Scientific Blog Article

Hyperpigmentation is a common skin condition that can affect people of all skin types, all ages and on any part of the skin. It is a condition where certain areas of the skin become darker than the surrounding area which leads to visibly uneven skin tone. Hyperpigmentation is caused by several factors, including excess melanin production which is often triggered by inflammation, hormone imbalance, genetics, pollution, injury, chemical/ingredient reactions and UV light [1,2,3]. The most common forms of hyperpigmentation include sunspots, melasma, and post-inflammatory hyperpigmentation (PIH), which can occur after skin injuries such as acne scars [4,5].

Hyperpigmentation is not completely preventable due to its multiple causes; it is the third most common dermatological disorder and can cause psychosocial impairment [3,8,9,10]. Everyone is impacted by hyperpigmentation, but not equally. Individuals with darker skin types are more susceptible to hyperpigmentation. Dendy Engelman, MD, a board-certified dermatological surgeon said, “Brown skin is more prone to pigmentation because it tends to produce more pigment in response to injury, whether it’s sun damage or picking at a pimple.” [7,9].

Treatments for hyperpigmentation include laser treatments which can be very expensive and topical treatments which also have their limitations. For example, for many years hydroquinone was the leading and most common ingredient used topically to reduce hyperpigmentation, but regulation changes and negative side effects have limited its use. Hydroquinone has been banned in the EU, Australia and Japan, and has restricted usage in Canada, US and UK [6,7]. Furthermore, excessive and prolonged usage of hydroquinone can lead to further skin unevenness with a “halo effect” and/or pigment rebound [5,7,8].  Hydroquinone derivatives are also facing restrictions and other chemistries are gradually being scrutinized.

Consumers continue to seek topical treatments to prevent or try to reduce hyperpigmentation. Vitamin C, Niacinamide, alpha hydroxy acids (AHAs), and retinoids are the most common ingredients used in skin brightening topical treatments. The key targets to treating and preventing hyperpigmentation are melanosome transfer inhibitors, tyrosinase inhibitors, α-MSH inhibitors, anti-inflammatory actives and actives that increase cell turnover (Figure 1) [8]. The figure provides an illustrative overview of the common ingredients that are able to address hyperpigmentation. Overall, there are several ingredients that are able to address each key target but no ingredient that is able to address all the key targets to provide a single complete solution.

Social media platforms have increasingly influenced the education, standards, and treatment of skin concerns like hyperpigmentation. Influencers on Instagram, TikTok, and YouTube have had both positive and negative impacts on the modern cosmetics market. On the positive side, they have raised awareness, helped destigmatize hyperpigmentation, offered product and ingredient recommendations, and made skincare knowledge more accessible. However, they have also contributed to the spread of viral misinformation, often reaching a wide audience before it can be corrected by fact-checkers or experts. While these platforms can help consumers navigate the vast array of skincare products, it’s important to approach viral posts with caution and conduct further research.

The global skin brightening product market continues to grow, valued at $9.22 billion in 2023. This market is expected to reach $9.67 billion in 2024 and $16.42 billion by 2032, with a compound annual growth rate (CAGR) of 6.85%. The Asia Pacific region currently leads the market, holding 53.7% of the market share in 2023 [11,12]. As demand for clean and effective products rises, there will be an increase in the development of innovative ingredients through new techniques and processes. For example, in 2022, BASF partnered with Caregen to create biomimetic peptides designed to brighten skin. This ingredient features a unique blend of mechanisms, including inhibiting melanin synthesis, blocking tyrosinase, reducing the production of melanin-related enzymes and transcription factors, limiting melanin uptake, and enhancing melanosome degradation [13]. This multi-functional ingredient provides broader efficacy than the commonly used solutions on the market. As the demand for targeted hyperpigmentation solutions grows, more partnerships like this are expected to emerge, creating unique and effective treatments.

