Author: james.runkle@drummondst.com

Ever since the FDA published their proposed monograph ruling in February 2019 recognizing titanium dioxide and zinc oxide as the only Category I (Safe and Effective) sunscreens, a cascade of reformulations of most sunscreens products on the US market took place.  Inorganic sunscreen formulations are now center-stage and are slowly replacing organic sunscreen formulations.  In fact, the trend started in 2018 when the state of Hawaii proposed a ban on Octinoxate and Oxybenzone stating that these two sunscreens have a negative effect on coral reefs.  Now that the ban is in effect, another bill is proposing to ban sunscreens containing Octocrylene and Avobenzone for the same reasons.  It is true that many regulatory bodies including the FDA did not support the Hawaiian ban, and the Personal Care Product Council (PCPC) is addressing the proposed monograph rulings. All these actions might lead to uncertain outcomes.  In fact, in a few years the US consumers might be limited to the use of products containing inorganic sunscreens only (with the exception of Ensulizole and Ecamsule).  There is some hope that certain Time and Extent (T&E) molecules are being reviewed by the FDA and may be approved for launch.  Bemotrizinol is a front-runner and its use in formulation is quite good as it protects both in the UVB and UVA areas.

Selecting the right inorganic sunscreen

Zinc oxide and titanium dioxide not only refract light but also absorb it.  The refractive index of titanium dioxide is 2.8 whereas that of zinc oxide is only 2.0.  This makes titanium dioxide much more effective at scattering light in a formulation.  From and absorption point of view, zinc oxide and titanium dioxide have conductance bands around 3.4 and 3.1 eV, respectively.  This makes zinc oxide a bit more efficient in protecting against UVA rays and titanium dioxide more efficient at shielding UVB rays.  As particle size decreases you get much more pronounced blue shift due to a change in the band-gap width.  For example, a 0.15 eV blue shift has been reported for 4.7 nm titanium dioxide compared to bulk.

Keep in mind, when particles become smaller than their optimal light scattering size (typically half their wavelength) they become much more transparent.  For example, zinc oxide becomes transparent at below 200 nm whereas titanium dioxide becomes transparent at sizes around 10-20 nm.  This makes formulating with zinc oxide much easier to achieve transparent formulations but harder to reach high SPF due to its performance in the UVB region.

Sometimes the so-called “boosters” can help many formulators resort to using salicylates as UVB boosters in their formulations.  Butyl octyl salicylate is not an approved sunscreen in the US but many formulators use it to boost their inorganic sunscreen SPF while claiming no organic sunscreens added.

Dispersion versus powder

The choice to use inorganic sunscreens as powder or dispersions in formulations is a very polarizing decision and many formulators prefer to use one type over the other.  In general, dispersions claim to have a smaller primary particle size which results in better dispersion of the pigment into the emulsion and leads to higher SPF and less whitening on the skin.  However, dispersions come at about 50% w/w solvent/pigment which limits the flexibility the formulator to tweak the formulation.  In addition, when working with w/o or w/Si formulations, it is harder to control the viscosity of such emulsions when using dispersions.  In these types of emulsions, the viscosity is built by the internal phase (water).  Using dispersions  ultimately increases the amount of external phase and reduces the amount of water used which will make such emulsions less viscous and less stable.

The use of powders, on the on the other hand, gives the formulator a lot of flexibility and reduces the cost of the formulation.  Although, when using powders, it is important to have manufacturing capability to grind the pigments at the factory scale to reduce agglomeration and produce formulations with good aesthetics.

Selecting emulsion type

Most inorganic sunscreen formulations on the market are w/o or w/Si emulsions.  These types of emulsions are much easier to preserve, as you only preserve the internal phase, and their pH does not fluctuate since they are anhydrous.  These types of emulsions inherently have very good water resistance as well.  Some of the drawbacks of w/o emulsions are their greasy feel mainly imparted by the surfactants and co-surfactants used. They tend to be more whitening on the skin and harder to spread.  W/Si emulsion have a superior end-feel, but they are not particularly biodegradable or earth-friendly by today’s standards.  They share the same characteristics as w/o emulsions when it comes to preservation, pH and water resistance.  In general w/Si emulsions are harder to stabilize and require the use of more than one surfactant to obtain stable emulsions.

It is very rare to see o/w emulsion formulations on the market, since they are harder to preserve and stabilize.  The presence of zinc oxide ultimately shifts pH towards 7.5 which renders most preservatives less effective.  In addition, at that pH very few polymers work well at stabilizing such emulsions especially naturally derived polymers.  On the other hand, these emulsions typically have a nicer feel on the skin and could be cost effective.

