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A R m - 0 H6f| Attachments to Letter to C. Auer dated May 25, 2000 Toxicology Studies and Other Information on PFOA Human Sera/Medical Surveillance/Epidemiology 1) F. A. Ubel, et al. Health Status o fPlant Workers Exposed to Fluorochemicals- A Preliminary Report, 41 Am. Ind. Hyg. Assoc. J. 584-589 (August 1980), with Summary. 2) Leonard M. Schuman & Jack S. Mandel, An Epidemiologic Mortality Study o f Employees at the Chemolite Plant (February 1980), with Summary of study. 3) Jack S. Mandel & Leonard M. Schuman, "Mortality Study at the 3M Chemolite Plant" (January 1989), with Summary of study. 4) Frank D. Gilliland & Jack S. Mandel, Mortality Among Employees o f a Perfluorooctanoic Acid Production Plant, 35 JOM 950-954 (September 1993), with Summary of study. 5) Frank Davis Gilliland, Fluorocarbons and Human Health: Studies in an Occupational Cohort (October 1992)(unpublished Ph.D. thesis, University of Minnesota), with Summary. 6) Geary W. Olsen, et al., An Epidemiological Investigation o f Reproductive Hormones in Men with Occupational Exposure to Perfluorooctanoic Acid, 40 JOEM 614-619 (July 1, 1998), with Summary of study. 7) Frank D. Gilliland & Jack S. Mandel, Serum Perfluorooctanoic Acid and Hepatic Enzymes, Lipoproteins, and Cholesterol: A Study o f Occupationally Exposed Men, 29 American Journal of Industrial Medicine 560-568 (1996), with Summary of study. 8) Geary W. Olsen, et al., An Epidemiologic Investigation o f Plasma Cholecystokinin and Hepatic Function in Perfluorooctanoic Acid Production Workers, 3M Final Report EPI-0003, (1997), with Summary of study, Protocol, and Manuscript accepted for publication in 2000, Drug & Chemical Toxicology. 9) Physician Plant Summary Reports Regarding Medical Surveillance Program at Cottage Grove (1978-1991) a) Summary of Program Reports b) Blood Levels of RF/F in Selected Employees, dated June 20,1978 c) 3M Internal Correspondence re 1981 Chemical Division Health Evaluations from DE Roach to PF Riehle, dated February 16, 1982 d) 3M Internal Correspondence re 1981 Chemolite Health Evaluations, from DERoach to PF Riehle, dated August 12, 1982 8 003117 f Attachments to Letter to C. Auer dated May 25,2000 Toxicology Studies and Other Information on PFOA e) 3M Internal Correspondence re Inorganic Fluoride Determinations, from DE Roach to PF Riehle, dated April 9, 1984 f) 3M Internal Correspondence re Organic Fluorine Levels, from DE Roach to PF Riehle, dated August 31,1984 g) 3M Internal Correspondence re Medical Examinations, from L Zobel to DW Dworak, dated March 20,1987 h) 3M Internal Correspondence re Chemolite Evaluations, Fall, 1990, from Larry R Zobel to Clair Murphy, et al., dated May 10, 1991 Previously submitted with April 21, 2000 letter to Charlie Auer, Fluorochemical Exposure (Serum) Assessment of (3M) Decatur Chemical and Film Plant Employees. Ongoing Studies See list of planned studies submitted with letter of April 21, 2000, which will address perfluorooctanoic acid as well as perfluorooctane sulfonate. 9 003118 Corporate Occupational Medicine 3M Center, Building 220-3W-05 St. Paul, MN 55144-1000 651 737 4230 Telephone 651 733 9066 Fax 1. Health Status of Plant Workers Exposed to Fluorochemicals - a Preliminary Report This published paper by Ubel et al (Am Ind Hyg Assoc J 1980;41:384-389) provides an overview of fluorochemical industrial hygiene, medical surveillance and epidemiology research data collected in the late 1970's at the Chemolite (Cottage Grove, Minnesota) facility. The authors concluded that total organic fluorine was found in the blood of workers exposed to industrial fluorochemicals. Medical examination of exposed workers and a brief summary of the initial retrospective epidemiologic mortality study (see study # 2) of the plant employees indicated that there were no ill health effects attributable to fluorochemical exposure. C03119 ... her lh en n o rmI levels of orBnic fluorine w ere found in the blood of workers exposed To fluorochem icels in an Austria! en v iro n m en t. No ill health effects attributable to exposure to fluorochemicals were found am ong these rkers The a m b ie n t sir in the process operation areas in the plant was found to contain m easurable am ounts of d i k anic fluorine. Through certain modifications in th e process steps end improvements in engineering controls, a ^ P sta n tia l re d u c tio n in the airborne fluoroehem ical levels w ithin the plant w as achieved. Health status of plant workers exposed to fluorochemicals a preliminary report F. A . B E L . M .D .. S . O. SO R EN SO N . M .P.H. and D. . R O A CH , M.D. 3M M edical Departm ent, 220-2E 3M Center, S i. Paul, Minnesota 55144 BEST COPY AVAIl ABLE NO *5C5r This M r.ifnel rr.ey ,. , -u.