title: Cutaneous toxicity and absorption of paraquat in porcine skin.
abstract: Paraquat, a commonly used herbicide, has been shown to be toxic in exposed field workers. The objectives of this study were to (a) assess the cutaneous toxicity of paraquat in vivo in pig skin and in vitro in the isolated perfused porcine skin flap (IPPSF) and (b) quantitate its absorption in the IPPSF. The amounts of 3, 24, and 200 mg of paraquat were topically applied (5 cm2 surface area) on the ventral abdomen of pigs and biopsied after 6-8 hr for light microscopy (LM) and transmission electron microscopy (TEM). IPPSFs were topically dosed with the same concentrations and perfused for 8 hr (n = 4/treatment). The dosed area of the skin was sampled for LM, TEM, and enzyme histochemistry. IPPSFs were also treated topically with [14C]paraquat dichloride at the aforementioned concentrations (n = 4/dose) and hourly perfusate samples were collected for radiolabel determination and assessment of biochemical and physiological parameters. The epidermal changes were similar both in vivo and in vitro. The changes included epidermal intercellular edema which increased with dose and epidermal-dermal separation at the 200-mg dose. Acid phosphatase and nonspecific esterase activities were increased in the upper layers of the epidermis, while alkaline phosphatase showed a greater activity in the stratum basale layer. Glucose utilization of all treated IPPSFs was lower than that of the controls and a variation in the vascular resistance profiles was seen in all the treated flaps. Radiotracer studies indicated that a majority of the compound remained on top of the application site and minimal absorption or penetration into skin was observed. Thus, at high concentrations and prolonged exposure, paraquat may have deleterious effects on epidermal morphology in the absence of significant percutaneous absorption.
authors.affiliation: Cutaneous Pharmacology and Toxicology Center, North Carolina State University, Raleigh 27606.
authors.forename: V
authors.initials: V
authors.lastname: Srikrishna
authors.forename: J E
authors.initials: JE
authors.lastname: Riviere
authors.forename: N A
authors.initials: NA
authors.lastname: Monteiro-Riviere
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D004487:Edema / Q000139:chemically induced; D004950:Esterases / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D010269:Paraquat / Q000493:pharmacokinetics / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012869:Skin Absorption; D013552:Swine
chemical_list: D004950:Esterases; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D005947:Glucose; D010269:Paraquat