Document 0gKVyDY6OoErrgZ4V1RjN4kmJ

Library of C ongress Cataloging in Publication Data Mam enby under fifie* Human and envronmental risks of chlorinated dioxins and related com pounds (Environmental science research; v. 26) Proceedings of an international sym posium on Chlorinated Dioxins and Related Com pounds. held October 2 5 -2 9 . 1981 in Arlington. Va. Includes bibliograonical references and index I.Tetrachlorodibenzodioxm-- Environmental aspects-- C ongresses. 2. Tetrachloro rfijenzodioxin--'Toxicology-- C ongresses. I. Tucker. Richard E. U. Young. Alvin L. Ill Grey. Allan P. IV. Senes. Q H 545.P4H 85 1982 6 6 1 '.8 8 1 5 62-18121 E S N 0-306-41170-9 Proceedings of an international sym posium on Chlorinated Dioxins and Related Compounds, held October 2 5 -2 9 , 198 1 , in Arlington. Virginia 6 1 9 8 3 Plenum Press. New York A Division of Plenum Publishing Corporation 2 3 3 Spnng Street. New York. N.Y. 1 0 0 1 3 A l rights reserved No pari of this book m ay be reproduced, stored in a retrieval system , or transmitted to any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or omerwise. without written perm ission from the Publisher Printed in the United States of America PREFACE Allan M. K - - ;(>-j ElS* ' Increasing international concern is being expressed regarding" the contamination of the environment with polychlorinated dibenzo-pdioxins (PCDDs) and polychlorinated dibenzofurans because certain of these chemicals have been shown to be highly toxic to animals anc are ubiquitous in the environment. They are known to be distributed as contaminants of commercial products and as by-products from com bustion processes. A considerable volume of information has accumulated on these chemicals in the past two decades, particularly for the most toxic of them, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). However, this body of knowledge has not succeeded in resolving genuine judgmental differences among experts in the field as to the degree of hazard to human health and the environment. In light of the widespread public concern, it is clearly imperative to come to grips with the continuing scientific controversy, to review the data assess the issues, to see where areas of agreement exist, and where further research is needed to resolve remaining areas of disagree ment. This volume represents an effort to contribute to these goals. The volume contains the Proceedings from an International Symposium on Chlorinated Dioxins and Related Compounds which was held October 25 to 29, 1981, in Arlington, Virginia. The objectives of the meet ing were to bring together scientists from a wide range of disci plines, all of whom were directly concerned with one aspect or another of the dioxin problem, to review the existing information, evaluate controversial data, present new data, identify areas of agreement, and indicate directions for future research. The 56 papers and panel reports that comprise this volume testify to the success of the Symposium. The meeting was divided into nine sections: Definition of the Problem Analytical Chemistry Environmental Chemistry Animal Toxicology v LINDA KAlli B LE A R S -- T r "*7T. VO. g n tiro* rnf*-k ! St'itnoiU Sk- A MORTALITY STUDY OF WORKERS EMPLOYED AT THE MONSANTO 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 highly toxic impurity that is formed in trace quantities during the production of 2,4,5-trichlorophenoxyacetic acid (2,4t5-T). Exposure to TCDD can cause chloracne, a skin disorder characterized by comedones, cysts, and abscesses.* Outbreaks of chloracne have been reported among workers associated with the production of 2,4.5-T and 2,4,5-T based products. Such incidents resulting from both accidents and routine occupational exposures have been reported from several countries.2 The first reported industrial accident involving exposure to TCDD occurred in 1949 at the Monsanto Company plant in Nitro, West Virginia. A total of 122 employees developed symptoms of chloracne following a trichlorophenol (TCP) process accident. An undetermined number of other employees developed symptoms of chloracne resulting from exposure to the regular operations concerned with 2,4,5-T pro duction over the period 1948-1969. Between 1949 and 1953, Ashe and Suskind^*1* examined thirtyeight Nitro plant employees with chloracne. Twelve of these had developed symptoms of chloracne directly following the 1949 TCP acci dent; twenty-six other chloracne cases had resulted