-.cr::V i-, ctpyrighf loI* (Tili 17 US C&ie), introduction This report provides merini results of an ongoing program which evaluates the health status of a group of production workers exposed to fluorochemicals. It was recognized as early as 1856 that normal human, animal and avian blood contains small amounts of fluorine.111 It was recently reported that human blood contains two forms of fluorine, "exchangeable" and "nonex changeable" . T h i s finding was corroborated by another study which described "ionie" and "nonionic" fluorine fractions in the blood.131Essentially, in either study ' i t form can be regarded as inorganic fluoride and the other ^ ^ .-o v a len tly bound organic fluorine. ^ ^ V e r y little organic fluorine was found in the blood sera of several species of animals, when the samples were processed by an open ashing procedure.1' 1However, when the samples were analyzed following confined combustion in an oxygen bomb, the concentrations of organic fluorine found in some bovine sera were comparable to those found in human sera.'51 No clear cut relationship between the two forms of fluorine in a given sample could be demonstrated.15'*1 The precise nature of the organic fluorine fraction in the blood is still speculative and could be very complex, containing more than one organic fluorine compound and from more than one source, including the diet. Organic fluorine compounds such as fluoroaeetate and fluorocitratc have been identified in lettuce, forage crops, soybean and tea, when the growing plants or single cell cultures of plants were exposed to high levels of inorganic fluoride.1'' 131 Perfluorooctanoic acid (C?FuCOjH) or a similar compound of industrial origin was believed to be present in a plasma fluorine fraction isolated from a large pool of human plasma samples.1*1 Since some 3M plant workers are exposed to industrial fluorochem icals, we considered it im portant to (a) determine the fluoroehemical levels in the blood of the plant workers, (b) monitor the fluoroehemical levels in the jm bient air in the fluoroehemical plants, (c) minimize irker exposure to fluorochemicals. (d) conduct special 'dica! examination of selected workers and (e) institute a retrospective epidemiological investigation in order to Mr * * ->nnn <, . no C*m--**t IIU , Am* , . evaluate the overall impact of exposure of fluorochemicals on the health of workers. In addition, w have also undertaken toxicological and m etabolic' studies in experimental animals. We believe that it is'now appropriate to report in a preliminary way on blood organic fluorine levels and the health status of a group of chemical production workers at one chemical plant which produces amm onium perfluorooctanoate. As the program progresses and as other investigations art completed, it is expected that more detailed papers and more definitive conclusions will be forthcoming. m ethods and investigations o. F luorine determ ination in b lo o d serum : The concentration of organic fluorine in blood was determined by subtracting the inorganic fluoride concentration from total fluorine concentration. The latter was determined by gas chromatography.1131 following combustion of the sample by a modified oxygen bom b technique.131 Perfluorooctanoic acid was also determined by gas chromatography following its extraction from serum ani conversion to its methyl ester using diazomethane.,1`1 b. Fluorine measurement in air samples: Air samples wer< obtained by using midget im pingers containini spectrogradc methanol through which the air was drawi with a portable battery-operated sampling pump Particulate sampling was done using Nuclepore * 0.8 ftr pore sized filters in 37 mm plastic cassettes. Samples s collected were analyzed for perfluorooctanoate ion by th method described above.11*1 c. Health evaluation: Evaluation of the health of tl employees was based on a careful study of the clinic history, a review of the multiple laboratory tests and physical examination by a physician (Table I). Subseque annual screenings included the same questionnaire < clinical history and the laboratory tests, while examinatio by the physician were conducted on employees selected < HW M AWU.HW. tm im nft a m n e t ] IS P ..0 3 03120 ( TABLE I IfcS IC O PYA V M u M edical Exam ination !