In conclusion, hyperpigmentation is a complex condition creating challenges with treatment and prevention. As one of the leading skin concerns with significant psychosocial impacts, it continues to drive innovation in the skincare industry. Whether targeting melanin production or addressing inflammation, advancements in skincare science are creating more effective and inclusive solutions. The rise of social media has led to an increase in informed consumers, but social media is also replete with misleading or false statements. This has unquestionably heightened awareness and access to information about hyperpigmentation and other top skin concerns.

With growing demand for efficacious products, the industry is primed for future growth and innovation. Hyperpigmentation may be complicated, but with advancements in skincare science and a focus on consumer education, we may be closer to helping people find solutions that work for their unique skin needs.

References:

1. Callender, V., St Surin-Lord, S., Davis, E., & Maclin, M. (2011). Post-inflammatory Hyperpigmentation. American Journal of Clinical Dermatology, 87-99
2. Cayce, K. A., McMichael, A. J., & Feldman, S. R. (2004). Hyperpigmentation: An Overview of the Common Afflictions. Dermatology Nursing, 401-406
3. Desai, S. (2014). Hyperpigmentation Therapy: A Review. J Clin Aesthet Dermatol., 13-17
4. Wang, R., Ko, D., Friedman, B., Lim, H., & Mohammad, T. (2022). Disorders of Hyperpigmentation. Part I. Pathogenesis and clinical features of common pigmentary disorders. Journal of the American Academy of Dermatology
5. Shi, Y., Zen, Z. L., Zou, P. F., Ma, Q. Q., Xiaong, W., Zhou, C. Z., & Xiao, R. (2021). Particulate matter promotes hyperpigmentation via AhR/MAPK signaling activation and by increasing α-MSH paracrine levels in keratinocytes. Environmental Pollution, 116850
6. Nieuweboer-Krobotova, L. (2013). Hyperpigmentation: types, diagnostics and targeted treatment options. J Eur Acad Dermatol Venereol, 2-4
7. Pandya, A., & Guevara, I. (2000). Disorders of Hyperpigmentation. Dermatologic Clinics, 91-98
8. Asma. (n.d.). What Is Hyperpigmentation And How To Get Rid Of It? Retrieved from Pharmacist Pill: https://pharmacistpill.com/what-is-hyperpigmentation-and-how-to-get-rid-of-it/
9. Allen, M., & Hopp, D. (2022, June 6). How to Even Out Discoloration on Darker Skin Tones. Retrieved from Byrdie: https://www.byrdie.com/how-to-get-rid-of-dark-spotss
10. Tian, X., Cui, Z., Liu, S., Zhou, J., & Cui, R. (2021). Melanosome transport and regulation in development and disease. Pharmacol Ther, 107707.
11. Fortune Business Insights. Skin Lightening Products Market Size, Share & Industry Analysis, By Form (Creams, Soaps, Lotions, Gels, and Others), By Formulation (Synthetic and Organic & Natural), By End-User (Women and Men), By Distribution Channel (Hypermarkets & Supermarkets, Specialty Stores, Pharmacy Stores, Online Channels, and Others), and Regional Forecast, 2024-2032
12. Grand View Research. Skin Lightening Products Market Size, Share & Trends Analysis Report By Product (Creams, Cleanser, Mask), By Nature, By Region, And Segment Forecasts, 2022 – 2030
13. BASF Active Ingredient Finder. https://www.personal-care.basf.com/products-formulation/products/

Anne Young is the Director of Business and Development at Biocogent.

Anne has previously held several leadership roles, including Director of Cosmeceutical Active Ingredients at Unigen, Inc., where she oversaw global sales and the R&D pipeline; Director of North America – Cosmetics Active Ingredients at Expanscience, managing the North American market; Global Product Development and Technology Manager at Vantage Specialty Ingredients; Technical Service for Active Ingredients at BASF; Lubricant Development Technologist at Infineum USA LP, where she led the Global R&D platform on LSPI; Senior Scientist at L’Oréal USA; and Senior Scientist at Johnson & Johnson Consumer & Personal Products Worldwide. Anne holds a Ph.D. in Chemistry From New York University. Anne has several patents, authored numerous scientific papers and has received numerous awards.

Pet Nutrition Innovations and Trends – An Overview of Current market

Sue Feng, Ph.D.

