Document nmmo763k8zxg0nO3nZqLz9Yv8

2>V 1 --- * Audi S^ 7 t // ,97S' Since 1944 the general U.S. population has been absorbing organochlorine pesticides, which have recently been largely banned because of a concern that they would cause or contribute to the production of liver cancer. This survey is related to the quantities of these pesticides used and the incidence of liver cancer deaths in the U.S. from 1930 to 1972. Liver canGer deaths in tHe continental USA from 1 930 to 1972.* WM. B. DEICHMANN, PU.D., M.D. (hon.) and W. E. MAC DONALD, Ph.D. Research and Teaching Center of Toxicology, Department of Pharmacology, University of Miami School of Medicine, Coral Gables. Florida 331 24. ------- --------------------) t"fcO a R, T. GOTTESMAN Since 1944, the general population of the USA has been absorbing DDT or other organo chlorine pesticides with food and drink, because of the use of these agents as house and garden insecticides or because of their inhalation in Dolluted atmospheres. It was in June 1972 that She Environmental Protection Agency ordered The use of DDT banned in the USA, declaring it a potential human carcinogen. Two years later (September 1974), the EPA's Chief Administrative Law Judge suspended the use of aldrin and dieldrin, to "e(jminate an imminent hazard." And on July 30,1975, Russell E. Train, Administrator of the EPA, announced the suspension of chlordane/heptachlor because they pose an unreasonable risk and "imminent hazard" to the American people. publications, "Pesticide Situation" and "Pesticide Review." "Domestic disappearance" is defined as: "the quantities that leave the U.S. manufacturers' premises for(l) intermediate use (manufacture of other chemicals), (2) consumer use (industry, agriculture, home and garden, etc.), and (3) formulation (which may or may not include direct export after formulation)."1 From 1950 to 1970, the quantity of DDT manufactured was in excess of 1.2 billion kilograms, while its "domestic disappearance" was about half this amount. From 1950 to 1972, the aldrin-toxaphene group reached a total of 865.6 million kilograms manufactured, with a domestic disappearance of 706.6 million kilograms (Table I). Apart from some consideration for the environment in general, the primary reason for these bans was the concern that these organochlorine compounds would cause or contribute to the production of cancer of the liver in the USA population. Obviously, the quantities of these pesticides which might contribute to this dread disease are of interest. Table I presents a summary of the quantities of DDT and of the aldrin-toxaphene group (aldrin, chlordane, dieldrin, endrin, heptachlor, and toxaphene) manufactured in the USA and their ''domestic disappearance" in this country. These 'ata were obtained from the USDA *Tht it pn of a report presented by Df. Wm, B. Deichmann at the Fourth International Symposium. Chemical and Toxicolofical Aspecit of Environmental Quality, in Munich. Germany. September 9*10. 197$ Since it is impossible to prove a biological negative, the only approach that will provide useful information is an attempt to prove the positive--in this case, an increased incidence of liver cancer deaths in the years following the introduction into our environment of DDT and related organochlorine pesticides. Our approach to this hypothetic question was to review the vital statistics of the USA from a period before the introduction of these compounds (1930) in the expectation that some trend in the incidence of liver cancer in the U.S. population might be uncovered. The data and information for this review were obtained from publications of the U.S. Bureau of the Census2 and from personal communications with the Project Statistician of the American Cancer Society, Inc.3 Foe more information about uuthor*. m pg 550 ... American Industrie! Hygiene Association JOURNAL 