>U l t . C linical huiorv and physical examination 2. Height. weight, blood pressure 3. Electrocardiogram . Chest examination, lorced vital capacity, (oread expiratory volume per secona. 5. Vision 6. Audiogram; 7 . Complete blood count: Hemoglobin. B B C . W BC . Differential count. Cell indices B. Urine analysis 9. Blood chemistry Glucose Urea Cholesterol Uric acid Calcium Phosphorus T ctii protein Albumin Globulin A/G ratio Bilirubin Alkaline phosphatase Cacate dehydrogenase ISIDH) Giutamic-oxa/oacaiaie transaminaseiSGOT) Glulamie-pyruvate transaminase (SGPT) Gemma-glutamyl transferase (SGGT| the basis of test results. Routine clinical laboratory determinations were carried out according to standard procedures by an outside contract laboratory. d. Epidemiological investigations: These investigations were structured after the principles of relative survival and proportional mortality analysis described recently."31The overall analysis essentially converges on a comparison of the observed to expected death rates specific for cause, age, time, sex and race. Other supportive studies: In vitro mutagenicity test (Ames) and animal toxicity studies related to ammonium p e rflu o ro o c ta n o a te were conducted by contract laboratories under 3M sponsorship. The studies included acute oral toxicity, primary skin irritation, eye irritation, one hour inhalation effects, two 28-day oral toxicity studies in rats and mice and 90-day oral toxicity studies in rats and monkeys. results and discussion a. Fluorine levels in bloodserum: The first series of workers was chosen on the basis of their estimated degree of exposure to fluorochemicals: Group A, 3M controls, who are never directly exposed to fluorochemicals; Group B, laboratory personnel who routinely handle fluorochemicals on a laboratory scale during their research and development work and Group C, selected employees in a chemical plant where fluorochemicals have been produced over approximately 30 years and where the potential for the exposure to fluorochemicals is the greatest. The results of fluorine analysis of serum samples are presented as ranges of values obtained and the number of samples involved per group (Table II). The inorganic fluoride levels in the case of all groups arc within generally reported normal ranges. The levels of organic fluorine in blood serum in Group A, 3M controls (0.01 to 0.08 ppm) are similar to those reported in the literature for normal human plasma/scrum (0.01 to 0,13 ppm).,,'*"*l*'l,| The concentrations of organic fluorine in Group B, laboratory personnel (O.Od to 2.0 ppm) are somewhat higher than those of Group A and the concentrations of organic fluorine in Group C, plant T A B L E II Le ve ls of Inorganic Fluo ride and O rg an ic Flu o rin e in Blood Group Normal Human sera (fe te n te in pub lished Staratura). A . 3M Controls. 8. Laboratory personnel, ovar 2 0 years axpoaura. C. Chemical Plant workers. Number of Samplaa Analysed 4 6 as inorganic Fluoride PPn 0.01 - 0.17 0.04 - 0.06 0.01 0-07 0.01 0.09 Organic Fluorine ppm 0.01 0.13 0.01 - 0.0B 0.04 - 2.00 1.00 - 71.00 **rriun tnduftinal Kj|nt Aucoilwi jOl/RWAl M i) /90 SIS 03121 0 & $ T COPYAVAILABLE TABLE III Levels of Organic Fluorine in Blood Serum end Urine o f Worker Removed from Exposure to Fluorochemicals Dutsliort of No Exposure to Fluorcchtm icel* Oronic fluctir in Blood Serum. ppm Pertluoroocienoete Excreted in Urine. vg /2 4 hr. 1Wilt 2 w ttki 2 months 3 months 5 months 8 months 11 months 1* months 18 months 66 387 7t 278 66 128 55 175 59 160 45* 220 47 no 4 60 39 * 80% of the organic fluorine was perlluorooclanoate ion. workers, (].0-71.0 ppm), are higher than ihose in the other groups. The highest levels were found in workers with the longest work history in fluorochemical production. The majority of the values have remained at about the same level during monitoring over a two and one-half year period. Throughout the years of service, these plant employees were in situations with a potential for multiple chemical exposures. There was considerable mobility of workers within the chemical plant itself, as well as transfer to and k'rom other non-flucrochemical production areas on the PLmc site. These circumstances make it difficult to define precisely