What Works
Novel Approaches to Hazard Assessment
Identifying Potential Skin Allergens
As discussed above, a key step in the human safety risk assessment process for cosmetics or personal care products is identifying ingredients that may cause skin sensitization, the allergic response of the skin to an ingredient following repeated exposure. In recent years, the mouse local lymph node assay (LLNA) has becoome one of the preferred methods for assessing skin sensitization potential, as it allows for a considerable reduction in the number of animals required compared to the traditional guinea pig test.31
Did You Know?
Dr Frank Gerberick's Pioneering Work in Skin Sensitization Assessment
In the field of skin allergy, few scientists are as highly regarded as P&G's Frank Gerberick. One of the world's foremost experts on skin sensitization and hazard assessment, Dr Gerberick pioneered the use of the LLNA,32 dendritic cells, 33 and a peptide reactivity assay for screening contact allergens.34 His development and validation of the LLNA has won him numerous awards, including the 2000 SmithKline Beecham Laboratory Animal Welfare Prize and the 2003 Society of Toxicology Award for the Enhancement of Animal Welfare. Dr Gerberick's groundbreaking work in skin sensitization revolutionized the way ingredients are cleared for human use, and continues to influence thinking among government regulators and dermatologists.35
However, there is still a need to develop nonanimal test methods for skin sensitization. One promising area of research is focusing on dendritic cells (DC), a distinct group of leucocytes that can initiate immune responses by processing and presenting antigens, which are widely distributed throughout the body. A type of DC known as Langerhans cells (LC), located near the dermal-epidermal junction, form a network designed to "trap" foreign antigens that have entered the skin, including chemical allergens. By extracting LC from humans, or by developing cell lines that could be used as DC surrogates, scientists hope to develop cell culture test systems that measure changes in gene expression induced by topical exposure to contact allergens or irritants. Additionally, microarray "gene chip" technology can be used to identify new gene candidates as potential markers of allergen-induced changes in DC. Such novel approaches may someday make it possible to exploit DC responses in vitro not only to identify chemical allergens, but also to characterize the type of allergic response they will likely induce.36
Gene chip technology (left) and skin equivalent cultures (right) are two major methods helping to eliminate testing on animals.
Another approach to skin sensitization and irritation testing involves the use of skin-equivalent culture systems, which provide an in vitro, three-dimensional model of the skin with the major structural components intact, and have very similar structural features as intact skin. A key advantage of these cultures is the ability to test anything that can be applied to and tested on intact human skin, including toxic materials.37
In Vitro Eye Irritation Models
Researchers also report advances in developing alternatives to the standard eye irritancy test. These alternatives include the use of isolated whole eyes and cornea models obtained from remnant slaughterhouse carcasses, as well as in vitro three-dimensional tissues constructed from human epidermal or corneal cells. The human cell-derived models can differentiate degrees of irritancy between mild test substances, and are useful for assessing both water-soluble and water-insoluble products and ingredients.38
Screening for Endocrine Disruptors
Other novel approaches involve development of a series of in vitro receptor binding and reporter gene assays that are used to assess the ability of agents to interfere with hormonal function in humans and wildlife.39 Another alternative assay is the extended fish early-life stage test, which focuses on assessing ingredients' effects on endpoints such as sexual differentiation, early gonadal development and reproduction, and which takes less time and is simpler to run.40