Promising Cosmetic Safety Innovation Areas for the Future

P&G Beauty & Grooming continues research across a number of safety science disciplines, including genotoxicity, skin allergy, reproductive toxicology, environmental and aquatic toxicology, as well as the emerging field of genomics. Much of this effort places a further emphasis on in vitro approaches that will reduce or replace more traditional safety testing methods. Our scientists have presented their research and findings at key scientific meetings in toxicology as well as before the National Academy of Sciences.

Toxicogenomics - The Future of Safety Evaluation

Molecular biology continues to reveal a complex world of signaling within a cell. Chemical signals from both inside and outside the body affect gene activity and other cellular components (i.e., proteins, enzymes, etc.) by a complex matrix of interconnected pathways. Recent advances in molecular biology have fueled a dramatic increase in knowledge as to how genes in the cell can respond to various changes, contributing to the growth of a new sub-discipline of toxicology known as toxicogenomics. Toxicogenomics uses tools, such as DNA microarrays, that provide an unprecedented opportunity for complete and simultaneous analysis of thousands of genes.

The microarray analysis gives scientists an instant snapshot of how the human body might react to cosmetic ingredients on a cellular and genetic level.

The global analysis of the response of genes to exposure from various chemicals or toxicants as opposed to the historical method of examining a few select genes provides a more complete picture of toxicologically significant events. One such application of this technology is for providing mechanistic insights into the response of cells to DNA damage (genotoxicity). Array-based gene expression profiling may be useful for differentiating compounds that interact directly with DNA from those that are genotoxic via a secondary mechanism.

Much of the excitement surrounding toxicogenomics lies in its potential to facilitate identification of potential human and environmental toxicants, and to improve monitoring of the effects of exposures to these toxicants. Possibilities include discovery of new families of safety biomarkers, increased understanding of the influence of genetic variation on toxicological outcomes, and defining environmental causes of genetic alterations and their relationship to human disease. These potential breakthroughs should make the process of cosmetic ingredient safety assessment even more efficient and precise. Innovations in Technology and Clinical Testing »

Identifying Potential Skin Allergens using Genomics

One promising area of research for developing non-animal methods for identifying potential skin allergens is focusing on dendritic cells (DC), a distinct group of white blood cells that can initiate immune responses by processing and presenting antigens (i.e., things that the body recognizes as "foreign") and are widely distributed throughout the body. A type of DC known as Langerhans cells (LC) 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 develop DC responses in vitro, not only to identify chemical allergens, but also to characterize the type of allergic response they will likely induce.

Gene chip technology and skin equivalent cultures are two major methods helping eliminate testing on animals

Using in vitro human skin tissue equivalent models for assessing genotoxicity

While current in vitro genotoxicity studies such as the Ames assay are useful tools in screening potentially DNA-reactive chemicals, these tests have also been shown to have a high rate of false-positive results. As a result, we often use a "battery" of several tests to assess different indicators of potential damage to DNA. Developing in vitro studies that can screen the potential for a chemical to cause chromosomal damage as a follow-up test would provide another vital in vitro tool to evaluate ingredient safety. Recent development of a new in vitro method using human tissue equivalent models has been shown to accurately predict chromosomal damage for previously known genotoxicants. This assay provides a promising new approach that will continue to be refined further with the ultimate goal of becoming a validated method to screen new cosmetic ingredients.

Resources

Aardema MJ, MacGregor JT. Toxicology and genetic toxicology in the new era of "toxicogenomics": impact of "-omics" technologies. Mutation Research 2002;499:13-25.

Ryan CA, Kimber I, Basketter, DA, Pallardy M, Gildea, LA, Gerberick, GF, Dendritic cells and skin sensitization: Biological roles and uses in hazard identification, Toxicology and Applied Pharmacology, 2007; 221, 3:384-394.

Hu T, Kaluzhny, Y, Mun GC, Barnett B, Karetsky V, Wilt N, Klausner M, Curren RD, Aardema MJ. Intralaboratory and interlaboratory evaluation of the EpiDerm® 3D human reconstructed skin micronucleus (RSMN) assay. Mutation Research 2009;673:100-108.