Document MJmOXXK8XXJ7eZNm5bRjXMnpk

FOR ADMINISTRATIVE USE LIMITED DISTRIBUTION NOT FOR PUBLICATION TO : Director, Center for Disease Control FROM : Chronic Diaeaaea Division Bureau of Epidemiology PUBLIC HEALTH SERVICE-CDC-ATLANTA EPI-79-AA-A juiy 22. I960 SUBJECT: FCB Levels in a Community with Exceptional Exposure to DDT, Triana, Alabama SUMMARY The geometric mean serum level of polychlorinated biphenyls (PCB) of 45B persona in s comunityvide study was 17,2 parts per billion, with S0X-90X having levels within the range found in other comunity groups, PCB levels were found to be directly related to age--the older the sge group, the higher the PCB level--even when controlled for other variables positively associated with PCB level: male sex, fish consumption, serum cholesterol level, and alcohol consumption. No major point source of PCB contamination was found, snd fish taken in the drainage of a major population center had mean PCB levels below the current enforceable Food and Drug Administration tolerance of 5 parts per million. Serum PCB levels were positively associated with measured blood pressure, with gamne-glutamyl transpeptidase level (a liver function test), and with serum cholesterol level, all independent of major confounding variables. These findings, along with the unknown remote consequences of PCB accumulation in tbe body, support our recommendation for Triana residents to avoid eating fish taken from contaminated areas. INTRODUCTION Polychlorinated biphenyls (PCB) are complex mixtures of fat-soluble aromatic hydrocarbons that were manufactured in the United States from 1929 until 1977. Their thermal end electrical ineulating properties led to widespread use in transformers and capacitors. They were also used in plasticisers, inks, adhesives, pesticide extenders, and carbonless duplicating paper. PCBs are now widely distributed in the environment. Like DDT residues, PCBs are accumulated and concentrated by fish. Nonoccupattonal human exposure to PCBs occurs primarily via the diet. The Food and Drug Adminiatretion (FDA) reduced the tolerance for PCB residues in fish from 5 to 2 parts per million (ppm), but this reduction is stayed pending further hearings. Once ingested, PCB residues concentrate in adipose tissue, and human metabolites of these compounds have not been studied. Concern for human accumulation of these persistent compounds is baaed on their hepatic carcinogenicity in rodents and reproductive effects and immune response changes In several species. Human health effects associated with heavy PCB exposure include chloracne, liver function abnormalities, and serum lipid concentration abnormalities. HONS 211215 BACKGROUND In Hay 1979 a communityvide atudy was conducted in Triana, Alabama, where the population hae had exceptional exposure to DDT residues as a result of eating Locally caught fish. During laboratory analyses of serum specimens for DDT residues, interference from PCB* was encountered. A pilot effort suggested that some Triana residents had PCB levels above the range found in the general population and that a strong correlation existed between serum PCli and DDT levels. The background, methods, and results of thia cross-sectional study are described in EPI-79-44-3 (dated January 31, 19B0). To confirm these findings and to explore the possible relation of PCB levels to health parameters, we analyzed sera frozen at -60 C in the May study for PCB levela. In the meantime, the U.S. Environmental protection Agency (EPA) conducted exten sive environmental sampling for PCBs in sediments, water, soil, sewage, and fish. These efforts were complemented by the Department of Army and the National Aeronautics and Space Administration on Redstone Arsenal and by the Tennessee Valley Authority, bow level* of PCBa were found in a variety of aemplee, but no major point source of PCB contamination wet discovered. Indian Creek, which receives drainage from Redstone Arsenal and from Huntsville (population 13B,000), enters the Tennessee River at Triana, Fish taken from Indian Craek and Cataco Creek, the embayment on the opposite bank of the Tennessee, had PCB levela many times those found in fi*h taken in other embaymenta or in the Tennessee River (Appendix 1). A composite sample from 6 Indian Creek catfish averaged 3.64 ppm (range 0.35 - 7.57 ppm), and from 4 Cataco Creek catfish 4.34 ppm (range 1.04 - 6.28 ppm). Catfish from 13 other sites in tht river system averaged 0.59 ppm (range " 0.05 - 4,94 ppm; H " 73). The EPA findings corroborate those reported by CDC for 12 Indian Creek fish that had PCB level* ranging from 0.36 - 3.32 ppm with a mean of 1.08 ppm. A strong positive correlation existed between log PCB and log DDT levela in 47 individual catfish taken from the Tennessee River system (Pearson correlation coef ficient 0.697; p<10"^). This correlation resulted from correfation coefficients above 0.9 in catfish taken from Indian Craak, from Tennessee River mile 310 (the point at