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Teratogenesis, Carcinogenesis, and Mutagenesis 7527-540 (1987) Leukemias and Blood Dyscrasias Following Exposure to Chlordane and Heptachlor Samuel S. Epstein and David Ozonoff School of Public Health, University of Illinois Medical Center, Chicago, Illinois (S.S.E.); Environmental Health Section, Boston University School of Public Health, Boston, Massachusetts (0.0.) We preSefitL`25new cases of blood dyscrasia, including leukemias, production defects, and thrombocytopenic purpura, generally following home termite treatment with the chlorinated hydrocarbon pesticides chlordane and heptachlor (CI H). These newly reported cases are consistent with 34 previously published case reports associating blood dyscrasias with CIH exposure. Additionally, the newly reported leukemias are consistent with epidemiologic evidence of excess risk of leukemia and other cancers in CIH-exposed populations and with the carcinogenic action of CIH in animals. The importance of case reports in warning of the associationof blood dyscrasias to C/H exposure is emphasized. Until the voluntary halt in production in July 1987, millions of homes in the United States were treated with chlordane and heptachlor for termites even though their agricultural uses were phased out in 1978, largely on the grounds of ``imminent hazard" because of carcinogenicity. In view of the rmgnued myelotoxicity, carcinogenicity, and other chronic toxic effects of these pesticides, a national program for monitoring all homes treated is urgently needed to detect persistent contamination. Key words: aplastic anemia, knniticides, pesticides, thromobocytopenia INTRODUCTION The literature on the association between blood dyscrasias and exposure to the chlorinated cyclodiene pesticides chlordane and heptachlor ( C M ) was last reviewed in 1978 when six new cases of blood dyscrasias in children (along with five cases of neuroblastoma) following prenatal or postnatal chlordane exposure were presented [l]. In approximately one half of the 34 cases of blood dyscrasias (includmg five Address reprint requests to Dr. David Ozonoff, Chief Environmental Health Section. Boston University i School of Public Health,Boston University M d c a l Center, 80 East Concord Street, Suite T3C.Boston, M A 02118. I leukemias) then reported, there was also exposure to ocher potentially myelotoxic agents. The very low incidence of most blood dyscrasias limits the feasibility of epidemiologic study [2,3], so the association of these diseases with specific toxic agents depends largely on observations and case reports by alert clinicians. The importance of such reports is illustrated by results of a large population-based, case-control study on the relation between analgesic use and agranulocytosis and aplastic anemia that confirms associations previously accepted on the basis of case reporting [2]. The present communication presents a series of 25 previously unpublished cases of blood dyscrasias following C/H exposure, including two illustrative case reports. Additionally, the epidemiological and other literature relevant to the myeloto&c hazards of C/H is briefly reviewed. New Cases of Chlordane/Heptachlor-AssociatedBlood Dyscrasias The myelotoxic hazards of C/H have been well-recognized for over three decades [4]`. Chlordane was judged to be "one of the most hazardous hydrocarbon insecticides" in 1955 after aplastic anemia was reported following exposure to this agent [4]. Chlordane vaporizing devices were specially singled out as a "serious health menace" [5]. In addition to reports in the medical literature, industry files2 contain information on unpublished cases resulting from physician inquiries about blood disorders in patients who had been exposed to C/H. Other unpublished cases in industry files include complaints and personal injury claims filed by patients developing blood disorders following exposure to C/H. Tables I and II, respectively, list 12 litigated and 13 nonlitigated previously unpublished cases of C/H-associated blood dyscrasias; most of these cases do not appear to have been disclosed to the Environmental Protection Agency (EPA) and listed in their voluntary reporting system [6,7]. More than one half of the 25 cases occurred prior to 1975 Tables I and II summarize all of the available data. Table III