495 OCC 6099 W * rv rs m * ' ^ ,rr" TABLE I . Manufacture and Domestic Disappearance* of the Major Organochlorine Pesticides Taken from USDA "Pesticide Situation" end "Pesticide Review"*" \ (Thousand pound units given in the publications converted to thousand kilogram unitsi "DOMESTIC DISAPPEARANCE** (IN THOUSANO kg UNITS) U S PRODUCTION OF ALDflIN (1954-)"" * ALDRlN* CHLORDANE (1945 ) DDT D1ELDRIN (1954-) BENZENE- 5 YEAR DDT T0XAPHENE (1944)*** ENDRIN (19S7-) HEXACHLORIDE i c V GROUP IN THOUSAND kg UNITS HEPTACHLOR (1952 ) TOXAPHENE (1946-) STROBANE (1964-69) (1947)*"" 19K> 1951 1952 1953"** 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 35.200 47.800 45.000 37.800 41.000 56.300 62.600 55.BOO 63.300 70.100 73.800 79,200 73.100 84.600 61.200 63.400 63.400 46.500 62.600 55.300 26.700 -- -- -- 22.000 13.000 20.300 34.600 39.000 33.900 44,200 39.100 40.800 46.700 47.800 47.700 47,600 53.500 58.700 54,000 52.200 48.300 39.900 52.300 64,000 26.100 32.800 31,500 28.100 20.300 27.800 33.800 32.000 30.000 35,400 31.400 28.80Q 30.200 27.500 27,000 22.500 19.300 14.400 13.500 12.100 9.000 6.000 10 600 17.100 22.700 17.100 15.500 16,000 25.600 27,700 23,600 35.500 33.000 34.100 35.200 37.000 35.700 37,000 40,000 39,000 39.000 17.400 40,400 28.000 38,300 47.800 3.800 4.300 5.000 3,300 3.800 3.500 4.200 3.000 2.500 1,900 2,300 2.200 1,100 600 -- __ -- -- -- -- __ -- -- TOTALS: 1.204.700 B65.600 550.100 702.600 41.500 ^Domestic Diipp*ranct" refer* to*the quanitiic* lhai leave ihc manufacturer)* premuc* for f I) intermediate use (manufacture of other chemicals). (2) consumer use (industry, farmer*, home 4 garden use4c). (J) formulation (which may or may not include indirect export after formulation),* ""The values for '`domestic disappearance* were supplied by courtesy of W. B. Weaver. Associate Librarian. University of Florida, Gainesville. Florida. ""Year the pesticide was introduced. (Strotune was included in this group from 1964 to 1969.) " " " " Beginning with 19?3. the six pesticide* of the aldrm-ioxaphene group were lumped together in PrSthiJesituation, and'only one figure is given for the group. For 1950.193). and 1932. individual figures were published, but arc presented in this table as the total. It was not until 1949 that the National Office of Vital Statistics began to classify cancer of the liver and biliary passages in some detail, differentiating between: "Malignant neoplasm of biliary passages and of liver (stated to be primary site)," "Malignant neoplasm of liver (secondary and unspecified) not stated whether primary or secondaryand "secondary" (emphasis added). From 1930 to 1972 the total number of liver and biliary cancer deaths increased from 10,833 to 11,622, while the U.S. population increased from 123 million to more than208 million. Thus, the death rate (per 100,000 population) due to all liver cancers decreased from 8.8 in 1930 to 5.6 in 1972. This decrease in the liver cancer death rate was gradual and essentially continuous with the exception of the period 1942~1946 (World War II), when a-large segment of the younger U.S. population was removed from the continental USA. The increase in the percentage of older people, who are more prone to liver diseases ant liver cancer deaths, was reflected in the temporarily increased death rate, from 7.6 it 1940 to 8.5 in 1945. Since 1949, with improved diagnostic ant reporting procedures, there has been, a. expected, a constant and marked decrease in th; rate of liver cancer deaths diagnosed as "No stated whether primary or secondary" ant referred to as "unspecified"--from 3.7 in 1949 tf 1.5 in 1972. The improvement in diagnosis am reporting is further reflected, as expected, in at increase in the cancer identified as metastatic ti the liver, reported as "...secondary"--fromO.2' in 1949 to 0.95 in 1972. This increase, however, i too modest to be accurate and is in disagreemen with the general experience in this country, ii that metastatic cancer of the liver is much mor frequent than primary liver cancer. Simultaneously, for the period 1949 to I960 there was a modest increase in reported deati 496 September. 