Document jNNyEXbya2E9EY8Ja2noybq55

AR226-2761 LIVER STUDY OF WASHINGTON WORKS EMPLOYEES EXPOSED TO C-8: RESULTS OF BLOOD BIOCHEMISTRY TESTING WILLIAM E. FAYERWEATHER JANUARY 15, 1981 ;ompany Sanitized. Does nul contain TSCA C31 Acknowledgements for the I want to thank J. many days they spent F. Doughty consulting and and Y. L. Power^ssSr'- for this project; P. Thistlcton for his consulting, especially as it related to assembling data industrial hygiene at the plant? V. helpful advice A. Brewster for his C-8 exposure potential direction? S. Pell for his review. and comments? and R. M. Shepherd for a critical :o.ff'.pam San'tizsd. Does iw d;:^ii' TSCA C5S Summary Dr. y. L. Power assembled biochemical data on some recent Washington Works employees. Based on a crude analysis of these data, the results suggested that certain workers with potential ammonium perfluorooctanoate (C-8) exposure night be showing liver effects. Also, several unpublished animal studies have shown that C-8 produces liver damage when it is given at moderate or high doses. As a consequence of these findings, a more detailed assessment of C-8's health effects in Washington Works employees was undertaken. Data from routine blood tests were collected and compared among groups of Teflon area and non-Teflon area workers. SGOT, LDH, AP, and bilirubin were studied, since these tests are generally good for detecting liver disease. Within the Teflon area, C-8 exposure groups were defined by work history and by blood organic fluoride level. These data provided no conclusive evidence of an occupationally related health problem among workers exposed to C-8. Although initial analyses suggested that there might be liver effects attributable to C-8 exposure, further analyses did not support this position. Background The Teflon area consists of two divisions; the Teflon Polymers Division and the Teflon Copolymers Division. %ers.These polymers aremadeDyDatchprocllsses. Ammonium perfluorooctanoate (C-8) is a dispersing agent added to nearly all of the polymer processes. The monomers do not contain C-8. The Teflon Polymers Division makes three types of polymer products: fine powder, dispersion, and granular. More C-8 is used for dispersion than for fine powder products. Granular products use less C-8 than do dispersion products. Two continuous driers remove nearly all the C-8 from fine powder, and washing and drying processes remove essentially all of the C-8 ^rgjjL granular products. Dispersion products contain roughlyM----B--------Qc-8 based on solids. The Teflon Copolymers Division produces four copoly- mers, all of which confcainQB^I Three of these copolymers are made by batch processes. The fourth, Tefzel, is made t-" " continuous process. C-8 is added as a.diapers ing sgent fcgll of the copQjymers except Tefzel. MBT"TMTM" '" ' '""BHIHHBBU tne major ^opg^ymer, makes. the copolymer produced. QUfponsisfcs of| Company Sanitized. Does not contain TSCA CB Tha^Bypolymerization process also generates an in situ dispersing agent. In June, 1976 the plant began adding C-8 dispensing agent to increase the reaction rate. This change reduced the amount of time needed for the process and also reduced the amount of in situ dispersing agent that was formed^JJowever, some in situ dispersing agent is still formed in allj|Hfpatches. ^^^^^^^t TM* ^^ Unti-1 thefHHpolymer reaches the humid heat treating ^^ ^^^spso, l y imt e c r ont is ains very i n d situ usty. as well So, in as C-8 dispersing agent. the processing steps between ' theHHpolymerizers and the ovenSr there is significant poten tial for exposure to C-8 and in situ dispersing agents. r--^| ^djspersionjroducts contain in situ dispersing agent ana about QBUBMC-8 based on solids. In situ dispersing agent is not well characterized. It is relieved tfi be a mixture of homologs of low molecular weightyBB------Vcompounds, some with acid end groups. On a weight basis it is less surface active than C-8. Several unpublished animal toxicity studies done at 3M Corporation and at Du Font have found that moderate and high dose levels of C-8 produced liver damage. Both