the duration of exposure of the subject to fluorochemic3h. One group of 15 employees had a range of 1.0-10.5 ppm organic fluorine in serum when their serum samples were analyzed before changing to a job involving packaging the dry fluorochemical powder. In seven months, 11 of the employees had an increase in serum organic fluorine concentration to a range of 2.2 to 18.1 ppm. These levels were approximately the same or somewhat lower when their sera were again analyzed three months later. The majority of serum samples were analyzed solely for organic fluorine and inorganic fluoride. When a method became available, a selected number of serum samples from the workers engaged in the production of Bmmonium perfluorooctanoate were analyzed for perfluorooctanoic acid. About 90% of the organic fluorine in these serum samples was composed of the perfluorooctanoate anion. In the case of one worker, the organic fluorine in blood, . which was about 40 ppm over a one year period, suddenly rose to 70 ppm for no apparent reason. The worker was then moved to a plant location free of fluorochemical exposure and his blood and urine samples were periodically analyzed for organic fluorine and perfluorooctanoate over several months. The results presented in Table 111 indicate a gradual s >ut slow return of the serum organic fluorine levels toward *he earlier level. Eighty percent of organic fluorine in the 8th month serum sample wju found to be perfluorooctanoate ion. These blood and urine values suggest that some fluorochemicals are very slowly eliminated in humans. b. Fluorine levels in air samples: There has been an industrial hygiene program at the plant for a number of years. When it was recognized that organic fluorine could be found in the employees' blood, the level ofindustrial hygiene activity was increased. Air sampling was'conducted at points throughout the various process steps. The samples were collected in the operator's breathing zone (OB2 samples) or in work areas while the particular step was in progress (area samples). The latter was considered representative of an operator's exposure while in the area. Many of the samples were collected during charging and draining steps when exposure levels were likely to be highest. Table IV shows the four main stages and the process step: in the production of ammonium perfluorooctanoate, th< concentrations of perfluorooctanoic acid or its ammoniur salt in area samples and in OBZ samples and the time span o sample collections. Stage 1 involves preparation an isolation of perfluorooctanoic acid and its conversion to a ammonium salt slurry, Stage II involves conversion of tl salt slurry to a salt cake, Stage III involves drying the cai and Stage IV involves further processing and fin oackacins of the ammonium salt. Phase A in Table IV refers to the circumstances as th existed when the present studies were initiated. Duri Phases B and C, new measures were introduced in Stages III, and IV to minimize the levels of exposure fluorochemicals. No changes were made in Stage 1. Phase A: The concentrations of fluorochemicals in a samples and OBZ samples in Stage I were 0.03 to 0.3 mg, and the concentrations in OBZ samples in Stage 11 werc( to 1.04 mg/m1. However, the fluorochemical levels in OBZ samples i relatively higher, 3.90 m g/m \ during drying in the < (Stage III) and 3.27 mg/m1, during further processing packaging (Stage IV). These operations entailed a enclosed procedure with more opportunity for expc than in the previous stages. Phase B: Because of the higher levels, attention focused on minimizing the exposures in Stages 111 an By making appropriate modifications such as (a) repl Aw U* Hft Aiwc 1<*U *utn 003122 l * O L C < C o n c n u t ic n o< P a rftu o ro o c ta n o ic A d d t n d Ha A m m o n iu m S i l t in A ir D u ring V rloua S ta g e s o f P ro d u c tion St*g nd Process Step in P ro d u ctio n Pha A -- ------------------------------------------ --- Tim * Cone. S *m p l M in. m g/rn' -- ---- S im p l PnS* B ----------- ------------------- Tim Cone. M in*. m j/m 1 Ph* C ---------------------------------------- --- -- Tim Cone, Sem ple M in. m g/m 1 A (PU U 0.51 (Bl A 75 0.05 A 40 0.01 A 21 <0.07 A 37 0.02 A 60 <0.06 A 55 0.66 A 48 <0.07 A 55 0.03 A 30 <0.06 A 18 0.14 BEST copyM i l ABLEA 60 <0.03 A 27 0.0a A average: 0.05 A average: 0.051 082 12 0.34 OBZ 5 0.50 OBZ 5 0.17 average; 0.34 082 6 <0.01 OBZ 5 0.25 average: 0.13 10 