from exposure to the regular 2,4,5-T production operations. In addition to chloracne, other signs and symptoms were observed in this group. These included severe aches in Che lover extremities, fatigue, nervousness and irritability, loss oz decrease of libido, dyspnia, and vertigo. These findings are consistent with those that have been reported in other industrial incidents.5 675 576 J. A .Z A C K A N D W . R GAFFE To examine the chronic health effects of exposure to TCD2, a mortality study of the Nitro plant employees vho had developed symptoms of chloracne following the 1969 TCP accident vas conductt The study cohort vas comprised of 121 of the 122 chloracne cases; one female vho vas living as of the endpoint of the study vas excj from analysis. At the time of the incident, it vas assumed that t symptoms were caused by exposure to unknown products of decocpcsi; From today's vantage point, these symptoms suggest exposure to TCI The 121-member study cohort, with a presumptive high-peak exposure Co TCDD, was followed for mortality through 1978. The entire cchc vas traced: thirty-two deaths were observed and eighty-nine persor 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 plan workers vho were assigned to an area of TCP or 2,4,5-T production, with potential for exposure to TCDD. The mortality of these vorke is examined in the context of the mortality experience of the tota 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 fro the Rubber Service Laboratories and entered the rubber chemicals business. Over the years, the Nitro plant has diversified to vher it now produces agricultural chemicals, paper chemicals, plasticiz fine chemicals, and intermediates, in addition to rubber chemicals The plant is* situated in the Kanawha River Valley, an area contain one of the largest concentrations of chemical production facilitie 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 i". man. Para-aminobiphenyl (PAB), used from 1941 through 1952 for us as a rubber antioxidant and dye Intermediate, vas shown in 1956 by Walpole et al.7 to induce bladder cancer in dogs. In 1955, Melick et al.8 confirmed the carcinogenicity of para-aminobiphenyl to can with the reporting of bladder tumors -among workers exposed to this chemical at two Monsanto plants. Para-aminobiphenyl vas produced ; one plant and then transferred by tank car to the Nitro plant vher additional processing vas carried out. The minimum duration cf exposure reported to have produced a bladder tumor Is 133 days; th< latent period has ranged from 15 to 35 years.9 An intensive scree: ing program vas instituted at Monsanto Company about 1955 to exaai: on a continuing basis, all workers exposed to this chemical. 5eve: deaths from bladder cancer have occurred among Nitro plant employeenrolled in this program. These seven deaths are Included In the present study. MORTALITY STUDY OF WORKERS 577 Other chemicals with known health effects produced at the Nitre plant Include methylparathion and carbon disulfide. The acute effects of exposure to each of these chemicals have been described'*"' while the chronic effects are less well understood. Besides p-aminobiphenyi, several other rubber chemicals are of potential health concern. For all of these, there is insufficient evidence to evaluate their carcin ogenicity to man. Tetramethyl thiuram disulfide is considered an animal carcinogen1* and there is some evidence, although not suffi cient. that N-methyl-N,4-dinitrosaniline is also an animal carcin ogen. 2 For several other rubber chemicals, there is insufficient evidence to evaluate the carcinogenicity to animals. Novever, these chemicals have the potential for forming nitrosamines, certain of which are known animal carcinogens.1J Zinc dimethyl dithiocarbamate. tetramethyl thiuram disulfide and tetramethyl thiuram monosulfide have the potential to form N-nitrosodimethylamine. N-Nitrosomorpholine has been found in product samples of 2-(morpholinothio) benrothiazole and U ,A '-dithiodimorpholine (Frisone, G.J., The General Tire and Rubber Company, unpublished data). Although several of the chemical compounds produced or used at .the Nitro plant over the years have been associated with adverse health effects, no attempt has been made to relate chemical exposure to mortality with the exception of decedents exposed to the TCP or 2,4,5-T operations and potentially exposed to TCDD. As a result, the only specific hypothesis that can be tested is whether a