reversible and irreversible liver damage, elevated liver enzyme tes'ts, and enlarged livers were found. Study results depended on the dose level, exposure route, sex and species tested. Dr. Y. L. Power assembled biochemical data on some current Washington Works employees who had had company physical examinations in 1978. Based on a preliminary analysis of these data, the results suggested that certain workers with potential C-8 exposure might be showing liver effects. , As a consequence of the previous animal studies of C-8 and of Dr. Power's preliminary findings, a more detailed assess ment of C-8*s health effects in Washington Works employees was undertaken. Study Objective The objective was to determine whether occupational exposure to C-8 adversely affects liver functions as measured by blood levels of glutamic oxaloacefcic transaminase (SGOT), lactic dehydrogenase (LDH), alkaline phosphafcase (AP), and bilirubin. Note: These blood tests are neither 100% sensitive nor 100% specific for detecting liver disease. There are a number of circumstances under which the test may give false positive or false negative results. These circumstances sre discussed a^ the end of the paper under Liver function tests: limitations. Company Sanitized. Does 'c'> coniah'. TSCA CB' Methods 1. General design Recent blood test results for SCOT, AP, LDH, and bilirubin were compared between C-8 exposed and non-exposed workers at Washington Works. Test results were studied -by specific Teflon area job and by blood fluoride level. 2. Selection of study groups The initial group consisted of 96 Washington Works employees who were in one of the following Teflon area jobs as of October, 1979: arocess operator process operator service operator ervice operator Laboratorian; monomer operator; Teflon area engineer, chemist, or foreman. This group included 78 workers who had been tested earlier in the year for blood fluoride levels. Only^UHlkprocess and service operators were con sidered to have had significant potential for exposure to C-8. Monomer operators, semi-works laboratorians, and Teflon area foremen were kept as a separate comparison group, since they worked in the Teflon area but had only limited C-8 exposure potential. The number in this group was later dropped to 88, since 8 workers had not worked in the Teflon area prior to their most recent blood test. These 8 workers were added to the non-exposed group (i.e., the control group). For these 88 employees, J. F. Doughty gathered detailed Teflon area work histories from plant records and from personal interviews. Work histories were copied to code sheets (table 1). 3. Selection of a nonexposed control group The control group consisted of a 10% systematic sample of all active Washington Works employees who, as of August, 1979, had never worked in the Teflonarea. Mechanics and laborafcorisns were excluded from the controls, since their exposure potentials could not be well documented. Company OU.lH.-yU. ^uu^ ^ i-^..i"..l at/M -dl The group was selected in the following manner: Dr. Y. L. Power pulled every tenth record from the plant's alphabetized medical files for active employees. These workers' names were then g.iven to J. P. Doughty. From plant records and through personal interviews. Doughty obtained these workers* work histories. Workers who had worked in the Teflon area or who had worked as mechanics or laboratorians were then dropped from the list. The remaining workers constituted the control group. Eight- more workers were later transferred from the exposed to the control group, because these 8 had had no poten tial C-8 exposure prior to their most recent blood test. 4. Biochemical blood tests As a part of routine physical examinations, each worker's blood is tested for 12 biochemical markers. These 12 tests are called the SMA-.12. From plant medical records, every SMA-12 on the exposed and control workers was copied to code sheets (table 2). All SMA-12 tests had been performed by the same laboratory and by the same methods. Very few SMA-12's had been done before 1974-75. Every worker's most recent SMA-12 had been done since 1977. Only tests pertaining to the liver were studied. These included the SGOT, AP, LDH, and bilirubin. 