Document LKn06d24avxgkXz90QBERdLX3

Increasing internacional concern is being expressed regarding Che contamination of che environment with polychlorinated dibenzo-pdioxins (PCDDs) and polychlorinaced dibenzofurans because certain of these chemicals have been shown to be highly toxic co animals and are ubiquirous in the environment They are known co be distributed as contaminants of comercial 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 mast toxic of them, 2,3,7,8-cetrachlorodibenzo-p-diaxin (2,3,7,8-TCDD). However, chis body of knowledge has noc succeeded in resolving genuine judgmental differences among experts in the field as to the degree of hazard co human health and the environment. In light of the widespread public concern, it is clearly imperative to cone to grips vich the continuing scientific controversy, to review the data, assess the issues, co 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 CulcvirwiZF : D; oxius .nd- related Compounds which was held October 25 to 29, 1981, in Arlington, Virginia. The objectives of the meet ing were co bring together scientists from a vide range of disci plines, all of whom were directly concerned vith 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 5 papers and panel reports chat comprise chis volume testify to the success of the Symposium. The meeting vas divided into nine sections; Definition of the Problem Analytical Chemistry Environmental Chemistry Animal Toxicology v LINDA N.ML OSSAK5 .T- c tP A H0R7AL1 TY STUDY OF, UORXERS EMPLOYED AT THE MONSANTO COMPANY PLANT IN NITRO, VIST VIRGINIA Judith A. Zack and Villiaa, R. Caffey Monsanto Company Sc. Louis, Missouri USA j BACKGROUND II | I | j r* The compound 2,3,7,3-tetrachlorodibenzo-- p-dioxiu (TCDD) is a highly toxic impurity chat is formed in trace quantities during*the production of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Exposure to TCDD can cause chloracne, a skin disorder characterised by comedones, cysts, and abscesses.1 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 accidental and routine occupational exposures have been reported from several countries.2 j The first reported industrial accident involving exposure to TCDD occurred in 1949 at the Monsanto Company plant in Nitro, West lir^inia. A total of =12?. employees developed symptoms of cnloracne following a crichlorophenol (TC?) 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. : { ! " I* I 1 I Between 1949 and 1953, Ashe and Suskind3 *1* examined thirty-- eighc. N i c m plant employees .v'ch chloracne-. Twelve of these had developed, symptoms of -hloracne directly following the 1949 TCF acci--dent; twentyrsi* ocher chloracne cases had resulted from exposure to -the tegular 2,4,5-T production operations. In addition to chloracne. other signs and.symptoms-were observed in this group. These included severe aches in the lower extremities, fatigue,' nervousness and irritability, loss or decrease of libido, dyspnia, and vertigo. These findings are consistent with those that have been reported in other industrial incidents.5 575 \\ \'l\ 1 3 V 5 ^ 576 J. A. ZACK AND W. a. G A fFY To exanine che chronic health effects of exposure co TCDD, a Eorcalicy study of che Micro plane employees who had developed symptoms of chloracne following'the 1949 TCP accident vas conducted. The study cohort was comprised of 121 of the 122 chloracne cases; one female vho was living as of the endpoint of che study '-as e n d u e from analysis. At the time or the incident it was assumed that the symptoms were caused by exposure to unknown products of deconpesicic 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 cohor: was traced: thircy-cwo 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 Micro plant 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 workers is examined in the context of che 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 Micro plant fren che 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, plasticize: fine chemicals, and intermediates, in addition to rubber chemicals. The plant is- situated in the Kanawha River Valley, an. area