A 30 0.04 A 23 0.05 A 4B 0.07 average: 0.05 OBZ 26 0.16 OBZ 26 0.03 - avarag; 0.10 II (a) A 90 1.10 A 60 0.06 A 325 1.50 A 60 0.05 ID) OBZ 30 <0.03 OBZ 30 <0.03 OBZ 20 0.21 10 OBZ 28 1.04 OBZ 21 0.40 > Id) OBZ 20 o .i e III OBZ 59 3.90 oez 11 0.42 P 11 0.20 IV OBZ 285 3.27 A Are Semple PL - Peak Level eicluding the 55 min. v ilu e or 0.68 m g/m ' OBZ Oprion bretihmg io ne sim ple OBZ OBZ OBZ 062 OBZ OBZ OBZ OBZ OBZ OBZ OBZ OBZ 250 340 129 212 120 223 65 19fi 370 180 123 45 average: 2.12 1.18 2.30 0.30 0.07 2.56 7.60 0.04 0.33 0.95 0.40 0.08 1.49 OBZ 48 0.30 OBZ 49 0.S7 OBZ 30 0.54 average: 0.47 -- the tray drying in the oven with closed system drying, from which point the sail could be passed .through a grinder, directly into the packaging drums and (b) improving the ^ 'ocal exhaust system, the iluorochcmical levels in Stages 111 ta m c m uvJutuul Kjiunt tsvrcuMn JOUSHIt m j n/gQ and IV were reduced from 3.9 and 3.27 mg/m1in Phase A to 0.42 and 1.49 m g/m 1 in Phase B, respectively. Phase C: In Stage II, Phases A and B, two successive filtration steps were involved. Under Phase C, the fust 517 C0C123 nitration step was replaced by a more rapid nitration process, which was also amenable to a better local exhaust .system. As a result, it was possible to shorten the exposure f.ime during the first filtration from 6-8 hours to 1-2 hours nd also to reduce the level of fluarcchrmicals in the area ampies from I.J-J.5 to 0.05-0.06 mg/m1. most difficult to evaluate. In a few instances, through episodes unrelated to plant work, the elevated SGGT levels were traceable to alcohol consumption. A consultant hepatologist who examined the subjects concurred with our conclusion that these minor deviations from the normal in the liver function tests were most likely unrelated to plant Further, in Stage IV. Phase C, grinding was eliminated resulting in a lower mean concentration, 0.47 mg/m1in the OBZ air samples compared to mean concentrations of 3.27 and 1.<9 mg/ m3in Phases A and B, respectively. The period of exposure during Stage IV was also reduced from 6-8 hours in Phases A and B to 1-2 hours in Phase C. work and are com patible with the individuals' predisposition toward alcohol. Further a review of the results of laboratory tests performed on other plant workers and on a large number of management personnel shows the same general degree of variations from the normal values as in the cast of fiuorochemical production area employees. Careful examination of the data in Table IV reveals During the course of this three year monitoring program sporadic high values relative to ocher values in the same set of samples (Phase B, Stage I, 0.68 mg/m3, 55 min. area sample; Phase B. Stage IV, 7.60 mg/m3, 65 min. OBZ there has been a genera! decline in the number of individuals with "abnormal" laboratory findings. This is possibly attributable to the implementation of a concerted program sample). However, the overall results do show a decrease in of medical concern and personal health care counsellingand levels of exposure to fluorochemicals as a result of the to improved personal habits of the employees process modifications described. In addition to exposure by inhalation, exposure by dermal absorption has been considered and measures have No relationship was observed between the few test result deviations (from normal) and the blood levels of organic fluorine. been taken to reduce this type of exposure. Additional modification and process changes ere under continual review. The objectives of these changes are better containment of fluorochemicals and reduced reliance on personal protective devices. Until complete control of the fiuorochemical dust is achieved, the personal protection As was mentioned earlier, we have not detected any disease pattern attributable or related to fiuorochemical exposure. Furthermore a review of absenteeism and illness patterns in these employees does not suggest any w ork related problems. program consisting of a dust respirator (3M Brand No. 9900), daily clean overalls and rubber gloves will continue to '|ie enforced. d. Epidemiological studies: A retrospective cohort mortality study of employees at this plant site, covering a period of the past 30 years (1948-78), was conducted by an c. Health evaluation: Beginning in late 976, special health screening examinations were offered on a voluntary basis to employees in the chemical plant. About 300 employees have been