5. Blood fluoride levels Prior to this study, blood fluoride levels had been measured on 78 of the plant's Teflon area workers and on 25 Wilmington office workers. Blood fluoride measurements had been made at Jackson Laboratory by the 3M (bomb) method. Most of the workers tested at the plant had had potential C-8 expo sure. Liver function test results were analyzed according to blood fluoride levels, 6. Statistical methods SMA-12 results were studied by exposure status, by specific Teflon area job, and by blood fluoride decile. Analyses were based on (1) test means and (2) the proportion falling into the highest liver function test decile. The highest decile was defined as the range in which the top 10 percent of all control and exposed groups' test values lie. On the average, then, one would expect that 10 percent of the control group's values would fall. into this decile. Unless stated otherwise, test values were from the worker's most recent SMA-12. Group differences in Biochemistry test means were studied by analysis of covariance and least significant difference tests (LSD) This analysis adjusted for any group differences in age or sex. The statistical significance of differences in propor tions was assessed by Fisher's exact test. Two-tail tests were performed, and p-values less than 0.10 were reported. Company Sanifeed, Do"". n"t contain TSCA Cm Results 1. , Test validation Dr. Y. L. Power provided preliminary data on the SMA-12 results for 1978 (table 3). These data showed that the plant population as a whole had an unusually large percentage of elevated SGOT's. SGOT's were elevated in 19 percent of the workers whereas elevations would only have been expected in about 5% based on random statistical variation. AP, bilirubin, and LDH tests showed plant-wide elevations in 8, 4, and 3 percent of the workers, respectively. The large, plant-wide elevations in SGOT's suggested one of two things. Either workers in many different areas were affected, or the plant's SGOT test was invalid. Dr. Power took two steps to validate the SGOT test. First, he took blood samples from about 100 workers and sent half of each blood sample to the standard laboratory (General Consultants, Inc.) and the other half to an Upjohn Laboratory to be tested. When the results of the standard laboratory were plotted against the results of Upjohn (figure 1), the two laboratories were correlated. High SGOT's at the standard laboratory were high at Upjohn, and low SGOT's at the standard were low at Upjohn. However, at all SGOT levels the standard laboratory's value was higher than Upjohn's. Furthermore, about 16 percent of the standard laboratory's values were "abnormal," whereas none from Upjohn fell in the "abnormal" range. Dr. Power also had the standard laboratory use a second method (manual enzymatic) to reanalyze samples that showed elevated SGOT's by the first method (automated colorimetric). In the 22 retested samples, only one sample was found to be elevated by the second method (table 4). When the results of the first method were plotted against the second, the results were correlated (figure 2). The interlaboratory and intermethod comparisons sug gested that SGOT's measured at the standard laboratory by the standard method were systematically higher than the true blood levels. By the standard method the standard laboratory's observed range for "normal" SGOT values was con siderably higher than the stated normal range. e Valid SGOT level comparisons can be made between exposed and nonexposed groups, provided that test Company Sanitized. Doss not contain TSCA CB1 means or the proportion falling into the highest test decile are used. Since SGOT levels were correlated between laboratories and between methods, valid between-group comparisons are possible. 2. Liver tests by job ^^BByprocess workers' nmieeaannSSGGOO"]T of 45 was higher than the connttrol group's mean of 39..