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Mortality of Pesticide Applicators Helen H. Wang, M.D., and Brian MacMahon, M.D. .- _ _._________ __. lnformation has been obtained on a cohort of profes- that do not produce acute symptoms i s still not known. In sional pesticide applicators which will be followed p r e particular, there is concern, deriving from experimental spectively. The cohort consists of 16,126males employed work on laboratory animals, that chronic exposure may for three months or more between 1967and 7976 b y any of be associated with increased risk of malignancy. There three nationwide pest control companies. Deaths which has been little published epidemiologic work addressing occurred between 7%7 and 1976 were reported by the this problem in humans. Sock1Security Administration as a result of a search of its The cancer experience of professional pesticide a p records. Overall, 311 deaths were ascertained, giving a plicators would seem to be relevant. Although, from any standardized mortality ratio (SMR)of 84. SMRs were over 7 0 0 for three causes of death - cancer of the lung (1751, presently available information, it is not possible to assess the doses to which professional applicators are, or in the cancer of the skin (173)and cancer of the bladder (277). past have been, exposed, it is unquestionable that as a The confidence intervals of two of these ratios include group their exposures exceed manyfold those of the , 700, and the observed numbers therefore do not differ general population. It is reasonable, therefore, to look significantly from those expected. For bladder cancer the among this group for the first signs of a carcinogenic ef- <excess is on the border of statistical significance(p 0.05). fect of pesticides in man. The excess of deaths from lungcancer was not seen for a p This paper reports on the establishment of a cohort of plicators classified as termite control operators, a group professional pesticide applicators which will be followed more likely to be exposed to chlordane and heptachlor. prospectively. It also reports the results of sixh observa- There were significantly low SMRs for cancer of the tions as can be made retrospectively on the same cohort. digestive organs (46)and for other diseases of the digestive (55) and respiratory (29)systems. Deaths from cerebrovas- Materials and Methods cular disease were also less than expected, though not Employees of three nationwide pest control companies significantly so. form the study cohort. The three companies have head- quarters in Atlanta, Ca., Memphis, Tenn., and Tucson, Ariz., respectively, but their branch offices cover more than 40 states. At the time this study was begun, central- c h e m i c a l control of insect pests essentially began in ized personnel records had been maintained only for a p the middle of the nineteenth century with the introduc- proximately 10 years in all three companies because of tion of arsenical pesticides. However, pesticide use was the record storage problems associated with rapid turn- I confined to fruit and high value crops, or to instances of over and a large number of employees. In two companies severe infestation, until the development of the chlori- January 1, 1%7, was identified as the earliest date for nated hydrocarbons a little over 30 years ago. The high which a roster of all personnel - those inactive as well as -I potency and residual action of these compounds reduced those still active in 1976 could be assembled, and in the cost of pest control and led to a rapid increase in the the third, and largest, company this date was lanuary 1, levels of chemical pesticides in the environment 1968 Perswael records of all persons in job categories generally. potentially involving exposure to pesticides and I Acute health effects of heavy exposure to chemical employed those dates or hired between those dates I pesticides are reasonably well known. Thev can be and June 30.1976,were reviewed. From a total of 44,083 serious and sometimes fatal. Whether there am long-term records, 16,126 subjects were identified who ca?isfied the Ith effects of chronic exposure of humans to-ievels criteria of (1) being male, (2) being employed for three months or more, and (3) having name, Social Security number, date of birth and dates of employment recorded. The assembly of the cohort involved a combination of 0.Warn IS Dmenttv at the CommhemnnC computer and manuet'pocdures and, without c m slderable clerical labor, it is not possible to say precisely + 1 Taw t. i- DirMbotiw ol s w y