1971 V T' uP . U I OCC 6100 , hlJip i O O o G\ o > TABLE II I Uvor Cancer Death* in the Male end Female Population of the Continental United States fi 9at 1 I5 YtAfl S Jr i <s 1 POPULATION OF CONTINENTAL USA (EXCLUDING ARMED FORCES OVERSEAS) CANCER OF LIVER AND BILIARY PASSAGES II______________ 3b NUMBER OP DEATHS DEATH RATE PER 100.000 MALIGNANT NEOPLASM OF BILIARY PASSAGES AND OF LIVER (STATED TO BE PRIMARY SITE) 4.___________ 4b NUMBER OF DEATHS DEATH RATE PER 100.000 malignant neoplasm OF LIVER (NOT STATED WHETHER PRIMAHY OR SECONDARY) 5.___________ 6b NUMBER OF DEATH S DEATH RATE PER 100.000 6 MALIGNANT NEOPLASM OF Rl LIARY PASSAGES AND OF LIVER TOTAL OF THOSE STATEOTO BE PRIMARY SITE (COLUMN 4a| PLUS THOSE NOT STATEO WHETHER PRIMARY OR SECONDARY (COLUMN S) 6a *b NUMBER OF DEATHS DEATH RATE PER 100,000 7 MALIGNANT NEOPLASM OF LIVER SECONDARY Ta NUMBER OF DEATHS 7b DEATH RATE PER 100.000 C 1930 1931 1932 1933 1934 123.076.741 124.039.648 124,840.471 125,678,763 126.373,773 10.633 10.664 10.656 10.550 10.618 B.B 66 67 84 B4 1935 1936 ;937 1938 1939 1940 1941 127,250,232 128.053,160 126.624 329 129.624,939 130,879,718 131,954,144 133,060,045 10.439 10.376 10,034 10,124 9,948 9.768 9.846 62 61 60 76 76 74 7.4 1942 133.770.500 10.204 7.6 1943 1944 1945 133,971.000 132.622.000 132.137,000 10.972 11.177 11.207 83 84 B5 1946 1947 139.893.406 143,376.000 10.804 tO.572 7.7 7.3 1948 1949. 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 I960 1961 1962 1963 1984 (965 1965 1967 1968 1969 CO 1970 197) 1972 146 045,000 148.558,000 150,697,361 153,363.000 157.022.000 158,308.000 16). 163.000 164.308.000 167.259.000 170.293.000 173.232.000 176,420.000 179.323.175 182.953.000 185.822.000 188.531.000 191,334.000 193,618.000 t95.657.000 197.B63.000 199,861.000 201.921.000 203.235.296 206.212.000 208.230.000 ' 10.598 10.438 10.648 10.323 10.468 10.440 10.227 10.320 10.284 10,641 10,476 10,367 10.668 10.578 10,474 10.655 10.843 11,083 11,083 11.355 11,251 11.340 11.355 11.482 11.622 7.3 7.0 7.2 6.7 6.7 66 63 6.3 6.1 6.2 60 59 59 58 56 57 5.7 5.7 5.7 5.7 56 56 56 56 56 4.432 4.653 4.753 4.946 5.121 6.237 5.328 6.622 6.692 5,948 6,077 6.248 6,359 6,423 6,324 6.425 6.589 6.584 6.845 6.605 6,626 6,626 6.728 6,616 2 98 3 09 3 09 3.15 3 23 3 31 3.25 3.36 3.34 3.43 3 44 3.4B 3.47 346 3.35 3.36 3.39 3 36 3 45 3 40 3 26 3 25 3.26 3.16 5,570 5,653 4,943 4,881 4,736 4.435 4,358 3.967 4,037 3,688 3,431 3,483 3,192 2.959 3,233 3,264 3.195 3,149 3,136 2.981 3.012 2,932 2.860 3,036' 37 36 32 31 3.0 27 36 24 24 31 19 19 1-7 16 1.7 1.7 1.8 16 16 15 'S 14 1< 15 10.001 10.311 9.656 9,837 9 847 9.663 9.686 9-689 9.739 9.636 9,508 9.736 9,551 9.381 9,546 9.669 9.784 9.733 9,961 9,786 9,638 9.558 60S 9.653 67 68 63 62 62 60 58 5.7 57 56 54 54 5.2 50 5.1 5.1 50 5.0 5.0 49 46 4.7 47 47 436 537 627 641 593 565 734 695 912 B40 859 94 2 1.02? 1.093 1.109 1.154 1.299 1.350 1,374 1.465 1.662 1.797 1.874 1,970 0 29 036 041 041 0 37 0 35 0 45 042 054 0 48 049 0 53 0 56 0 59 059 0 60 067 0 69 0 69 073 OC3 0 88 091 0 95 1973 209,844.000 1974 2U ,390.000 rales for "malignant neoplasm of biliary passages and liver, staled to be primary site"--from 2.98 to 3.48, followed by a drop to 3.18 in 1972 (Table II). It is expected that similar analyses conducted on smaller population groups, limited as to sex, age, occupation, race, religion, etc., would reveal deviations from the report presented. To arrive at valid conclusions for such individual groups, it would be necessary to consider, for each group, at least the following variables: (1) extent of exposure to specific organochlorine pesticides, (2) dietary habits