Ethnicity as a possible endogenous factor in irritant contact dermatitis: comparing the irritant response among Caucasians,blacks, and Asians

Irritant contact dermatitis (ICD) is a common dermatological diagnosis in which endogenous and exogenous factors have been implicated. This review explores ethnicity as a possible endogenous factor. While there is a clinical consensus that blacks are less reactive and Asians are more reactive than Caucasians, the data supporting this hypothesis rarely reaches statistical significance. The studies reviewed do not provide sufficient evidence to determine that race is a predisposing factor to the degree of irritation in ICD. We conclude that race could be a factor in ICD, which has practical consequences regarding topical product testing requirements, an ever-expanding global market, occupational risk assessment, and the clinical thinking about ICD. Pitfalls in defining differences are discussed.     

In vitro skin irritation testing on reconstituted human epidermis: reproducibility for 50 chemicals tested with two protocols.

Since it is of high importance to establish the skin irritation potential of industrial chemicals, toxicologists developed tests on various skin models. Most test data come from the rabbit Draize test, but its reproducibility is questionable. Some human in vivo test data exist, but they concern only few compounds. The emergence of new tools such as reconstituted human skin tissues offers a promising future to alternative methods. We describe here two in vitro skin irritation test protocols performed on reconstituted human epidermis. One is a direct topical application test and the other an in vitro patch test. Both protocols were performed using multiple endpoint analysis including cell viability (MTT reduction), histology, and IL-1alpha release. Fifty chemicals were tested: 20 compounds were used in the ECVAM pre-validation study and 30 products were previously tested in a human in vivo patch test. These in vitro skin irritation tests have not only the advantages of enhanced convenience and of reduced costs, but a good reproducibility is observed by endpoint, and by compound. A prediction model is proposed to classify the chemicals as irritant or non-irritant, and the results are compared to available rabbit and human data. We do not wish to overgeneralize from these 50 compounds; but, instead suggest that this data set be extensively extended to include chemicals of varying physico-chemical properties.     

High dissociation constants (pKa) of basic permeants are associated with in vivo skin irritation in man

Previously, we have investigated the relationship between dissociation constant (pKa) and skin irritation potential. In the present experiment, 12 basic compounds, with varying pKa values ranging from 1.4 10 11.2, were applied on the hacks of 12 healthy adult panellists. Cutaneous reactions were measured objectively using reflectance speetrcscopy and transepidermal water loss (TEWL), and evaluated subjectively with a modified Draize scale. A positive correlation between increasing pKa and skin irritation capacity, measured either visually or by reflectance spectroscopy, was found, but only mecamylamine (pKa= 11.2) induced a significant increase in transepidermal water loss. Compounds with low pKa also induced a paradoxical vasoconstriction measured by reflectance spectroscopy. Only high pKa appeared predictive of in vivo skin irritation, and these chemicals apparently induce skin irritation with only minimal disruption of the skin barrier. A simple 1-variable model is predictive of skin irritation for this series of organic permeants with increasing PKa.     

Growth and filament production of Pityrosporum orbiculare and P. ovale on human stratum corneum in vitro

When Pityrosporum orbiculare and P. ovale were incubated with stratum corneum epithelial cells, suspended in phosphate-buffered saline for 90 min at 37 degrees C, short filaments were produced in 11-17.5% of the yeast cells. A successful culture of P. orbiculare and P. ovale on human stratum corneum in vitro is described. When the stratum corneum pieces were incubated for 5 days in an environment with 7% CO2, a picture resembling that seen microscopically in tinea versicolor was observed. Filaments were produced in 39-48% of P. orbiculare and P. ovale cells; the longest pseudohyphae, 40-60 microns, were produced by P. ovale. This culture method provides the possibility of studying the parasitic mycelium form of P. orbiculare and P. ovale in vitro. The influence of antimycotics, other drugs, and interaction with other microorganisms can be studied.