|p4Bifluusservice and process workers' mean AP's of 101 and 81" rreessppeectively, were higher than the control group's mean of 64. These differences were statistically significant at th&O.QS probability level (table 5). Similarly, ylljprocess andu----^ervice workers had sig nificantly (p<0.05) larger proportions of the AP values falling into the highest test decile (table 6). There were no other significant differences between Teflon area workers and controls with respect to SGOT, AP, bilirubin, or LDH. 3. Liver tests by blood fluoride level The mean SGOT. for the highest blood organic fluoride decile was significantly higher than the mean for the lower nine deciles (52 vs 40, respectively). However, when the data were broken down into individual organic fluoride deciles, the data did not show a typical, steadily rising dose-response curve (tables 7 and 8). In fact, the second and third highest mean SGOT's were found in the first and third deciles. It is still possible, however, that the high SGOT's seen in the highest decile are somehow related to these workers' organic fluoride levels -- the highest decile could be the effect/no effect threshold. AP, LDH, and bilirubin showed no unusual elevations when compared by organic fluoride decile. Likewise SGOT, AP, LDH, and bilirubin showed no relationship to inorganic fluoride levels. 4. Blood fluoride level by job Ifprocess operators made up about one third'of the 78 workers tested for blood fluorides. But when the 16 workers from the two top organic fluoride decile^ were listed by Teflon area, 12 of the workers had beenlMHUprocess operators at the time they were tested. Four others had worked ^AlBL^ process operators within 1 to 2 years prior to the time Diey were tested. The number of years of working with C-8 or of working in the Teflon area did not appear to be related to organic fluoride level (table 9). In fact, the third highest organic fluoride level was measured in a worker having less than 3 years experience with C-8. l;on-ip; .....-.-on^TSCACS; - 7 - These data suggest thatgftMUprocess operators have the highesit potential for exposure^afnld that only 3 years of . . C-8 con lleevveels., ta^cctt-rmoajy be y4--ijp--ro9pcics s s ufficie operat nt ors t o u eleva sually t e h a blo ve od mo r o e r ganic servic fl e uorid than e j^lfEesrevrvicicee ooppeerators. Blood inorganic fluoride level and Teflon area assign ment appeared to beuor elated,^ The highest inorganic fluoride levels occurred in^ByandjUprocess operators, monomer operators, and semiworks laboratorians (table 10). Wilmington office workers' blood fluoride levels have been included for comparison; their levels should represent the norm for workers who are not occupationally exposed to fluorides (table 11). 5. Liver tests by job: differences between before and after exposure Very few workers had liver tests that were done before and after exposure began. Since the workers having both before and after tests may have been a select group, the results of these comparisons should be treated with caution. Thlee^rbeeffoorre and aftej^C-fi exposure comparisons weakly suggest thaitt|jUBHAprocess aanndd--j--fl--sIef rvice workers' AP levels may have risen following C-8 exposure (tablel2). This result supports the earlier observation thaffuworkers' most recent AP levels were higher than the controTniean. However, these two observations are not independent. imfocess andlMservice operators showed no unusual before aTidarcer differences with respect to SGOT, AP, LDH, or bilirubin. The result does not support the earlier observation that SGOT was elevated in TFE process workers. All "after" tests were based on the worker's most recent physical examination. For exposed workers, the "before" tests were based on the worker's most recent physical examina tion prior to moving into the C-8 exposed job. In the control group, the "before" tests were based on the worker's physical examination immediately prior to his 1979-physical. Discussion Based on the data above, there is no conclusive evidence of an occupational^ related health problem among workers exposed to C-8, Some of the SGOT data suggested that there might be a liver effectaaipng certain C-8 exposed "workers. The mean SGOT for theyBB^rocess operators was significantly (p<0.05) higher than chenon-Teflon area control mean. [flHIfrocess operators ss a group had considerably higher organic fluoride blood levels than other Teflon area workers. Workers in the highest organic fluoride decile had a significantly higher SGOT mean than workers in the lower nine deciles. ^"^any sanifeed. DOM;?; nft.  