including dietafy deficiencies, and (3) the extent of exposure to the well recognized human hepatotoxic substances, including certain synthetic industrial and household chemicals, certain anesthetic agents and drugs, and radioactive materials. The increasing incidence of alcoholic cirrhosis and its relationship to liver cancer deaths deserves mention. According to a review on "Alcoholism and the Risk of Cancer,"' . .the chance that a patient with alcoholic cirrhosis will subsequently develop a hepatoma has been reported to range from 8 to 30% and the longer the cirrhotic patient lives the greater the risk of this tumor." Conclusions 1. Based on the U.S. vital statistics for the general USA population, the total death rates for cancer of the liver and its biliary passages (classified individually as "pri mary," "secondary," and "not stated whether primary or secondary") lead one to the conclusion that there has been a significant, almost constant decrease in the total rate of liver cancer deaths, namely, from 8.8 in 1930 to 8.4 in 1944 (when DDT was introduced) to 5.6 in 1972. This almost constant decline in total liver cancer death rates for the past 42 years fails to support the "positive," namely, clearcut evidence, of any increase in liver cancer deaths since the introduction of the first organochlorine pesticide into the U.S, V environment. This decrease in liver cancer N deaths is even more significant in light of the increasing life span of the people of the USA, which has resulted in an increased percentage of the population "at risk" to liver cancer over these years. True, the data presented do not provide specific information for a particular organochlorine pesticide, nor for that matter for any of the synthetic or "natural" chemicals that are known to be hepatotoxic in man. 2. If any of the organochlorine pesticides actually do possess very law potential for causing liver cancer in man, we consider it most unlikely that general population studies would uncover this fact. As we have often said, the population groups that should be studied in detail for liver and other cancers are those who are engaged in the manufac ture, formulation, and extensive use of these compounds. Experience has shown that adverse effects of chemicals are generally observed first in those who are occupation ally exposed. 3. Obviously, the incidence of liver cancer deaths presented in this report is no more accurate than the original death certificates which provided the data for the U.S. vital statistics. In spite of the limitations inherent in the interpretation ofsuch data, this report, to say the least, should retnind us that today--more than 30 years after the intro duction of DDT--we have no evidence what soever that DDT is carcinogenic in man. References 1. Fowler, D.L.: Agricultural Stabilization and Conservation Service, US Dept, of Agricul ture, Washington, D.C., private communi cation July 8, 1975. 2. Vital Statistics of the United States 1942 1946, U.S. Dept, of Commerce, Bureau of the Census (1943-1946); Federal Security Agency, USPHS, National Office of Vital Statistics (1947-1951); USDHEW, PHS National Office of Vital Statistics (19521956); USDHEW, PHS, National Center for Health Statistics, National Vital Statistics Div. (1961-1970); and Current Population Reports No 520, 533, and 542, Population Division, Bureau of the Census, USDHEW, PHS. 3. American Cancer Society, Inc., private communication with Edwin Silverberg, Project Statistician, Research Department, August 30, 1974 and January 17 and March 7, 1975. 4. Gall, E. A.; Tumors of the Liver, in Diseases of the Liver, 3rd ed., edited by Leon Schiff, J. B. Lippincott, 1969. 5. Lowenfels, A. B.: Alcoholism and the Risk of Cancer, Medical Consequences of Alcohol ism, p. 366, New York Academy ofSciences, 1975. Accepted February 24,1976 498 September, 1976 OCC 6102