R.: Reports on chloracne cases, Monsanto Chemical Company, Nitro, West Virginia. Reports of the Kettering Laboratory, December 1949 and April 1950. 4. Suskind, R.R.: A clinical and environmental survey, Monsanto Chemical Company, Nitro, West Virginia. Report of the Kettering Laboratory, July 1953. 5. International Agency for Research on Cancer. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man, Vol. 15. Some Fumigants, the Herbicides 2,4-D and 2,4,5-T, Chlorinated Dibenzodioxins and Miscellaneous Industrial Chemicals. Lyon: IARC, 1977. 6. Zack, J.A. and Suskind, R.R.: The mortality experience of workers exposed to tetrachlorodibenzodioxin in trichlorophenol process accident. J. Occupy Med, 22:11-14, 1980. 7. Walpole, A.L., Williams, M.H., and Roberts, D.C.: Tumours of urinary bladder in dogs after ingestion of 4-aminodiphenyl. Brit. J. Inauscr. Med. 11:105-109, 1954. j'. MORTALITY STUDY OF WORKERS 591 8. Melick, W.F.: First reported cases of human bladder tumors due to a new carcinogen - xenylamine. J. Urol. 74:760-766, 1955. 9. Melick, W.F., Naryka, J.J., and Delly, R.E.: Bladder cancer due to exposure to para-aminobiphenyl: a 17-year followup. J. Urol. 106:220-226, 1974. 10. Key, M.M.: Ocuppational Diseases: A Guide to Their Recognition. U. S. Department of Health, Education and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health. DHEW (NIOSH) Publication No. 77-181. Washington: U.S. Government Printing Office, 1977. 11. International Agency for Research on Cancer. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Vol. 12. Some Carbamates, Thiocarbamates, and Carbazides. Lyon: IARC, 1971. 12. International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 1. Lyon: IARC, 1971. 13. Magee, P.N.,: N-nitroso compounds and related carcinogens. In: Searle, C.E.(ed): Chemical Carcinogens. Monograph 176. Washington: American Chemical Society, 1976. 14. Eighth Revision, International Classification of Diseases, Adapted for Use in the United States. U.S. Department of Health, Ed ucation, and Welfare, Public Health Service, PHS Publication No. 1693. Washington: U.S. Government Printing Office, 1977. 15. Monson, R.R. ,: Analysis of relative survival and proportional mortality. Comput. Biomed. Res. 7:325:332, 1974. 16. Decoufle, P. , Thomas, T.H., and Pickle, L.W. : Comparison of the proportionate mortality ratio and standardization mortality ratio risk measures. Am. J. Epidemiol. 111:263-269, 1980. 17. Ott., G. , Holder, B.B., and Olson, R.: A mortality analysis of .employees engaged in the manufacture of 2,4,5-trichlorophenoxyacetic acid. J. Occup. Med. 22:47-50, 1980. Attach '(f't'T X Original Articles \ J The Mortality Experience Journal of Occupational Medicine January 1980 Vol. 22 No. 1 of Workers Exposed to Tetrachlorodibenzodioxin in a Trichlorophenol Process Accident Judith A. Zack, and Raymond R. Suskind, M.D. A standardized mortality analysis was conducted on workers exposed to tetrachlorodibenzodioxin in a trichlo rophenol process accident at the Monsanto Company plant in Nitro;West Virginia. One hundred and twenty-one workers who developed chloracne resulting from this acci dent on March Q. 1949. were selected for studv. Follow-up o f this group was 100% complete. The standardized mor tality ratio for all causes of death was shown to be 0.69. with 32 deaths observed and 46.41 expected. For the categories o f malignant neoplasms and circulatory diseases. the standardized mortality ratios were 1.00 and 0.68. respectively. Because o f the small size of the cohort and the relatively small number of deaths observed, the results of this study cannot be considered conclusive. However, it 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 o f workers with a high peak exposure to tetrachlorodiben zodioxin who were follow ed over a period of nearly 30 years. The results of this study will be incorporated with those o f a larger study which will include plant workers ex posed in the course o f 2.4.5-trichlorophenoxyacetic acid production during the period 1948 to 1969. A wide variety of acute and sub-acute health effects has been reported in workers involved in the manufacture of 2.4,5-trichlorophenoxyacetic acid (2.4.5-T) from 2.4,5-trichlorophenol (TCP). The most consistent clinical finding is chloracne. a skin disease characterized by com- From the Department or M edicine and Environmental Health. Monsanto Company. dOO N Lin dbergh B lv d . St L o u is. M O 6J166 (Ms Zack. Epidemiologist), and the institu te or Env.ronmental Health. Kettering Laboratory, the University or Cincinnati Mnju:ji Center. Cincinnati O H 45267 > lO f Suskind. Director) ~" edones. cysts, pustules, and abscesses. Hepatic dysfunc tion. 