containi: one of the largest concentrations of chemical, production facilities * in the United States. . . . Of. Che many chemicals used over the years at the Nitro plant, one has an established association with che occurrence of cancer ic man. Para-aminobiphenyl (PAS) , used from 1941 through 1952 for use as a rubber antioxidant and dye Intermediate, was shown in 1954 by Valpole et al. 7 co induce bladder cancer in dogs. In 1955, Helick et al.8 confirmed the carcinogenicity of para-aminobiphenyl to can with che reporting of bladder tumors among workers exposed to this chemical, at two Monsanto plants. Para-aminobiphenyl was produced a* one plane*and then transferred by tank car to the Micro 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. An intensive screen lug program was instituted at Monsanto Company about 1955 co exacin on a continuing basis, all workers exposed to this chemical. Seven deaths from bladder cancer have occurred among Nitro plant employee enrolled In this program. These seven deaths are Included in che present study. L< MORTALITY STUDY OF WORKERS 577 Other chemicals wich known health effects produced at the N'itro plant include mechyIparathion 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-aminobiphenvi, several other rubber chemicals are of potential health concern. Tor all of these, there is insufficient evidence co evaluate their carcin ogenicity to can. Tetramethyl thiuraa disulfide is considered an | anical carcinogen** and there is soce evidence, although not suffi cient. that b'-raethy 1-N ,4-dinitrosaniline is also an animal carcin ogen.** Tor several other rubber chemicals, there is insufficient l i evidence to evaluate the carcinogenicity to anicals. however, these I chemicals have the potential for forcing nicrosamines, certain of l which are known anima.1 carcinogens.1'* Zinc dimethyl dichiocarbamate. tetranethyl chiurac disulfide and tetramerhyl thiuram monosulfide li have the potential co form N-nitrosodiuethylaciine. N-Nicrosomorphc-- line has been found in product samples of 2 - (corpholinochio) ben- zothiaxole and 4,4'-dichiodinorpholine (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 atteepe has been cade co relate chemical exposure i to mortality with che 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 chat can be tested is whether a relation l ship exists between pocential TCDD exposure and proportional mortal ity, especially for malignant neoplasms. The eortalicy for this group is examined in addition to that of the total Micro plant vorker population. c POPULATION AND METHODS A study cohort was developed from the Micro plant consisting of employees active on. or after January. 1, 1?55 with one :-'i. 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 co the plant environment and, for,che most part, their exposure cannot be determined from plant records. Females and non-white males were also excluded because of their small numbers. The-cohere 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, dace of sepa ration, and, if deceased, 2,4,5-T exposure vaa abstracted from these records. Ascertainment of 2,4,5-T exposure was confined to decedents only because it was too tedious to do for the entire cohort. The i I 57S J. A. Z A C K A N D W. R. GAFFEY information from the work hiscory records was used to determine which naoes identified from the annual earnings records net the cohort entrance criteria. Employees identified fron the earnings records who terminated prior to 1955 were'not included in this scudv because work hiscory records for all such eaployees 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 che potential for exposure to 2,4,5-7 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 osologist for the underlying cause of death, according to the rules of the Eighth Revision of the International Classification of Diseases, Adapted.1u Data for che total Hltro 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 j cause-specific mortality rates for the U.S. general population are ? applied to the person-years lived classified by age, race, and time. 1 A standardized mortality ratio (S>R) was calculated for 23 selected , cause of death categories. Cause-specific SKR's for 15 selected j cancer sices were calculated for subgroups or the total ilicro plant j study population defined by date of death, age at death, and year of j hire.