However, in other respects SGOT showed poor correlation with organic fluoride level and with C-B exposure. Teflon area workers with little or no C-8 ^ exposure had. a nean SGOT that was nearly as high as theUBIf>rocess operators' mean. Since Teflon area workers with little or no C-8 expo- --sure also had the lowest blood organic fluoride levels, their elevated SGOT could not realis tically be caused" by C-8 exposure. Workers from the third lowest blood organic fluoride decile had an SGOT mean that was nearly as high as the top decile's mean. Other puzzling findings were that neither AP, LDH, nor bilirubin means were elevated amongflfSoperators. If a patient truly had a chemically induced livef disease, one would expect one or more of these other blood tests to be elevated. MeanAP was significantly (p<0.05) higher amongMB^j service andfl----Rprocess operators. Yet none of the other blood tests were elevated among these workers, and AP did not corre late with blood organic fluoride levels. ^ . ' < It seems very unlikely that a single material would raise only SGOT levels in one worker group and raise only AP levels in another worker group. More likely explanations for the SGOT and AP eleveafcions are: "The elevations resulted from chance events and "were not causally related to C-8 exposure. Certain unmeasured confounding factors such as alcohol consumption or drug use may have influ enced the blood test results. It is also possible, however remote, that occupational exposures to other toxic materials were responsible for the observed elevations. For instance, acute and chronic exposure to inorganic fluorides can produce osteomalacia, a bone disease. This bone disease is often associated with elevated levels of. serum AP. Liver function tests: limitations Bilirubin, SGOT, AP, and LDH assess different compo nents of a liver's health and function. Only serum bilirubin is a true liver function test. SGOT, AP, and LDH are actually enzymes that are normally present afc "soderste levels in the serum. They may attain higher levels after various types of liver damage have occurred. SGOT and LDH leak out'of damaged liver cells and into the blood stream. Elevated AP levels, on the other hand, appear to result from damaged liver cells synthesizing and releasing more enzyme. Company Sanitized. Does not contain TSCA CBI When assessing positive and negative test results, several points should be kept in mind: The liver has a large functional reserve and a great capacity to regenerate itself after it has been damaged. Studies have shown that within about a week after having removed over 80 percent of a ._ rat's liver, one can find a liver of essentially normal weight and function. Consequently, mild and sometimes moderate liver injury often may not be accurately reflected by changes in liver function tests. / Some liver functions are much more sensitive to injury than others. Thus, some liver functions (and function tests) may show changes while others do not. i There is no one single test or procedure that effectively measures the total function of the liver. There is no direct quantitative correlation between the amount of liver cell injury and the height of serum enzyme levels. However, higher levels are generally found with more severe injury. If the serum enzymes are measured sometime after the acute insult or injury, the initial rise may have been missed. Thus, normal or low serum enzyme levels may be found as a consequence of a decreased functioning liver cell mass. Simi larly, certain types of cirrhosis are associated with only slightly elevated or even normal SGOT levels. SGOT, AP, and LDH may be elevated from causes other than liver