The pet nutrition and care trends on social media are focusing heavily on gut health, probiotics, and pet-specific supplements. Many pet owners are increasingly concerned about their pets’ digestive systems, with discussions about probiotics for dogs and homemade dog food recipes gaining significant attention. The interest in gut health is reflected by a rise in searches related to natural remedies, such as the use of coconut oil, and probiotics that support pets’ gastrointestinal health. Pet-specific CBD products are also trending, especially for treating anxiety and inflammation in pets.

Another key topic is the growing popularity of “humanized” pet products, where pet owners are treating their furry friends more like family. This includes purchasing premium pet care items like non-slip socks, goat milk-based treats, and even mobile grooming services to accommodate busy schedules. The rise of mobile services and products designed to enhance pets’ physical comfort reflects the evolving expectations of pet care, especially among millennial and Gen Z pet owners.

The current market for pet products, in general, is expected to significantly increase over the next several years due to the swiftly growing demand for these products. Specifically, pet supplements have become more popular because of the rise in pet humanization resulting in greater expenditures on pet nutrition. In 2023, “The global pet supplement market size was estimated at USD 2.49 billion”. (Grand View Research). In the United States, the pet supplement market is expected to grow at a compound annual growth rate (CAGR) of 5.9% from 2024-2030. (Grand View Research).

In the United States, pet owners have been putting more emphasis on their pets’ health and overall well-being. According to Luke Santos, more than half of the pet owners in North America (61%) “agree that their pet’s happiness and well-being is more important than their own”. The potential benefits of pet supplements can help meet the desires and needs of pet owners, helping their furry loved ones live long and healthy lives. Pet supplements are also readily available and are generally affordable. In 2023, “Over-the-counter (OTC) pet supplements dominated the market and held the largest revenue share of 86.6%” (Grand View Research).

In general, the pet treat market is quite large, encompassing not only pet supplements but also treats that do not have functional health benefits. Many pet owners believe that giving treats to their pets helps strengthen their bond. As a result, they are often eager to purchase pet treats. Beyond fostering their relationship, approximately 69% of American pet owners express interest in providing their pets with treats that offer health benefits.

Top Trends in North America

Hip and Joint

Glucosamine is an ingredient that has been used in pet foods for around twenty years and is commonly used in pet supplements because of its benefits for the hips and joints, specifically with dogs. Glucosamine is a natural compound that is in cartilage between the joints. Taking this supplement can help with arthritis, pain, and can protect joints from excessive wear and tear in many different animals, including humans and dogs. “The hip and joint segments dominated the market for pet supplements and held the largest revenue share of more than 21.49% in 2023 and is expected to maintain its dominance over the forecast period” (Grand View Research).

Skin and Coat

Beyond aesthetic appeal, ensuring a pet’s skin and coat remain healthy is vital as it plays a protective role for the animal. Not only does it serve as a protective barrier from the external world, but it also is part of your pet’s immune system, helps your pet regulate their body temperature, ensures proper hydration – since cats and dogs don’t have sweat glands, and more. Pet supplements or foods that contain ingredients such as fish oil, biotin, amino acids, omega-3 fatty acids, etc. can help to promote the pets’ skin and coat health. Pet supplements that claim to help with skin and coat health overall is already popular, but this “segment is projected to register the highest CAGR during the forecast period from 2024 to 2030” (Grand View Research).

Reduced Allergens

The rising number of pets in America with skin and/or food allergies has increased the demand for low-allergen or hypoallergenic pet products. In North America, 35% of pet food and product launches, in 2023, were advertised as low/no/reduced allergen. Ingredients that companies are avoiding when it comes to producing low/no/reduced allergen pet food products are wheat, corn, sugar, and soy.