- The statistical significance of the deviation in a SMR from 100 was tested using the formula: ; i-.- - v.rd eiror ofjSMR * 1QU~`Vnc. "observed deaths no. expected deaths If the observed SKR differed from 100 by 1.96 standard errors, it was regarded as significant `at the 52 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 (FMR) -was calculated for 23 selected cause-of-death categories. FMR'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 PKR from 100 was tested by calculating the 952 l mortality study of WORKERS 579 confidence interval for the ?MR for a given cause It according to the formula: confidence interval _ KCconflder.ce U n i t s for 2 of observed deaths) for PMR^ " expfc vhere K " number of observed deaths for all causes Both the standardized and proportional mortality analyses were conducted using the computer program developed by Mor.son.*3 The observed mortality was compared to that of the United States white male population far 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 far all deaths. Seven hundred tvency-ane (82") were verified as living and 163 *(152) were confirmed dead by death certificates. _ .. .......... ... . Tables 1-3 characterize the total Kicro 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. Hone 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 I period 1940-1959, while smaller percentages of workers were hired prior to 1940 (10.82) and after 1960 (13.92). '; .An eM-.ainati or. oy the study population by 'tngth of emplc/.r "7 ? Indicates a fairly even distribution over the intervals less chan 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 Nicro plant study population are shown by cause in Table 4. The SMR for all causes of death was 103 with 163 deaths observed and 15B.10 expected. There were 35 deaths from malignant reoplasms vith 30.92 e.xpeeced, yielding a SMS. o.^ 113. Singifleantly elevated SMR.fs were seen for the categories of malignant neoplasms of the genitourinary organs and of the bladder. The SMR for bladder cancer v u 989 with 9 deaths observed and 0.91 expected. This excess in bladder cancer deaths is reflected in the elevated 5HR 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 5HR for 580 J. A. ZACK AND W. R. GAFFEY Table 1. Distribution of Total Nitro Plant Study Population by Age at Hire Aie at Hire Nu-ber Percent . <20 20-29 30-- 39 AO-69 50+ . Total 122 518 191 53 0 884 13.8 58.6 21.6 6.0 0.0 100.0 Tabla 2. Distribution of Total Nitro Plant Study Population " b y Year of Hire Year of Hire N naher 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 Eoployment Length of Eaployaenc (yrs.) Nuaber Percent .,, <10 10-19 20-29 30+ Total 225 213 204 242 884 25.5 24.1 23.1 27.4 100.1 *( l V'' MORTALITY STUDY OF WORKERS --- i ... ____ / Table 4* Observed and Expo Ced Number of Death During 1953-1977 by Cauac Showing Standardized Mortality Ratios (SMR'S) for Total Nltro Plant Study Population 1 ICDA Codes Cause of Death > Otli Rev. Observed Expected SHR t All causes of death. 163 158,10 103 All malignant neoplasms Buccal Cavity and pharynx Digestive organs and peritoneum Stomach Liver AIL other digestive organs Respiratory syBfem Lung All other respiratory organa Skin Ccnltourlnary organs Bladder All other genitourinary organs Lymphatic and hematopoietic tissue Other slteo ' T 140-209 140-149 150-159 151 155-156 -- 160-163 162-163 -- 172-173 185-169 188 -- 200-209 --- 35 30.92 113 0 1.03 0 4 8.65 46 1 1.63 61 0 0.60 0 3 6.42 47 14 10.51 133 14 9.91 161 0 0.60 0 0 0.50 0 12 3.75 320* 9 0.91 989* 3 2.84 106 1 3.15 32 4 3.25 123 Diseases of the nervous system and sense' organa 320-309 0 1.28 ' 0 Diseases of the circulatory system Arteriosclerotic heart disease) including CUD ' All utlier diseases of the circulatory system 390-458 410-413 --- 92 82.59 111 79 59.40 133* U 23.19 56* Diseases of the respiratory