which Indian Creek enters the Tennessee River), and from Tennessee River mile 275 (downstream at Wheeler Dam), Catfish taken at other sites in the Tennessee River system had no significant correlation between log PCB and log DDT levels. Again, these EPA data corroborate the CDC findings of a high log PCB-log DDT correlation in 12 fish taken in Indian Creek (total DDT range 1.2 - 498.4 ppm; r 0.67). METHODS ., Study design, clinical chemistry, and laboratory analyses are described in EPI-79-44-3, and only supplementary information i* given here. Single readings of systolic and diastolic blood pressure were taken on seeted participants 12 year* and older, according to procedures used by the Health and Nutrition Examination Survey (1). Normal blood pressure wee defined e* a systolic measurement leae than 140 an Hg and a diastolic measurement leas than 90 an Hg. Borderline hypertension was defined es e systolic measurement of 140-159 na Kg or a diastolic measurement of 90-94 on Hg. Definite hypertension waa defined ae a systolic measurement of 160 na Hg or greater or a diastolic measurement of 95 on Hg or greater. A body me** index for obesity was calculated from welght/height*, where R 2 for males, 1.5 for females. Social class was measured by Hollingshead Index (2h Analysis of acre for PCB* a* Aroclor* 1260 waa performed at CDC. After protein denaturation with 1 ml of methanol, 0,5 - 2.0 ml aerum was extracted with 5 ml hexane 3 times. The combined extracts were concentrated to a volume of 1 ml, and DDT residue* were adiorbad onto a tilver nitrate/*ilice column (Needham LL, Smrck AL, Head SL, Bursa VW, Liddle JA, Column chromatography separation of PCB* from DDT and metabolite*. Manuscript submitted for publication). After hexane elution and *TJse of trad* name* is for identification only and doea not constitute endorsement by the Public Health Service or the U.S. Department of Health and Human Services. 2 MOMS 211216 concentration, the sample was analyzed on an electron capture gee chromatograph, with a 31 se 30 column. Injector, column, and detector temperaturaa were ISO, 195, and 330 C, respectively. Quantifies!ion vaa made by adaptation of the Webb-McCall method (3) to the Sigma I data ayatem, with Aroclor 1260 uaad aa the calibration atandard. The limit of detection vaa 3 parta per billion (ppb). Quality control over time wae assured with 2 poola of bovine aerum spiked in vitro with Aroclor 1260, 1 pool of unspiked bovine aerum, and 1 human pool conai.ati.ng of aere from Triana residents; the last pool was introduced into the daily run as a "blind" satapla. Recovery was 96.5t when PCB*-free bovine serum was spiked with 61 ppb Aroclor 1260. RESULTS PCB Levels Of the 500 persona giving blood specimens in the study, 658 gave sufficient serum for PCB (Aroclor 1260) analysis. Those persona without sufficient aerum for PCB analysis were younger (mean age 19.1 vs 32.2 yra), were more often male (57,1 va 62.SX) and had a lower geometric mean total DDT level (52.5 va 79.6 ppb). For individuals with PCB measurements, the geometric mean PCB level was 17,2 ppb with a atandard deviation of 20.8 (arithmetic mean 22.2 ppb; S.D. 22.3; range "3.2- 157.9 ppb). Ninety-eight persona (21,6X) had PCB levels greater than 30 ppb, 60 (13,12) had levels 360 ppb, 61 (9.OX) had levels 350 ppb, and 7 (1.5X) had levels 3100 ppb. Aa with DDT, age was the moat powerful predictor of the log PCB level (Pearson corrslation coefficient " 0.56) (Table 1). Kales had a higher geometric mean PCB level than females (23.5 va. 13.7 pb; p <.0001), a difference present in each group (Figure 1). Race had no independent effect in multiple regression analysis. Fish consumption before publicity about DDT contamination correlated positively with log PCB levels independent of ege (Figure 2). The commercial fishermen and their adult family members had a higher geometric mean PCB leval than the other study participants aged 319 years (32,6 vs. 20.2 ppb, p " .0003). Years of residence, proximity to cotton fields, farm work, and social class were not associated with PCB levels independent of age, sex, and fiah consumption. In contrast to our finding with DDT, breast-fed children did not have significantly higher PCB lavela than bottle-fed children. Table 1 Relative Weight of Significant Correlated of Log PCB in Serum, Triana, Alabama, Hay 1979 Variable Standardised^ Coefficient F R2 Change Age .531 116.1 .310 Sex .223 23.8 .128 Fiah coaesnption .210 30.0 .062 Body mate index -.162 10.7 .015 Cholesterol .167 11.9 .015 Alcohol consumption ,117 8.5 .012 ' .523 MONS 211217 3 Fig. t PCB LEVELS tN SERUM SPECIMENS, BY AGE GROUP AND SEX, TRIANA, ALABAMA, MAY 1979 Alcohol consumption was positively associated with log PCB levels when controlled for age, sex, fish consumption, and serum cholesterol level. Cigarette smoking was not associated. The 10 adults who had taken ensyme-inducing medications in the preceding yeer had a lower geometric mean PCB level than