Innovation Trends

– Probiotic

Everyone has microorganisms that live in and outside our bodies and pets have these microbes as well. Probiotics are a type of bacteria that live in the gastrointestinal tract of animals and are helpful to both people and pets. Probiotic supplements can be given to pets to help maintain a healthy gut which can prevent disease and promote their overall health. Usually, healthy pets can maintain a good gut microbiome, but there are many instances where an imbalance can occur – for example, in times of stress or sickness. Probiotic supplements can be used proactively if you are expecting your pet to go through a stressful event soon. Aside from that, probiotics can also be given to pets daily to help them maintain a healthy balance of gut bacteria. If your pet has allergies, anxiety, immune disorders, bad breath, is older, is on antibiotics, etc. then your pet may benefit from probiotic supplements. There are many different species of probiotics and the species that are beneficial to dogs are listed below.

– Bacillus coagulans
– Bifidobacterium animalis (strain AHC7) helps with acute diarrhea
– Bifidobacterium bifidum
– Bifidobacterium longum (BL999) helps with anxiety
– Enterococcus faecium (strain SF68)
– Lactobacillus acidophilus improves stool quality and frequency
– Lactobacillus casei
– Lactobacillus plantarum
– Lactobacillus rhamnosus (strain LGG) maybe effective for diarrhea, since it is beneficial for humans with diarrhea

(List from Cornell Richard P. Riney Canine Health Center)

Probiotic species that are beneficial for cats are listed below.

– Bifidobacterium
– Enterococcus
– Lactobacillus spp
– Streptococcus

(List from Paddock Park – Animal Care Center)

– Upcycled Ingredients

Upcycling ingredients has become more popular with food and cosmetics. Upcycled ingredients are materials that would have otherwise gone to waste but are repurposed for use in a different product. “Globally, we lose around $1 trillion per year on food that is wasted or lost” (Up Cycled). Especially among young pet owners, sustainable products that are friendly to the environment are considered when purchasing pet food products. Typically, younger pet owners are more conscious of the environmental impact of their food sources. By choosing pet products made from upcycled ingredients, they can feel that they are contributing to protecting our planet.

– Low allergens (Free from wheat, corn, and sugars)

As mentioned above, a popular trend with pet foods and products is a low/no/reduced allergen claim. In 2022-23, “The number of pet owners reporting both skin and food allergies show an upward trend over the last two years” (Mintel). Since there were so many pets in the United States that had allergies (and still do), the market reflected these needs.

References

1. AKC Staff. (2022, May 26). Can Glucosamine for Dogs Help Treat Arthritus and Joint Pain?.
2. American Kennel Club. https://www.akc.org/expert-advice/health/glucosamine-dogs-arthritis-joint-pain/#:~:text=It%20is%20one%20of%20several,dysplasia%20or%20other%20structural%20changes.
3. Canadian Academy of Vetinary Nutrition et al. The Importance of Your Pet’s Skin and Coat and the Role of Nutrition. VCA Animal Hospitals. https://vcahospitals.com/know-your-pet/the-importance-of-your-pets-skin-and-coat-and-the-role-of-diet
4. Cornell Richard P. Riney Canine Health Center. The power of probiotics.
5. https://www.vet.cornell.edu/departments-centers-and-institutes/riney-canine-health-
6. center/canine-health-information/power-
7. Grand View Research. Pet Supplements Market Size, Share & Trends Report, 2030 (grandviewresearch.com)
8. Manucy, T. (2024, March 26). Probiotics for Dogs: Do They Work?. Pet MD.

ABOUT THE AUTHOR

– Sue Feng is the Chief Scientific Officer leading E.T. Browne’s Global Research and Innovation.
– Sue Feng is an Adjunct Professor at Fashion Institute of Technology University in the Cosmetics and Fragrance Marketing department.
– Prior to joining E.T. Browne Drug Co., Dr. Feng held senior leadership positions at REVLON, L’Oreal, and Procter & Gamble.
– Sue Feng has extensive global experience, having lived in Asia, and having worked in the US and Europe. She has in-depth expertise in skin care, personal care, raw materials, third party manufacturing, active skin care, dermatologist and medical relations, and product innovation. She has unique combinations for advance research, applied research and product development including luxury and mass skin care, cosmetics, laundry, surface cleansers, hair care, medical device and understands what it takes to win in the Global Beauty markets. Her knowledge span all parts of the product life-cycle, from original concept through product development, to manufacturing and successful launch.
– Feng received her Ph.D. in Chemistry from Purdue University. She has authored numerous scientific papers, and patents in personal care, skin care and color cosmetic chemistry and advance research fields.
– Feng is the co-founder of Chinese American Cosmetic Professional Association CACPA.