Popubtha by Genenl LndOs xxposun to PltWdos and by wkrtsrr Y Nol Employwl in Termite Control. EX~@SUN Level Minimal Modera!? Heavy Total Termih Control YES No 2713 (40 3) 664 (9 9) 3357 (49 9) 6734 (100 1) 1426 (15 2) 4320 (46 0) 3642 (38 a) 9392` (100 0) fob1 4139 (25 7) 4984 (30 9) 6999 (43 4) 16126' ,100 0) Figures in parentheses are percentages Includes tour subpcts with unknown level of general exposure on what grounds each of the 27,957 excluded subjects was declared ineligible. However, a sample of 4,000 of these was examined and in this sample 11% had been excluded because they were female, 71% because they were employed for less than three months and 18% because of missing information. Information on race was not available on personnel records and could not be used as an eligibility criterion. However, ihe majority of the workers were white. In the course of the study death certificates - which did specify race - were obtained for 269 of the subjects; 253 of these subjects were white, 15 were black and the race ot one was unrecorded Individual follow-up was not attempted. fdentifying information on the 16.126 eligible subjects was submitted to the Social Security Administration which provided, for those known to be dead, information on date of death and the state in which the death certificate might be found. In another set of records submitted together with those from this study, the SSA search identified 104 of 109 deaths which had been ascertained through individual follow-up.' Among the 16,126 subjects in this cohort, SSA identified 311 deaths, for 269 of which death certificates number of "observed" deaths by cause, the actual number observed, plus the 42 deaths with missing certificates distributed by cause according to the distribution of causes noted in the death certificates obtained, were used. Expected numbers of deaths by cause have been estimated by means of a computer program described by Monson.*The program applied national mortality rates of white males specific for fiveyear categories of age and for calendar year to the person-years accumulated during the period of observation. The beginning of _this period was January 1, 1967, or January 1, 1968 (as described earlier). For employees entering after these beginning dates the beginning date was taken to be the end of the third month of employment. There were also two termination dates since records were submitted to SSA in two batches. For individuals whose record was submitted in the first batch the termination date was June30, 1976. For the second group it was December 31, 1976. In the computations, persons who were known to have died did not contribute person-years after the year of death but, otherwise, subjects were assumed to be alive until the end of the follow-up period. Standardized mortality ratios (SMR) were estimated by dividing the numbers of o b served deaths (with the 42 of unknown cause distributed as previously described) by the expected values and multiplying by 100. An extension of the Cornfield method' was used to compute 95% asymptotic confidence intervals of the SMRs. The applicators had been exposed to a broad spectrum of pesticides including fumigants, botanicals, carbamates, chlorinated hydrocarbons and organophosphates. Particular interest was focused on applicators exposed to chlordane and heptachlor. In addition, some measure of -Table 2. Observed and Expected Deaths from Selected Causes. Cause of Owth All causes Infective and parasitic diseases Malignant neoplasms Digestive organs and peritoneum Lung Skin Bladder Lymphatic and hematopoietic Other Diseases of circulatory system lschemic heart disease Cerebrovascular disease Other Diseases of respiratory system Diseases of digestive system External causes All other causes Observed A' et 31 1 31 1.O 2 2.3 47 54 3 6 69 K --3 - 3 35 3 35 5 58 9 10 4 111 128 3 86 99 4 7 81 18 20 8 4 46 10 11 6 82 94 a 551 15 0 Expected 370 9 28 65 2 15 1 --2t-. 