system 460-519 6 9.13 66 Diseases of the digestive system All other diseased External causes of death Number at rink: 804 Person-years at risk: 13960.7 1 *P < .05 520-577 -- 000-990 a 5 8.03 62 5 10.46 48* 20 15,_69,, 12 7 582 J. A. ZAC X A N D W. R. GAFFEY other circulatory diseases was significantly low at 56. A significant deficit was also seen for the category of all other diseases wh e r e che SKR was 8 with 5 deaths observed and 10.46 expected. Trends for malignant neoplasia deaths with calendar ti.ne are shewn in Table 5. SKR's which increased consistently over the period 19551977 are seen for the categories of all-malignant neoplasms and malig nant neoplasms of che respiratory system. The SMR for all malignant neoplasms rase from 32 to 131. The Shit for malignant neoplasms of che respiratory system rose from 0 to 172 reflecting a SMR for lung cancer which increased from 0 to 1B1. 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 SMS for malignant neoplasms of the genitourinary organs peaked during the period 19601969. This is reflected in che SMS 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 cost of che cause-- of-death categories, the SHS peaked at age 45-64 rather than continuing to rise with increasing age. Bladder cancer is one category where the SMS 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 chose hired prior to 1945 and for chose 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 highesc for those hired' prior to 1945 with a SMS. 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, 5B (35.62) were considered to be exposed to 2,4,5-T based on their work history records, while 104 (63.82) were considered to be noa-exposed. The exposure of one decedent was unkown. The results of the .preporciunal.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 che non-exposed group (FKR: 82 vs. 122). The ?MR for lung cancer deaths is slightly higher in the exposed group (FKR: 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 m '*$3 MORTALITY STUDY OF WORKERS \ O J i t Tab! 5* Observed and Expected Deaths from Malignant Neoplasms During 1955-1977 by Calendar Time Showlpg Standardized Mortality Ratios (SHR' S) for Total NLtro riant Study P o p u la t io n Cause of Death Calendar Time 1955-1959 : 1960-1969 1970-1977 Observed Expected SMR Observed Expected. SMR Obncrved Expected SMR All nallgnsnt neoplasms 1 Buccal covi:y 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 0.11 1.01 0,25 0.09 0.67 0.1)7 0.00 0.07 0.07 0.33 0.09 0.2*. O.'tO 0.3/. 32 13 11.01 ' n o 21 . 15.90 131 00 0.41 0 0 0.50 0 99 2 3.48 57 1 4. 16 24 0 *0 0.70 0 1 0.69 145 0 i0 0.20 0 0 0.23 0 149 2 2.50 00 0 3.24 0 04 3.03 104 10 5.01 172 0 !4 .3,59 111 10 5.52 101 0 : 0 ' 0.24 0 0 0.29 0 00 0.23 0 0 0.20 0 0 !5 05 0 0 1.37. 365 0.34 1471'k 1.03 0 7 4 3 2.05 0.4 0 1.5 7 341 033 m 0 0 1 1.24 0 l 1.50 67 0 !2 1.25 160 2 1.60 119 s 583 * 5 5 4 J. A. ZAOC AND W. H. GAFFEY I Table 6. Observed end Expected Deaths from Malignant Neoplasms During 1955-1977 by Age at Death Shoving Standardized Hortaltty Ratios (SMR'S) for Total Mltro Plant Study Population Cause of Death i : Age at Death <45 45-64 65+ Observed Expected SHR Oboerved Expcc ted SUR Observed Expcc ted SHR All malignant neoplasms 2 Buccal cavity and pharynx 0 Digestive organs and peritoneum 0 Stomach ` 0 Liver 0 All other'digestiva organa 0 Respiratory ay^tea 0 Lung 0 All other respiratory organi 0 Skin 0 Genitourinary organs 1 Bladder 1 All other genitourinary organs 0 Lymphatic and hematopoietic 0 tlosue Other altea 1 *p < .05 2.39 0.06 0.51 0.10 0.03 0.30 0.54 0.51 0.03 0.13 0.20 0.02 0.10 0.55 0.40 64 ..21 0 io 04 0 '1 0 1o 0 !3 0 : 11 0 , ;a 0 10 0 500 5000 0 :o *i 3 :2 .l 0 !l 250 i * 1 16.05 0.67 4.5B 0,85 0.32 3.4L 6.36 5.99 0.37 0.31 1.43 0.39 1.04 1.60 125 0 07 110 0 00 173 104 0 0 210 513 96 63 12 . 