damage. For instance, most of the AP present in normal serum is derived from the bone. High levels of AP occur in patients with bone diseases characterized by osteoblasfcic ' activity. These include rickets, osteomalacia, and healing fractures. Growing children and pregnant women in the third trimester have elevated serum AP levels. SGOT and LDH may also be elevated in patients during episodes of acute myocardial infarction, cardiac arrhythmias, congestive heart failure, pericarditis, and pulmonary infarcfcion. e There are other enzyme tests that are more sensi tive to certain types of liver disease than are SGOT, AP, and LDH. One of these is gammaglufcainyl fcranspepfcidase (GGT). This enzyme is elevated in Sanitized. Doe. not contain TSCACa Company the serum of almost all patients with hepatobiliary disorders. It is the most sensitive test for alcoholic liver disease. A liver test's sensitivity can be defined as the ability to correctly identify persons who have liver disease. Specificity can be defined as - the ability to correctly identify persons who do not have liver disease. Sensitivity and specificity have not been adequately studied for liver function tests. "While a large amount of information is available concerning biochemical measures of acute hepatic injury, we have limited data about the effects of chronic lesions on the biochemical tests and on the sensitivity of these tests in detecting chronic injury or the sequelae of acute injury" (Guidelines for the Detection of Hepatotoxicity Due to Drugs and Chemicals. NIH Publication No. 79-313. Oct. 1979. pp. 33-34). Liver function tests are most useful if they can be used serially to assess health before, during, and after exposure. So-called "abnormal" values for one individual may be "normal" for another. Normal/abnormal dichotomy vs the continuous approach The basis for classifying a liver test value as normal or abnormal can be either functional or statistical. On a func tional basis, any value could be considered normal if there were no increased risk associated with it. On a statistical basis, a normal value could be any one that fell within the limits in which X percent (e.g., 95%) of the population fell. There is a major disadvantage to classifying continuous measurements as normal or abnormal: it oversimplifies a com plex problem. Disease and health lie along a continuum. For instance, ^even within the central 95% of the total range of blood pressures, there is a gradient such that persons at the upper end are at a greater risk of coronary heart disease or stroke than those at the lower end.'^' A similar situation may also hold for liver function test's. Thus, analyses based on group means most often 'use the data more efficiently than analyses based on the percent "abnormal". A possible theoretical advantage to the dichotomous approach is that it might be more sensitive to "outliers", values on the high side of normal, than is an analysis of means. However, in animal toxicity studies practically all statistical analyses of biochemical tests are based on means rather than on- the proportion above or below a certain value. Furthermore, the number of experimental observations needed to detect a real effect is considerably less when the analysis is based on means than when it is based on proportions (all else being equal and assuming an underlying continuous variable). s.,,,,..-.------0"'2'"^81 c.-'mpany TABLE 1: C-B STUDY CODE SHEET FOR WORK HISTORIES __ ___ ___ .1 Payclass (1 = wage, 2 = salary): Date hired (month/year): / ____ Nane (last, first intitial, middle initial): ___ Sex (1 = male, 2 = female): SS<:___________________ __ __ __ __ Birth date (month/year): / Present or past Teflon area jobs or mechanic-type Current C-8 exposure (0 = no; 1 = yes): ___ Org. P = inorg. F^---- jobs (0 = no; 1 = yes): Potential present or past C-8 exposure (0 = no, 1 = yes): ___ Number of jobs listed below (list all Teflon area and/or irechanic jobs): C-8 Potential Job (0=none? l=some) Job code Date in (jno./yr.) Date out (no./yr,) Conments 1 2 3 4 5 6 7 -8 9 10 11 12 i 13 14 15 16 17 18 19 ,,.,,----'"" TABLE 2: C-8 STODY CODE SHEET FOR MEDICAL HISTORIES \fane (last, first initial, middle initial): ___ 5S 1: 2 456 current cigarette smoking status: 20 7~_~T_"_~T_' Birth date: ____ 12 13 _Tr_~_l5_~_" Mo. Vr. Sex (l=ni Payclass (1 = wa Current hyperten (1 = hyper.; 2 s 5 = smoker, no. packs unkown 7 a unknown 8 = pipe/cigar Height; Weight; ixam. date / Blood pres. / SMA-12 to. Yr. Dia. Sys. B.P. B.P. Ca++ In. Phos. ' Glu. BUN Uric Acid Chol. T.P. Alb. Bill. Alk. LDH Phos. ; T Oo65.