Pets play a significant role in many of our lives, and the pet care market reflects this, with an estimated value of 13.88 billion USD according to a 2023 global market analysis of the pet grooming product market.¹ From our loyal companions like dogs and cats to our majestic equine friends, pets come in all shapes and sizes, each with their unique grooming needs. Understanding how to formulate for pets is crucial from a regulatory perspective. Allow me to walk you through remaining compliant and various formulations essential to animal care.

FDA Cosmetic Counterpart for Animals: Grooming Aids

Understanding how pet care is categorized from a legislative perspective will greatly help your formulation journey. Pet care falls within its own realm, similar to personal care, and requires compliance with specific regulations. We will still need the FDA’s help on this one. Sec. 653.100 Animal Grooming Aids from the U.S. Department of Health and Human Services Food and Drug Administration Office of Regulatory Affairs and Center for Veterinary Medicine will guide everything we need from a United States-based formulation perspective. Very similar to cosmetics, “products intended solely to cleanse or beautify animals, commonly referred to as “grooming aids,” are not subject to the FD&C Act and are not regulated by FDA.”² Just like with the cosmetic vs drug debate, “if a product purporting to be a grooming aid is intended to cure, mitigate, treat, or, prevent disease in animals or to affect the structure or function of the body of animals, the product is a drug under section 201(g) of the FD&C Act.”² Another similarity is to demonstrate a product’s safety and effectiveness; likewise, anything unapproved or adulterated is subject to FDA enforcement. Of course, there could be hybrids, just like cosmetics; however, these lean more toward the drug side of things. Medicated shampoos for pests like fleas and ticks would be considered a drug over a shampoo that just cleanses. If you’re wondering if your product would be considered a drug, you can always reference the monthly updated FDA Green Book for all the information you need on approved animal drugs. Even though grooming aids have their own special category, the Federal Trade Commission (FTC) labeling regulations still play a role in pet products. As you can see, cosmetics and grooming aids have some similarities, but then again, there are stark contrasts.

EPA Defined Ingredients

From a cosmetic lens, we look to the Environmental Protection Agency for regulations concerning issues such as volatile organic compounds (VOCs). The EPA comes into play for pet care for two major purposes, and that would be for registered pesticides and the Toxic Controlled Substances Act (TSCA). While humans deal with pesticides, most commonly thought of from a narrowed perspective as insecticides for pesky mosquitoes and biting flies, animals need protection from these often injurious pests. The EPA ensures the safety of pesticides, even when used on animals, in accordance with label directions.³ A vital callout is not all pesticides are universal. What might be okay for a dog, can be toxic to a cat. This is critical to keep in mind when formulating or purchasing products for your pet. The EPA wonderfully outlines the requirements and guidelines that need to be met. Through the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the EPA’s regulated pesticides on the market are well-established and researched, allowing for an expansive choice for your product needs. It is imperative to understand that the FDA regulates certain medicated products for animals as drugs, while the EPA regulates others as pesticides. Always double-check regulations and ensure you’re registered with the right government agency.

What is TSCA? According to the EPA, The Toxic Substances Control Act of 1976 provides EPA with authority to require reporting, record-keeping and testing requirements, and restrictions relating to chemical substances and/or mixtures.⁴ Regarding TSCA, certain substances are generally excluded from TSCA, such as food, drugs, cosmetics, and pesticides. In the realm of personal care, we are privy to the TSCA exemption for cosmetics; therefore, we can continuously use novel and exciting ingredients. Around every six months, the TSCA inventory will get updated.⁵ As it stands, the TSCA Inventory contains 86,770 chemicals, but only 42,377 are active.⁵ You can download the TSCA inventory and search by chemical CAS number. You can also go to your raw material SDS and check section 15 for regulatory information. The green light is when your ingredients are listed on the U.S. Toxic Substances Control Act (TSCA) Chemical Substance Inventory. If you can’t find it on TSCA, it’s considered a new chemical to U.S. commerce. The reason you want to be compliant is if you use an item not registered on TSCA, expect to follow Section 5 of TSCA, which requires anyone who plans to manufacture a new chemical substance for a non-exempt commercial purpose to provide EPA with a Premanufacture Notice (PMN) at least 90 days before initiating the activity or incur repercussions from the EPA for violation.⁶ If you think regulations for U.S. commerce seem daunting, keep in mind other countries’ inventory lists, along with requirements for pet products.

