title: Chemomorphic analysis of malathion in skin layers of the rat: implications for the use of dermatopharmacokinetic tape stripping in exposure assessment to pesticides.
abstract: The dermatopharmacokinetic (DPK) method of dermal tape stripping may prove to be a valuable addition to risk assessment protocols for toxic substances as it has been for the assessment of bioequivalence and bioavailability of topical dermatologic drugs. The measurement of drug penetration into stratum corneum (SC) with respect to time is thought to be comparable with drug distribution in underlying tissues. To examine this possibility, the dermal penetration and absorption characteristics of [(14)C]malathion in the Sprague-Dawley rat was examined by three analytical techniques. [(14)C]Malathion was applied in different vehicles for 30-min and 1-h periods of exposure. Penetration into the SC was assessed by tape stripping followed by instant electronic autoradiography (IEA). Also, the (14)C activity retained in three successive 16 microm sections of the skin application site was determined by IEA and malathion was identified by Fourier transform infrared microscopy (FTIR microscopy). Absorbed [(14)C]malathion was measured in selected tissues, organs, and the residual carcass by liquid scintillation counting (LSC). Penetration into the SC followed a linear trend. The capacity of the SC reservoir for malathion amounted to approximately 1% of the dermal dose, while approximately 6% of the dose was absorbed. Results from this study support the view that LSC remains the method of choice to efficiently and reliably quantify absorption of a radiolabeled test substance. IEA offers the ability of the user to visualize the extent and profile of dermal absorption. When IEA is combined with FTIR microscopy, an effectual tool for studying the penetration of chemicals into layers of the skin emerges. The combined use of the three analytical techniques can be used to test the validity of the DPK method in hazard evaluation and exposure assessment of the organophosphorus insecticides.
authors.affiliation: United States Environmental Protection Agency, National Exposure Research Laboratory, Las Vegas, NV 89119, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Dary
authors.forename: J N
authors.initials: JN
authors.lastname: Blancato
authors.forename: M A
authors.initials: MA
authors.lastname: Saleh
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D004781:Environmental Exposure / Q000032:analysis*; D004784:Environmental Monitoring / Q000379:methods*; D004817:Epidermis / Q000378:metabolism; D007306:Insecticides / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D008294:Malathion / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011934:Reagent Strips / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D013810:Therapeutic Equivalency; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D007306:Insecticides; D011934:Reagent Strips; D008294:Malathion