reviews the 34 previously published case reports of blood dyscrasia and C/H exposure. The distribution of the major categories of dyscrasias is similar in the published and unpublished sources, with the exception of a greater prevalence of thrombocytopenia in the latter (Table N).Thrombocytopenia was as common in the unlitigated series (three cases) as in the litigated series (twocases). In 15 of the 25 unpublished cases (60%),no potentially myelotoxic exposures besides C/Hwere reported. Among the 16 cases for which exposure data are avail- able, the majority, 75%, involved homeowners and their families following home, lawn, and garden applications, particularly after home termite treatment. The remain- `Despite these reports, a review of available labels for pesticides containing chlordane shows they contain no references to agranulocytosis, aplastic anemia, thrombocytopenia, leukemia, or any other disorder of the blood. `These involve the files of Velsicol Chemical Co., Chicago, IL, the sole manufacturer of C/H; formulators such as Chevron and Chemagro; and applicators such as Orkin. We have been unable to obtain independent verification of all diagnoses. Chlordane and Heptachlor Exposure 529 TABLE I. Some Litigated Cases of Blood Dyscrasias Associated With Exposure to Chlordane/ Heptachlor that Apparently Have N d Been Reported in the Scientific Literature Case (Year) C/H Litigation reference exposurea Blood dyscrasia Comments C.N. Dist. Ct., Upton, TX + Aplastic anemia Nil (1959) S. Case No. 1360 Memphis, TN + Aplastic anemia Nil (1962) J.B. Wisconsin State Cir- + Thrombocyto- Exposure in office follow- (1%2) cuit Court, Eau Claire Country penic purpura ing contamination from spraying in adjacent S.W. California State store premises + Aplastic anemia Exposure following home .(1969) C.S. court U.S.Dist. Court. 4th + Aplastic anemia treatment for termites Exposure following spray- (1971) Div. Minnesota ings of garden; suit not 4-71, CIV. NO. 318 *,R.H. Oklahoma OK prosecuted a Acute dissemi- Recent exposure following (1972) nated hemor- extensive sprayings of rhages and ? garden; suit not 1.R. U.S.Dist. Ct., E. leukemia prosecuted + Myelomonocytic Nil (1975) Michigan Case leukemia +No. 76-71904 T.R. Superior Court, Cali- Hemolytic ane- Developed in baby girl fol- (1975) fornia Case No. mia and ? lowing home termite 468R.K. State of N.Y. Supr. leukemia + Leukemia treatment Nil (1978) Ct. Index No. 4937-79 R.B. U.S. District Court, b Thrombocyto- Exposure following spray- (1980) Massachusetts penic purpura ing of own home: fatal Case No. 83- 0927-S C.L. U.S.District Court, C Myelomonocytic Nil (1985) West Michigan leukemia Case NO. K-83- 149CAB-NP D.P. 17th Circuit Court, + Aplastic anemia Exposure following home (1985) Michigan Case termite treatment: fatal No. 8 % 6 7 f - N I '+, No record other exposure; a, with aminopyrine; b, Teldrin exposure 6 months previously; c, with malathion. ing 25% involved professional applicators. Of the classifiable dyscrasias, 14 were production defects, five were thrombocytopenic purpuras, and four were leukemias. A long-term follow-up of the production defect cases would be of particular interest in view of their high case-fatality rate [16] and the well-recognized sequential relationship between aplastic anemia and leukemia [13. Further details of most of these 25 cases cannot be evaluated in the absence of complete disclosure and reporting by the manufacturing, formulator, and applicator industries involved. Two cases for which additional information is available are presented for illustrative purposes. TABLE II. Some Nonlitigated CM of Blood Dyscrasias Assoripted With Exposure to Chlordane/ Heptachlor That Apparently Have Not Been Reported in the ScientiRc Literature Case (Year) CIH exposurea Blood dyscrasia Comments S.P. (1958) D.B. (1966) Anon. (1%9) Anon. ( 1969) J.H. (1969) Anon. ( 1970) B.P. ( 1974) M.S. ( 1974) M.R. (1975) R.S. (1976) J.M. (1979) J.M. ( 1982) Anon. (1984) 4- Aplastic anemia Nil a Aplastic anemia Worked as exterminator; fatal b Aplastic anemia Worked as exterminator; possible causahty ad- + Aplastic anemia mitted in lndusay files Exposure following extensive use for termite and eradication and garden applications; fatal (EPA, PIMS No. 360, 1980) + Thrombocytopenic Nil Purpura f Aplastic anemia In young female child exposed to chlordane