Document a478pJ5Jkj5R685doEEjj9OzN

802000 6i jiiie -9WVV \&k /)AA 6 - W ? ~ KSMUSMK0VQ2 \~t *.'*** E , I. du P ont de N em ours S om pany incorporated Ha sk e ll Laboratory for Toxicology and Industrial Medicine ' 5" Elkton Road, Newark, Delaware 19711 - * M CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT PERSONAL AND CONFIDENTIAL August 25,"1982 J. G. LOSCHIAVO POLYMER PRODUCTS DEPARTMENT PARKERSBURG ': ; -i r ' ` : AMMONIUM PERFLUOROOCTANOATB (C-8) in hdman~'blq6d ' ~~ " I In reference to your^July^29, 1:982/ letter to R. j. zipfel' (Retention of Ammonium Perfluorboctanoate [C-8] in Blood of... Teflon Workers") I would like"to make several important sugges tions- Acquisition ..and/interpretation "pf C-8 blood concentrar-^. tions in workers is'"very important in "understanding how the r : human body handles C-8 and h e w ,accurately our animal models ht Haskell correlate to the/human'situation,. To better, interpret these data, consider the following modificationst^7 "T ~ ' 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 employmentThe 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 man). j ! ': ( ` .! 4 Crmnny Sanitized. Does not contain TSCA CBI B E T T E R T H IN G S FO R B E T T E R LIVING . . . TH R O U G H C H E M IS T R Y 000209 J. G. Loschiavo. 2 f Jr*. 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-thierapy regimen can be employed. -i. -rWZ** - ' Assumptions;; - The blood level, Cp, is at a plateau . {steady-state).concentration (i,e . , `H. . 'absorption and elimination approximately^ equal) ..,, ... .. ' .' .V - The"volume' of distribution, Vd, is in ' T " total body water, or 42 liters. - The daily .dose (D/T) is 0.081 mg/day. * . - .The elimination half-life., t 1/2, is 'V^es timated from a literature report on ^^^^otfe^individuai^.yjie value* is 655 days, ,.c o u l d ^ y a ^ ^ n s i d e r a b l y . ' .*V>f-* sgjfj. *-iVt` Then fro^'^toodm^^n^Gilman (1970) : "$*~ i\t'sp t i/2 t,d ,. "-i-. Vd r . V *" V.f /Syp. - w h e r e f -- fraction absorbed ..M-V -x . . * - solving for f , 'I .t 2~ - "Cp Vd . T ;" _ 0.546 mg/1' 421 * 1 day - 1.44 t 1/2 D ... 1.44 t 1/2 0..081 mg/1 - then: t 1/2 - (days) f % Absorbed _ 30 6.55 197 . 1.00 360 J: 0.55 ' " 6 5 5 - 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. ooozio j. G. Loschiavo -r 3 August 25, 1982 Regarding'"'these calculations and in response to your suggestions in the July 29 memorandum, - More human data^ is necessary from two sources: v . 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 0 8 . ?rstf-v *~Ori AVAILABLE 0 0 0 Z1 X