the rest of the adult study population (13.7 vs. 21.7 ppb, p .03). Serum cholesterol was positively associated with log PCB level independent of the other variables included in Table 1. Serum triglyceride or high density lipoprotein cholesterol (HDLC) made no additional independent contribution. Obesity had a significant negstive correlation with log PCB. Height loas, gamma-glutamyl tranapeptidase (GT), and creatinine were insignificant when included in multiple regression. Health Effects Nona o{ the following health indices were associated with log PCB independent of age group: prevalence of illness or weight loss in the preceding year, use of medication, use of medical cars, history of heart disease, or percentsge of pregnancies ending in miscarriage, stillbirth, or infant death. Rates of measured borderline end definite hypertension among study psrticiponts were 302 higher than expected on the basis of national rates for a population of the same age, race, and sex composition (_1_). Curing the study, 3 persons were referred to emergency medical services for extreme hypertension, and sera for PCB levels were not obtained. Log PCB did maka a significant contribution to explaining the variability of log systolic and log diastolic blood pressure in multiple regression analyses (Tables 2,3). Ubeaity and sex were stronger predictors of blood pressure than log PCB. Age waa the strongest predictor for the systolic measurement. The PCB effect on blood pressure wea indapendent of social class. For systolic blood pressure, addition of serusi cholesterol or triglyceride to the list of independent variables rendered the PCB contribution insignificant; addition of smoking habit or race made no additional contribution. For diastolic blood pressure, however, addition of serum cholesterol, triglyceride, smoking habit, or race made no additionel contribution and did not nullify the PCB effect. - 4 HONS 21121S Table 2 Relative Weight of Significant Corralatea of Log Systolic Blood Preaaure, Triana, Alabama, May 1979 Variable Age Sex Body Maaa Index Hollingahead Index Log PCB Standardised^ Coefficient .427 .177 .158 .123 .111 F 52.9 13.0 9.0 R. 7 4.2 R2 Change .355 .020 .011 .015 .007 .408 Table 3 Relative Weight of Significant Corralatea of Log Diastolic Blood Pressure, Triana, Alabama, May 1979 Variable Standardised** . Coefficient F R2 Change Body Mass Index .258 18.8 .068 Sex .198 12.8 .083 Log PCB .176 8.2 .063 Age .151 5.2 .015 Hollingahead Index . 109 5.3 ` .011 .241 Since many factora--age, a**, obesity, end aocial claaa--influence blood preasure, aimpla correlation of blood preaaure measurement and FCB level ahowa a wide acatter. Many peraona with hypertenaion have comparatively low sarum PCB levela, and converaely aoae peraona with PCB levela of 100 ppb or graater are normotensive. The trend of peraona with hypertaaaioa to have higher PCB levela ia preaent in both young and old adult age groupa (figure 3). The correlation between log PCB and log DDT aeruai levela waa very high (Pearaon correlation coefficient " 0.83, Figure 4). Deapite thia, no DOT effect on blood preaaure weS evident when log PCB and log DOT were both included in regreaaiona controlled for ege or obeaity. Log QT waa poaitively correlated with log PCB (Figure 5) independent of alcohol consumption and age (Table 4). The other liver function teata (total bilirubin and aerum glutamic pyruvic tranaaeinaaa) were not ao affected. Addition of log DDT as a third independent veriable to log PCB and age made no aignificant contribution to log CT. Tha relative contributions to log CT of alcohol conaumption, log PCB, and log DDT are unknown aince the collinearity of the latter 2 reaulta in no aignificant contribution whan theae 3 independent variablea are uaed to predict log CT. Aa mentioned above, aerum cholesterol--but not triglyceride level--was a aignificant independent predictor of aerum PCB level in atultiple regression analysis. Ua than uaad log PCB aa an independent variable to predict aerum lipid levela. Although a weak correlation existed betwean log PCB and log triglyceride (Pearson -5 HONS 211219 frf.t pea LEVELS IN SERuM SPECIMENS, St AGE GROUP ANO FISH MEALS PER MONTH, TRIANA, ALABAMA, MAY itrt r>9 3 SERUM PCS LEVELS f.' 10 ANO HYPERTENSIVE P> ts" ,l' AGE GROUP. TRIAN*. 4. ** MAY 1970 44 40 0 noamotensivs S 0 HYPERTENSIVE ( ) NUMBER St { t4(0 If*' IS It i 1*91 S' S III) 41 0 <I-M t*-4S 4P V* AGE GROUP <VRS) Fig.4 CORRELATION BETWEEN LOG DOT ANO LOG PCB LEVELS IN SPECIMENS, TRIANA, ALABAMA, MAY 1979 i* nurvi t.i I.B- 2 15 V * 4 i an ow Of- o.s- 0 3- * ** + 4 * **|* * i i mi ** <4* * !* # It * *;. wwia # . *.i %;ntiM*.*; , ' T-rn t It** I I*M*t l .