Percutaneous absorption of parathion in vitro in porcine skin: effects of dose, temperature, humidity, and perfusate composition on absorptive flux.
The effect of environmental factors on the percutaneous absorption of parathion in excised porcine skin was assessed in a flow-through diffusion cell system by varying the temperature (T), relative humidity (%RH), perfusate flow rate (F), and composition (porcine serum) at three parathion doses (4, 40, and 400 micrograms/cm2) compared to standard conditions (air temperature = 37 degrees C, perfusate temperature = 37 degrees C, %RH = 60, flow rate = 4 ml/hr, and standard bovine serum albumin medium). Parathion absorption was assessed by monitoring total radiolabeled activity appearing in the perfusate over time. High relative humidity significantly increased parathion penetration, as did two elevated temperature conditions. The effects of flow rate and perfusate composition were variable and dose dependent. In the present studies, lower applied doses appeared to be more sensitive to changes in the environmental conditions studied. These results suggest that these parameters have independent and different degrees of effect on parathion percutaneous absorption. Experimental conditions should be strictly controlled and dose-response studies need to be conducted when evaluating transdermal studies. Finally, if similar effects occur in vivo, the risk assessment calculations on percutaneous absorption should take these parameters into consideration.
Chang
S K
SK
Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Riviere
J E
JE
D000818:Animals; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D006813:Humidity; D066298:In Vitro Techniques; D010278:Parathion / Q000378:metabolism / Q000633:toxicity*; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine; D013696:Temperature
D010278:Parathion