Document MMMQMVb70KZ205jO2KOMMaw2z

ftfL&ab-bk i 27 000230 fi(L0.H6 - P R O P O SA L FOR FEASIBILITY A SSE SSU E H T Estim ating Exposure, B iopersistence, and Potential liv e r E ffects front W orkplace Exposures to O rganofluorines: A determ ination o f the feasibility o f appropriate analyses of historical surveillance date Introduction Concern regarding organofiuorine exposure (C-8 etc.) is based on the results of rodent testing. In a n im a l. ,, e compounds induce a biological response known a s peroxisome proliferation. Research with chem icals known to produce this response suggests that long term administration to rodents results in the development of benign tumors of the liver, pancreas, and testis. However, other data indicate that man m ay be at little risk for occurrence of tumors since man is a low responder to this class of chem icals, i.e ., peroxisome prolifsrators. However, other liver toxicity m ay occur in man that is independent of peroxisome induction. Based on experimental data, changes in liver function may be a means of detecting human biological response to these chem icals. Additional concern with these compounds has been that these materials have been detected in the blood of exposed em ployees. Exposure potential is by inhalation or skin contact it is known that these compounds are eliminated from tiie body very slowly. It is estimated that the half-HFe o fC -8 m aybe a s long a s 35 years. At present, there are no available human data that demonstrate increased levels of blood organofluorines with discernible adverse health effects. However, there remains concern about th possibility o f such effects, particularly with regard to Hver function. Background in 1978, the 3M Company notified DuPont that they had observed elevated organic fluorine levels In the blood of their workers exposed to ammonium perfluoro-octanoate. Although the specific 3M product w as not used at Cham bers W orks, Chambers Works conducted a special blood monitoring program in 1978-79for our fluorosurfactant em ployees. Organic fluorine levels in the blood were found to be no different than the Wilmington control group levels. A s a result, tire blood monitoring program was terminated In 1979, In 1999, Cbam bers Works conducted another special blood monitoring program for a subset o f ourffuorochemicals em ployees. Organic fluorine levels in the blood were found to be no (tifferentthan the 1978-1979 Chambers Works levels and the 1978-1979 Wilmington control group levels. Company Sanitized. Does not contain TSCA CBI 1 000231 Purpose The objective of medical and exposure surveillance in a workplace population is to detect people with exposure-associated dysfunction who are at risk for developing clinical disease. When the exposure markers and effect markers are wefi-quantitated, such surveillance programs can provide valuable information as to safe occupational exposure levels. In addition, risk evaluations can be based on human data. This proposai describes a biomonitoring project with the following objectives; 1. Establish pre-placement baseline levels of fluoride ion in blood and blood perfluorooctonoate level, 2 . Monitor workplace exposure to C-fl by repeating the blood sampling everym onth, 3. Correlate biomonitoring results with Industrial Hygiene workplace air and personal monitoring results, 4 . Establish rate of bioaccumuiation of C -8 in workers 5. Establish level of biopersistence in workers by continued surveillance following cessation of exposure. 6. Correlate data on biomarkets of effect (serum fiver enzym e levels) with the biomarkers of exposure (fluoride ion in biood and blood perfluorooctonoate level). 7 . Examine other health effect measures (medical history questionnaire, including smoking history; complete blood count, 3MA-12) for potential, confounders or modifiers. Approach A C -8 surveifiance program at Chambers Works will take advantage of the proposed C -8 recycling program soon to be initiated. If the project Is approved before work begins, the ability to collect pre-exposure baselines on both the biomarkets of exposure and of effect wifi not be compromised. T he data matrix should contain the foHowmg variables: 1. Name 2. SSN 3 . Date of Hire 4 . d ate of C -8 task initiation 5. Date of Birth 6 . Current T ask Assignment (job title, task name) 2 000232 7. Tim spent In task 8. Standard !H measures of exposure (preferably personal monitoring, but area data could be used), with an assessm ent of the potential for dermal exposure 9. U se of personal protective equipment 10.Laboratory results of 0 8 , fluoride ion, and liver enzyme m easurem ents retained as serial data variables. The protocol will prescribe data collection at monthly intervals for liver enzyme measurements, and area or personal monitoring at either w eekly, or bi weekly Intervals, for a period of one year. The range ami variance of these measurements, along with tire total number of individuals in the potentially exposed population, will provide a good indication of whether there is clinical and/or epidemiological value in continuing the data collection. It should be recognized that while fiver enzymes are generally highly sensitive, they are nonspecific and of poor positive predictive value in identffying tree occupational fiver disease. (In low-risk workplaces, where measured exposure is taw, the prevalence of occupation-associated liver disease may be so low that the positive predictive valu of the screening test m ay also be very low. In these circumstances, other causes of fiver dysfunction are the more likely reason for abnormal screening results.) However, the widely available batteries of enyzme tests are inexpensive and have the advantage of large bodies of general population data and associated "normar values that are useful for comparison. In addtion, the availability of pra-exposttre levels wifi enable each C-8 exposed worker to serve as his own control a s the primary purpose of the study is to measure change in these biomarkers over time. Responsibilities and the industrial hygiene monitoring data. The Corporate Epidemiology Program will assum e responsibility for constructing the analytic data file and doing the assessm ent of the descriptive statistics on the population results at the end of the first year of data collection. Employees will be asked to participate in a descriptive epidemiology project that will be directed to understanding whether or not C~8 exposures result in measurable Wood changes. This communication will be done in person by site completion of the project, the employees wifi be notified, in person and in writing, of the results. Questions concerning medical surveillance wilt be handled by site Several of our fluoroprotectant and fluorosu rfactan A M B m xliJcts and intermediates were tested in an oral dose animal screentagstuay at Haskell Lab to compare the btopersistence of toted fluorine to the blood with the specific 3 / Company Sanitized. Does not contain TSCA CBI 000233 fluorochemical that 3M had identified. The preliminary screenina information from the blood analysis after repeated oral doses s o far in d i^ tes thatS i r products do not absorb into the blood to the sam e high level nor oerslst in tha blood com pared with the 3M specific fluorochemical. H ( 4 000234