Regulatory

Test guidelines for the assessment of skin tolerance of potentially irritant cosmetic ingredients in man

Skincare products intend to enhance or restore skin to a healthy state. Despite the immense size of the cosmetics market and product availability, mass production still lags behind customers' demand for individualization and the use of natural ingredients. 3D printing technologies have revolutionized various industries including, more recently, the cosmetics market, providing personalized solutions based on individual's skin type and ingredient preferences. In this study, we have screened natural polymers to identify printable inks for the development of extrusion-based 3D printed hydrogel face patches. Iota carrageenan was selected as base material of the hydrogel inks and was co-formulated with sodium hyaluronate, glycerol, or Camellia sinensis leaf distillate to address the requirements of individual skin types.

Human repeated insult patch test (HRIPT) is regarded as one of the confirmatory test in determining the safety of skin sensitizers. A number of important factors should be considered when conducting and interpreting the results of the HRIPT.

To investigate for probable critical factors that influence the results of HRIPT with the same protocol in Shanghai and Mumbai.

Two HRIPTs were carried out in Shanghai and Mumbai in 2011. Six identical products and 1% sodium lauryl sulfate were tested. Two Chinese dermatologists performed the grading in the two cities. Climate conditions of Shanghai and Mumbai were also recorded.

For four lower reaction ratio products, cumulative irritation scores in the induction phase were higher in individuals whose ethnicity was Indian rather than Chinese. Reaction ratio of the same four products was highly correlated to the climatic parameters. The other two higher reaction ratio products and the positive control had no difference between the two ethnicities.

Greater attention ought to be paid to the impact of climate on the results of HRIPT, especially for the mild irritation cosmetics when giving the interpretation. Greater emphasis also needs to be placed on the ethnicity of the subjects.

Amphiphilogels, gels that consist solely of non-ionic surfactants, are being developed as dermal/transdermal drug delivery vehicles in our laboratories. The irritation potential of two amphiphilogels was investigated on shaved mouse skin, in vivo, and compared to those of Aqueous Cream BP (a moisturiser) and 5% sodium lauryl sulphate (SLS) solution (a known irritant). The skin irritation potential of one of these gels was then investigated in human, using Aqueous Cream BP as a negative control. Skin irritation (following daily application of gels and of controls for 5 days) was assessed by laser Doppler velocimetry, a visual erythema scoring method, and histological evaluations of excised mice skin. We found that the amphiphilogels caused no significant increase in blood flow and in epidermal irritation. In contrast, the SLS solution caused significant perturbation to mouse skin. From this study we conclude that these amphiphilogels may be used as dermal/transdermal drug delivery vehicles.

The dermatotoxicologist today is faced with a dilemma. Protection of workers and consumers from skin toxicities (irritation and allergy) associated with exposure to products, and the ingredients they contain, requires toxicological skin testing prior to manufacture, transport, or marketing. Testing for skin corrosion or irritation has traditionally been conducted in animals, particularly in rabbits via the long established Draize test method. However, this procedure, among others, has been subject to criticism, both for its limited predictive capacity for human toxicity, as well as for its use of animals. In fact, legislation is pending in the European Union which would ban the sale of cosmetic products, the ingredients of which have been tested in animals. These considerations, and advancements in both in vitro skin biology and clinical testing, have helped drive an intensive effort among skin scientists to develop alternative test methods based either on in vitro test systems (e.g. using rat, pig or human skin ex vivo, or reconstructed human skin models) or ethical clinical approaches (human volunteer studies). Tools are now in place today to enable a thorough skin corrosion and irritation assessment of new ingredients and products without the need to test in animals. Herein, we describe general testing strategies and new test methods for the assessment of skin corrosion and irritation. The methods described, and utilized within industry today, provide a framework for the practicing toxicologist to support new product development initiatives through the use of reliable skin safety testing and risk assessment tools and strategies.

Skin irritation safety testing and risk assessment for new products, and the ingredients they contain, is a critical requirement before market introduction. In the past, much of this skin testing required the use of experimental animals. However, new current best approaches for skin corrosion and skin irritation testing and risk assessment are being defined, obviating the need for animal test methods. Several in vitro skin corrosion test methods have been endorsed after successful validation and are gaining acceptance by regulatory authorities. In vitro test methods for acute, cumulative (repeat exposure), and chronic (prolonged exposure) skin irritation are under development. Though not yet validated, many are being used successfully for testing and risk assessment purposes as documented through an expanding literature. Likewise, a novel acute irritation patch test in human subjects is providing a valid and ethical alternative to animal testing for prediction of chemical skin irritation potential. An array of other human test methods also have been developed and used for the prediction of cumulative/chronic skin irritation and the general skin compatibility of finished products. The development of instrumental methods (e.g., transepidermal water loss, capacitance, and so on) has provided the means for analyzing various biophysical properties of human skin and changes in these properties caused by exposure to irritants. However, these methods do not directly measure skin inflammation. A recently introduced skin surface tape sampling procedure has been shown to detect changes in skin surface cytokine recovery that correlate with inflammatory skin changes associated with chemical irritant exposures or existing dermatitis. It holds promise for more objective quantification of skin irritation events, including subclinical (sensory) irritation, in the future.