in garden yard; soil levels, 4 ppm; father who often used chlordane and other insecticides, died of aplastic anemia (reported in EPA, Pesticide Incident Monitoring System, Report No. 3M), 1980) Aplastic anemia Worked as groundskeeper Pernicious anemia Nil Aplastic anemia Developed in infant following home treatment for termites; remitted Thrombocytopenic Associated with myeloproliferative syndrome purpura and pulmonary fibrosis; exposure following treatment of fruit trees in garden; serum chlordane, 250 ppb; soil levels, 234 ppm; pa- tient assured by industry that chlordane caus- ality was very unlikely a Megaloblastic anemia Worked as exterminator; possible causality ad- mitted in industry files a Chronic myeloid Exposure following 5-year extensive use as pes- leukemia ticide in home + Thrombocytopenic Remitted; patient's doctor told by industry that purpura the only way of establishing causality was to see if patient relapsed following further exposure a + , No record other exposure; a, with other unspecified exposures; b, with other "agricultural chemicals"; c, with other chlorinated hydrocarbon insecticides. CASE REPORTS Case 1 A white, 37-year-old commercial airline pilot (R.B., Table I) saw his FAA flight physician in May 1980 because of a 2-week history of backache, general malaise, and dizziness and a few days history of petechiae and ecchymoses over the lower extremities. Laboratory tests revealed a platelet count of 20,000/m3, and he was hospitalized with a working diagnosis of idiopathic thrombocytopenic purpura. He had previously been in good health except for mild "hayfever" for which he had f I I Chlordane and Heptachlor Exposure 531 taken Teldrin once, 6 months previously, and a backache for which he had taken aspirin intermittently just prior to hospitalization in late April 1980. On admission, his hematocrit was 37.6; hemoglobin, 13.2 gm%; white blood cell count, 6,700 cells/mm3with 46% polymorphonuclear leukocytes, 5 % bands. 9% lymphocytes, 1%monocytes, 1% basophils. and 35% eosinophils; platelets, 19,0001 mm3;prothrombin time, 28 sec @atient)/27sec (control); fibrinogen, 110 mg%. A tourniquet test was normal. Bone marrow aspiration of marginal quality showed adequate megakaryocytes but no evidence of platelet formation and an eosinophil hyperplasia with a shift toward immaturity. A stool guaiac test was positive. The patient was placed on prednisone while awaiting further studies, but 2 days after admission he was found on the bathroom floor in hypotensive shock. Emergency laporatomy was performed and a ruptured. infarcted spleen removed. Transfusion with 20 units of platelet concentrate brought his platelet count level to about 200,000! mm3, and multiple infusions of whole blood and fresh-frozen plasma were given in the perioperative period. Twenty-four hours postoperatively, he began to show signs of upper gastrointestinal and inpaabdominal bleeding, and intensive platelet replacement therapy was again initiat& He was then transferred to a tertiary care hospital for further evaluation and trda$.&pt, at which time his platelet count had fallen to 75,000/mm3. He followed amp& downhill course, with peritonitis and disseminated intravascular coagulation leading to death approximately 2 weeks after initial admission. Before his fatal illness in late April 1980. the patient sprayed five cords of wood for carpenter ants with a half quart of chlordane formulation, which he diluted with water and applied with a hand sprayer without a nozzle. He had performed similar applications once or twice yearly since 1977, using a total of 1-2 quarts of chlordane concentrate. case 2 A 41-year-old white male (C.L.,Table I) was admitted for diagnostic work-up to a community hospital in November 1980 by his family physician after an office visit indicated mild anemia and thrombocytopenia. He had a 5-month hstory of easy bruising and slow wound healing, a 3-month history of easy fatiguability, and a 6week history of sore duoat. Just prior to admission he developed severe apthous ulcers. The patient had been rejected as a blood donor in July 1980 because of "low hemoglobin." He informed his physician that in July he had sprayed his house with chlordane. No history of other toxic exposures was then elicited. He worked as a diesel truck driver and had a 25 pack-year smoking history. h o r to