Of course, we know regulations are not only everchanging but also nuanced. Just within the U.S., remaining compliant is important. While easier said than done, do not forget about state regulations! Medicated products might not be as accessible given your company’s bandwidth to support and keep up with hefty regulations, but showcasing them is an option since these are popular within the pet space. Just like every cosmetic manufacturing site might not be making OTC, grooming aids alone might make the most sense, given your company’s capabilities. While R&D folks typically need a slice of regulatory knowledge to commence formulating, it is vital to utilize government resources, trusted industry sources, and regulatory consultants for utmost compliance for your unique development needs. This overview should be enough to whet the regulatory knowledge perspective so we can get down to some fun formulations.

Pet Chemistry

As we learn more about concepts like microbiome, we can understand skin pH is not necessarily ubiquitous depending on the region. This same concept applies to pets. While human skin is more so on the acidic side, dogs are more alkaline, with a recent report revealing the mean pH of 7,48 for canine skin.⁷ The skin pH level for a cat is around 6, which is slightly on the acidic side.⁸ We find bigger pets like horses to have a pH from 7.0-7.4, around the neutral arena.⁹ Little fuzzy pets like guinea pigs zone in at 5.5 while a rabbit will circle around 6.7, which shows variation between all types of animals.¹⁰ Of course, there is a massive list of all kinds of pets, from skunks to turtles, but not all of these types of pets necessarily need assistance from grooming aids. Having a baseline understanding of skin pH will help keep animals in balance and avoid adverse skin reactions.

There is a question: can pets share products with humans? It is complicated. In a pinch, it should be okay, but it is really best to use products intended for the subject itself. There are hybrid products on the market that say they are for humans and other types of animals. In that case, you need to follow the most stringent regulations; although, is best practice to separate church and state to avoid weighing what you need from each category to be compliant.

What a Pet Wants, What a Pet Needs

It is paramount to consider all pets have special needs, and they should be addressed per the veterinarian’s recommendations. The first product most people think of is a pet shampoo. We know pets can get into messes or have the proclivity to get dirty and smelly sometimes. Maintaining cleanliness and perhaps primping can be ideal for a pet’s appearance. We can heavily hinge on our knowledge of personal care based formulas to help build our pet grooming line. I’ll be providing the best items to add to a product line with some tips and tricks along the way.

One concept is how often pets are groomed. Typically, a domesticated animal will not bathe as often as a human would. So consider what your final sizes for finished goods will be. On the other hand, large and bulk sizes might make sense for someone with multiple pets, larger pets, or for groomers. Travel sizes can come in handy because pets can often tag along for the ride or may need to be presented for showings, like horses or dogs.

Let’s talk about why we should mirror cosmetic protocol. Safety substantiation is key. Test all of your standard specifications, conduct stability, run microbial studies, and test/substantiate all claims on your bottle. While a list of ingredients is not necessary for animal products, it is a good practice to follow cosmetic labeling guides for transparency and courtesy to the consumer. We owe it to the special members of the family to give them the best they deserve!

Let’s start with a good wash. We can keep the classic picture of a shampoo/body wash in mind, but consider the pH of the pet you want to formulate for. Pets may not be able to close their eyes or anticipate the sting that some anionic surfactants might cause. It is best to go with surfactants that have a low irritation profile based on results from reliable ocular studies. These are often gentle but still offer robust foam. Fragrance can really make a product, but if this is used around the eye area or for pets with allergenic tendencies, it might not be ideal. Be sure to advise your fragrance house that you are working on pet products, so they can help develop the best fragrance for your application. Consider adding humectants and detangling agents to nourish the animal’s skin and keep their hair from tangling post-bath… or shower… or sink! Once you have a favorable base, you can add actives, just ensure they are on TSCA and registered with the FDA or EPA.