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-tetrachlorodibenzodioxin (TCDD).2 a byproduct in the synthesis of 2.4.5-T. The sub ject 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 chloracne following a trichlorophenol pro cess accident at the Nitro, West Virginia, plant in 1949. Production of trichlorophenol began in the fall of 1948 at the Nitro plant. In this process, the reactants 1,2,4,5-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 symp toms immediately following exposure to the material which was discharged from the autoclave. Symptoms in cluded eye and respirator/ 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 Suskind1"* 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 1953. The Journal of Occupational Medicine/Vof 22: No. 1/January 1980 .. .- 11 clinical symptoms, in order of relative frequency.4included accidental industrial intoxication. c- *orm lesions; severe pains in muscles of upper and In 1976. a TCP process accident in Meda. Italy, resulted lo..er extremities, shoulders and thorax on exertion: in the contamination of a large and densely populated fatigue: nervousness and irritability; decrease in libido; area.8 A preliminary mortality studv has been conducted dyspnea: vertigo and intolerance to cold. On examination, in two of the 11 towns affected. The overall mortality rate ail of the cases had chloracne. Several were severely hyper- did not differ from that expected, but increases in deaths pigmented. especially on the face Of the six workers ex from liver cirrhosis and leukemia were suggested. amined in 1949 and 1950. four had liver enlargement and The chronic toxicity of TCDD exposure to animals has one had sensory loss in one foot. Liver impairment as in been more extensively studied. TCDD toxicitv has been dicated by hepatomegaly, tenderness and soreness in the thoroughly reviewed.7 Chronic toxicity to TCDD is right upper quadrant and epigastrium and a delayed pro manifested by liver necrosis, thymic atrophy, and deple thrombin time, was observed.354 tion of the lymphoid organs. Two studies indicate that In 1953. four of the six workers examined in 1949 and chronic administration of low levels of TCDD to rats is 1950 were re-examined and six additional workers involved associated with an increased incidence of neoplasia. In in the accident were 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 noncutaneous symptoms which had carcinomas of the lung, hard palate/nasal turbinates, or been present earlier. All of the workers showed a marked tongue.12 In another study, TCDD fed to rats produced improvement in their skin lesions -- there were residua of tumors in 38% of the test animals.13 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 The study reported here will examine the mortality ex tremities 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.4 ticularly of the stomach, liver, lung, and skin. 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 for he literature,7 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 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 employees who developed chloracne following this incident were development of a variety' of neoplasms.8'1' These reports, however, are generally of small groups of workers with identified from plant safety records dating to the time of the accident, and from workmen's compensation and relatively short periods of follow-up and are considered to plant medical records. One hundred and twenty-one be preliminary in nature. In a 25-vear follow-up studv. 