his presenting illness he had been in goad health. On admission his hemoglobin was 9 gmZ; platelets, 40,000/mm3, and WBC, 8,100/mm3with 69%lymphocytes and 10%monocytes. There were petechiae on his anterior chest and both legs and a diffuse hardening in the right axilla but no organomegaly. The physical examination was otherwise noncontributory. A bone marrow biopsy showed normal cellularity without blast infiluation and a relative increase in monocytes. Megakaryocytes were average in frequency but showed no significant platelet maturation. The pathologist's impression was of a reactive phase following toxic depression, "probably due to pronounced exposure to chlordane in July 1980." The patient was discharged to a university medical center for further 2 a 30 0 N u) 9 -.0- I 2 0 0 00 0 m "f? m -9x) ad iY) 000 00 0 *-- N \o a 4- c I 534 EpsteinandOlwoff TABLE N.Major Categories of Blood Dyscrasias Associpted With Chlordane Exposun Published in the ScientifII Literature and From Unpublished zodustry F k i Dyscrasia Published Number of cases Unpublished Total Production defects" Thrombocytopenia Hemolytic anemia Leukemia Unclassifiable 27 1 1 5 14 41 56 1 49 22 Tntn I ~~ ~ ~ ~ 3A 25 59 "Includescases reported as aplasuc anemia (pancytopenia), agranulocytosis,and megaloblastic anaemia. therapy with a diagnosis of "bone marrow depression from chlordane . . . most likely currently in a pre-leukemic state." A bone marrow aspirate 2 weeks later at the referral hospital was hypercellular, with the erythroid series decreased, an increase in the myeloid series with a left shift (57%myeloblasts, 11% progranulocytes), and a marked decrease of megakaryocytes. His disease was diagnosed as acute myelocytic leukemia, later specified as acute monomyelocytic leukemia on the basis of special studies. He was treated with chemotherapy and achieved remission, which has lasted to the present (April 1987). The only other pesticide exposure the patient remembered was occasional malathion use in his garden. In the course of maintaining his automobile he very occasionally cleaned his hands with gasoline after working on the engine, but in his occupation as a truck driver he used a commercial detergent for this purpose. He was also exposed to diesel fumes and particulates and had unsuccessfully Ned a workers' compensation claim in 1981, alleging that his occupation conmbuted to his leukemia. He later filed complaints against the formulator and manufacturer of chlordane, but settled out of court. A more detailed history revealed that in 1975, 5 years before the diagnosis of leukemia, he had bought a 1-gallon bottle of chlordane concentrate in a hardware store and used approximately half of it to treat a utility room,a crawl space, and the perimeter of his house for termites. At that time he used many gallons of a solution prepared by mixing one tablespoon of chlordane with a gallon of water in a pump sprayer. This work extended over several days. He used no protective clothing or mask, but showered after each application. In July 1980, he repeated spraying his garage and outside the house, using a large portion of the remaining half gallon. Carcinogenicity of Chlordane/Heptachlor Chlordane, heptachior, and its metabolite heptachlor epoxide are carcinogenic in mice and in rats, inducing hepatic and extrahepatic tumors following oral administration [17,181. C/H has also been shown to promote hepatic and extrahepatic tumors in mice following initiation by diethylnitrosamine [19]. It should also be noted that commercial chlordane formulations contain carcinogenic "inert ingredients" and contaminants, such as propylene oxide, hexachlorobutadiene, and carbon tetrachloride, apart from some 40 other ingredients so far undisclosed by the manufacturer, formulators, and applicators of C/H. Chlordane and H e p t a c h Exposure 535 Unfortunately animal bioassays are, in general, a poor model for myelotoxic effects in humans. A recent survey of a wide range of human leukemogens showed that all produced only solid tumors in mice or rats, including lymphomas, but no nonlymphatic leukemias [20]. This review noted that the lack of suitable animal models necessitates more reliance "on single case reports or clusters of cases in which chemical exposures are associated with acute leukemia." However, in an unpublished study sponsored by