Abstract
Skin is the largest organ of the human body and although it serves as a barrier to absorption of topically applied chemicals and water loss, it also is being increasingly studied for the trans-dermal delivery of both locally and systemically acting chemicals including pharmaceuticals, cosmetic agents, toxicants, and toxins. Over the past three decades, the state of the science has progressed in this area to include a variety of model systems that are used with increasing regularity in toxicology and pharmacology to evaluate dermal absorption of various substances for a variety of purposes.
This new book edited by Jim E. Riviere, an acknowledged and respected expert in this field, serves as a review of basic principles and methods in current use as well as presents some of the fundamental applications of these methods to different dermal absorption scenarios. It is intended as an introduction to dermal absorption problems in toxicology and pharmacology and the contemporary methods being used to address them. This is the first edition of what may become a leading text on this subject.
The book opens with an outstanding, up to date, treatise on the structure and function of skin by Nancy Monteiro-Riviere. The micrographs, anatomical drawings, and tables in this chapter are well done and should be particularly informative and valuable to readers. Although Table 1.1, on comparative epidermal and stratum corneum parameters from various species, does not include values for humans, this information is readily available in other texts and literature and values for some species that are included such as those for the equine, bovine, and feline may be more difficult to find. Overall, this chapter provides a solid basis for understanding and essential up to date dialogue on skin anatomy and function that most should find useful.
A well-written chapter by Robert Bronough follows and provides a basic introduction to in vitro skin penetration studies using diffusion cells. Somewhat surprisingly, the very popular and widely used Franz diffusion cell is only mentioned briefly in this chapter and there is not a single photo or diagram of this system anywhere in the entire text which seems unusual. However, because diagrams and descriptions of Franz cells and their use are fairly ubiquitous in the literature on this subject, this may not be too much of a shortcoming and the methods presented by Dr. Bronough are generally applicable to most all in vitro diffusion cell systems.
Additional chapters follow and a wide variety of topics are included as follows:
Perfused Skin Models
In Vivo Models A Novel System Coefficient Approach for Systemic Assessment of Dermal Absorption from Chemical Mixtures Biologically Based Pharmacokinetic and Pharmacodynamic Models The Prediction of Skin Permeability Using Quantitative Structure-Activity Relationship Methods How Dermal Absorption Estimates Are Used in Risk Assessment Gulf War Syndrome: Risk Assessment Case Study Estimating the Absorption of Volatile Compounds Applied to Skin Modeling Dermal Absorption from Soils and Powders Using Stratum Corneum Tape Stripping In Vivo
Assessing Efficacy of Penetration Enhancers Dermal Blood Flow, Lymphatics, and Binding as Determinants of Topical Absorption, Clearance and Distribution Chemical Mixtures Animal Models: A Comparison of Permeability Coefficients for Excised Skin from Humans and Animals
As one might expect, the chapter on perfused skin models by Jim Riviere is comprehensive and well done as is the chapter on in vivo models. These two chapters are probably the best presentations on these two subjects that have come out in book form over the past few years.
Following the initial chapters that introduce fundamentals, the book content then branches out into a variety of state of the art techniques and considerations for various contemporary aspects of dermal absorption research and risk assessment. Overall, this portion of the book constitutes a general introductory collage of the contemporary literature on this subject from a collection of international scientists and authors actively engaged in their respective topics. For example, the chapter on how dermal absorption estimates are used in risk assessment by Ken Walters and Keith Brain is essentially the basis of a recent presentation on the same topic presented at the biannual Perspectives in Percutaneous Penetration Conference in April of this year. Of course, as is usual for this sort of text, there are many prominent researchers in this field that are not contributors but a comprehensive treatise on the subject of dermal absorption models was not the objective of this book and as an introduction to this subject, the content meets the editor’s objectives quite well.
Chapter 5 by Xia et al. is a particularly interesting and useful introduction to the use of thermodynamic linear free energy relationship (LFER) parameters to assess dermal absorption from chemical mixtures. This is a complex and contemporary problem that is attracting a fair amount of attention and the reader should find this chapter valuable as an entry point into this advancing and important approach toward describing the skin absorption characteristics of chemical mixtures.
Similarly, the chapter by McDougal et al. on the use of biologically based pharmacokinetic/pharmacodynamic models is useful in its presentation of the historical context and is a good overview of this relatively popular area of skin absorption modeling. As has seemingly become typical of publications on biologically based modeling for toxicological purposes, this chapter does not provide sufficient detail as to the actual methods employed to allow the reader to completely understand and construct their own biologically based models. Nor does it provide any guidance on the selection and use of the computer software necessary to accomplish this task. It does however reference various reviews and writings of other authors that may assist the reader interested in a more in depth understanding of these models and the methods and systems used to develop them.
