Model animal, percutaneous absorption

R. L. Bronaugh, R. E Stewart, and E. R. Congdon. Methods for in vitro percutaneous absorption studies. II. Animal models for human skin. Toxicol. Appl. Pharmacol. 62 481 188 (1982). 

F. P. Schmook, J. G. Meingassner, and A. Billich. Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int. J. Pharm. 215 51-56 (2001). 

Bartek MJ, LaBudde JA (1975) Percutaneous absorption in vitro. In Maibach HI (ed) Animal Models in Dermatology. Churchill Livingstone, New York, pp 103-120 Bronaugh R, Maibach HI (1999) Percutaneous Absorption. 3rd edn. Marcel Dekker, New York and 4thedn in press Guy RH, Wester RC, Tur E, Maibach HI (1983) Noninvasive assessments of the percutaneous absorption of methyl nicoti-nate in humans. J Pharm Sci 72(9) 1077-1079 Guy RH, Tur E, Bugatto B et al. (1984) Pharmaco-dynamic measurements of methyl nicotinate percutaneous absorption. Pharm Res 1 76-81... 

There are many different animal models that have been used to assess the percutaneous absorption of toxic chemicals. There is little question that while in vivo human studies are best for predicting the absorption of percutaneous applied chemical warfare agents, ethics preclude conducting such studies. Rats have been widely used in the study of skin contamination, wounds, and healing and the efficacy of different decontamination modalities (Wester and Maibach, 2000 Shah et al, 1987 Baynes et al., 1997). 

Regional variations in percutaneous absorption contribute to differences in the systemic availability of a drug depending on the site of topical application. The Rhesus monkey Macaca mulatta) could probably serve as an animal model for human skin regional variation.f ° ... 

Dermal absorption of agricultural chemicals and animal drugs in food-producing animals must be considered as a potential route from which tissue residues of drugs and chemicals may occur. This has been supported in studies of topical pesticide exposure in cows and sheep. Despite the many advances made in in vitro and in vivo techniques for assessing percutaneous absorption in laboratory animals and man, very little systematic attention has been focussed on food-producing animals. The only exception is the pig since it is an accepted model for human studies. The purpose of this manuscript is to overview the literature on dermal xenobiotic absorption in food-producing animals to illustrate the risk that is present, and to outline how in vitro and in vivo methods could be applied to this problem. 

Bartek, M.J. LaBudde, J.A. Percutaneous absorption, in vitro. In "Animal Models in Dermatology". H. Maibach, ed. Churchill Livingston New York, 1975 pp 103-120. 

The route and duration of administration of the agent is also critical for the development of the teratogenic anomaly. Human industrial exposure is almost always by inhalation or percutaneous absorption of fumes, aerosols or vapors. Consumer or other secondary exposure would be by more varied routes. Experimental teratology endeavors to duplicate the human route of exposure for experimental animal models. Inhalation presents problems of... 

The presentation here provides an overview of tlie uses of a perfused skin model such as the IPPSF in percutaneous absorption and dermatotoxieokinetie studies. One of its major advantages is that both absorption and toxicity may be assessed in the same preparation. The pharmaeokinetic models developed arc experimentally verifiable. The major limitations are centered on the cost of the preparation and the technical expertise required to successfully conduct the studies. The overall cost is significantly greater than in vitro diffusion cell studies or in vivo rodent experiments, comparable to human skin equivalent and larger mammal (dog, pig, primate) in vivo work and much less expensive than human trials. However, cost alone is not a sufficient criterion. These studies are humane more information may be gathered than is obtainable with either in vitro or in vivo work. Optimal benefit may be achieved if these studies serve as a bridge between in vitro human/animal and in... 

The mass balance approach was used to develop an in vivo animal model for skin penetration of topically applied dmgs in hairless rats (Simonsen et al., 2002). Two dmgs, C-sahcylic acid and C-butyl salicylate were topically applied for the assessment of the model. Rapid and differentiated percutaneous absorption of both compounds was indicated by urinary excretion data. Total mass balance on the applied radioactivity was performed, and 90% recovery was achieved. Carver and Riviere (1989) conducted an extensive mass balance study with " C-labeled xeno-biotics after topical and intravenous administration to pigs. These authors reported that dermal absorption of C-benzoic acid, caffeine, malathion, parathion, progesterone, and testosterone was 25.7, 11.8, 5.2, 6.7, 16.2, and 8.8%, respectively, following topical administration to pigs. 

Percutaneous absorption of topically applied substances is important in the fields of dermatotoxicology of chemicals that pose a threat to human exposure and of der-matopharmacology of drugs used to treat local or systemic medical disorders. Direct measurements of percutaneous absorption of compoimds in humans are often difficult because of ethieal issues and lack of sensitive analytical techniques. Many alternate animal models have been developed for in vivo prediction of dermal absorption. It is generally agreed that in vivo animal models should mimie anatomical, physiological, and biochemical similarities to humans as closely as possible so that extrapolation errors ean be minimized. However, direct measurements of dermal absorption in hiunans will remain the reference standard. 

Kraeling, M.E., Reddy, G., and Bronaugh, R.L., 1998, Percutaneous absorption of trinitrobenzene animal models for human skin, J. Appl. Toxicol, 18, 387-392. 

Priborsky, J. and Muhlbachova, E. (1990). Evaluation of in-vitro percutaneous absorption across human skin and in animal models, J. Pharm. Pharmacol, 42 468-472. 

Wester, R.C. and Maibach, H.l. (1989). In vivo animal models for percutaneous absorption, in R.L. Bronaugh and H.l. Maibach (eds.). Percutaneous Absorption, Mechanisms—Methodology—Drug Delivery, New York Dekker, pp. 221-238. 

Stoughton, R.B. (1975). Animal models for in vitro percutaneous absorption, in H. Maibach (ed.). Animal Models in Dermatology Relevance to Human Dermatopharmacology and Dermatotoxicology, Edinburgh, U.K. Churchill Livingstone, pp. 121-132. 

In order to assess the risk from topical exposure a number of investigators have sought animal models that could predict percutaneous absorption rates of chemicals in humans. Considerable efforts by Wester and Maibach (2-6) have shown that monkeys and pigs give dermal absorption data most comparable to humans with a range of drugs and pesticides which varied in their physicochemical properties as well as use. A similar rank order for species comparisons has been observed in in vitro (12-14) absorption data which in most cases exceeded the human values (Table I). For this reason, and because of the availability of rhesus monkeys within our facility, dermal absorption studies with rhesus monkeys were considered an appropriate model. 

Bartek MJ, Labudde JA (1975) Percutaneous absorption in vitro. In Maibach HI (ed) Animal models in dermatology. Churchill Livingstone, New York, p 103 Baselt RC (1988) Biological monitoring methods for industrial chemicals. PSG Publishing Company Inc., Littleton... 

---