In vivo and in vitro percutaneous absorption of [14C]pyrene in Sprague Dawley male rats: skin reservoir effect and consequence on urinary 1-OH pyrene excretion.
The skin reservoir effect of [14C]pyrene (in vivo and in vitro) on percutaneous absorption was determined in male Sprague Dawley rats. The urinary 1-OHpyrene (1-OHPy) excretion was compared between dermal exposure and intravenous administration. In vivo, the percutaneous absorption flux of [14C]pyrene (200 microg/cm(2); 50 microL/cm(2) of ethanol) determined by sacrificing batches of rats after different exposure times over 4.5 h was 1.0 +/- 0.1 microg/cm(2) h(-1). During exposure, penetration flux was twofold higher than absorption flux, indicating a gradual accumulation of pyrene in the skin. [14C] skin content at the end of exposure was 16 microg/cm(2), which decreased gradually over time to 2 microg/cm(2) 68 h after the end of exposure. The total absorbed dose during exposure was threefold lower than that after exposure, indicating a high contribution of pyrene skin content to the systemic availability of the compound. Similar results were obtained in vitro. The apparent elimination rate of [14C]pyrene (23 h) contained in the skin after an exposure of 4.5 h was similar to the apparent urinary excretion half life of 1-OHPy (21 h). These values are threefold higher than the urinary excretion half life of 1-OHPy after an intravenous administration of pyrene (0.5 mg/kg). In conclusion, absorbed dose and percutaneous absorption flux were well estimated from the 1-OHPy urinary excretion rate. For risk assessment purposes, the penetration flux rather than the absorption flux should be taken into account for topical pyrene exposure.
Payan
Jean-Paul
JP
Institut National de Recherche et de Sécurité, Avenue de Bourgogne, B.P. No. 27, 54501 Vandoeuvre Cedex, France. payanjp@inrs.fr
Lafontaine
Michel
M
Simon
Patrice
P
Marquet
Fabrice
F
Champmartin-Gendre
Catherine
C
Beydon
Dominique
D
Ferrari
Elisabeth
E
D000279:Administration, Cutaneous; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D011721:Pyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D014556:Urine / Q000737:chemistry
D015415:Biomarkers; D002250:Carbon Radioisotopes; D002273:Carcinogens; D011721:Pyrenes; C030984:pyrene; C033146:1-hydroxypyrene