20 13 88 16 9 139 9 104 4 15 3 20 2 16 0 20 9 98 7 27 4 SMRS 84 83 83 46 115 173 277 66 61 92 95 53 103 29 55 96 55 C.I. of SMRg 75- 94 25-281 64-109 22- 95 77-1 70 63-473 101-761 30- 146 34-112 77-109 78-116 27- 104 67- 158 12- 70 3T- 98 79-117 33- 90 `Actual numbers lor which causes of death known tWith 42 deaths with missing certificates distributed according to the distribution in Column A :SMR = Observed (E)/Expected x 100 (computed from values expressed to two decimal places) $95% asymptotic contidence intervals' (Including 42 with missing death certificates 742 Mortality of Pesticide Applicators/Wang and MacMahon -Table 3. Observed and Expected Deaths from Selected Causes in Termite Control Operators and Other Applicators. I f G C, * _& a%y@- Cause of Death All causes Malignant neoplasms Cancer of digestive organs and peritoneum Cancer of lung Cancer of skin Cancer of bladder Ischemic heart disease Cerebrovascular disease External causes Termite Control Operators Observed' Expected 138 21 6 12 150 1 25 9 59 SMR 92 a3 20 7 2 8 3 a7 1 2 0 8 148 1 2 0 5 245 37 2 41 2 90 2 4 6 1 39 50 4 41 a 120 Observed' 173 32 6 56 16 9 22 22 61 8 56 44 9 Others Expected 220 9 39 3 91 12 9 12 08 63 2 92 56 9 SMR 7a 83 62 131 la7 296 9a 61 79 `Deaths with missing certificates distributed according 10 the distribution of actual observed numbers for each cause TCOs . 23 others - 19 of exposure was desired Each company was with a list of all the job titles found among the members and a knowledgeable person or FeTGSE asked to classify each title into one of three groups relative intensity of exposure In an attempt he effect of exposure to chlordane and heprate analyses have been conducted for per- g jobs as "termite control operators" COS)Chlordane and heptachlor are particularly effec- in the control of termites and, since 1975, their use been legally restricted to the subterranean control of and to a very few other applications It is recogthat TCOs are also exposed to a variety of other hat general pest control operators may posure to chlordane and heptachlor, par1975 Nevertheless, it IS almost certainly as a group, TCOs have heavier exposure to ane and heptachlor than those in other job s The distribution of the study population as to on-TCO status and by estimated relative intensiosure is shown in Table 1 The 243 applicators held job titles under more than one level of intensity of exposure are classified according to the one Id for the longest period of time ewrlts nce interval of 75-94 Underascertainment of that the S M R is less than 100. although the value of 84 is not atypical for an occupational cohort. SMRs are over '1RJTtoron~thrSe-causesof death - cancer of the lung (115), cancer of the skin (173) and cancer of the bladder (277). The confidence intervals of two of these ratios (for lung and for skin) include 100 and so the excess is not for- >mally significant (p 0.05). For bladder cancer the excess is on the borderline of statistical significance. The very low SMRs for cancers of the digestive organs and for other diseases of the digestive and respiratory systems are notable. The extent to which occupational selection is responsible for these low ratios can only be conjectured, but it is probably considerable. There was one death from cancer of the common bile duct but none attributed to cancer of the liver. Table 3 gives observed and expected deaths separately for the TCOs and for other applicators. The only signifi- cant differences between expected and observed values <(p 0.05) are those for cancer of digestive organs and for cerebrovascular disease, both in TCOs and both in the direction of lower observed values than expected. None of the differences betweer; SMRs in TCOs and non-TCOs i s significant but the slight excess of lung cancer is -restricted to the non-TCO group. Table 4 shows observed and expected deaths by estimated relative intensity of exposure. For lung cancer there is no evidence that risk increased with intensity of exposure as judged from job title; in fact, there is a slight, though not significant, trend in the opposite direction. Further analysis of the lung cancer data showed only one curious feature. The lung cancer deaths were 6 6 138 75 6 2 120 71 8 2 87 12 0.6 198 11 0 6 187 12 0 9 138 0 4 530 0 03 0 12 0 5 243 31 5 344 92 23 5 294 80 44 1 40 7 108 50-64 Total 012 6 010 t 1218 1 5/84 010 6 519.8 1/04 312 8 413 2 6/11> 31 35 21121.2 'Obsetwd numbers not adlustd for deaths of unknown cause 'Obsenred deaths not adlusted for deaths of unknown cause clustered among workers who were first employed prior tn age 45 and who died before age 50 (Table 5). In fact. in this subgroup the excess is formally significant (p C 0.051, seen in the applicators were not reflected in the manuf turing workers Similarly the unexpected excess of dea from cerebrovascular disease seen in the manufacturing if one disregards the facts that this was not an a priori workers is not seen in the applicators, either in the group hypothesis and that manv comparisons have been made as a whole or in the termite control applicators in the data No explanation for this observation has been The principal limitation of the