The chapter by Cronin on the use of quantitative structure-activity models is particularly good and should provide the reader the background necessary to understand what these approaches have to offer particularly as they are currently being evaluated for the prediction of percutaneous concerns in some chemical inventory programs.
Chapter 9, which is indicated to contain a risk assessment case study on Gulf War Syndrome, by Baynes, appeared interesting as a contemporary study but turned out to be perhaps a little out of place for a book on dermal absorption models. Surprisingly, there is no background as to the current thinking as to defining what Gulf War Syndrome actually is and no description of this syndrome was provided. Instead the chapter presents a rather rambling discourse of known facts about some exposures and mixes this with a variety of presumed or postulated exposures to several substances which were associated with either real or presumed topical exposures. As has become the hallmark of most writings on this topic, a fair amount of supposition, based on some laboratory work and much conjecture derived from reports of exposures both known and imagined, paints an interesting if not somewhat enlightening montage of the sorts of topical exposures that military service and associated contract support personnel might encounter in modern battlefields and regions of conflict. As someone experienced with this particular campaign, the misspelling of “desert” as “dessert” in the opening paragraph put the icing on the cake with respect to how some researchers have hypothetically approached this relatively serious issue facing a significant number of Gulf War veterans, presumably in an attempt to help the afflicted and to advance scientific knowledge to present future problems of a similar nature. That the U.S. Gulf War Commission chose to focus more effort and funding toward collecting histories and providing substantive medical support to veterans, rather than researching the myriad of exposures and circumstances that may or may not be significant contributors, seems particularly laudable given the rambling nature of the discourse in this chapter. Nevertheless, this is a very challenging subject and as a case study, this chapter, although not meeting initial expectations, could be viewed as an example of how the use of dermal exposure models have been instrumental toward a more complete understanding of topical exposures to chemicals, particularly insect repellants such as (DEET) that may be found in areas of modern conflict.
The chapters on estimating the absorption of volatile compounds applied to skin by Gerald Kasting and on modeling dermal absorption of chemicals from soils and powders by Annette Bunge et al. were both very well written and presented state-of-the-art approaches to these two topics. Readers interested in both occupational and environmental exposure modeling should find these chapters valuable and the content quite satisfactory as good introductions to these subjects with a number of valuable references for more in depth study.
There is a chapter on assessing the efficacy of skin penetration enhancers by Babu Medi et al. that, although being somewhat dated in content, provides a useful overview and introduction to this subject. The list of penetration-enhancing chemicals and compounds provided in the chapter is intended to provide a few important examples, but is definitely not a complete rendering of the hundreds of known penetration enhancing substances.
Chapter 13 on dermal blood flow, lymphatics, and binding as determinants of topical absorption, clearance, and distribution by Sheree Cross and Michael Roberts is outstanding and is one of the best presentations in this book. Its descriptions of cutaneous microcirculation structure and function as well as the measurement of the effects of blood flow effects on absorption and distribution are well done and should be valuable to all readers, particularly those interested in constructing various types of skin absorption models. This chapter even includes a brief but useful discourse on pathological conditions that affect cutaneous blood flow and clearance.
The final two chapters, on chemical mixtures by Jim Riviere and a comparison of permeability coefficients for excised skin from humans and animals are very well done. They provide a solid basis for understanding contemporary research into understanding how skin absorption of chemical mixtures is modeled and how current permeability coefficient databases are used for understanding and comparing differences between human and animal skin permeability. The tables and large appendices of permeability coefficients and input parameters as well as documentation of permeability coefficient data should be of significant value to have together in one text on the overall subject of dermal absorption modeling.
The indexing is not extensive or comprehensive, but is useful in finding major topics and the overall quality of the paper, binding, and artwork throughout is up to standards that one expects from a durable and quality CRC volume.
Overall, this book is informative, thoroughly enjoyable, and quite interesting. It is a well written, expertly edited, multiauthored volume that meets its objectives in providing a bridge between general risk assessment considerations and systemic toxicology texts concerned with the dermal absorption of chemical substances for the scientist needing an up to date introduction and more in depth understanding of contemporary dermal absorption models and their use. It should be a good value for any individual or library desiring up to date knowledge of the subject of dermal absorption modeling for toxicological and pharmacological purposes.