17 white males were included in this studv -- one female deaths were observed among a cohort of 75 German who was living as of the endpoint of the study was not in workers who had been involved in a 1953 TCP process cluded in this mortality analysis. It is assumed that all of accident.8 Of the 17 deaths observed (11-25 expected 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/2A5-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.'4 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.8 Eight deaths have been standardized mortality ratio was calculated as the ratio of observed among 93 exposed workers. Five or six of these the observed deaths to the expected deaths for 22 deaths were from cardiovascular disease. The 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 al* 10 and Pazderova" followed 55 of the 78 cance wSs determined at the 5% level of significance. techoslovakian workers who were affected by chlor- For th i 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 pentachlorophenol. In this study, five deaths were ob 8. 1949. the date of the accident. The vital status of each served. These included two deaths from bronchiogenic member"was determined using standard follow-up tech carcinoma (less 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 fbund to be deceased, a death certificate was ob- 12 Mortality Experience of Workers Exposed to Tetrachlorodibenzodioxin/Zack and Suskind Table 1. -- Observed and Expected Deaths Among 121 Males Exposed to Tetracbiorodibenzodioxin in a Trichlorophenol Process Accident. Causa All causes or aeatn All malignant neooiasms 3uccai cavity and onarynx Digestive organs ana oentoneum Stomacn liver All other digestive organs Resoiratory system lung All other respiratory organs Skin Genitourinary organs lymonatic ana nematoooietic tissue Other sites Oiseases of the nervous system and sense organs Oiseases of the circulatory system Arteriosclerotic heart disease, including coronary heart disease AH other disease of the circulatory system Oiseases of the resoiratory system Oiseases of tne digestive system All other diseases External causes of death ICO No. (Eighth Revision) 140-209 140-149 150-159 . 151 155-156 160-163 162.163 -- 172.173 185-189 200-209 -- 320-389 390-458 410-413 -- 460-519 520-577 -- 800-998 Observed 32 9 0 0 0 0 0 5 5 0 1 0 3 0 0 17 13 4 1 0 2 3 Expected 46.41 9.04 0.30 2.59 0.50 0.18 1 91 3.02 2.85 0.17 0.15 1.16 0.38 0.94 0.36 25.01 1774 7.27 2.78 2.26 3.18 378 SMR 0 69' 1 00 r r t 7 r 1 66 1 75 r r r r r r 0.68 073 T. 7 r r r p < 0.05 flsss tnan 5 observed deatns tained. The underlying cause or death was coded to the 8th Revision of the International Classification of Diseases, Adapted'5 by an experienced nosoiogist. Results All of the 121 members of the study cohort were traced. Eighty-nine were verified living and 32 were verified deceased by death certificate. The results of the standardized mortality analysis of the 121-member study cohort are shown in Table 1. The standardized mortality ratio for all deaths is shown to be 0.69, with 32 observed deaths and 46.41 expected. This is the only statistically significant difference shown in this table. There were nine deaths from malignant neoplasms with 9.04 expected. There were no deaths from stomach or liver cancer. There were five lung cancer deaths versus 3.02 expected and one skin cancer death with 0.15 ex pected. The malignant tumor was a fibrous histiocytoma presumably of dermal origin, which is rare. There were three deaths from neoplasms of lymphatic and hematopoietic tissue with 0.88 expected. There were 17 observed deaths 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. Discussion Because the study cohort was small and only 32 deaths were observed, the results cannot be considered con clusive. Nevertheless, the analysis of the mortality 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 studv 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 years Table 2. -- Cancer Deaths Among aCohort of 121 Males Exposed to Tetrachlorodibenzodioxin in aTrichlorophenol Process Accident. Year of Birth 1909 1910 1911 1922 1915 1920 1919 1907 1910 Year of Hire 1943 1927 1939 1945 1939 1946 1943 1943 1939 Year of Oeath 1962 1970 1964 1973 1970 1978 ^ 1973 1971 1978 Oeath Certificate Statement of Cause of Oeath lung cancer (162.1) Pulmonary carcinoma (162.1) Sronchiogemc carcinoma ( 162.1) 3roncniogentc carcinoma (162.1) lung cancer (162.1) Malignant fiDrous histiocytoma of soft tissue origin (173.9) Hodgkin's disease (201.0) lymonatic leukemia (204 9) Acute myelogenous leukemia (205 