present study, particular- found yet -Table 6 examines the question of "latency" the in- terval between the time the individual's employment began and the years during which he was observed in the study The table shows that relatively few of the study subjects so far were followed for 10 years or more after ly as it relates t o cancer experience, is that there were relatively few workers who had substantial work ex- pertence and who were followed for long periods after first employment Thus, only about 15% of the person. years were contributed by workers who had more than five years of employment and who were observed more I I I first employment None of those with lung cancer fell into this category If the excess of lung cancers had been of than 10 years after first employment It is hoped that the establishment of the cohort at this point in time will per- occupational origin, one would have expected to see mit more decisive analyses in the future most of the excess in this categow Discussion Although there have been several clinical studies of workers occupationally exposed to pesticides, these The authors are indebted to Mr john D Conner I r of Sellers Conner and Cuneo Washington D C for suggesting this study and for making ar- rangements with the companies for provisionof data Management and staff of Rollins. Inc , Terminex International. Inc, and Truly Nolen International wem helpful in supervising data abstractionand in providing other intormatlon fhr Social Security Administrationarraqged for the data ~rocessinyin that a y e m generally have been based on small numbers and have involved clinical and laboratory examination at a single point in time.*-l2Essentially no data could be found on the long-term mortality of occupationally exposed workers other than a study of workers employed in the manufacture of chlordane and heptachlor.' There is no consistent pattern of excess mortality seen in either of these two studies.The overall SMRs were 72 in -the manufacturing workers and 84 in the applicators both figures expressing the reduced mortality generally found in occupational cohorts. SMRs for deaths from cancer were 82 and 83, respectively. In both groups there References 1 Wang H H and MacMahon B Mortality of workers employed in the manufacture of chlordane and heptachlor I Occup Med 21 741748,1979 2 Monson RR Analysis of relative survival and proportional mcy- tality Cornput Biorned Res 7 325-332. 1974 3 Wang H H and Miettinen 0 Evaluation of three asymptotic methods of interval estimation for the odds ratio In preparatmn 4 Princi F and Spurbeck C H A study of workers exposed to the i w secticides chlordane, aldrin. dieldrin Arch Ind Hvg Occup Med 3 64-72. 1951 5 Alvarez WC and Hyman S Absence of toxic manifestations in workers exposed to chlordane Arch Ind Hyg Occup Med 8 4 8 0 4 3 . 1953 i was s slight excess of deaths from lung cancer but in neither is it significant, and even if the two series are com- bined, there are 36 3 observed and 30.2 expected - a dif- ference that is neither significant nor remarkable in the absence of data on cigarette smokingin the-twa.cohcutL- 6 Ortelee MF Study of men with prolonged intensive occupational exposure to DDT Arch Ind Health 18433440. 1958 7 Fishbein WI. White I V and lsaacs H I Survey of workers exposed t o chlordane Ind Med Surg 33 726727. 1964 8 Stein W l and Hayes W J Health survey of pest control operators Jnd-Med Surg 33 549-555. 1964 - Moreover, the manufacturing workers were exposed predominantly to chlordane and heptachlor. Among the applicators, the excess lung cancer mortality occurred not among the group most likely to be exposed to chlor- dane and heptachlor - the termite control operators - but among the general pesticide applicators. Nevertheless, special attention should be paid to this cause of death in the future follow-up of these cohorts. The excesses of cancer of the skin and of the bladder 9 Laws ER, Curley A, and Biros F J Men with intensive occupational exposure to DDT Arch Envrron Health 15 76&775 1967 10 Sandifer SH Keil I E Finklea I F . and Cadsden RH Pesticide effects on occupationally exposed workers A summary of four years observation of industry and farm volunteers in South Carolina Ind Med 41 9-12, 1972 11 Warnick SL and Carter ] E Some findings in a study of workers occupationally exposed to pesticides Arch nvrron Health 25 265-270. 1972 12 Morton WE, Crawford ED, Marlcle RA et a1 Hypertension m Oregon pesticideformulating workers / Occup Med 17 182-185.1975 I I I 744 Mortality of Pesticide Applicators/Wang and MacMahon