relation ship exists between potential TCDD exposure and proportional mortal ity, especially for malignant neoplasms. The mortality for this group is examined in addition to that of the total Nitro plant worker population. POPULATION AND METHODS A study cohort was developed from the Nitro plant consisting of employees active on or after January 1, 1955 with one or more years of employment on the hourly roll prior to December 31, 1977. Salaried personnel who had never worked on the hourly roll were excluded from study because many of these employees had no appreciable exposure to the plant environment and, for the most part, their exposure cannot be determined from plant records. Females and non-white males were also excluded because of their small numbers. The cohort was assembled using government earnings reports, independent of the plant work history records. Annual earnings reports were available on a computer file from 1951 through 1977. Names and social security numbers were Identified from this source. Work history records were used to supplement the earnings records. Information on race, sex, date of birth, date of hire, date of sepa ration, and, if deceased, 2,4,5-T exposure was abstracted from these records. Ascertainment of 2,4,5-T exposure was confined to decedents only because 1c was too tedious to do for the entire cohort. The 576 J.A.2ACK AND W.R.GAFFEY information from the work history records was used to determine which names identified from the annual earnings records met the cohortentrance 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 benonexposed. The vital status of each member of the study cohort was deter mined using standard follow-up techniques and ascertained as of December 31t 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. 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 (SMR) was calculated for 23 selected cause of death categories. Cause-specific SKR'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 Vno. observed deaths no. expected deaths If the observed SMR differed from 100 by 1.96 standard errors. It was regarded as significant at the 5Z 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-death 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 FMR from 100 was tested by calculating the 95X MORTALITY STUDY OF WORKERS 579 confidence Interval for the PMR for a given cause k according to the formula: confidence interval WCconfidence limits for 2 of observed deaths) for PMR^ " *xpk vhere N number of observed deaths for all causes Both the standardized and proportional mortality analyses vere conducted using the computer program developed by Monson.1-5 Tne 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 vere 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 (822) were verified as living and 163 (182) vere confirmed dead by death certificates. _ . . . .-- ......... Tables 1-3 characterize the total Nitro plant study population by age at hire, year of hire, and length of employment. The dis tribution 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 (75.32) were hired during the period 1940-1959, while smaller percentages of workers vere hired prior to 1940 (10.82) and after 1960 (13.92). ' 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 Che 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 vere 35 deaths from malignant neoplasms with 30.92 expected, yielding a SMR of 113. Singificantly elevated SMR's vere seen for the categories of malignant 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 bladder cancer deaths is reflected in the elevated SHR for malignant nioplasms 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 660 J. A. Z A C K A N D 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 122 518 191 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 Deathf Standardized Mortality Ratios (SMR'S) t Cause .of Death All causes of death. All malignant neoplasms Buccal cavity and pharynx Digestive organs and peritoneum Stomach Liver All other digestive organa Respiratory system Lung All other respiratory organs Skin Genitourinary organa Bladder All other genitourinary organs Lymphatic and hematopoietic tissue Other sites D1 seases of the nervous system and sense organa Diseases of the circulatory system Arteriosclerotic heart disease, including CHD All other diseases of the circulatory system Diseases of the respiratory system Diseases of the digestive system All other diseases External causes of death