examined yearly over the three year period. Approximately 90% of the plant workers participated in the program each year, although only 50% of the employees took pan for three consecutive years. The examination results were given to the employees and, at their request, were sent to a physician of their choice. No health problem s related to exposure to fluorochemicals were encountered among those examined. In any large scale clinical laboratory testing program such as the present one, difficulties invariably arise in assessing the weight to be pliced on those laboratory test results which show minor excursions from the norma] values. This is especially true in the absence of clinical evidence of any health impairment as is the case now. All deviations from the norma) values in the laboratory test results were critically scrutinised during our clinical assessment, and were also evaluated statistically when possible. Occasional variations from the normal in isolated liver enzyme tests were encountered. Detailed histories were again reviewed with the employees about medication, alcohol consumption independent group under 3M sponsorship. The main objective was to determine (a) whether the mortality experience of employees at the plant was significantly different from that expected in a population group of the same demographic composition and (b) whether (he mortality experience of the chemical workers of the plant was significantly different from that expected. Records of 4218 employees at the plant site were screened and a comprehensive mortality study was carried out on the 3688 employees who had worked at the plant for at least six months. In this group, a total of 180 deaths were identified (159 males and 21 females) and death certificates for 177 of these cases were traced. A11efforts to locate the remaining 3 death certificates were unsuccessful. The number of deaths among females was too few to permit statistical evaluation. Results of m ortality analyses for the males indicated no disagreement between the observed mortality and that expected. This was true of all the various causes o f death and also of various specific causes o f death due to cancer. In addition, mortality analyses for the chemical workers at the plant revealed no disagreements between observed and expected mortality for any cause of death. and other personal habits. The most frequently encountered Uiver enzyme exceeding the norma) range was the serum P^amma-glutamyl-transferase (5GGT) included for the first time in our liver function profile. With its exquisite sensitivity to alcohol consumption,1 the SGGT was the e. Other su p portive studies (details in o separate p u blication): Am m onium perfluorooctanoate was examined for mutagenic activity in microbial assays employing Salmonella typhimurium strains TA-98, TA100, TA-1535, TA-JS37 and TA-1538 and Sacchatomyets su amme n ,f a ju x j n i ) iolvil. 1910 003124 * ccrevsite strain D*. The compounds were tested by two laboratories with and without liver microsomal enzyme preparations from Aroclor ' -induced rats. Ammonium perfluorooetanoate was not mutagenic under the test conditions. The toxic effects of ammonium perfluorooetanoate (LDjC: MO m g/kg, rat) were fairly consistent in rodents. The liver was the target organ- An apparent sex related difference in toxicity was also evident. The males developed hepatotoxic effects at lower treatment levels than the females and at comparable treatment levels the males had more pronounced histopathologic effects than the females. Serum and liver concentrations of organic fluorine were appreciably greater in males than in femaJes. These findings have been corroborated in our laboratories by metabolism experiments in rats involving the use of C'Mabelled ammonium perfluorooetanoate. In the rhesus monkey, the major site of toxicity appeared to be the reticuloendothelial system. The sex related difference in the concentrations of organic fluorine in serum and liver noted in the rodent studies was not evident in the primate study. Such species and sex differences in the toxicity of ammonium perfluorooetanoate make extrapolation of results of these studies to the human difficult. references 1 . Nielli. M .J .: Presence du Fluor dans la Sang Comp, rend. 43-MS (16561. 2. la v o , D .R .: Evidence That There re T w o Form * ot Fluoride in Human Serum. Nature 2 1 7 .1050-1 O SI (1568). 