Penetration of ammonium perfluorooctanoate through rat and human skin in vitro

被引:40
作者
Fasano, WJ [1 ]
Kennedy, GL
Szostek, B
Farrar, DG
Wards, RJ
Haroun, L
Hinderliter, PM
机构
[1] DuPont Co Inc, Haskell Lab, Newark, DE 19714 USA
[2] Ineos Chlor Ltd, Chester, Cheshire, England
[3] Syngenta, Macclesfield, Cheshire, England
[4] ENVIRON, Emeryville, CA USA
关键词
ammonium perfluorooctanoate; Fluorad FC-118; in vitro dermal; penetration; liquid chromatography-mass spectrometry; penetration rate; permeability coefficient;
D O I
10.1081/DCT-200039707
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Rat and human epidermal membranes were mounted onto in vitro diffusion cells with an exposure area of 0.64 cm(2), and skin integrity was confirmed using electrical impedance. Following membrane selection, Fluorad FC-118, a 20% aqueous solution of ammonium perfluorooctanoate (AFPO), was applied to the epidermal surface of each skin replicate at approximately 150 muL/cm(2) and the donor chamber opening occluded with Parafilm. Serial receptor fluid samples were collected hourly from I to 6 h and at 12, 24, 30, and 48 h and analyzed by liquid chromatography-mass spectrometry (LCMS) for APFO anion (PFO-). For rat skin, the time to steady-state penetration (6500 +/- 3000 ng APFO (.) cm(-2) (.) h(-1)) occurred in less than 12 h, which was sustained until termination (48 h). Based on the concentration of the applied test material, the permeability coefficient (Kp) for APFO in rat skin was calculated to be 3.25 +/- 1.51 x 10(-5) cm/h. By end of the 48-h exposure period, only a small portion of the total APFO applied (1.44 +/- 1.13%) had penetrated through rat skin. For human skin, steady-state penetration of APFO (190 +/- 57 ng APFO (.) cm(-2) (.) h(-1)) was reached by 12 h. Based on the concentration of the applied test material, the permeability coefficient for APFO in human skin was calculated to be 9.49 +/- 2.86 x 10(-7) cm/h. By the end of the 48-h exposure period, only a negligible amount of the total APFO applied (0.048 +/- 0.01%) had penetrated through human skin. Thus, under infinite dose and occlusive conditions, the steady-state penetration of APFO from a 20% solution was approximately 34-fold faster through rat skin than human skin.
引用
收藏
页码:79 / 90
页数:12
相关论文
共 23 条
[1]  
American Conference of Governmental Industrial Hygienists (ACGIH), 2003, THRESH LIM VAL BIOL
[2]  
[Anonymous], SKIN BARRIER PRINCIP
[3]   METHODS FOR INVITRO PERCUTANEOUS-ABSORPTION STUDIES .7. USE OF EXCISED HUMAN-SKIN [J].
BRONAUGH, RL ;
STEWART, RF ;
SIMON, M .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1986, 75 (11) :1094-1097
[4]   The Tinsley LCR Databridge Model 6401 and electrical impedance measurements to evaluate skin integrity in vitro [J].
Fasano, WJ ;
Hinderliter, PM .
TOXICOLOGY IN VITRO, 2004, 18 (05) :725-729
[5]   Rapid integrity assessment of rat and human epidermal membranes for in vitro dermal regulatory testing: correlation of electrical resistance with tritiated water permeability [J].
Fasano, WJ ;
Manning, LA ;
Green, JW .
TOXICOLOGY IN VITRO, 2002, 16 (06) :731-740
[6]  
Gilliland FD, 1996, AM J IND MED, V29, P560
[7]   ANIMAL TOXICITY STUDIES WITH AMMONIUM PERFLUOROOCTANOATE [J].
GRIFFITH, FD ;
LONG, JE .
AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL, 1980, 41 (08) :576-583
[8]   Compound-specific, quantitative characterization of organic: Fluorochemicals in biological matrices [J].
Hansen, KJ ;
Clemen, LA ;
Ellefson, ME ;
Johnson, HO .
ENVIRONMENTAL SCIENCE & TECHNOLOGY, 2001, 35 (04) :766-770
[9]   The toxicology of perfluorooctanoate [J].
Kennedy, GL ;
Butenhoff, JL ;
Olsen, GW ;
O'Connor, JC ;
Seacat, AM ;
Perkins, RG ;
Biegel, LB ;
Murphy, SR ;
Farrar, DG .
CRITICAL REVIEWS IN TOXICOLOGY, 2004, 34 (04) :351-384
[10]   INHALATION TOXICITY OF AMMONIUM PERFLUOROOCTANOATE [J].
KENNEDY, GL ;
HALL, GT ;
BRITTELLI, MR ;
BARNES, JR ;
CHEN, HC .
FOOD AND CHEMICAL TOXICOLOGY, 1986, 24 (12) :1325-1329