Velsicol. inhalation exposure of monkeys to chlordane, over a dose range from 100 to 1,OOO j.4g/m3for a Wday period, induced a statistically significant incidence of leukopenia and thromobocytopenia with effects at the lowest dose tested [21]. EpidemiologicalStudies Pertinent to C/H Exposure Effects The current series brings the number of reported cases of leukemia or other blood dyscrasia following C/H exposure to 59. Many such blood disorders are uncommon. For instance, estimates of agranulocytosis incidence in a recent 6-nation study ranged from a low of 1.7/106/year for Milan, Italy, to a high of 9.O/1O6/year for Budapest, Hungary [2]. The populatinn-weighted average of the age- and sexstandardized, region-specific agranulocytosis rates was 6.2/106/year for the years 1980-1984 [2]; leukemia, by contrast, is more than one order of magnitude more frequent, occuring in the United States at a rate of approximately 1/104/year ~221. Thus, cohort or cross-sectional studies to examine the relationship of C/H exposure to agranulocytosis would require extremely large populations with known domestic or occupational exposures together with a comparison group in whom such exposures could be excluded. Moreover, the validity of death certificate data for blood dyscrasias is questionable, making readily accessible routinely collected vital data of limited use. The traditional method of studying rare diseases is by a case-control design. For adequate power, this requires sufficient numbers of cases and ascertainable exposure that is not too rare. The international cooperative study of aplastic anemia and agranulocytosis previously cited attempted to identify all cases in a total population of almost 15 million over a span of 2 to 5 years, depending on the country [ 2 ] . Intensive case-finding, achieved only with difficulty, was able to identify only 113 hospital admissions for aplastic anemia in this population. With this number of cases, the prevalence of known C M exposure in the control population would have to exceed 25% to pick up a doubling of risk (P = 0.05, one-tailed, unmatched and equal sized control, 80% power). While past and unrecognized exposures of the general population to C/H is likely common (see below), the rate of recent and known exposure may not be. If, for example, 17% of the total U.S.population had a recent exposure of which they were aware, the same number of 113 cases would require an eightfold elevation of risk to be detectable under the same conditions [23]. Given such serious obstacles to investigation, it is not surprising that only one study, contracted by Velsicol, has specifically examined the relationship between aplastic anemia and exposure to chlorinated hydrocarbon pesticides [24]. Sixty cases of aplastic anemia among North Carolina males aged 15 to 65 years who died between 1968and 1977 were matched for age and race with 120controls. On death certificates usual occupations listed as farming, landscaping, gardening, or pest exterminating were taken as Mcators of possible occupational exposure to unspecified chlorinated hydrocarbon pesticides. The authors found no dosedependent relationship between pesticide exposure and aplastic anemia (RR = 0.67, 95%CI = 0.26-1.7), but were unable to exclude such an association "in view of the several case reports of aplastic anemia following exposure to pesticides . . . [which] may induce idiosyncratic bone marrow reactions in rare individuals" [24]. Velsicol has also funded a number of cohort studies of their employees by outside contractors. None, however. was of sufficient size even to consider the question of blood dyscrasia. A retrospective mortality study of C/H manufacturing workers showed significant excesses of both lung cancer in young workers and cerebrovascular disease, but had no separate classification for blood disorders [25]. With only 1,403 workers being followed, the expected number of aplastic anemia deaths, even with much longer follow-up than was possible here, would have been too few to have been detected. Even for the more common malignancies, the authors acknowledge that "the study population was too small and the period of follow-up too short to translate . . . into a statement that there is no excess risk of cancer" associated with C/H e x p u r e [25]. Two more recent Velsicol-sponsoredstudies of these workers