title: In vitro dermal absorption of methyl salicylate, ethyl parathion, and malathion: first responder safety.
abstract: In vitro tests with fresh dermatomed (0.3 to 0.4 mm thick) female breast skin and one leg skin specimen were conducted in Bronaugh flow-through Teflon diffusion cells with three chemicals used to simulate chemical warfare agents: 14C-radiolabeled methyl salicylate (MES), ethyl parathion (PT), and malathion (MT), at three dose levels (2, 20, and 200 mM). Tests were conducted at a skin temperature of 29 degrees C using a brief 30-min exposure to the chemical and a 6.5-h receivor collection period. Rapid absorption of all three chemicals was observed, with MES absorbed about 10-fold faster than PT and MT. For MES, PT, and MT, respectively, there was 32%, 7%, and 12% absorption into the receivor solution (Hank's HEPES buffered saline with 4% bovine serum albumin [BSA], pH 7.4) at the low dose (2 mM), 17%, 2%, and 3% at the medium dose (20 mM), and 11%, 1%, and 1% at the high dose (200 mM) levels. Including the skin depot for MES, PT, and MT, respectively, there was 40%, 41%, and 21% (low dose), 26%, 16%, and 8% (medium dose), and 13%, 19%, and 10% (high does) absorption. Efficacy of skin soap washing conducted at the 30 min exposure time ranged from 31% to 86%, varying by chemical and dose level. Skin depot levels were highest for the relatively lipophilic PT. "Pseudo" skin permeability coefficient (K(p)) data declined with dose level, suggesting skin saturation had occurred. An in-depth comparison with literature data was conducted and risk assessment of first responder exposure was briefly considered.
authors.affiliation: Health Canada, Environmental Occupational and Toxicology Division, Systemic Toxicity and Pharmacokinetics Section, Ottawa, Ontario, Canada.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Moody
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akram
authors.forename: Eva
authors.initials: E
authors.lastname: Dickson
authors.forename: Ih
authors.initials: I
authors.lastname: Chu
mesh_terms: D000042:Absorption; D001940:Breast; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics; D015386:Hazardous Substances / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007306:Insecticides / Q000493:pharmacokinetics*; D008294:Malathion / Q000493:pharmacokinetics*; D010278:Parathion / Q000493:pharmacokinetics*; D010539:Permeability; D018570:Risk Assessment; D012449:Safety; D012459:Salicylates / Q000493:pharmacokinetics*; D012867:Skin / Q000737:chemistry / Q000187:drug effects*; D013696:Temperature
chemical_list: D002619:Chemical Warfare Agents; D015386:Hazardous Substances; D007306:Insecticides; D012459:Salicylates; D010278:Parathion; C033069:methyl salicylate; D008294:Malathion