Document aJR46RLp9Lbw8vxbprw5nGbVN

S - 3 5 7 5 R E V 3-81 15TAIUSMCD 0 2 E. I. du Pont de N emours & C o m pany IN C O R PO R A T ED H a s k e l l La b o r a to r y for T o xic o lo g y an d In d u s t r ia l M e d ic in e El k t o n R o a d , N e w a r k , D el-a w a r e 19711 CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT PERSONAL AND- CONFIDENTIAL J. G. LOSCHIAVO POLYMER PRODUCTS DEPARTMENT PARKERSBURG cc : J. M. Cordrey D. A. Erdman T. A. Foster T. L. Schrenk P. Thistleton J. W. Raines G. L. Kennedy PPD - PARKSBG PPD - PARKSBG PPD - PARKSBG PPD - PARKSBG PPD - PARKSBG PPD - M-5625 C^l&D - Haskell C-H "-f August 25, 1982 AMMONIUM PERFLUOROOCTANOATE (C-8) IN HUMAN BLOOD In reference to your July 29, 1982, letter to R. J. Zipfel (Retention of Ammonium Perfluorooctanoate [C-8] in Blood of Teflon Workers) I would like to make several important sugges tions. Acquisition and interpretation of C-8 blood concentra tions in workers is very important in understanding how the human body-handles C-8 and how accurately our animal models at Haskell correl-ate to the human situation. To better interpret these data, consider the following modifications: The 0.006 ppm blood level is termed a "rate" of accumulation when it would be more appro priate to call it an "average concentration" over the average of 91 days of employment. The average blood level of 0.006 ppm/day x 91 days gives the plateau, or steady-state, con centration (0.546 ppm) that more closely represents the dynamic aspects of exposure and elimination. The calculations assume a volume of distribution (Vd) equal to the blood compartment only (5.5 liters). Since C-8 is water soluble and binds protein, the Vd would actually be closer to the volume of total body water (approximately 42 liters/70 kg ma n ) . DUP000574 E1D072164 BETTER TH IN G S FOR BETTER LIVING . . . THROUGH C H EM ISTR Y 000216 J. G. Loschiavo 2 August 25, 1982 To more accurately assess the retention of C-8 in the body as well as predict blood levels anticipated with continued low-level exposure, formulas commonly used to estimate drug-therapy regimen can be employed. Assumptions: - The blood level, Cp, is at a plateau (steady-state) concentration (i.e., absorption and elimination approximately equal). - The volume of distribution, Vd, is in total body water, or 42 liters. - The daily dose (D/T) is 0.081 mg/day. - The elimination half-life, t 1/2, is estimated from a literature report on one individual. The value is 655 days, but could vary considerably. Then from Goodman and Gilman (1970): f 1.44 t 1/2 ,Di Cp = ------ Vd-------- T - where f = fraction absorbed - solving for f, - Cp Vd T _ 0.546 m g / 1 * 422, 1 day Z ~ 1.44 t 1/2 D " 1.44 t 1/2 0.081 mg/2 - then: t 1/2 (days) f % Absorbed 30 6.55 197 1.00 360 0.55 655 0.30 655 100 55 30 Thus, depending on the actual t 1/2, we can estimate only that greater than 30% of atmospheric C-8 is absorbed. This is in general agreement with your estimate, but until we know the actual t 1/2 we will not be able to accurately calculate fractional absorption. EID072165 000217 DUP000575 J. G. Loschiavo 3 August 25, 1932 Regarding these calculations and in response to your suggestions in the July 29 memorandum, - More human data is necessary from two sources: 1. current employees for determination of plateau (steady-state) concentra tions 2. employees no longer exposed to C-8 for determination of the blood t 1/2 and the urinary excretion rate. - We have performed radiochemical and biochemical analysis of the distribution and effects of C-8. TPP:sgl RESEARCH TOXICOLOGIST DUP000576 000218 EID072166