Number nt risk: BH4 Person-years nt risk: 1396B.7 * / nu .'I Y MORTALITY STUDY OF WORKERS 1 During 1955-1977 by Cause Shoving for Total Nitro riant Study Population 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 -- 460t519 520-577 -- 800-998 163 35 0 4 1 0 3 14 14 0 0 12 9 3 1 4 0 92 79 13 6 5 5 20 158.10 30.92 1.03 8.65 1.63 0.60 6.42 10.51 - 9.91 0.60 0.58 3.75 0.91 2.84 3.15 3.25 1.28 82.59 59.40 23.19 9.13 -8.03 10.46 15.69 SHR 103 113 0 46 61 0 47 133 141 0 0 320* 989* 106 32 123 0 111 133* 56* 66 62 48* 127 v 61 662 J. A. Z A C K A N D W. R. GAFFE ocher clrculacory diseases was significantly low at 56. A slgnifi deficit was also seen for the category of all ocher diseases where SHR was 48 with 5 deaths observed and 10*46 expected. Trends for malignant neoplasm deaths with calendar time are s\ In Table 5. SKR's which increased consistently over the period 15; 1977 are seen for the categories of all malignant neoplasms and cal nant neoplasms of the respiratory system. The SMR for all maligr.ar neoplasms rose from 32 to 131. The SHR for malignant neoplasms o: respiratory system rose from 0 to 172 reflecting a SMR for lung car. which increased from 0 to 181. Although based on very snail number the SMR for malignant neoplasms of the digestive organs and peritcr consistently decreased over time from 99 to 24. The SMR for malign neoplasms of the genitourinary organs peaked during the period 1950 1969. This is reflected in the SMR for bladder cancer which increa 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 net plasms by age at death revealed little in terms of consistent treed; 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 increas; age. Bladder cancer is one category where the SHR remained high at age 65 and over. The distribution of deaths from malignant neoplasms by year cf hire is shown in Table 7. No deaths from malignant neoplasms were observed among workers hired after 1960. The SMR for all malignart neoplasms was similar for chose 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 occur with bladder cancer. The SMR for bladder cancer is highest for tins 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 (35.62 were considered to be exposed to 2,4,5-T based on their work histcryrecords, while 104 (63.82) 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 thes 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 MORTALITY STUDY OF WORKERS ; Table 5. Observed and Expected Deaths from Malignant Neoplasms During 1955-1977 by Calendar Time Showing Standardized Mortality Ratios (SMR'S) for Total Nltro Plant Study Population Cause of Death Calendar Time 1955-1959 i 1960-1969 1970-1977 Observed Expected SMR Observed Expected SHR Observed Expected SHR 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 organa 0 Lymphatic and hematopoietic 0 tissue Other sites 0 *p < .05 3.13 0.11 1.01 0.25 0.09 0.67 0.07 0.80 0.07 0.07 0.33 0.09 0.24 0.40 0.34 32 13 00 99 2 0 :0 0 i0 149 2 04 0 ;4 0 :0 00 0 ;s 05 00 0 '0 0 !2 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 21 0 1 1 0 0 10 10 0 0 7 4 3 1 1.25 160 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 Table 6 I I Observed and Expected Deaths from Malignant Neoplasms During 1955-1977 by Age at Death Shoving Standardized Mortality Ratios (SMR'S) for Total Nltro Plant Study Population oi os Cause of Death Age at Death <45 45-64 65+ Observed Expected SMR Observed Expected SMR Observed Expected SMR All malignant neoplasms 2 Buccal cavity and pharynx 0 Digestive organs and peritoneum 0 Stomach 0 Liver 0 Ail other digestive organs 0 Respiratory system 0 Lung 0 All other respiratory organa 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 ,21 0 1o 04 0 ;i 0 10 0 13 0; n 0 , ;n 0 10 0 \ :o 500 ; 3 5000 : 2 01 0 !1 250 !1 2 16.85 0.67 4.58 0.85 0.32 3.41 6.36 5.99 0.37 0.31 1.43 0.39 1.04 1.60 125 0 87 118 0 80 173 184 0 0 210 513 96 63 1.90 105 12 0 0 0 0 0 3 3 0 0 8 6 2 0 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* 123 0 0.94 106 i. > N > O X > z o $ mu !I MORTALITY STUDY OF WORKERS Table 7. I li I Observed and Expected Deaths from Malignant Neoplasms During 1955-1977 by Tear of Hire Showing Standardized Mortality Ratios (SMR'S) for Total Nltro 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 organa 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 43 160 169 0 0 310* 1111* 46 51 2,03 148 10 0 2 1 :0 1 4 '4 io :o ^3 1 :2 .0 1 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 During1955-1977 Among Total Nltro Plant Study Population 2,4,5-T Exposure Classification Number of Deaths Percent Exposed Non-exposed Unknown Total 5B : 104 1 163 35.6 63.8 0.6 100.0 685 I I Table 9. Observed and Expected Humber of Deaths During 1955-1977 by Cause and 2,4,5-T .Exposure Category Showing Proportional Mortality Rntios (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 organa Respiratory system Lung All other respiratory organs Skin Genitourinary 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 CHD 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 ; 10.94 o i 0.38 0 : 2.80 0 0.52 0 0.19 2.09 6 . 