* --t-- 0.4 --1-- o. 1.2 i-- IS 2 0 2.4 LOG DDT (m*/D t .B29 P< lO-* n 45T 1 .31 x + .JIT --r-- T- 2.B 3.2 J i MONS 211220 6 r/g.S CORRELATION BETWEEN LOG PCB AND LOG GAMMA-GLUTAMYL TRANSPEPTIDASE LEVELS IN SERUM SPECIMENS, TRlANA ALABAMA, MAY 1979 * Tab la 4 Relative Waight of Significant Corral atea of Log Cana-Glutaayl Tranapaptidaaa in Serua, Triana, Alebaaa, Nay 1979 Variable Standardised^ Coefficient W Change Alcohol consumption .242 24.S .101 Age .200 12.6 .082 Log PCB .169 8.5 .019 .201 correlation coefficient 0.299, p * 8.5 X 10"9), no aaaociation vaa found between thaa independent of log choleaterol and log CT, both better predictora of log triglycerida laval. There wee no correlation batwaen log PCB and HOLC. In contraet, log PCB aa an independent variable waa weakly aaaociatad with choleaterol (Figure 6); thia aaaociation exiated independent of log triglyceride and age (Table 5). Whan log DDT waa added ea a fourth independent variable in predicting . log choleatarol, ita contribution and that of log PCB becaae ineignificant. Thua, the relative contribution of log PCB and log DDT to predicting aerua choleatarol ia unknown becauae of their col linearity. 7 HONS 211221 Table 5 Relative Weight of Significant Correlate* of Log Cholesterol In Serum, Trlana, Alabama, May 1979 Variable Standardised^ Coefficient F R2 Change Log triglyceride Age Log PCB .355 .309 .127 60.6 34.6 5.7 .221 .131 .011 .362 Fig.6 CORRELATION BETWEEN LOG PCB AND CHOLESTEROL LEVELS IN SERUM SPECIMENS, TRIANA, ALABAMA, MAY 1979 Ho comparable published data exist on aerum PCB level* in the general population of the United Statea. The only study with a large number of community volunteers (4_), sampled in I960, ia difficult to interpret because no limit of detection won specified and no quality assurance in PCB measurement was described. He*n* for subgroups with measurable residues (43X of the atudy population) ranged from 1,50 - 20.6 ppb, with a aiaximum individual measurement of 29.0 ppb. One hundred ten person* in Bloomington, Indiana (1977), without occupational PCB axpoaure (aludge-users and controls), had a mean aerum PCB level of IS,8 ppb (S.D. 10,8) with a range of 6 - 79 ppb (5, plus per sonal communication from Matthew K. Zack) The CDC Toxicology Laboratory has unpublisht data on 2 other community groups: In Billings, Montana (1979), 17 resident* had a mean PCB level of 7.5 ppb with a range of 2 - 30 ppb; in Michigan (1978-79), 370 residents had a mean of 8,0 ppb (S.D, 7.2) with a range of 1 - 61 ppb. Unpublished *8 HONS 211222 data from (he Michigan Department of Public Health On lb notrfisheater sampled in 1973-76 show a mean aerum PCS level of 17 ppb with a range of 7 - 62 ppb (6). The aerum PCB levels of most Triana residents fall within the range seen in other communities in the United States. Since PCB residue* appear to accumulate with age and are higher in males, only age- and sex-standardised comparisons are appropriate. The 10X-20X of Triana participants with PCB levels somewhat above those found in other investigations tended to eat fiah more frequently. The only major dietary source of PCBa in the United States is fiah (7_). Moat fish contain PCB levels well below 1 ppm in the edible portion( although freshwater fiah from polluted waterways, such as the Hudson River or Lake Michigan, may have much higher level*. The Michigan Department of Public Health (6) investigated 71 sport fishermen who consumed >26 pounds per year of fish taken from Lake Michigan (M fish eal/wk). Their ne7n serum PCB level was 77 ppb with a range of 25 - 366 ppbThe mean PCB level* in whole raw fish in Lake Michigan for the 3 years 1972-1976 were 13, 19, and 23 ppm for trout and 11, 12, and 10 fpa for coho aalmon, PCB levels in cooked fish collected from the Michigan fishermen were much lower: 1,03 - 6,67 ppm for cooked trout and 0.68 - 5,38 ppm for cooked salmon. Thus the level of fiah contamination by PCBa in Lake Michigan is higher than that in Indian Creek; the mean and range of human PCB levels in Michigan fishermen are higher than the mean and range of PCB levels in Triana resident* eating comparable amounts of fiah. Nonetheless, the higher than expected number of Triana residents with high PCB serum value* ia probably explained by the consumption of fiah that at present have a mean PCB level very close to the stayed FDA tolerance of 2 ppm. The FDA tolerance for PCBa ia based on a 200-mg total dose safety limit, the lowest PCB dose thought to have caused overt Yuaho disease in the 1968 Japanese episode of rice oil contamination O). However, Yuaho disease resulted from a mixed exposure to PCBa, chlorinated quaterphenyls, and chlorinated dibentofurans, the last of which are more toxic than PCBa. The FDA recommendation for maximum allowable ingestion of PCBa over a protracted period ia 1 pg/kg/day. The only study of a population exposed to dietary PCBa of this magnitude is that in Michigan (mean daily dose " 1.7 pg/kg/day; range * 0.69 - 3.96), which identified no adverse health effects. However, blood preaaure measurements, serum lipida, and gsnma-glutamyl transpeptidas* teats were not done. The high correlat ion between total DDT and PCB residues in serum specimens is explained by their common dietary source in fish