^contain comply Sanded. irpup .utacite* AP eirin* ilaments ucite* ?flon* fker ichanical isearch 'chnical is. Ser. pi. Rel. wer & Ser. Nb. of Tests 1978 119 78 82 131 71 212 241 380 77 251 103 32 63' tal Plant 1840 tal Plant .s Teflon* ia 1628 1 ABLE 3: WASHINGTON WORKS 1978 SGOT (Normal 10-50 ) 'Itotal> 50 Blood Test Results AUG. PHOS. (Normal 30-85) Total>85 30 (25%) 14 (12%) 16 (21%) 6 (8%) 15 (18%) 7 (9%) 23 (18%) 14 (20%) 34 (16%) 29 (12%) 79 (21%) 16 (21%) 50 (20%) 14 (14%) 7 (22%) 14 (22%) 11 (8%) 7 (10%) 23 (11%) 8 (3%) 2--7' / \ '7"& \ 1 4 (5%) 15 (6%) 8 (8%) 3 (9%) 7 (11%) 341 (19%) 140 (8%) 307 (19%) ir ?) Bill (Nonna 1 0-1.0) Tofcal>1.0 6 (5%) 4 (5%) 1 (1%) 7 (5%) 3 (4%) 5 (2%) 11 (5%) 16 (4%) 4 (5%) 11 (4%) 4 <4%) 3 (9%) 2 (3%) 77 (Id'*9"i/\ Company Sanitized. 72 (4%) TABLE 4: SCOT RESULTS FKOM TWO DIFFERENT METHODS PERFORMED AT THE SAME LABORATORY (GENERAL CONSULTANTS, INC.) Subject Date Standard SMA-12 (1) SOOT (normal = 10-50) Alternate Method (2) SOOT (normal = 0-27) 1 11/12/79 60* 19 2 11/14/79 58* 17 3 11/26/79 150* 42* 4 11/27/79 60* 18 5 12/10/79 55* 21 6 12/10/79 54* 14 7 12/10/79 51* 15 8 12/10/79 60* 9 12/10/79 62* 15 ' 19 10 12/10/79 55* 13 11 12/11/79 54* 14 12 12/11/79 55* 17 13 12/11/79 63* 19 14 12/1 V79 57* 23 15 12/11/79 85* 23 16 12/12/79 73* 21 17 12/18/79 52* 15 18 12/20/79 82* 24 19 12/26/79 57* 15 20 12/28/79 89* 24 21 12/31/79 60* 19 22 12/31/79 75* 27 (1) Automated colorunetric method (2) Manual enzymatic method *Abnonnally high based on limits set by the laboratory ^s.^.oo--------------- TABLE 5: AGE AND BLOOD CHEMISTRY ^MEANS BY OCCUPATIONAL GROUP^ Group Control (no Teflon, mechanic or laboratory work) / roosss service process [ j ^rvice Monomer operator, semi-works laboratorian, foreman Group Size Age 80 38 13 49 3 37 25 45 25 37 22 47 SGOT AP Bill LDH 39 64 0.7 156 37 81* 0.5 154 41 101* 0.6 146 45* 64 0.5 158 35 59 0.5 160 44 69 0.7 151 (a) Based on nost recent SMA-12 as of October, 1979 (b) Based on job title at the tine of the worker's most recent SMA-12 (c) Ten percent sample of current wage roll employees plus eight workers currently exposed to C-8 but who had never worked in Teflon at the time of their nost recent physicals. * Significantly (p<0.05) higher than the control group after adjusting (by analysis of covarianoe) for age. W ^ - ^ ^ ^ ^ ^>-> -o;-i .'!'-! TS.CACB! TABLE 6: BLOOD CHEMISTRY (a) BY OCCUPATIONAL GROUP (b): PROPORTION OF TEST VALUES FALLING INTO THE HIGHEST DECIL Group Group Size Control 80 (no Teflon, mechanic. . or laboratory work) ' w 13 3 Process 25 MW h'Service 25 Monomer operator, semi-works laboratorian, foreman 22 Mean Age. 38 49 37 45 37 47 Propo rtion in iHighest ;Decile SGOT AP Bill LDH 0.10 0.05 0.18 0.10 0.08 0.0 0.20 0.04 0.31* 0.67* 0.12 0.12 0.0 0.0 0.08 0.0 0.23 0.14 0.18 0.08 0.0 0.12 0.16 0.09 (a) Based on nost recent SMA-12 as of October^ 1979. (b) Based on job title at the time of the worker's most recent SMA-12. (c) Ten percent sample of current wage roll employees plus eight workers currently exposed to C-8 but who ha3 never worked in Teflon at the tijne of their nost recent physicals. * Significantly (p<0.05) higher than the control group by Fisher's exact test (two tail). - ampany Sanitized. Does not contain TSCA CBf % TABLE 7: hORKERS GROUPED BY ORGANIC FLUORIDE DECIUSS - BIOCHEMISTRY TEST MEANS Op(a]1 Decile Group Si;ze Of,(a) Limi ts 1 2 3 4 5 6, 7 1s rs 10 6 0.08^D.30 8 0.35-0.45 9 0.47-0.69 7 0.70-1 .17 - 8 1.31-1 .80 8 1.81-2 .30 8 2.33-3.55 8 3.70-4. 64 8 4.84-6. 