3.78 6 3.57 0 0.21 0 0.29 2 0.96 2 0.22 0 0.74 1.35 1\ 1.38 o 0.61 31 26.4B 27 19.72 4 6.76 2 2.67 1 3.70 3 4.31 12 9.29 58 . 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 M n> x z o CT *>n mn -< MORTALITY STUDY OF WORKERS 587 0.22 expected. PMR's 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 PKR'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 in Table 10. Table 11 listed the cancer deaths among the non-exposed group. DISCUSSION* The observation made many years ago of an apparent excess in bladder cancer among Nltro plant workers was confirmed and quantified in the mortality analysis of the total Nitro plant population presented here. The SMR for bladder cancer was 989 and was the only statisti cally significant SMR among those for malignant neoplasms. Tne excess In mortality is not seen until 1960. The SMR peaked in the 1960's and declined somewhat in the 1970*s. The excess also appeared to be clustered in those decedents aged 65 years and older at death and in those hired prior to 1945. This would suggest that we should see a further decline in the SMR for bladder cancer over time. Although not statistically significant, the SMR for lung cancer appears to be elevated. The SMR increased with calendar time and was highest in those hired prior to 1945. The elevation appears to be clustered in those aged 45-64 years of age at death (SMR 184) and does not show a gradient with. age. Further analyses to evaluate trends in lung cancer deaths as they relate to occupation cannot be carried out due to limitations In the data collected in this study. The SMR for diseases of the circulatory system was elevated at 111. This is most likely a reflection of the higher mortality from heart disease which has been observed for Charleston, Vest Virginia and Kanawha County, Vest Virginia (unpublished data, Neas LM, 1979 and Enterline PE, 1979). For the total Micro plant study population, there vas a statistically significant excess in deaths from arterio sclerotic heart disease and a deficit in deaths from otheT circulatory diseases. This variation in the distribution of deaths from that of the U.S. may be due to risk factor or medical care differences in the plant population and the local area. These may include differences In smoking habits, the availability and use of medical services and the specificity of diagnoses. The proportional mortality analysis of decedents by 2,4,5-T .exposure classification Indicated no unusual patterns of mortsliry In the 2,4,5-T exposed. The proportional mortality ratio (PMR for malignant neoplasms was low (PMR 82) in the exposed group. Lung cancer vas the only site among the malignant neoplasms which vas somewhat higher in the exposed group. J 588 J. A. ZACK A N D W. R. GAFFE Table 10. Deaths Due to Mallgnhnt Neoplasms Among Nitro Plant Workers Exposed to 2,6 5-T Year of Birth Year of Hire Year of 1st Exposure Year of Term. 1 Year of Death Smoking History* Cause of Death as Clven on Death Certificate 1917 1966 1951 1972 1972 Ci gnret tea Carcinoma left lung with mtastass (162.1) 1911 1968 1955 1972 1972 Cigarettes Metastatic carcinoma of the lung (162.1) 1916 1966 1959 1968 1968 1 Ci garettes Bronchiogenic carcinoma of 1 right upper lobe (162.1) 1901 1911 1922 1966 1961 1965 1956 1968 1968 1963 1971 1972 1973 ! 1 ;1 1975 !1 Cigarettes Cigarettes . 1i 1973'1 Non-smoker Corclnoma lung with mtastass (162.1) Bronchiogenic carcinoma with cerebral metastoses (162.1) Bronchiogenic carcinoma with mtastass (162.1) 1923 1966 1950 1972 1972 ; Cigarettes Cenerai lied llpoaarcoma (171.9) 1902 1910 1922 1966 1968 1968 1966 1968 1966 i Non-smoker ! i 1968 Non-smoker 1 * Obtained by interview with former coworkera of decedents. ** Included on the Nitro plant PAB roster. 