and aimilar accumulation in the body once ingested. We have laboratory data to demonstrate that carryover of DDT residues into the PCB measurement did not occur. Whether DDT residues affect the toxicity or metabolism of PCBa is unknown. For another pair of chlorinated hydrocarbons, kepone exposure is known to increase the excretion of lindane in rata (8). Both DDT and some PCB congeners induce cytochrome P6S0-type mixed function oxidaaeT, and some PCB congeners induce cytochrome P648-type enzymes ae well (9-11), No other studies have been conducted to determine wiieTher PCBa affect blood preaaure, The contribution of PCBa to tha systolic measurement wee email end of borderline significance; however, the PCB contribution to the diastolic measurement wee unequivocally significant. We think thet the exceaa prevalence of measured hypertension among Triana raaidenta ia not explained by their PCB levels. The hypertensiom axeaaa could be due to the environment in which they were measured, a noisy gymomeiiae, whereas the national prevalence data used for comparison were generated in medical vena. The absence of a control group with blood preaaure measuremeote does not weakan our observation of tha trend of persona with higher serum PCB levels to have higher blood preaaure readings, Ue can think of no reason why participants with higher PCB levels would react to tha blood pressure measurement in a different faahion, end indeed neither participant! nor measurera had knowledge of PCB levels at the timt of the study. Our study confirms many others (12-13) that PCB exposure ia associated with liver function teat changes. In this popuTatTon, CT was mors sensitive than the other liver function testa. The large study population allowed demonstration of a small PCB-CT association independent of alcohol consumption, a stronger predictor of CT level. Deapita relatively low PCB levels in moat Triana residents, we were ebla to confirm aspects of other human studies which show an association between PCB exposure 9 HONS 211223 nd lipid levels (^, _12_ - _19_) . In our analyses, PCB level (as dependent and independent variable) wee positively sss ocieted with serum cholesterol level independent of other major confounding variable*. Discrepancies between our results and those of others finding a PCB-triglyceride association (5^ _14 - may be due to this control of confounding, or to the lower PCB burdens of the Irian* population, or to differing nixed exposure*. We were unable to confirm the suggestion (19) of an inverse association between HDLC and PCB. ~ The long-term implication* for human health of the associations between PCB level and blood pressure, liver function, and serum cholesterol are unknown. A recent study of the causes of death in a cohort of 2,367 PCB workers showed no excess of nervous or circulatory system causes of death (Brown DP, Jones a. Mortality and industrinl hygiene study of workers exposed to polychlorinated biphenyls. Unpublished manuscript. National Institute for Occupational Safety and Health). A preliminary report (20) of an increase in malignant melanoma and pancreatic cancer among PCB-expoeed workers haa not been eubatantiated by this cohort mortality study, which showed slight exceasea of mortality due to rectal and liver cancer and due to cirrhosis of the liver, none of which wae statistically significant. Since 802-907. of the Triana study population haa PCB level* in the range probably found in the general population, we would not expect to be able to detect differences between causes of death in Triana and causes in the general population aaaociatcd with PCB exposure. Our preliminary finding of associations between serum PCB level and blood pressure, liver function, and cholesterol concentration merits further medical tudy--eapecially since the associations are found in a population with PCB level* overlapping those found in other coimsunitiea. Triana remain* unique in the degree of DDT metabolite burden of its citizens, the source of both PCB and DDT being the consumption of contaminated fiah. Given the uncertain remote consequences that theae 2 compound* may have on human health, especially since they both accumulate in the body, we recommend that Triana residents avoid eating fiah taken from contaminated areas. REFERENCES 1. Health and Nutrition Examination Survey for 1971-74, Washington, DC (DHEW publication No. (HRS) 78-1648 - Series 121, No. 203). 2. Hollingahead AB, Redllch FC. Social Class and Mental Illness: A community study. New York; John Wiley 6 Son*, 1938. 3. Webb RG, McCall AC. Quantitative PCB standards fbr electron capture gas chromatography. J Chromatogr Scl 1973*,ll*.366-73. 4. Finklea J, prlaster LE, Creaaon JP, Hauser T, Hlnnara T, Hamser Dl. Polychlorinated biphenyl residues In human plasma expose a major urban pollution problem. Am J Public Health 1972;62:645-51. 5. Baker EL, Landrlgan PJ, Glueck CJ, et al. Metabolic consequences of exposure to polychlorinated biphenyl* (PCB) in sewage sludge. Am J Epidemiol (in press). 