Adding a film former or SPF booster

Selecting a film-former or SPF booster for the emulsion is a critical step and one that should not be avoided.  The selection of the appropriate polymer depends mostly on the experience of the formulator and the in vivo results previously obtained with such polymer.  Many polymers are marketed to the formulators and some of them could work in one formulation or another.  However, it is crucial that the film former works across many formulations and especially in vivo since such tests are quite costly and hard to schedule.  As scientists, we should always test the formulations in vitro for water resistance and SPF to ensure that the addition of the polymer will give the desired results.  This will enable the formulator to refine the level of polymer in the emulsion as well.

In conclusion, I hope I shed some light on formulating inorganic sunscreen emulsions and I leave it up to the creativity of formulators to create excellent formulations with great aesthetics and high SPF.

Biography

Dr. Fares started his career in personal care studying the effect of solvents on sunscreen chemicals.  His interest in skin drug delivery especially from polymeric matrices grew during his graduate work at Rutgers, where he received his Ph. D.

Dr. Fares worked at Block Drug and GlaxoSmithKline where he held positions in research and development in the areas of skincare and oral care.  After that, he joined L’Oréal where he held several positions of increasing responsibility leading to AVP of skincare.  He is currently the Senior Director of skincare and oral care at Ashland Specialty Ingredients.  Dr. Fares is the author of many publications, and patents and made many presentations in national and international meetings in the areas of suncare, skincare, and oral care.  Dr Fares chairs the NYSCC scientific committee and has won multiple awards in the areas of sun care and polymer chemistry.

The recent introduction of holistic wellness as a major component of “I feel better and I look better” is not new to the beauty and cosmetic market. However, the explosion of nutritional formulations in the space of beauty from within is today associated with more robust and convincing scientific evidence than in the past. Supplement formulations appear more complex and not limited to collagen, vitamins and minerals to cite some of the most popular ingredients. The introduction of phytochemicals, sometime in the form of standardized plant extracts, along with vitamin and minerals, is providing an increased targeting and holistic approach to inner mechanisms associated with stress, diet, metabolism, aging, etc. that eventually influence our external look. This is not surprising as our cosmetic targets such as skin, hair, nail are part of our body and therefore react to our body unbalance. The connection between our gut and our skin, when a diverse gut environment is associated with skin conditions such as acne, psoriasis, atopic dermatitis, etc.¹ and the influence of hormonal and stress-induced changes that can trigger hair conditions such as androgenetic alopecia and telogen effluvium.² are some examples.

Modern formulations would use a wide range of ingredients that, when ingested, specifically target biological mechanisms associated with our health and wellness as well as our look (and I underline the specificity). It is possible then to create formulation that when tested deliver real efficacy and stand up to the claims.

Natural ingredients are taking center stage in these formulations, also inspired by the use of naturals in traditional medicine, with the possibility to merge knowledge from the western and eastern world.

When having a closer look at the applications and studies of supplements targeting wellness and beauty, recent reviews have highlighted their use as adjuvants and/or treatment for different dermatology or cosmetic conditions such as hair loss, acne, skin aging^3-5. Since supplements are not FDA regulated, large, peer-reviewed clinical studies are necessary to determine the efficacy and safety of these supplements, especially since most of them haven’t been clinically tested. To avoid running lengthy and sometime expensive clinical trial, product manufacturers often rely on supplier’s data and/or academic literature about the ingredients in the final supplement composition. However, it is necessary to test the finish product since ingredient’s dosage and ingredients interaction and/or synergy can determine the outcome both from a safety and efficacy point of view. The quality of the clinical study is also important (number of subjects, inclusion/exclusion criteria, end points measures, data significance). Finally, Institutional Review Boards (IRB) approval is becoming increasingly in demand prior to the clinical study especially if dealing with compositions that are new to the market and carry some safety risk, and is often requested by scientific journals when trying to publish the data.

In conclusion, the cosmetic and the nutrition (supplements) industry are getting closer, with beauty as a shared target. Innovative supplement formulations carrying high end natural ingredients are becoming popular and demanded by the market. Rigorous science and testing is mandatory to make sure the formulation can survive scrutiny by the consumers and the FDA. Combination of topical and ingestible treatments in the beauty market will continue to grow in the following years.

