title: Closed cup vapor systems in percutaneous exposure studies: what is the dose?
abstract: Percutaneous vapor dosing studies have generally used saturated vapor concentration (SVC) measurements to estimate the exposure dose (Ct) of vapor produced from a volatile liquid within a closed system. The purpose of this study was to clarify whether the assumption was valid when translated to a biological system (pig skin) using sulfur mustard (SM) as a model skin penetrant. Three systems were evaluated, two containing skin and a control system (without skin). At set time points, samples from the headspace of each dosing system were extracted using a gas-tight syringe and analyzed by gas chromatography in conjunction with a flame-ionization detector. This demonstrated the rapid achievement of a constant vapor concentration within the biological and control systems and enabled a comparison with previously determined SVCs attained under ideal conditions. All three systems attained a constant vapor concentration within 2 min of exposure to SM. The control system reached an equilibrium vapor concentration of 1179 +/- 164 mg/m3, a value not significantly different from that derived from the SVC (1363 mg/m3). Because of absorption in the skin systems, SM vapor concentrations were significantly lower than that derived from the SVC and were dependent on the skin surface area within the dosing chamber (592 +/- 246 mg/m3 for a surface area of 10.15 cm2 and 740 +/- 224 mg/m3 for a surface area of 2.54 cm2). The assumption that SVC gives an acceptable measure of the Ct was shown to be valid by comparison with sulfur mustard recovered from the skin.
authors.affiliation: Dstl Biomedical Sciences, CBD Porton Down, Salisbury, Wiltshire, SP4 0JQ, United Kingdom. chdalton@dstl.gov.uk
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Dalton
authors.forename: Michael P
authors.initials: MP
authors.lastname: Maidment
authors.forename: John
authors.initials: J
authors.lastname: Jenner
authors.forename: Robert P
authors.initials: RP
authors.lastname: Chilcott
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D005740:Gases / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D009151:Mustard Gas / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013552:Swine; D018675:Toxicity Tests / Q000379:methods; D014835:Volatilization
chemical_list: D005740:Gases; D009151:Mustard Gas