6. Humphrey HEB. Evaluation of change* of the level of polychlorinated biphenyl* (PC*) In human tiaaue. Final report on FDA Contract No. 223-73-2209, 1976- Washington, DC: II.S. Department of Health, Education, and Welfare, Food and Drug Administration. 7. Cordle F, Corneliussen P, Jellnek C, et el. Human exposure to polychlorinated biphenyls end polybrominsted biphenyls. Environ Health Per9p 1978;24:157-72. 8. Chadwick RU, Copeland MF, Rosenateln L. The effect of kepone exposure during gestation and lactation on the metabolism of lindane by weanling rats, Toxicol Letters 1979;4:247-52. 9. Bickers DR, Kappas A, Alvares AP. Differences In induclbillty of cutaneous end hepatic drug metabolizing enzymes and cytochrome P-450 by polychlorinated biphenyls snd 1,1,l-trlchloro-2,2-bls(p-chlotophenyl)ethane (DDT). J Phsrm Exp Thersp 1974;188:300-9. 10. Alvsree AP, Bickers DR, Kappas A. Polychlorinated biphenyls; a new type of Inducer of cytochrome P-448 in the liver. Proc Net Acad Scl USA 1973;70;1321-5. 10 HOMS 211224 11. Alvares AP, Flschbeln A, Anderson KE, Kappas A. Altar*tIons in drug metabolism In workers exposed to polychlorinated biphenyls. Clin Pharn and Therap 1977{22:140-6. 12. National Institute for Occupational Safety and Health. Criteria for a recommended standard....occupational exposure to polychlorinated biphenyls (PCBs). Washington DC: II.S. Government Printing Office, 1977. (DHEW (NIOSH) Publication No. 77-225), 13. Flschbeln A, Wolff MS, lilts R, Thornton J, Sellkoff IJ. Clinical find ings saong PCB-exposad capacitor manufacturing workers. Ann NY Acad Scl 1979;320: 703-15. 14. Nagnl J, Purukawa M, Yae Y, Ikeda Y. Cllnlco-chealcal Investigation of chloroblphenyla poisoning--especially on the eerum lipid analysis of the patients. Fukuoka Acta Med 1969;60:475-66. 15. Ucawa H, Ito Y, Notool A, Kataukl S. Hypertriglyceridemia resulting from Intake of rice oil contaminated with chlorinated biphenyls. Fukuoka Acta Med 1969; 60:449-54. (English translation: Air Pollution Technical Information Center TR 1497, U.S. Environmental Protection Agency, Research Triangle Perk, NC). 16. Uzeva H, Ito Y, Notoml A, Horl S, Ikeure T, Kataukl S. Clinical and exparlnental studies on the hyperglycerldemle induced by oral ingestion of chlori nated biphenyl*. Fukuoka Acta Med 1971;62:66-73. 17. Okumura M, Maauda Y, Nakumuta S; Correlation between blood PCB end serum triglyceride levels In patient* with PCB poisoning. Fukuoka Igaku Zaashl 1974; 65:84-7. (Engllah translation: NIH-76-142C). 18. Sak M, Ahlera I. Serum lipid change* under condition* of occupational axpoaure to chlorinated biphenyl* (author's translation). Cask Dermatologle 1977;52:62-5. 19. Smith AB, Cartald* PS, Cluack CJ, et al. Lipid and llpoprotaln alterations: occupational expoaurt to polychlorinated biphenyl. Clin Rea 1978;26:549A, 20. Bahn AK, Roaenwalk* I, Herrmann N, Cover P, Stallman J, O'Leary K. Melanoma after exposure to PCBs. N Engl J Med 1976;295:450. Kathleen Krelas, M.D, EIS Officer Special Studies Branch Chronic Diseases Division Bureau of Epldamlology Chief Toxicology Branch Clinical Clfanlstry Division Bureau of Laboratories Matthew M. Zack, M.D. Medical Epidemiologist Chronic Dlsasaas Division Bureau of Epldamlology Clinical Chemistry Division Bureau of Laboratories Clark W. Heath, Jr., M.D. Director Chronic Disease* Dlvlalon Bureau of Epidemiology 11 MOMS 211225 DISTRIBUTION: Nailing Raya 33,1,2,3,6 Clyde Foster, Mayor, Triana, AL 35758 Sanford W. Harvay, Jr., Director, Enforcement Division, Environmental Protection Agency, 343 Courtland Street, N.E., Atlanta, GA 30308 David Harrla, Public Affaira Officer, U.S. Army Miaaile Material Readiness Coonand, Redttona Araenal, AL 35809 Wayland Hayea, M.D., Profeaaor of Biochemistry, Diviaion of Toxicology, Room T-1219, Vanderbilt University Medical Center, Naahville, TN 37232 Harry Moore, Ph.D., Chief, Environmental Planning Diviaion, Tennessee Valley Authority, 401 Building, Chattanooga, TN 37401 Larry Lane, Ph.D., Mississippi State Chemical Laboratory, P.O. Box CR, Mississippi State University, MS 39762 Frederick Ruts, Ph.D., Ecological Monitoring Branch, U.S. EPA, TS-768, 401 N St., SW, Washington, DC 20460 George Stabbing, M.D., Dept, of Army, Office of Surgeon General, Attn: D.A.S.C.p.S.P.'O, Washington, DC 20310 Thomas Chester, M.D., Chief Epidemiologist, State Departaient of Public Health, State Office Building, Montgomery, AL 36130 Rebecca Hanmer, Regional Administrator, Environmental Protection Agency, 343 Courtland Street, N.E., Atlanta, CA 30308 John R. Weasel, Scientific Coordinator, Offics of Regulatory Affaira, Food and Drug Administration, 5600 Fishers Lana (HFC-13), Rockvillt, MD 20852 _ Marian Bishop, Ph.D., Chairman, Dept, of Comnunity Medicine, Univeraity of Alabama. 