title: Transcutaneous penetration of toluene in rat skin a microdialysis study.
abstract: Percutaneous absorption of lipophilic substances has major implications for therapeutical use or toxicological effects. We, therefore, using dermal microdialysis, measured local toluene concentrations and assessed the effects of duration of exposure, skin barrier disruption and the use of skin-care products. Three microdialysis membranes (3000 kDa) were inserted intradermally at a length of 2 cm in the abdominal skin of 82 anaesthetized male Wistar rats. They were perfused with albumin solution (5%) at 10 microl/min. A skin area of 1.5 x 0.6 cm above the membranes was exposed to toluene (100%, 200 microl) for 15 or 240 min. Dialysate was sampled at 20-min intervals. Using GC-FPD (gas charomotography flame photometric detector), it was analysed for toluene. In addition, the effects of tape stripping and pretreatment with topical products were assessed. In each of the 12 permutations of exposure time, pretreatments and tape stripping, five to eight animals were investigated. Maximum toluene concentrations were reached at 60 min after exposure (3.07 +/- 0.40 microg/ml, 15 min; 5.38 +/- 0.92 microg/ml, 240 min). In 15-min exposure experiments, dermal toluene concentrations decreased slowly to reach baseline values after 240 min. After 240-min exposure, a plateau of approximately 6 microg/ml was reached after 60 min. Neither tape stripping nor the pretreatment with barrier cream induced a significant change on dermal toluene concentrations. The slow kinetics of toluene penetration results in a steep concentration gradient in the skin with very-high local toluene concentrations and a delayed wash out, which might be relevant not only toxicologically, but also therapeutically.
authors.affiliation: Department of Physiology and Experimental Pathophysiology, University of Erlangen/Nürnberg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Klede
authors.forename: Harald
authors.initials: H
authors.lastname: Schmitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Göen
authors.forename: Manigé
authors.initials: M
authors.lastname: Fartasch
authors.forename: Hans
authors.initials: H
authors.lastname: Drexler
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012869:Skin Absorption; D012879:Skin Physiological Phenomena; D013997:Time Factors; D014050:Toluene / Q000493:pharmacokinetics / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D014050:Toluene