3. V enkaU aw erlu , P .. L. Singar nd W .D . A rm stro n g : Determination c l Icnlc (plus ionl2abla) Fluoride in Biological Fluids. Procedure Based on Adsorption o( Fluoride Ion on Calcium Phosphat. An*/. Biochem. 02:350-359 (1971). 4. T e v e i, D .R .: Comparison o I "O rganic" Fluorid in Hum an and Nonhuman Serums. J. Dent. Res. SO.783 (1971). 5. V e n k a te iw a rlu , P .: Determination o l ota I Fluorine in S eru m and Other Biological M aterials by Oxygen Bomb and Reverse Extraction Techniques. Anal. Biochem . 58:512-521 11975). 6. Guy. W .S.. D .R . la v e s and W .S. Bray: Biochem istry Involving Carbon Fluorine Bonds, pp. 117*134. A C S . Washington. DC |1 976). 7. W ade. R .H .. J . M. Rosa and H.M , Benedict: A Method tor the Detection and Isolation of Traces of Organic Fluorine Compounds in Plant*. J . Chromatog. 14:37-45 (1964). 8. Lo ve la ce. J . . G .W . M ille r nd G .W . W a lkio : The Accum ulation e l Fluoroocetat and Fluorocnrate in Forage Crops Collected Near a Phosphate Plant. A tm os. Environ . 2:107-190(19681. 9. Cheng. J . Y -O ,. M -H. Y u . G .W . M iller end G .W . W alkie; Fluoroorganlc Acids in Soybean Leave* Exposed to Fluoride. Environ. Sei. Techno/ 2:367-370 (1968). conclusions Organic fluorine was found in the blood of workers exposed to industrial fluorochemicals. The levels of organic fluorine in blood appear to be related to the degree and duration of exposure. Although it is assumed that high organic fluorine levels in the blood are a result of high concentration of airborne fluorcchemicals, the contribution from dermal absorption may also be significant. Limited data from the study of one individual who was removed from exposure to industrial fluorochemicals suggest that some fluorochemicals are very slowly eliminated from the body.. Medical examination of exposed workers and a retrospective epidemiologic mortality study of the plain employees indicate that there are no ill health effects attributable to fluorochemical exposure. In vitro mutagenicity testing has shown that perfiuorocctanoic acid is nonmutagenic. Certain species and sex-related differences were found in animal toxicity studies, which make extrapolation of results of such studies to the human difficult. This observation emphasizes the importance of the information on humans, such as that presented in this paper. acknowledgment The authors wish to thank R. A. Prokop and R. E. Oher for reviewing the manuscript, J. Bclisle and-D. F. Hagen for the analyses related to fluorochemicals, and P. Venkaieswarlu for help with the manuscript preparation. 10. Y u , M -H . an d G .W . M ille r: G a t C h ro m a to g ra p h ic Identification ol Fluoroorgamc Acida. Environ. Set. Techno/. 4 :4 9 2 - 4 9 6 (1 8 7 0 ). 1 1 . P e te r*. R .A . and M . S h o n h o u ie : Fluorocitrate in Plants and Food-stuff*. Phytochem istry 1 f:1 337-1338 ( 1972). 12. P e t e r s . R .A . and M . S h o r t h o u ie : F o rm a tio n of Monofluorocerbon Compounds by Single C ell C ultures of Glycine M a i Growing on Inorganic Fluoride. Phytochem istry I lit 339 (1972). 13. Batiste, J . and O .F. Hegen: Method for the Determ ination of the Total Fluorine Content by Whole Blood. S tru m /P ia e m a . and Other Biological Sem ple*. Anal. Biochem . 8 7 :5 4 5 -5 5 5 (1978), 14. B e litle . J . end D .F . H agen: A Method (or the Determ ination of Perflucrooctancie A cid in Blood end Other Biological Sam ples. Anal. Bioehem. 107:369-376 (19801. 15. M o n a o n . H . R .: A n a ly s is o l R e la tiv e S u r v iv a l e n d Proportional Mortality. Com puters end Biom ed. B e t. 7:3253 3 2 (1 9 7 4 ). 16. C o x . F .H . end O . B a c k e r D irk t: The Determ ination ot Fluoride in Blood Serum , Caries Res. 2 :6 9 -7 8 (1968). 17. Frasen, J .A ., F .H . C o* and M .J . W in e r The Determination o l Fluoride In Biolog ical M aterial* by M e a n t ol G a t Chromaiography. Phatm. W eakbled 703:909-914 (1968). 18. S in g e r. L. and R.H. Ophaug: Concentration* of Ionic, Total, and Bound Fluoride in Plaim a. Clin. Cham. 25:523-525 (1979). 19. Rollon. J .G .. G . Pincharle and O . Robinaon: Serum G am m e -glutamyl Transpcptidose m Relation to A lcohol C onsum ption. Clin. Chim. A c ta 3 9 :7 5 -8 0 (1 9 7 2 ). 20. R o aalkt. S .B . and D . H au : Serum G am m a-glutam yl T ran ip e p n ca se Activity in Alcoholism , din. Chim. Acta 39:41-47 II972). imenuri lnovmtt Asioculitn JOURNAL (if) BEST COPY AM l! ABLE MS * * TOTAL PA G E.08 * * 0 C 1 2 S