201 Governore Drive, S.W., Huntevllle, AL 35801 Jan Terr, National Wildlife Federation-Conservation Diviaion, 1412 16th St., N.W., Washington, DC 20036 Cheater R. Crawford, Ph.D., Aeaociete Profeaaor of Pharmacology, Meherry Medical - College, Neehville, TN 37208 Ralph Brookea, Ph.D., Aaeiatent Director, Diviaion of Water Reeourcee, Region IV, Tenneeeee Valley Authority, 448 Evens Bldg., Knoxville, TN 37902 Sandra Straaaman-Sundy, Projact Officar, National Human Monitoring Program, Survey 6 Analysis Uiviaion, (PS-793), U.S. Environmental Protection Agency, 401 M Street, ' S.W.. Washington, DC 20460 ' C. A. Reich, M.D., M.P.H., Regional Health Administrator, HHS Region IV, 101 Marlette Tower, N.W., Suite 1007, Atlanta, GA 30323 Mac Ray Gtaque, M.D., 01 in Corporation, Division of Hums*'Affairs, 120 Long Ridge Road, Stamford, CT 06904 Burton S. Shook, M.D., Httlth Officar, Madison County, P.O. Box 425, Huntsville, AL 35804 David Brown, Epidemiologist, National Institute for Occupatlonel Safety and Health, 4676 Columbia Parkway, Cincinnati, OH 45226 Ceorga White, Director, Atlanta District, Food and Drug Administration, 880 W. Peachtree Street, N.W., Atlanta, GA 30309 Col. Robart B. McClean, Cowmtndtr, Pox Army Hospital, Redatona Araenal, AL 3S809 Jacob Savage, Ph.D., Assoc. Profeaaor, Biology Dept., Alabame A4H, Normal, AL 35762 Paul Roper, Regional Consultant, NI0SH, HHS Region IV, Dlvlelon of Preventive Health Services, 101 Marietta Towar, Suite 502, Atlanta, GA 30303 Robert A. Wendell, Regional Administrator, U.S. Dept, of Labor - 0SHA, 1375 Peachtree Street, N.W., Suite 587, Atlanta, GA 30309 J. Gordon Edwards, Professor of Entomology, San Jose State Univeraity, Washington Square, $an Jose, CA 95192 Carolyn B. Goff, Librarian, B.B. Comar Memorial Library, 711 North Broadway, Sylocauga, AL 35150 James E. Karbottle, D.V.M,, USDA, FSQS, Epidemiology Branch, BARC-Eaat, Building 319, Beltvitle, MD 20705 Harold Humphrey, Ph.D., 3500 North Logan, P.O. Box 30035, Lansing, MI 48909 12 MOMS 21122* APPENDIX 1 H*M< lMtl M4 Correlation* of PC* .at 00T LVtl* ifl C*tfih . Ttanttt.t ki.*r (T* lit* ftwafeor of H*h PC* re* Rin| . <m) NttnOOT T , (PP>- OOT kanpt - CP* lo* PCI'l*! on Carrtlac ion Cotlliritnc TM* *00 * 0,0J 0.11 - 1,15 0.1 TM 0 * 0, 1* 0.05 - 0.50 0.1 Paint tack klvtr 5 0.5* 0.*} - 1,04 l.OJ 0.1 - 1.0 -0.51* TM J40 * 0. JJ 0.10 - 0.TO 1.1 Hint *i*r * o.*> 0.11 - 0.75 O.cj O.J * 1.0 -0,110 lati.a Crttk * J,o* O.JJ - Ml Jlf.l 15.5 - *11.0 o.m TM 110 * 0.M 0,*1 - 1.11 J.l O.t - 11.0 o,* Cat tea Ctatk * 4, 1,0* - O.li 00.0 l.J - 1J.1 0.1*1 liwitm Crtak * 1.10 0,15 - J.10 O.OJ Niu erttk * i.i* O.W * *.* O.M 0.0 - It.l 0.05J TM 10V * o.o* 0.04 - 1.1* . t.l 1.0 - 00.J O.SOJ tlk tl.tr * o.ji 0.10 - O.M l.JJ 0.0 - l.J -O.M* tprint Crttk * O.JJ o.if - a.if 1.0 TM in TM JW * 0.51 o, jo * o.n 0.) 1.1 - 10.1 0,001 * o.o* O.OJ 0.11 0.1 * tro* 4ttt KO*i4t4 %y (h IirwBt.l lWi*h cootie* Agtntr **4 Ttnottttt v.tltr tathotlt* ' illRIlflffl llvf Hit# r vtiu 0. 151 0.01* 0,002 0,007 0,404 0,t) 0.101 0,405 0.011 HOMS 211227 iNHlsiif) Robert L. Bouffard, Colonel, U.S. Army Corp* of engineer). Deputy Division Engineer for Military Construction, Room 610, 510 Title Building, 30 Pryor Street) S.W., At Lenta, GA 30303 James B. Hildreth, Chief of Environmental Quality Section, U.S. Army Corps of Engineers, P.O. Box 2288, Mobile, AL 36628 Walter J. Hogan, M.O., K.P.H., National Institute of Environmental Sciences, P.O. Box 12233, Raeearch Triangle Park, NC 27709 S. Hutson Hay, M.O., Suite 502, Bank of Huntsvllla Building, Huntsville, AL 35801 Carleton Pyfrom, Director, Triana Clinic, Triana, AL 35758 Joan Palmer, H.D., 20LA Longvood Drive, Huntsville, AL 35801 Sandra Cox, R.H., Hurts Clinician, Triene Clinic, Triana, AL 35758 Wallace B. Frierson, M.D., Professional Village, Suita F-C, 2227 Drake Avenue, SW, Huntsville, AL 35801 Carl McCandlish, M.D., Huntsville Clinic, 410 Lovell Drive, SE, Huntsville, AL 35801 Howard D. Jailer, Deputy Director, Enforcement Division, Environmental protection Agency, 345 Court land Street, Atlanta, CA 30365 Frank Cordle, Ph.D., Chief, Epidemiology, Bureau of Poodt, Food and Drug Administration, KFF-108, 200 C Streat, Washington, O.C. 20204 Jill Smith, Anthropology Department, 5240 Social Security Building, University of Wisconsin, Madison, WI 53706 Ronnia C. Flippo, Congressman, 439 Cannon Building, Washington, D.C. 20515 Donald Stawart, Senator, 110 Russall Building, Washington, D.C. 20510 Howall Heflin, Senator, 6327 Dirksan Building, Washington, D.C. 20510 t 13 HONS 21 *t*4 r*r Mt icictM tb* of tMltMHtUl CltvUtrj Aiarlcit CMKil ftotlogy Son rraiitiico, C*lirtra|ak A|i| IW& 1ilel4t; ( 3J4 ,*>1 'T|imiaPnmWtta o4 ) , J'l^.i^TatTaehUroaiaarMa^a J|^Uatli to lavfraMital fcqfrfk nT Scaka laaartMRt af lat#**logy #ii Cttr for laTtrM*t*l Taaltltf lalaanlt; of Vlataaala, ttotfloo#, SJ3M 3 . J ', *. * ` *1t( racM rwt%af <TCAt) **A 3*3'^**'aietcfttarvaiaifkavtaM (TCAOB) fi**t ta foooA la the poll aa Icrobloi a*|ra4atu proOacto fra* artpaall^ by f*l Ik* t*at taa*lciUr 1*M^IUC acTlaallUt krl(ei4* la tha lalt4 Rtcaaclf *atliraaka af cllar*i, attrtfevtai fCAi