suffer from the same deficiencies and are further burdened by arithmetic discrepancies and inadequate presentation of data, preventing evaluation of the results [26,27]. An independent mortality study of this and three similar cohorts reported nonsignificant excesses of stomach and bladder cancer, but likewise recognized there were too few deaths to draw any meaningful conclusions [28]; short follow-up and rapid labor turnover added to the dificuIties. Pest-control operators (PCOs) have often been exposed to C/H. A cohort mortality study supported by Velsicol identified excess skin, bladder, and lung cancers [29]. Whde only the bladder cancer excess achieved statistical significance, the authors acknowledged the insensitivity of the study since too few person-years of observation were of workers with more than 5 years of employment and who were more than 10years from first exposure. Additionally, there were insufficient numbers of workers to shed light on the question of blood dyscrasia or leukemia. Another retrospective cohort study of 3,827 licensed PCOs in Florida, followed-up at 10 years, revealed significantly elevated rates of lung cancer and excess deaths (O/E= 310.9) for acute myeloid leukemia [30]. Two case-control studies have examined the relationship of agricultural occu- pation to leukemia and related malignancies. One thousand eighty-four death certificates of leukemia cases among Nebraska residents during the years 1957-1974 were age-, sex-, race-, county-, and calendar year-matched with 2,168 control deaths from other causes [31]. These farmers exhibited an elevated risk of acute leukemia in countries where corn was grown in large quantities [31]. Similarly, death certificates from Iowa for 1,675 white males over age 30 years who died of leukemia were matched to two coritrols by age at death and country and year of death [32]. Iowa farmers had a higher risk for chronic or unspecified lymphatic leukemia in counties where there was extensive production of corn and soy bean. There was also an association of mortality from unspecified lymphatic leukemia with amount of corn produced per acre, as well as numbers of milk cows and egg-laying chickens. During the period of these studies, one of the major agricultural uses of chlordane was on corn crops. A case-control study of children with brain tumors matched 84 cases with 76 normal controls and 112 children with other types of malignancies. More children Chlordane and Heptachlor Exposure 537 with brain tumors were found to have had pest exterminations in the household prior to diagnosis of the index child than had normal children (OR = 2.3, P = 0.10)while there was no difference with the cancer controls [33]. Thus, the scanty epidemiological literature, in spite of its limitations and insensitivity, is consistent with an association between C/H exposure and leukemia and other cancers. However none of the studies has sufficient power to be meaningful with respect to blood dyscrasias such as aplastic anemia, agranulocytosis, or thrombocytopenia. For the foreseeable future, then, we will need to continue to rely. as we have in the past, on clinical reports associating C/H exposure with blood disorders. Domestic Exposureto Chlordane/Heptachlor The majority of C/H-associated case reports of blood dyscrasias, for which the circumstance of exposure is known, occurred following domestic application, particularly termite treatment (Table V). Such exposures continue to occur. In 1974, the U.S. Environmental Protection Agency proposed the cancellation of virtually all agricultural uses of CM, largely on the basis of its demonstrated animal carcinogenicity, which was found to pose an "imminent hazard.'' An exception was made for subterraneah use against termites by PCOs on the s s u .