Percutaneous penetration in the hairless dog, weanling pig and grafted athymic nude mouse: evaluation of models for predicting skin penetration in man

Abstract

The human skin grafted congenitally athymic (nude) mouse, pig skin grafted nude mouse, hairless dog, and weanling Yorkshire pig were evaluated as models for predicting skin penetration in man. Nine radiolabelled compounds previously tested on man were applied topically (4 micrograms/cm2) to each model. These compounds included caffeine, benzoic acid, N, N-diethyl-m-toluamide, three steroids, and three insecticides. To correct for incomplete excretion of the label following topical absorption, per cent penetration was calculated by dividing the per cent of the topically applied radioactive dose recovered in the excreta by the corresponding percentage after parenteral administration and multiplication by 100. Calculated values of per cent penetration were confirmed in the case of the grafted nude mouse because significant correlations (r = 0.78 for human skin grafted athymic nude mouse and r = 0.97 for pig skin grafted athymic nude mouse) were found between the calculated values and the actual values obtained by summing the radioactivity recovered in the urine, faeces, tissues, and carcass. The results also revealed a significant correlation between human skin grafted athymic nude mouse values and human values (r = 0.74, P = 0.05) and between weanling Yorkshire pig values and human values (r = 0.83, P = 0.05). In contrast, no significant correlation existed between human values and those of the hairless dog and the pig skin grafted athymic nude mouse.

The Pig as an Experimental Animal Model of Percutaneous Permeation in Man: Qualitative and Quantitative Observations – An Overview

“…Experiments with other chemical compounds resulted in the same conclusion, namely that porcine skin often yielded permeation values similar to those of human skin [42,56]. Comparative studies designed to predict skin permeation in man concluded that similar permeation values were obtained between pig and human skin when tested under identical conditions in vitro [43]. Permeation of paraquat, carbaryl, aldrin and fluazifop-butyl were also very close in man and pig skin [49].…”

Pharmacokinetics of Methyl Parathion: A Comparison following Single Intravenous, Oral or Dermal Administration

“…This value is within the range of estimates for transdermal absorption of other organophosphorus insecticides (e.g. malathion, parathion and chlorpyrifos) of 5-60% [5,33,35,41]. Similarly, percutaneous absorption of methyl parathion by human skin in vitro was 1-5% [21].…”

A Comparison of Cholinesterase Activity after Intravenous, Oral or Dermal Administration of Methyl Parathion

“…Likewise, the pattern of inhibition caused by oral administration of methyl parathion is consistent with high, albeit delayed, oral absorption and rapid clearance [7,26]. The slower onset of cholinesterase inhibition following dermal administration of methyl parathion correlates with a low dermal absorption coefficient resulting from limited penetration of the stratum corneum as well as sequestration within a lipophilic compartment in the dermis [9,13,24,31,41]. A slow redistribution from the dermis can also account for both a sustained increase in blood methyl parathion concentration [26] and prolonged inhibition of cholinesterase activity.…”