1 Metastatic carcinoma urinary bladder (188.0)** Carcinoma of the urinary bladder (188.0)** MORTALITY STUDY OF WORKERS I Table 11. Deaths Due to Malignant Neoplasms Among Nltro Plant Workers Not Exposed to 2,4,5-T Year of Year of Year of Year of Smoking Birth Hire Termln. Death History* Cause of Death as Given on Death Certificate 1911 190V 1099 1905 1909 1910 1912 1915 1915 1894 1912 1919 1901 1897 1898 1905 1698 1888 1905 1906 1925 1945 1935 1929 1944 1943 1927 1944 1937 1939 1944 1937 1946 1933 1941 1933 1943 1943 1944 1933 1946 1945 1966 1957 1959 1970 1962 .1966 1965 1977 1969 1960 1973 1963 1962 1962 1962 1971 1963 1956 1969 1968 1973 1968 Cigarettes Carcinoma of colon (153.8) 1957 Cigarettes Carcinoma of liver (157.9) 1960 Pipe lntraperltoneal carcinoma (158.9) 1972 Cigarettes Carcinoma of lung (162.1) 1962 Cigarettes Carcinoma of left lung (162.1) 1970 Cigarettes Pulmonary carcinoma (162.1) 1965 Cigarettes Carcinoma of apex of right lung (162.1) 1977 Cigarettes Carcinoma of lung (162.1) 1970 Cigarettes Carcinoma of lungs (162.1)' 1964 Non-smoker Carcinoma of lung (162.1) 1974 Clgarettes Carcinoma of lung (162.1) 1964 Cigarettes Carcinoma of urinary bladder (188.0)** 1977 Cigarettes Carcinoma of bladder (188.0)** 1965 Cigarettes Carcinoma of urinary bladder (180.0)** 1965 Smoked years ago Carcinoma of urinary bladder (18B.0)** 1975 Cigarettes Carcinoma of bladder (186.0) 1970 Cigarettes Bladder tumor (188.0)** 1970 Unknown Carcinoma of bladder (168.0) 1977 Cigars Prostatic carcinoma (185.0) 1977 Cigarettes Carcinoma of prostate (185.0) 1974 Smoked years ago Carcinoma of prostate (185.0) 1919 1901 1901 '922 1943 1941 1943 1944 1972 1964 1966 1964 1973 1965 1977 1964 Cigarettes Cigars Cigarettes Cigarettes Hodgkin's Disease (201.0) Osteosarcoma arising from left arm (170.4) Carcinoma of liver 6 pancreas (197.8) Adenocarcinoma (199.0) * Obtained by Interview with former coworkers of decedents. ** Included on the Nltro plant PAB roster. 6B9 690 J. A. ZACK AND W. R. GAFFi The FMR analysis Is Un i t e d In that an assessnent of the tots force of mortality cannot be made. The cause-specific PMR's only approximate what an SMR analysis would have produced.16 The FMR analysis presented here estimates the cause-specific risks associe with 2,4,5-T exposure and potential TCDD exposure. It is interesting to compare the results of this study of Nit plant workers potentially exposed to TCDD with the results of the study of Nitro workers involved in the 1949 TCP accident. The wor Involved in that incident had presumed TCDD exposure as evidenced chloracne. The results of the two studies are similar in that nei shows an excess in deaths from any site among malignant neoplasms. A recent study of Oct et al.17 found no excess in total corta or in deaths from malignant neoplasms among workers exposed to 2,3 These workers were probably exposed to very low levels of TCDD sin no cases of chloracne were observed. Other studies of workers who developed chloracne resulting from TCDD exposure have been conduct and have been reviewed.6 At the present time, data from these var studies do not constitute corroborative evidence of a cancer risk nan for any particular-cancer site. ------- ;-------- ----- ------ REFERENCES 1. Creig, J.B.: The toxicology of 2,3,7,8-tetrachlorodibenzo-pdloxin and its structural analogues. Ann. Occup. Hvg. 22: 411-420, 1979. 2. International Agency for Research on Cancer: Long-term hazard of polychlorinated dibenzodioxins and polychlorinated dibenz furans. 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 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 work exposed to tetrachlorodibenzodioxin in trichlorophenol proce accident. J. Occup. 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. Industr, Med. 11:105-109, 1954. MORTALITY STUDY OF WORKERS 591 8. Helick, W.F.: First reported cases of human bladder tumors due to a new carcinogen - xenylamlne. J. Urol. 74:760-766, 1955 9. Helick, V.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.H.: Ocuppational Diseases: A Guide to Their Recocniticn. U. S. Department of Health, Education and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health. DHEW (KIOSH) 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 Han. !I Vol. 12. Some Carbamates, Thiocarbamates, and Carbaziaes. Lyon: IARC, 1971. ii 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 *i for Use in the United States. U.S. Department of Health, Ed ucation, and Welfare, Public Health Service, PHS Publication No. 1693. 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