1. Ellis SR, Nguyen M, Vaughn AR, Notay M, Burney WA, Sandhu S, Sivamani RK. The Skin and Gut Microbiome and Its Role in Common Dermatologic Conditions. Microorganisms 7(11):550, 2019
2. Hadshiew IM, Foitzik K, Arck PC, Paus R. Burden of hair loss: stress and the underestimated psychosocial impact of telogen effluvium and androgenetic alopecia. J Invest Dermatol. 123(3):455-7, 2004
3. Adelman MJ, Bedford LM, Potts GA. Clinical efficacy of popular oral hair growth supplement ingredients. Int J Dermatol 60(10):1199-1210, 2021
4. Clark AK, Haas KN, Sivamani RK. Edible Plants and Their Influence on the Gut Microbiome and Acne. Int J Mol Sci 17;18(5):1070, 2017
5. Sardana K, Sachdeva S. Role of nutritional supplements in selected dermatological disorders: A review. J Cosmet Dermatol 21(1):85-98, 2022

Giorgio Dell’Acqua

Giorgio Dell’Acqua is Nutrafol’s Chief Scientific Officer. Part of the Leadership team, Giorgio spearheads the brand innovation, product formulation and scientific communication. After obtaining his PhD in Cell Biology in 1989, Giorgio worked in Academia for 15 years as an investigator in applied medical research. Moving to the private sector in 2000, he has spent the last 22 years as an executive and cosmetic scientist in the personal care industry. During his career, he directed R&D, Innovation, Science, and Product Development at multiple companies, including La Prairie and Kiehl’s. He has helped bringing more than 200 successful active ingredients and finished products to market, has authored more than 80 publications in medicine and cosmetic science, he holds 2 patents and has been a keynote speaker on clean beauty and natural ingredients. Giorgio serves on the NYSCC board as advisor.

1. Brief history of nanomaterial regulations

 According to Wikipedia, the word “nanotechnology” was first coined by Professor Norio Taniguchi of Tokyo University in 1974. He used it to describe semiconductor processes such as thin film deposition and ion beam milling, which exhibit characteristic control on the order of a nanometer.  Since the 1980s, the term nanotechnology has been referring to the fabrication, use/manipulation, control and characterization of structures devices or materials with a least one dimension in the size range of 1–100 nm. ^1,2

Nanotechnologies represent a fast-growing market, bringing with them a combination of benefits, promises, risks, and uncertainties.  It is synonymous with high technology and high efficacy. It has often been used as a buzzword in advertisements and label claims of many consumer products, including personal care products, to gain attention.  Various physical and chemical properties of a material can be affected by its particle size. Nanomaterials have been engineered to have enhanced properties and performance that are beyond their non-nano counterparts. However, these much enhanced properties also raises questions about their safety.

In June 2007, the safety of nanomaterials such as nano TiO₂ in sunscreen and fulluerene was raised in the article, Nanotechnology, the untold promise, and unknown risk, in Consumer Reports.  In August 2007, Friend of Earth (FOE) published Technology and Sunscreens, raising the particular concern over nano TiO₂ and ZnO in sunscreens and calling for labeling and regulation of nanomaterials in consumer products. Earlier in 2006, a coalition of environmental and consumer groups, including the International Center for Technology Assessment, Friends of the Earth, and Our Bodies, Ourselves, filed a legal petition with the Food and Drug Administration (FDA) asking FDA to regulate nanotechnology.

The first regulatory move was made by European Commission (EC).   EC acknowledged the safety concerns considering that nanomaterials could have very different physical and chemical properties over their non-nano counterparts, potentially resulting in different toxicological profiles. In 2005, the EU Scientific Committee on Consumer Products was requested by EC to provide a scientific opinion on the safety of nanomaterials in cosmetic products, in particular, the appropriateness of existing methodologies to assess the potential risk associated. This created public fear regarding nanomaterials in consumer products, especially in personal care products. In the meantime, the uncertainty of the future regulatory landscape made it extremely difficult for cosmetic formulators to incorporate nanomaterials in any formulation.