0) SmoKing mstory was ootamed oy interviews with former^co-workers of the decedents Journal of Occupational Medicine/Voi. 22. No. 1 /January 1980 Smoking History* Cigarettes Cigarettes Cigarettes NonsmoKer Cigarettes Cigarettes Cigarettes Pipe Cigarettes 13' is longer than that of any previous study, and the followo is complete Therefore, although the cohort is small, it presents the best opportunity so far to study the long term 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. The authors wish to thank Mrs lanet Yung. Mr Randy Picolet. and Mrs Phyllis Korte lor their assistance with the data collection References 1 International Agencv for Research on Cancer IARC Monographs on the Evaluation oi the Carcinogenic Risk of Chemicals to Man Vol 15. Some Fumigants, the Herbicides 2.4-0 and 2.4,5-T. Chlorinated Dibenzodioxms and Miscellaneous Industrial Chemicals Ivon IARC. 1977 2. Kimmig J and Schulz KH. Occupational acne (so-called chloracne) due to the chlorinated aromatic cyclic esters. Dermatologica 115:540- 546. 1957 3. Ashe WF and Suskind RR Reports on chloracne cases. Monsanto Chemical Comoanv. Nitro. West Virginia Reports of the Kettering Laboratory. December 1949 and April 1950. 4. Suskind RR: A clinical and environmental survey. Monsanto Chemical Company. Nitro. West Virginia. Report of the Kettering Laboratory, julv 1953. 5 Suskind RR. Chloracne and associated problems. Report to the Conference of the National Institute of Environmental Health Sciences on Chlorinated Dibenzodioxms and Dibenzofurans. April 3. 1973. b Suskind RR. Chloracne and associated health problems m the manufacture of 2.4.5-T Report to the lomt Conterence. National In stitute of Environmental Health Sciences International Agencv for Research on Cancer. Lvon. France, lanuarv 11. 1q78 7 Young AL. Calcagni JA. Thalken CE. et al The toxicology, en vironmental fate, and human risk associated with herbicide orange and its associated dioxin U S Air Force Occupational and En vironmental Health Laboratory Report OEHL TR 78-92. 8rooks Air Force Base. Texas. 1978 8. International Agency for Research on Cancer Long-term hazards of polychlorinated dibenzodioxms and poivchlormated diben zofurans IARC Internal Technical Report No 78'001. Lvon. 1978 9. Jirasek L. Kalehsky !. and Kubec K. Acne chlonna and porphyria cutanea tarda during the manufacture of herbicides Cesk Dermatol 48.306-317. 1973. 10. Jirasek L. Kalensky J. Kubec K. et al: Acne chlorma. porphyria cutanea tarda, and other manifestations of general poisoning during the manufacture of herbicides. II Cesk Dermatoi 49145-157. 1974 11 Pazderova I. Lukas E. Nemcova M. et al Chronic poisoning by chlorinated hydrocarbons formed in the production of sodium 2.4,5-tnchlorophenoxvacetate Prac Lek 26 332-339. 1974 12. Kociba RJ. Keves DC. Beyer JE. et al. Results of a two-year chronic toxicity and oncogenicity studv of 2.37.8- tetrachiorodibenzop-dioxin in rats Toxicol A ppl Pharmacol 46 279*303. 1978 13. Van Miller IP. Lalich )I. and Allen JR increased incidence of neoplasms in rats exposed to low levels of 2.37.8-tetrachlorodibenzop-dioxin. Chemosphere 6:537-544. 1977. 14 Monson RR: Analysis of relative survival and proportional mor tality. Comput Biomed Res 7:325-332. 1974 15. Eigth Revision. International Classification of Diseases. Adapted for Use in the United States. U.S. Department of Health. Education and Welfare. Public Health Service. PHS Publication No 1693 Washington: U.S Government Printing Office. 1977 Future Risk In the industrial countries we have 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 wav 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. Secondlv. 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 confedera tions of entrepreneurs. The firms and countries that will go bust in these circumstances are those that try to replace hierarchical corporations b y even more ossified forms of hierarchy -- say. by deciding that you mustn't have a boss trying to arrange what free men do with their imaginations, but can have a trade union committee doing so in stead. -- From United Sta te sC an Keep Growing -- And Lead 4- It It Wishe**' bv Norman Mat rat*. ! in Smithsonian. |ul\ 19~b 14 Mortality Experience of Workers Exposed to Tetrachlorodibenzodioxin/Zack and Suskind