The FDA recently issued a draft Guidance titled, “Safety of Nanomaterials in Cosmetic Products” which addresses FDA’s current thinking on how to assess the safety of using nanomaterials in cosmetic products. Somewhat ominously, the first paragraph of the Background section states that “[nano]materials can have chemical, physical, and biological properties that differ from those of their larger counterparts. Importantly, properties of a material might change in ways that could affect the performance, quality, safety, and/or effectiveness, if applicable, of a product that incorporates that specific nanomaterial.” In light of that introduction, it is not surprising that the Guidance recommends extensive safety testing of cosmetics that incorporate nanomaterials before those products are put on the market, even though only color additives are subject to FDA’s premarket approval.

The draft Guidance divides the safety assessment into two broad categories, nanomaterial characterization and toxicology considerations. Under nanomaterial characterization, the draft Guidance states that the characterization should include the nanomaterial name, the Chemical Abstracts Service (CAS) number, the structural formula, the elemental composition including the degree of purity and any known impurities or additives. For physicochemical properties, the characterization should further includemeasurement of particle size and distribution; aggregation and agglomeration characteristics; surface chemistry including zeta potential/surface charge, surface coating, functionalization, and catalytic activity; morphology including shape, surface area, surface topology, and crystallinity; solubility, density, stability, and porosity.

For impurities, the draft Guidance notes that any change in the manufacturing process may result in additional impurities and that the quantity and quality of any impurities should be considered in the safety assessment.

As to toxicology, in summary the draft Guidance states that safety testing should consider “each ingredient’s chemical structure and physicochemical properties, purity/impurities, agglomeration and size distribution, stability, conditions of exposure, uptake and absorption, bioavailability, toxicity, and any other qualities that may affect the safety of the product according to its intended use.” Further, the draft Guidance states that both short-term and long-term toxicity of nanomaterials must be considered.

Other factors addressed in connection with toxicology include routes of exposure, uptake and absorption, and testing methods. The draft Guidance notes that while most cosmetics are applied to the skin, some are applied in areas where there is a risk of exposure through the mouth or nose, so safety must be assessed in that context. With respect to uptake and absorption, the draft Guidance states that the reduced particle size of nanomaterials may result in increased absorption, which must thus be considered, and that tests should be conducted on both intact and damaged skin. Because of the different routes of exposure and potential for increased absorption, the draft Guidance recommends that safety assessments include the issues of toxicokinetics and toxicodynamics. The draft Guidance discusses several testing methods that will have to be considered depending on the type of product and other factors.

As with the simultaneously issued draft Guidance covering the use of nanotechnology in foods and food packaging, the draft Guidance on cosmetics states that because of the different properties of nanomaterials, it may be necessary to develop and validate new test methods to ensure safety of the products. FDA recommends that manufacturers request meetings to discuss “to discuss the test methods and data needed to substantiate the product’s safety, including short-term toxicity and other long-term toxicity data as appropriate.”

Cosmetics have traditionally received the least amount of regulatory attention from FDA, and this relative neglect has been justified by a relatively low number of safety issues. Manufacturers of cosmetics considering the addition of nanomaterials to their products, however, should consider increasing their research & development and regulatory budgets to account for the validation of safety tests and safety assessments that FDA will apparently recommend, or to evaluate whether the addition of the nanomaterials to their products will provide sufficient incremental benefit to their products and sales to justify the costs of the safety assessments.

As always, it is important to recall that FDA Guidance documents do not have the force of law, but rather simply represent the FDA’s current thinking on a topic.