In 2009, REGULATION (EC) No 1223/2009 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 30 November 2009 on cosmetic products stated the purpose and need of a definition of nanomaterial, which has been evolving since. Most recently, COMMISSION RECOMMENDATION of 10 June 2022 on the definition of nanomaterial, C 229/1, defines nanomaterial as follows:

Nanomaterial means a natural, incidental, or manufactured material consisting of solid particles that are present, either on their own or as identifiable constituent particles in aggregates or agglomerates, and where 50 % or more of these particles in the number-based size distribution fulfill at least one of the following conditions:

– one or more external dimensions of the particle are in the size range 1 nm to 100 nm;
– the particle has an elongated shape, such as a rod, fibre or tube, where two external dimensions are smaller than 1 nm and the other dimension is larger than 100 nm.
– the particle has a plate-like shape, where one external dimension is smaller than 1 nm and the other dimensions are larger than 100 nm

Moreover, Article 16 of Regulation (EC) No 1223/2009 on cosmetic products requires that, in addition to the notification under Article 13, cosmetic products containing nanomaterials shall be notified to the Commission by the Responsible Person using electronic means six months prior to being placed on the market. Notification should be done on Cosmetic Products Notification Portal (CPNP).

2. Interpretation of nanomaterial definition:

The interpretation of the nanomaterial definition depends to a large extent on the size measurement method. Because of the structural complexity of nanomaterials, no single test method is capable of measuring all nanomaterials precisely and properly. EC recommends determining nanomaterial by its primary particle size or internal structure while allowing sectoral interpretation according to the actual use conditions, which may vary drastically from industry to industry.

In 2011, Cosmetic Europe issued their own interpretation of EC definition of nanomaterial, and then an update in 2019, stating that “materials with constitutive elements having a dimension in the nano-range (e.g. aggregates, agglomerates, composites) but that are themselves greater than 100 nm in size should not be considered as nanomaterials unless they release nano-objects or aggregates of less than 100 nm in size in cosmetic products under normal use conditions”.  Accordingly, the size of aggregates or agglomerates is used to determine the nanomaterial for labeling cosmetic products. This interpretation has been followed by many cosmetic companies.

3. Commercial use of nanomaterials

According to a EC’s report, Sub-working group of on nanomaterial definition, published on January 28, 2021, 37,647 cosmetic products were notified with nanomaterials in EU market, (via Art.13 procedure), which corresponds to about 1.5% of all notifications. According to 2015 – 2020 data, on average, about 10 new cosmetic products containing nanomaterials are placed on the EU market every day.

Most common product categories with nanomaterials: (64% of all nanomaterials notifications):

1. Sun protection
2. Nail varnish/nail make up
3. Oxidative hair care
4. Foundation
5. Lip care products and lipsticks

The most used cosmetic ingredients are reported below (4 ingredients accounts for over 70% of all CPNP notifications):

1. Titanium Dioxide
2. Silica Dimethyl Silylate, Silane, dichlorodimethyl-, reaction products with silica
3. Carbon Black nano (CI77266)
4. Silica

Scientific Committee for Consumer Safety (SCCS) under European Commission is requested by EC to evaluate the safety of the listed nanomaterials via a process that was based on the scientific literature available at the time and SCCS’ expert judgment. In early 2021, SCCS published an advice on the safety of nanomaterials in cosmetics, in which nanomaterials of concern were separated into two groups. ³

     — 16(4) of the Cosmetics Regulation

28 substances including silica, Titanium dioxide, Zinc oxide, Methylene Bis Benzotriazolyl Tetramethylbutylphenol were listed in the appendix 1 in an order of priority according to risk potential (based on a number of criteria).

     — 16(6) of the Cosmetics Regulation

SCCS reviewed three previous inclusive opinions on colloid silver, nano styrene/acrylate polymer and nano silica, and identified certain aspects relating to each of these nanomateirals that raised safety concern.

4. Nano TiO₂ /ZnO in sunscreens

For personal care products, nano TiO₂ and ZnO are perhaps the two most concerning ingredients due to their wide use as sunscreen actives. Because of their very small primary particle size, nano TiO₂ and ZnO are much more transparent on the skin and much more potent in UV protection than their non-nano or pigmentary counterparts. For instance, pigmentary TiO₂ is known to be completely opaque and cannot be used in any skin care product for effective UV protection.  Nano TiO₂, with a primary size of 10 – 20 nm, is not only highly transparent but also provides 5 – 6 times higher SPF.   For this reason, nano TiO₂ and ZnO have been used widely in sunscreen products in Japan and Australia since 1980s.  They have been popular among those having sensitive skin and allergic to organic sunscreens.

Up to now, and after the use by hundreds of millions of consumers, there have been no reports of any adverse health effects for nano TiO₂ and ZnO. However, they were still put under great scrutiny due to the general concerns and fear that were raised for nanomaterials in early 2000s.  Many customers, especially in EU, became somewhat nanophobic at the time as the future of regulatory landscape remained uncertain.