a*4 CaOI kaaa *tctr*4 oooog oothtr* h4il*| cHI**laa|4 ),l* tcMorooollloo r it* fcorhicWo 4arlv*tlvoo tCAO i4 TCAOB, *i| loootortc to >f),3,|-ttracU*f*4 1k**R~~41tl (TCOI), 1*4 ait* high arnlti tt th* KID rca*ltr fovoA 1* tfco Mfle criaaal. T*il*l*|l(*t otoilo* <a4ia4 I* **tl**a **U *fat*a by Mr taWntcTT loJtcoto tkat 4i**ra t* TCAf M TCAO* ako14 k ca*Htra4 *a * |lr**t t* Ivm* htaltk :>ramUUl aa4 Tronoforo#tloo A clooW c*l 1 llM os aa4 *g * **{li4 f ttalcltf cr4*>U|4 aUc* kirattarl*t| *<b * |rt*rk( Mr*k*ln a*4 totorocttoo with :#*lc ckialcoli of tk*M * tvkrj* kata olvooAy >* ri^(ta4* U 44lll*4t C3N/lOT^ cotlo oro M|hli aaaaltlta : po*c cud***** |4hlklil4t of lltlal** ooi a* aaaaiaataai Hfkal|Ual tratifarMtiaa ka ktaa aa to ooy *f tka cootrol ttltaria la tho atfailHira raportoA* TCAt * (aval ta k* 1 t ) Maia Mra taalc to t*t taak)rak(*kaafl oW ttUa tka* 2*2*.5,V'-katacklankl*ki*il* tva oojr eiaftMaia *f Ar*clra (PC**)* kaa calli ttia ttaatal to Mfa<!aa. A 3W frttik tohlbltloo aaa akaartal atiaa coll* vara trr*4 with A aaf/at of TCAB for ) lifi. Rut4i tacaalaa van alia akaatviA lkra|kat tka Cjta|la*alc r*|laa to Ik* oi*po*oA collo* c)f/19^ I*U* tr*ot*4 with I i| of tCAl pof at of cwltoro o*ALoo for 10 toy* ak*v4 focol or*k*U|(c altaratl*a* ekaiaatarlattt of trooofovoW colto. Ac tkt ((* ar** Iff* 111 foci taro ikotrvof, vkteh atalaif ftrklf oo4 tar* caaat*t4 of ikltki4 opt41 cello with o avirltat growth |*tt*ra. Cootoct lii!*lt(oa wo* loot. oo4 Mil growth coottoooA aftiv o ooooloyor woo iaiakltak4. Cotlo ftoo t^po 111 rod hoo kaaa ohovo to ptofoco ttatra whoo lajoctaf loro oyogoootc C3* otco Tki ropl4 oopeoronco *1 *h*o foci at|t<aia th*t__TCa* to awcogootc* Troatoom n *0S, wos, <>/ PH* t taatfl* Viability AootofaIpyrooo 3.3\4, A'-TCAI 10 -4 10 l0"5 t0ll 10 4 to"? 10" 9 10" 10" *io # is *JJ t ** i 41 m * ti J 4 4) 4*1 4 1* *14 4 1* *14 4 *4 HI 4 so 1JJ It m 132 313 240 134 241 333 241 115 1*7 23 44 44 42 13 )0 47 57 71 44 * Tka eaauat aa* pa-ffln- t*ata|a|*| . ,--. . sT r*AanVa*. - ~ Coll viability woo 4ot*coloo4 by try poo kUa ooclooloo. MOMS 211229 *32 oit pot mat iitd pirolitont laiacor *o| th thro* tla|< aatad. in addition^ otlaoltiioQ of Hoar iitwcli a akitrvd la s truttl aniuli with i concnrrant 4tra*a |a Ia4f wnight lotioa to control aalaala, TMa ntndy lallcata# tho aktlitf of CAB and TCAOB co affact npaorgtoc1 cally ||| taildt^ of athar nokiottca aa4 ctio pha(acaU|lcal foadtp B4lkitd*nc 4tt|a v tod action of hnpattc atcroaaaal aaiya *patocal lolar PathoUUciUi?. Tbn htptataalcltf of TCAd and CAOft wan naaiaaf lo lataral ihatt tara aiyaflMtta tali| rota id nice. Vrioo MotapathaU|lcal altorottooo atta nbanraad by llbt* oo4 aloctron atcroaoptc atodioa. Uvaf bygnrtropby aa kaerwad to oil aalaala following tap. tajoatlaa of olthor TCAt or CAOB. ftyacocptn profllo* fro* ernatad oloalo area apprnxloatolj 01 laror Chon control coll* on dotamlnnd By canotlftf tka aaakar f hpatocyfna ontt aria In llvor nnctioaa fro* control o*d ipcrloootal aalaala Tbo atktr no jot htotopatbolaglcol Itaratloaa wore praaoacn of cytoplotalc vacaalav^ grolfforation f ooaotb omdoploontc raticolon, nod tbn ocurinca of oo*or*na iltaaaai arroyo. Tk 4a|iatratl?a chnngoa to Clio * Mm ctlona vara onto prooooncod tkaa choc obaarwad lo rot llwnr, bt ticpotlt nltotlc tadax for tha axporInontal an tool a aroo l|nifteaatlt grantor ebon control oalnoo# tCAt oppaor* to offoct b* nltotlc apindlo apparataa to tb# aaaaa hopotbeyto to vbteh tka hroaoionu nro oboorwod lo o diotlnet tricolor arraa|iaaat lottar nofpbologteal cbongoa worn. nbaorvod ohoo bogatocyto nltnrao worn traotod vttb TCAB ot o dooo of S og/*l foa br. ddttlonolly, tbo Incorporation rata of aoloctod pmenroora of nltalor nocrooolocoloa woo offoctod. tartha, * and 0* Prooor, Ad. Aotl* WlCToblol.. 12. 212 <l*2>. Poland, A., 1. Clotar, A,S, Rondo, w, DaCanp, and C.H. Ctood onontco . Scftooca IM. $22 U*7*>. 1, It*la, H.T.S. , F.T.I. Satratav. L.C.T. Stiiti, J.C. r.aata, aa< j.i. *n.. t. Can... Cfca.. Pathol. Pkiraacalff <2, JU *. Nall, M.T.S. and C.T. Br*nt, J, Aoa> Offtc* Anal* Cbon.. 42. 7** (itrt). 3. Kola, H.T.$. and B.L. Kraiair. Caneai Late.. *. **7 (1*7,). ft. ala, n.T.S. ai l.L. Kras.ar, ftoa, Connan- Chon. f*thnl. IS, JI* <1*7). ota, m,t.$i , B.L, ftroanor, C. r. Iiriai, aai N.l. Trtatalaar. Prod Cbon. Toxicol., in praaa (IVBO), *33 f ttt, fckraaktl , h.T,$. data, and J.C, bound* , ten. Coon*a, Cbon, Potbol* PkarnrcoU, tw pro** (lWO). ~" - VUlloaa, C.!1, . Caacar Lott.. 1 . 231 (17*>. 10, Toy lor. JS., ft.C. vthrlcb, R.M. Lloyd, and a. Poland, arcb, 0*raCol , 113. *U (1*72). Acbnonlodaonnwca* Tbo tbor vtikaa to tKaoh bla collofot for fmltfnl diocuaatona o*d offorta: J*t. Allan, c.l. Burant. B.L. Kroanor. J.C. bound*, ft.ft. 5bronbl. TMa atody vat aopportmd In part* by PobHc ftoaltb Sarvlci (ruti C$01222 and C$07012 (ran tbo Mattoool Iootttota of Bantroonant*1 ftoaltb Sclantaa, and tbo Callofto of Agricultural aod Ltfa Scloncta, 0nl**rtty of Vtoconoin, ffadlaan. HONS 211230