The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for

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Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy.

The pig has been a well-recognized experimental animal in biomedical research for many centuries. Physiological and anatomical similarities between man and pig made this animal a good model for man in many research areas. Pharmacological and toxicological research on the skin is often based on knowledge of skin absorption and percutaneous permeation. Anatomical, physiological and biochemical similarities are cited and various uses of the pig as a model for man in the investigation of skin permeation are reviewed. Further, several isolated organ models are reviewed. The importance of full details of the experimental animal, namely its age, sex, breed, size (weight) and body region, is emphasized.

The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantitative observations--an overview.

Pig skin has been shown to have similar histological and physiological properties to human skin and has been suggested as a good model for human skin permeability. In this series of experiments, the in-vitro permeability of pig ear skin was compared with human (abdominal) skin and rat (dorsal) skin using both hydrophilic (water, mannitol, paraquat) and lipophilic (aldrin, carbaryl, fluazifop-butyl) penetrants. Pig skin was found to have a closer permeability character than rat skin to human skin, particularly for lipophilic penetrants. Electrical conductivity measurements across pig skin membranes showed that skin conductivity could be a useful method for assessing the integrity of membranes, particularly when used in conjunction with water permeability assessments.

Pig Ear Skin as an In‐vitro Model for Human Skin Permeability

The ideal way to determine the percutaneous absorption of a compound in humans is to do the actual study in humans. Mechanism and parameters of percutaneous absorption elucidated in vivo with human skin are most relevant to the clinical situation. However, many compounds are potentially too toxic to test in vivo in humans, and so their percutaneous absorption must be tested in animals. Likewise, until more complete animal-to-human validation studies become available, not all investigators will have access to human volunteers. Mechanistic studies and studies on factors affecting absorption must, therefore, be conducted using animals and in vitro techniques. We have two basic criteria to judge whether an animal model is good. First, the animal model should give the same percutaneous absorption as that in humans. If this is not possible, then percutaneous absorption in the animal model should be consistently different from that in humans. Therefore, this chapter stresses studies where percutaneous absorption in an animal model (or the skin from that animal) is compared directly to that in humans.

Animal models for percutaneous absorption

Potential and problems of developing transdermal patches for veterinary applications

The isolated perfused porcine skin flap (IPPSF): I. A novel in vitro model for percutaneous absorption and cutaneous toxicology studies

Superiority of the power function over exponential functions for prediction of renal gentamicin residues in sheep.

Identification of a Subgroup of Sprague-Dawley Rats Highly Sensitive to Drug-Induced Renal Toxicity

Exponential intravenous infusions in toxicological studies: achieving identical serum drug concentration profiles in individuals with altered pharmacokinetic states.

A number of factors have been shown to predispose patients treated with aminoglycosides to nephrotoxicity. In a previous study in our laboratory investigating the interaction of prior renal dysfunction with gentamicin toxicokinetics, 9.4% of rats in all treatment groups were relatively more sensitive to gentamicin-induced nephrotoxicity. To determine if these outliers had an underlying disease or physiological abnormality, serum was collected from 99 Sprague-Dawley rats prior to daily treatment with 75 mg/kg gentamicin for seven days. Urea nitrogen, creatinine, Na, K, Ca, Mg, P, total protein, albumin, aspartate transaminase, serum osmolality, total white and red blood cell count, hematocrit, hemoglobin, blood gases, and thyroxine were measured. Blood was collected one and four hours after the first dose of gentamicin for pharmacokinetic analysis. Elevations in post-treatment creatinine and nitrogen were significantly greater in the outliers (4.10 ± 0.24 mg/dl (n = 12) vs 1.92 ± 0.06 mg/dl (n = 87) and 14...

https://journals.sagepub.com/doi/pdf/10.1177/019262338601400209

Lynn P. Dix

Papers

The isolated perfused porcine skin flap (IPPSF): I. A novel in vitro model for percutaneous absorption and cutaneous toxicology studies

Superiority of the power function over exponential functions for prediction of renal gentamicin residues in sheep.

Identification of a Subgroup of Sprague-Dawley Rats Highly Sensitive to Drug-Induced Renal Toxicity

Exponential intravenous infusions in toxicological studies: achieving identical serum drug concentration profiles in individuals with altered pharmacokinetic states.

Exaggerated response to gentamicin-induced nephrotoxicity in Sprague-Dawley rats: identification of a highly sensitive outlier population.