Permeability of abnormal rat skin.

We have measured the permeability (to water in vivo and in vitro) and examined the histology of rat skin after mild, superficial epidermal alterations: scalpel blade (Cat I) and sandpaper abrasion (Cat II), adhesive tape stripping (Cat III), and suction blister top removal (Cat IV). After each alteration the permeability was increased (Cat IV greater than Cat III greater than Cat II greater than Cat I) and the epidermis regenerated in a distinct, biphasic manner, as indicated by the permeability and histology data. The rapid first phase corresponded with a decrease in permeability and the development of a scab (the greater the increased permeability, the slower the rate of regeneration). The second phase was more gradual (with a similar rate of regeneration after each alteration) and corresponded with a return to normal permeability and gradual thickening of the stratum corneum (return to normal corresponded with degree of initial stratum corneum removal). A similar, though slower biphasic regeneration has been reported to occur in human skin following similar types of alterations. It is concluded that abnormal rat skin is suitable for quantifying absorption through abnormal epidermis.

Intrabronchial instillation of paraquat in rats: lung morphology and retention study.

Various amounts of paraquat (10(-5) to 10(-12) g) in 0.1 ml saline were instilled directly into the left bronchus of male adult rats. Gravimetric, macroscopic, and microscopic studies on the left lobe of the lung showed that 10(-5) g of paraquat produced lung oedema and macroscopic lesions two and 14 days after doing. The pathology of the lung was similar to that seen after systemic poisoning. When 10(-6) g of paraquat was instilled, some animals developed lung oedema and macroscopic lesions. Microscopic examination showed subtle changes in the parenchyma of the lung. With amounts of paraquat equal to or less than 10(-7) g (doses as little as 10(-12) g were used), no changes in the lung were seen. This is contrary to published accounts in which amounts as low as 10(-12) g (1 Pg) were reported to cause acute damage to the rabbit lung. When 3H paraquat was instilled into the left lobe (doses of 10(-5) to 10(-10) g were used), the loss of paraquat from the lung was biphasic. The initial half-life was less than one hour. The secondary phase obeyed first-order kinetics, and the half-life was dependent on the dose of paraquat instilled. This half-life was as short as 11 hours when 10(-5) g paraquat was instilled and was 76 hours after the instillation of 10(-10) g paraquat. The decrease in the half-life of the secondary phase with increasing doses of paraquat is possibly associated with the production of oedema or lung cell damage, or both. After the instillation of 10(-8) g 3H paraquat, the initial half-life was less than 15 minutes, and paraquat was detected in the urine and plasma at that time. This suggests that 50% of the instilled paraquat was rapidly absorbed from the lung into the plasma.