Kinetics of 3-(4-methylbenzylidene)camphor in rats and humans after dermal application.
The toxicokinetics of 4-MBC after dermal administration were investigated in human subjects and in rats. Humans (3 male and 3 female subjects) were exposed to 4-MBC by topical application of a commercial sunscreen formulation containing 4% 4-MBC (w/w), covering 90% of the body surface and resulting in a mean dermal 4-MBC dose of 22 mg/kg bw. In rats, dermal 4-MBC doses of 400 and 2000 mg/kg bw were applied in a formulation using an occlusive patch for 24 h. Concentrations of 4-MBC and its metabolites were monitored over 96 h in plasma (rats and humans) and urine (humans). In human subjects, plasma levels of 4-MBC peaked at 200 pmol/ml in males and 100 pmol/ml in females 6 h after application and then decreased to reach the limit of detection after 24 h (females), respectively, 36 h (males). After dermal application of 4-MBC, peak plasma concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were 50-80 pmol/ml at 12 h and of 3-(4-carboxybenzylidene)camphor were 100-200 pmol/ml at 24 h. In male and female rats, peak plasma levels of 4-MBC were 200 (dose of 400 mg/kg bw) and 1 200 pmol/ml (dose of 2000 mg/kg bw). These levels remained constant for up to 24-48 h after dermal application. Peak plasma concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were 18,000 pmol/ml (males) and of 3-(4-carboxybenzylidene)camphor were 55,000 pmol/ml (females) between 48 and 72 h after application of the high dose of 4-MBC. In human subjects, only a small percentage of the dermally applied dose of 4-MBC was recovered in the form of metabolites in urine, partly as glucuronides. The obtained results suggest a more intensive biotransformation of 4-MBC in rats as compared to humans after dermal application and a poor absorption of 4-MBC through human skin.
Schauer
Ute M D
UM
Institute of Toxicology, University of Wuerzburg, Versbacherstrasse 9, 97078 Wuerzburg, Germany.
Völkel
Wolfgang
W
Heusener
Alexander
A
Colnot
Thomas
T
Broschard
Thomas H
TH
von Landenberg
Friedrich
F
Dekant
Wolfgang
W
D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D002164:Camphor / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013473:Sunscreening Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity
D013473:Sunscreening Agents; D002164:Camphor; C038939:enzacamene