0 0 0 0 .0 3 3 0 0 0 6 2 0 11.69 0.31 3.57 0.60 0.2 4 2.65 3.61 3.42 0.19 0.14 2.12 0 i50 1.62 1.00 103 0 0 0 0 0 63 00 0 0 377* 1200* 123 0 1.90 105 1 0.94 106 i i t MORTALITY STUDY OF WORKERS / I Tabi* 7. Obaeirved and Expected Deaths from Malignant Neoplasms Dufing 1955-1977 by Year of Hire Showing Standardized Mortality Ratios (SMR'S) for Total Nitro Plant Study Population Cause of Death Observed Expected SMR Observed Expected SHK Observed Expected SHR All malignant neoplasms 25 Buccal cavity and pharynx 0 Dlgoatlve organa 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 organa 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 2.03 117 32 0 0 43 140 149 0 0 310* 1111* 46 51 146 10 .0 2 ;1 .0 11 4 :4 10 !0 ;3 1 2 ;0 1 ;i i 8.63 0.31 2.19 0.39 0.14 1.66 3.09 2.93 0.16 0.22 0.76 O.l 0.50 1.00 116 0 9L 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 0.00 0.20 0.16 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Table 0. 2,4,5-T Exposure Classification for Decendents During i 1955-1977 Among Total Nitro Plant Study !Population 2,4,5-T Exposure Classification Exposed Non-cxposed Unknown Total Number of Dea ths : 58 104 1 163 Percent 35.6 63.0 0.6 1(H) . 0 535 1 i ! i i "i ' Table' 9a Observed and Expected Number of Deaths During 1955-1977 by Cause and _ 2,4,5-T Exposure Category Showing Proportional Mortality Rntloa (PMR'S) Cause of Death * All malignant nAoplaams Buccal cavity and pharynx Digestive organs and peritoneum Stomach Liver All other digestive organs Respiratory system Lung All other respiratory organs Skin Cenltourinary organs Bladder All othef'genitourinary organa Lymphatic And hematopoietic tissue Other sites Diseases of the nervoua system and sense organs Diseases o f the circulatory'aystera Arteriosclerotic heart disease, Including CUD All other diseases of tho cii.>latory system Diseases of the respiratory system Diseases of the digestive system** All other diseases External causes of death Total number of deaths; *p < ,05 2,4,5-T Exposure Category Exposed Mon-exposed Observed Expected PH0 Observed Expected PHR 9 o 0 0 0 0 6 6 0 0 2 2* 0' o 1, o 31 27 4 2 1 3 12 50 10.94 02 0.30 0 2.00 0 0.52 0 0.19 0 2.09 0 3.70 159 3.57 160 0.21 * 0 0.29 0 0.96 200 0.22 909 '0.74 0 1.35 0 1.30 0.61 72 0 26.40 117 19.72 137 6. 76 59 2.67 75 . 3.70 27 4.31 70 9.29 129 50.00 25 20.43 122 0 0.64 0 3 5. 74 52 0 1.06 0 0 0.39 0 3 4.29 70 0 6.01 117 8 6.42 125 o - 0.39 0 0 0. 35 0 10 2. 70 370* 7 0.65 107 7* 3 2,05 146 1 2,07 40 3 2.12 142 0 0.03 0 61 55. 34 110 52 39.60 131* 9 15.66 37 4 6.49 62 4 4.93 01 2 6.70 30 0 9.20 06 104 104.00 586 J. A. ZACK A N D W, R. GAFFEY mortality stuoy of w orkers 587 i 0,22 expected. PMR's for both exposure groups are quite sinilar for ! diseases of circulatory and respiratory system. 5Iight differences [ appear in the PMR's between the two groups for diseases of the digesi rive system and all ocher diseases.. Kovever, the PMR's for both I groups are quite low. The PMR for external causes of death is slightly higher in the exposed group (PhS: 129 vs. 86). j A listing of the cancer deaths-among the 2,4,5-T exposed is given 1 in Table 10.Table 11 listed thecancer deaths anong the nan-exposed i group. I' } DISCUSSION ! The observation cade cany years ago of an apparent excess in bladder cancer acong Nitro plant workers was confirmed and quantified \ . in the mortalityaanalysis of the total Nitro plant population presented here. The SMR for bladder cancer was 989 and was the only statisti cally significant SMR among chose for malignant neoplasms,. The excess ! in mortality is net seen until 1960. The SbCR peaked in the 1960's and declined socewhat in-the 1970's. The excess also appeared to be [ ___ clustered in chose decedents aged 65 years and older at death and in those hired prior to 1945. This would suggest that we should see a { further declinein the S>iRfor bladdercancer over time, i ; Although not statistically significant, the SMR for lung cancer | appears to be elevated. The 5KR Increased with calendar time and was t highest in those hired prior to 1945.- The elevation appears to be | clustered in those aged 45-64 years of age at death (SMR 134) and j does not show a gradient with age. Further analyses to evaluate ; trends ^in lung cancer deaths as they relate to occupation cannot be j carried out due to limitations in the data collected in this study. ; The SMR for diseases of the circulatory system was elevated at 0 . 