66 8 6.84-21 .69 Mean No. of Years in C-8 5 2 9 5 7 6 10 9 15 14 Mean Mo. of Y rs. in Teflon Mean -"A?a~e 12 17 18 7 12 11 14 16 18 18 40 49 47 41 41 40 45 44 47 47 Mean SC2/Wyf^T. Heari AP Mean DRiiJ'l. i Mear LDH 46 40 49 34 40 36 37 36 39 52* 69 67 67 73 71 68 64 72 62 63 0.7 184 0.7 131 0.6 166 0.5 161 0.5 165 0.6 154 0.5 152 0.5 152 0.5 149 0.5 169 *i.greniafigcea-andtjluyst(epd<0b.0y5a) nhailgyhseisr othfancotvhaeriamnecaen boeffothree cloowmeprar9isodnesciwleesre. mTahdee. data OF = organic fluoride Company Sanitized. Does not contain 7SCACS TABLE 8: WORKERS GROUPED BY ORGANIC FLUORIDE DECILES PROPORTION PALLING INTO THE HIGHEST LIVER - FUNCTION TEST OP DECILE TEST VALU P lie Group Size 6 8 9 ' 7 8 8 8 8 8 8 OF L imits 0.08- 0.30 0.35- 0.45 0.47- 0.69 0.70- 1.17 1.31- 1.80 1.81- 2.30 2.33- 3.55 3.70- 4.64 4.84- 6.66 6.84-21.69 Mean No. c >f Years in C-8 5 2 9 5 7 6 10 9 15 14 Mean No. of Years in Teflon Mean Age 12 40 17 49 18 47 7 41 12 41 11 40 I4 45 16 44 18 47 11.Q0 47 gnificantly (p<0.06) higher than the lower 9 deciles by as organic fluoride Fisher's exact test (two tail) Propert SOOT 0.17 0.0 0.33 0.0 0.0 0.0 0.0 0.0 0.13 0.38* Company Sanitized. Does not contain TABLE 9: TEFLON AREA WORKERS WITH TOE 16 HIGHEST ORGANIC FLOURIDE LEVELS Worker Age A 50 B 59 C 36 D 60 E 53 F 48 G 42 B 35 I 49 J 53 K 44 L 56 M 42 . N 37 0 42 p 55 Years in C-8 20.5 23.8 2.8 23.2 4.0 23.4 2.6 13.4 21.7 20.3 16.1 24.5 14.8 5.6 11.8 3.2 Years in Teflon 23.4 25.8 4.1 23.9 22.3 23.4 4.8 14.6 23.9 20.3 17.2 24.5 17.5 13.6 20.4 3.2 Blood Organi C Flouric3e Level Job 21.69 20.81 16.89 14.38 9 .bt^ji 8.89 6.91 6.84 6.66 B process process ---- l^gprooess JHR|process ^^^jprocess f B|f process [iBgprooess ^By process ^HQprocess 111 10/78 5.90 5.64 5.61 5.29 4.97 4.96 4.84 l^lMprocess lB^K>rocess ' Elll 11/77 [Bijprocsss rii^ft Uprocess ^111 5/77 | process f|f 10/78 9Qll JUHproress J------Jservice Company Sanitized. Dees not contain TSCA CBi TABLE 10: TEFLON AREA WORKERS WITH THE 16 HIGHEST BLOOD INORGANIC FLUORIDE LEVELS Worker Age A B c D E F G H 1 J K L N 0 p 35 48 51 58 ^ 53 53 61 ^ 26 30 56 35 24 35 51 Years in C-8 Years in Teflon* 4.0 19.9 7.8 H.3 3.5 1,8 20.3 11.8 11.5 3.2 0.7 0.4 4.8 3.1 4.3 2.6 12.5 23.1 25.8 26.3 3.5 24.0 20.3 22.3 13.8 3.2 3.0 29.7 4.8 3.1 - 11.7 ' 2.6 Blood Organic Fluoride Level ^^---- Job 0.42 0.41 0.40 0.39 0.39 0.38 0.37 0.37 0.34 0.31 0.29 0.28 f/ cri^pryocess lUJIprocess Mononer ^ f - --'t ^jprocess ^^^^n & . , ,,^ Semi works laborafcorian Mononsr : *'* riBBi process |_^Hc>roo&ss nBll^rocess. TfflJfservias rm^brocess * Mononer 0.26 0.25 0.24 jri--^^ervice * J^BBi)581^103 Semiworks laboratorian * ,..., ^IVii1!^'-' /.v^^ :: ^' c&^ .."-i .T^A^i . TABLE 11; Sample 60 61 66 72 73 76 77 78 79 80 81 82 92* 93 94 95 96 97 101 102 103 106 107 109 111 TABULATION OP BLOOD SAMPLES FROM WILMINGTON PERSONNEL (25 TOTAL) total PP11 0.28 0.31 0.23 0.20 0.23 0.23 0.33 0.24 0.30 0.19 0.21 0.18 10.6 0.18 0.18 0.49 0.25 0.18 0.26 0.30 0.26 0.23 0.31 0.12 1.13 Inorganic Rpn 0.19 0.09 0.16 0.10 0.12 0.17 0.15 0.25 0.24 0.14 0.15 0.27 0.12 0.03 0.11 0.05 0.16 0.16 0.16 0.10 0.17 0.22 0.11 0.35 Organic Rpn (by difference) 0.09 0.22 0.07 0.10 0.11 0.06 0.08 -0.01 0.06 0.05 0.06 -0.09 10.6 0.06 0.15 0.38 0.20 0.02 0.10 0.14 0.16 0.06 0.09 0.01 0.78 *Vonalu6e/s13/7o9btaisnheodwed 3/1th5e/79f.ollowReisnagm:ple and rechedc of this person's blood Recheck f92 Itotal F^ 0.33 Inorganic apra 0.09 Organic PP"* 0.24 Sanit'zed. Does not contain TSCA C8i Company TABLE 12; MEAN DIFFERENCES IN SGOT AND AP RESULTS WHEN THE FIRST TEST IS BEFORE (a/MOVING INTO.A.C-8 EXPOSURE JOB AND THE SECOND TEST IS AFTER (b/ EXPOSURE (c/ Group Control FEP process operator FEP service operator TPE process operator TFE service operator Group size 45 3 2 2 7 AP3) - 3.3 + 11.7 + 8.0 - 3.0 - 0.4 SSOT^ - 4.7 - 4.0 + 7.5 - 11.5 - 8.1 la/ Most recent SMA-12 prior to starting C-8 exposure job fb) Most recent (primarily 1979) SMA-12 (c)' C-8 exposures ranged from 5 months to five years between tests ' Second test minus first test Company Sanitized. Does not contain TSCA CBI FIGURE 1: INTERLABORATORCYOMPARISON OF SGOT . . . 1. . . . I DETERMINATIONS . . . ^bU| LhYLL BY ALTERNATE METHOD AT STANDARD t^B