@Tun that this entailed little or no exposure to the general population. However, subsequent information and experience has clearly proven the contrary. There are no firm data on the number of homes in the United States that have been or are being treated for termites with C/H, although according to governmental estimates most of the nation's homes would have been or could be so treated [34]. The National Pest Control Association, whch represents many structural pest control firms,estimates that 1.5 million homes per year are treated for termite control 1351. Available monitoring data have demonstrated that a high proportion of termite-treated homes become contaminated with C/H and that such contamination can persist for decades after treatment. In slab construction houses in which the heating and ventilation ducts are below the ground floor, C/H residues can be carried into the air and onto surfaces of the living areas [36]. In a survey of 435 U.S. Air Force homes treated from 1964 to 1978 and monitored in 1979, 60% had chlordane levels over 1 pg/m3; the mean concentration in 77%of homes with detectable levels was 2 pg/m' [371. Similarly, a recent survey of 1,110 air samples from 422 homes in 14 counties TABLE V. Major Categories of Published and Unpublished Blood Dyscrasias Associted With Chlordane Exposure by Exposure Mode Dyscrasia Domestic' Occumtlonal Pest control operator Farming Unknown Total Pmduction defects Thrombocytopenia Hemolytic anemia Leukemia Unciassifiable Total 16 4 5 i7 21 5 5 2 18 41 26 11 49 2 3 24 59 'Includes termiticide and other home, lawn, and garden applications by householder 538 EpteinandOzonoff of New York state showed that levels of chlordane in excess of 5 pg/m3 were found in 33% of 289 nonliving area samples and 7% of 661 living area samples [38]. In 1985 the Commonwealth of Massachusetts banned tenniticidal uses of chlordane, and in 1986New York followed, adding the closely related cyclodiene pesticides Aldrin/Dieldrin to the list. Both states took note of the availability of noncarcinogenic alternatives to these termiticides. In March 1986, Japan banned the importation of all C/H-containing products because of their public health risks and high potential for contaminating the environment [39]. On December 31, 1986, the Environmental Protection Agency issued a new standard for C/H[a]re,stricting continued usage to licensed applicators on the unfounded assumption [4143] that such application does not result in contamination. EPA also called for further studies on the hazards of C/ H,notwithstanding the following considerations: Some 14 years earlier the Agency had found, on the basis of extensive hearings, that agricultural uses of C/H posed "imminent hazards" because of carcinogenicity and other toxic effects; that an extensive subsequent literature abundantly confirmed and extended data on such hazards; and that human exposure following termite treatment could be subsequently greater than that caused by food contamination following agricultural usage. In July 1987, following persistent pressure by environmental and consumer groups, the manufacturer of C/H termiticidesentered into an agreementwith the U.S.Environmental Protection Agency to halt production. The present case series of blood dyscrasias associated with C/H exposures lends weight to the urgent need for legislation creating a national program for monitoring homes known to have been treated to detect persistent contamination with these highly dangerous pesticides. SUMMARY 1. We present 25 new cases of blood dyscrasias, including production defects, thrombocytopenic purpura, and leukemia, the majority following home termite treatment with chlordane/heptachlor. 2. These new cases are consistent with previous literature reports on the association between exposure to C/Hand other chlorinated hydrocarbon pesticides and blood dyscrasias. 3. The new leukemia cases are consistent with epidemiological studies on associations between exposure to chlorinated hydrocarbon pesticides, including C/H, and leukemia and other cancers among pest control operators and in areas where corn and soy farming was prevalent. 4. The new leukemia cases are also consistent with numerous studies on the carcinogenicity of C/H in several strains of mice and rats, since there are no satisfactory animal models for blood dyscrasias and recognized human leukemogens induce solid tumors in rodents as opposed to leukemia. 5 . In view of the many millions of U.S.homes that have been, and continue to be, treated for termites with C/H and the relatively high rate of subsequent persistent contamination, the U.S.government, and all other governments, should immediately institute a national monitoring program of all homes known to have been treated to detect persistent contamination with these highly dangerous pesticides. `.1 '* REFERENCES 1. 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