111. This is most likely a reflection of the higher mortality from .. .r : ->* h^.xrc. dii*--ase which ..has been observed for ^Charleston,-Vest Virginia . and Kanawha County. Vest Virginia (unpublished data, Keas LM, 1979 and * Enterline PE, 1979). For the total Nitro plant study population, there was a statistically significant excess in deaths from arterio sclerotic heart disease and a deficit in deaths from ocher circulatory diseases. This variation in the distribution of deaths from that of ! the U.5. 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 us? of medical'.services and i Che specificity,of diagnoses. * The proportional mortality analysis of decedents by 2,4,5-T exposure classification indicated no unusual patterns of mortality in the 2,4,5-T exposed. The proportional mortality ratio (PMR for malignant neoplasms was low (FMR - 32) in the exposed group. Lung cancer was the only sice among the malignant neoplasms which was acarwhat higher in Che exposed group. f' k I I. i i Table 10 Dentha Due Co Kallgnhnt Neoplasms Among Micro Plane Workers Expoaed to 2,4,5-T 5B3 J. A. 2ADC A N D W. R. GAFFE Year of Year of Birth . Hire / Yearybf lot Year of Year of Smoking Cause of Death aa Given on Exposure Terra. Death* lllatorv* Death Certificate 1917 1946 ltei 1972 1972 : Clgarettee Carcinoma left lung with 1 mtastass (162. 1) 1911 1946 *19*35 1972 1972 ! Clgarct tea Metastatic carcinoma of the lung (162.1) 1916 1946 , 1959 1966 I960 j Cigarettes Broncliiogenic carcinoma of i right upper lobe (162.1) 1901 1911 1922 1944 1941 1945 1956 1948 13 iC 1963 1971 1972 1973 I Clgarct tea Carcinoma lung with .1 'j mtastases (162. 1) 1975 1! Cigarettes Broncliiogenic carcinoma with cerebral metastancs .* *1 i (162.1) Non-omoker -Broncliiogenic carcinoma li73\i with mcLasta9es (162,1) 1923 1946 * 1902 922 1910 * 1944 _______ 1950 1948. 19B 1972 *1966 I960 1972 ; Cigarettes 1. 1966 j Non-smoker I I960 Non-smoker I Generalized llposarcoma (171.9) Metastatic carcinoma urlnnry bladder (100.0)A* Carcinoma of the urinary bladder (100.0)** * Obtained by Interview with.former coworkera of decedents. ** Included on Che Nltro plcnt PAB rooter* j -- _ --------------- :------- -- ---------------- ------- ------------------: ^ < m o r ta lity s t u d y o f w o r k er s 1 Table lit Deaths Duo to Malignant Neoplaomo Among Nltro Plant Workers Not Exposed to 2,4,5-T Year of Year of Year of Year of Smoking Birth lire Termtn. Death History* Cause of Death as Given on Death Certificate 1911 1945 1904 . / 1935 1966 1957 196B 1957 Cigarettes Cigarettes Carcinoma of colon (153.8) Co re inoma of liver (157.9) 1699 1905 190* 1929 1944 1943 1959 1970 1962 1960 1972 1962 Pipe Cigarettes Cigarettes intraperitoneal carcinoma (158.9) Carcinoma oflung(162.1) 1 Co rei noma of left lung (162.1) mo 1912 1927 1944 1966 1965 1970 1965 Cigarettes Clgaret tes Pulmonary carcinoma (162.1) Carcinoma of apex of right lung (162.1) 1915 1937 1977 1977 Clgurettes Carcinoma of lung (162.1) 1915 1939 1969 1970 Cigarettes Carcinoma of lungs (162,1) 94 1944 1960 1964 Non-smnker Carcinoma of lung (162.1) 1912 1937 1973 1974 Cigarettes Carcinoma of lung (162,1) 1919 1901 1946 1933 1963 1962 1964 1977 Clgarct teo ClgaretLea Carcinoma of urinary bladder (180.0)** Carcinoma of bladder (100.0)** 1697 1941 1962 1965 Cigarettes Carcinoma of urinary bladder (100.0)** 1698 1933 1962 1965 Smoked years ago Carcinoma of urinary bladder (108.0)** 1905 1943 1971 1975 Cigarettes Carcinoma of .bladder (108.0) 1896 . 1943 1963 1970 Clgaret tcs Bladder tumor. (1Q.)** 1606 1944 1956 1970 Unknown Carcinoma of bladder (100.0) 1905 1933 1969 1977 Cigars Prostntle carcinoma (105.0) 1906 .1946 I960 1977 Cigarettes Core 1noma of prosiate (105.0) 1925 1945 1973 1974 Smoked years ago Carcinoma of prostate (105.0) Olii ' 1943 1972 1973 Cigarettes Hodgkin's Disease (201.0) 1901 1941 1964 1965 Clgnrs Osteosarcoma arising from left arm (170.4) 1901 1943 1966 1977 Cigarettes Carcinoma of 1Iver 6 pancreas (197.8) 1922 1944 1964 1964 Cigarettes Adcnornrei noma (199.0) * Obtained by Interview with former coworkers of decedents. ** Included on the Nitro plant PAIJ roster* i/i CD I 590 J. A. ZACK A N D W. R. GArr> The FMR analysis is limited in that an assessment of the total force of mortality cannot be made. Tne cause-specific rMR's only approximate what an SMR analysis would have produced.