For topical application, the major concern is transdermal adsorption or penetration.  After years of study, SCCS issued in 2012 OPINION ON Zinc oxide (nano form) COLIPA S76 stating that “There is no evidence for the absorption of ZnO nanoparticles through skin and via the oral route. Even if there was any dermal and/or oral absorption of ZnO nanoparticles, continuous dissolution of zinc ions would lead to complete solubilization of the particles in the biological environment.” ⁴ Two years later, the SCCS issued the OPINION ON 22 on Titanium Dioxide (nano form), stating “the main consideration in the current assessment is the apparent lack of penetration of TiO₂ nanoparticles through skin.” ⁵

Another concern is photo-catalytic activity of nano TiO₂ that lead to generation of free radicals and ensuing oxidation.  Surface treatment of nano TiO₂ had been quite common, and the data collected by SCCSs on commercial grades confirmed that the photo-catalytic activity could be much suppressed by surface treatment.

Finally, EU revised the nano TiO₂ monograph for use as UV filters in 2016. The key updates included a list of allowed surface treatments and a limit on the photocatalytic activity. In the same year, ZnO was officially approved as an UV filter, and a list of surface treatments and solubility specification were included in the monograph. ⁶

After years of investigation, EC finally concluded that nano TiO₂ and ZnO were safe for personal care use as long as:

1. They comply with the specifications in the EU monographs.
2. The final product will not lead to exposure of the end-user’s lungs by inhalation.

For other nanomaterials under review, the SCCS has yet to establish final opinions. The future regulatory status remains uncertain.

5. Regulations in other regions

Nanomaterial is generally defined as a material with internal or external dimensions in the range of 1 – 100 nm in other regions.   Many regulatory agencies share similar concerns to EC’s, but they have not acted as swiftly as EC.  Although there are guidelines for considering the safety of nanomaterials, there are few laws enacted to regulate them.  To the author’s knowledge, there are two regulations outside EU:

A) Canada – If a sunscreen product contains only inorganic UV filters, nano TiO₂ and/or ZnO, it is considered a Natural Health Product, for which the premarket approval is not needed. However, if any of the two is used with organic UV filters, the sunscreen is a drug product. Safety of nano TiO₂/ZnO needs to be addressed and approved, which can be painstaking. Further, there is no official test method and threshold for classifying nanomaterials.

B) China – “Regulations on the Supervision and Administration of Children’s Cosmetics” issued by the State Food and Drug Administration (2021 No. 123), was issued in 2021. Section 7.1 states that:

“….. New raw materials that are still in the monitoring period should not be used, and raw materials prepared by new technologies such as genetic technology and nanotechnology should not be used. If there is no alternative raw material that must be used, the reason should be explained, and evaluate the safety of children’s cosmetics”.

Since nano TiO₂ and ZnO are not new technologies, they could be exempted from this regulation. However, the ambiguity in interpreting the regulatory language and difficulty in effective communication with Chinese officials have made many company shy away from nano TiO₂ or ZnO, and instead turning to the non-nano grades.

6. Summary

Nanomaterial safety and regulations are important to personal care product development. Many nanomateterials used in our industry are under safety review and their future is uncertain. As far as nano TiO₂ and ZnO are concerned, it is official that they are safe as long as they are not exposed to end-users’ lung in application. Due to the complex structures of nanomaterials, their size analysis method, data interpretation and regulatory classification have been constantly investigated and are still evolving. Formulators are highly advised to consult with their regulatory experts as well as the suppliers when choosing nano or non-nanomaterials.

References:

1. (2007a) Opinion on: the Scientific Aspects of the Existing Proposed Definition Relating to Products of Nanoscience Nanotechnologies. Brussels: European Commission Health Consumer Protection Directorate General.
   SCENHIR. (2007b) Opinion on: the Appropriateness of the Risk Assessment Methodology in Accordance with the Technical Guidance Documents for the New and Existing Substances for Assessing the Risk of Nanomaterials. Brussels.

2. ISO/TS 27687. (2008). Nanotechnologies – Terminology and Definitions for Nano-objects – Nanoparticle, Nanofibre and Nanoplate.
3. SCCS/1618/2020 Scientific Advice; https://health.ec.europa.eu/system/files/2022-08/sccs_o_239.pdf
4. SCCS/1489/12; https://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_103.pdf
5. SCCS/1516/13 Revision of 22 April 2014; https://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_136.pdf
6. COMMISSION REGULATION (EU) 2016/1143 of 13 July 2016, amending Annex VI to Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products