*0 The PMR analysis presented here estimates the cause-specific risks associat vith 2,4,5-T exposure and potential TCDD exposure. It is interesting to compare the results of this study of Nltr plant workers potentially exposed to TCDD with the results of the , study of Hitro workers involved in che 1949 TCP accident. The work involved in chat incident had presumed TCDD exposure as evidenced b chloracne. The results of the two studies are similar in that neit shows an excess in deaths from any site among malignant neoplasms. i A recent study of Ott et al.*7 found .no excess in total mortal I or in deaths from malignant neoplasms among workers exposed to 2.3. These workers were probably exposed to very lov levels of TCDD sine no cases of chloracne were observed. Other studies of workers who developed chloracne resulting from TCDD exposure have been conducce and have been reviewed.5 Ac che present time data from these vari studies do not constitute corroborative evidence of a cancer risk t __ man for any particular-cancer sice. ------- - -- ------------ ------ REFERENCES * ~. 1. Creig, J.3.: The toxicology of 2.3,7,B-- tecraehlorodibenzo-p-- dioxin and its structural analogues. Ann. Occuo. Hyg. 22: 411-420, 1979. 2. International Agency for Research on Cancer: ' Long-term hazards of polychlorinated dibenzodioxins and polychlorinated dibenzo furans. IARC Internal Technical Report Ho. 78/001. Lyon: IARC, 1978. 3. Ashe, V.F. and Suskind, R . R . : Reports on chloracne cases, , Honsanto Chemical Company, NitrOirWest Virginia. Reports of the Kettering Laboratory;December 1 9 4 9 ;a: d April 19p w . 4. Suskind, R..R.: A clinical and environmental survey, Monsanto Chemical Company,- Micro, West Virginia. Report of che Kettering Laboratory, July 1953. 5. International Agency for Research on Cancer. IARC Monographs o the Evaluation of che Carcinogenic Risk of Chemicals to Man. Vol. 15. Some Fumigants, che Herbicides 2,4-D and 2,4,5-T, Qilorinaced Dibenzodioxins and .Miscellaneous Industrial .. Chemicals. Lyon: IARC, 1977. 6. Zack, J.A. and.Suski^d, R.R.: The nortality experience of workc - exposed to. tecrachlorodibenzodiaxln in trichlorophenol proces accident. J. Occup. Hed, 22:11-14, 1980. 7. Walpole, A.L., Williams, H.H., and Roberts, D.C.: Tumours of urinary bladder in dogs after ingestion of 4-atainodiphenyl. Brit. J. Industr. Med. 11:105-109, 1954. mortality study of workers 591 8. Kelick, W.F..: First reported cases of human bladder tumors due co a new carcinogen - xenylamine. J. Urol. 74:760-766. 195 9, Helick, U.F-Narylca, J.J.. and Delly, R.E.: Bladder cancer due CO exposure co para-aminobiphenyl: a 17-year followup. J. Urol 106:220-226, 1974. _ 10. Key, M.M.: Ocuppacional Diseases: A Cuide co Their Recccnition. U. S. Deparcnenc of Healch, Education and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Healch. 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 co Man. Vol. 12. Sooe Carbamates, Thiocarbanates, and Carbazides. Lyon: IARC, 1571. 12. International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risk of Checi.ca.ls 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, Adapte for Use is the United States. U.S. Department of Health, Ed ucation, and Welfare, Public Healch Service, FES Publication No. 1693. Washington: U.S. Government Printing Office, 1977. L5. Monson, R . R . A n a l y s i s of relative survival and proportional mortality- Compuc. 3ioocd. Res. 7:325:332, 1974. 16. Decoufle, P., Thomas, I.H., and Pickle. L.W.: Comparison~of the proportionate mortality ratio and standardization mortality ratio risk measures,. An. J. Eoidadol. 111:263-269, 1980. 17. Ott., G.i Holder, B.B., and Olson, R . : A mortality analysis of employees engaged in the manufacture of 2,4,5-trichlorophenoxyaee_tic acid. J. Occun. Med. 22:47-50, 1980.