Now that the pet is squeaky clean, adding a conditioner next will enhance their coat’s softness and shine. Something to note is animals are known to have fur; however, this is just the animal classification of hair. Regardless, fur is a special type of hair, and even animal hair varies from human hair. Pets need conditioning to maintain manageable hair. Given most pets are more alkaline, we need to reconsider our final pH with conditioning. A classic opaque base with conditioning agents will be a great start. If wanting to incorporate butters and oils, consider things like chocolate is toxic to dogs and cats. For that reason, it is probably best not to use something like cocoa butter, even though it only has trace amounts of theobromine, the compound toxic to these pets. Although we associate dogs with loving peanut butter, others might have some nut allergies, so consider this as well for nut-based butters and oils. Pets battle with issues like dry skin, excessive shedding, dander, tangles, matted hair, and malodor, to name a few. These are some elements to consider based on the solutions you want to provide the pet.

To help maintain the post-bathing conditioning, it is good to follow up with a leave-in conditioner. Consider where this product may be sprayed and if the pet will have interactions with licking around these regions. The same ideas apply to the butters and oils concept from the conditioner portion. You can choke up on the viscosity and focus on elements like detangling, moisturizing, and perhaps even deodorizing. You can have fun with the final dispensing form from a flip top to a manual spray to an aerosol. Again, actives can be administered once you have a satisfactory base. A fun project I worked on was creating a stellar leave-in conditioner for a horse, but incorporating insecticides to keep the biting flies off.

Next would be a deodorizing product or pet perfume/cologne because bathing processes for pets can be, well, a process! Maintenance between can help elongate the time between baths. For this product, we are focusing on neutralizing malodor and imparting some moisture. This formula is as simple as adding a deodorizing agent along with a pleasant fragrance. Just make sure everything is nice and soluble. Feel free to add humectants and extracts to bring the marketing story all together. You can even make a wipe version of this product for quick freshness, especially on the go. If you are using this on smaller pets or those that might self-groom, consider where they can lick or come into contact with this item.

Similar to the deodorizing spray would be a dry shampoo. Get the scent of your pet fresh from the bath without the water. This will help mattify your pet if they are prone to getting slick coats. Dry shampoos are simplistically solvent and mattifying powder. You can go the mineral route or even explore the many starches. Be sure to consider large micron sizes or wetter sprays and consider your pet’s sniffer.  You can go the classic aerosolized dry shampoo route or something in a pump bottle. Be cognizant of potential clogging issues. It might make sense to employ an anticaking agent. Work closely with your packaging engineer or vendor to perfect the dispensing of this item. You can add a hint of emollient to your dry shampoo. Feel free to top it all off with a pleasant fragrance. You can even add some deodorizing benefits to this formulation.

Cold weather, rough walking surfaces, and sensitive areas make pet balm essential. This would most likely be a hot fill item or squeeze tube fill. A semi-soft balm used to protect the pads of the paws, the nose, and any other areas of the body that need some extra love. Like in the conditioner section, consider the oils and butters used if the pet might lick this item off. You want this item to be safe if consumed. Focus on moisturizing and occlusivity for this item.

Certain pets might have the proclivity to have eye discharge buildup. Having a wipe to remove the tears and staining can help keep your pet healthy and looking fresh. Consider utilizing safe ingredients for use near the ocular area. Something hybrid of a gentle surfactant mix to loosen up debris with a mild saline-like solution to do the “rinsing” would be the silver bullet for this type of formula.

Just like fingernails, hooves need special care. Horses are prone to breaks, dullness, fungal infections, dryness, and brittleness. From a salve to a spray, you can really have fun with the application for a nail protection and maintenance formula. By going with humectants, occlusives, and emollients, you’re sure to help gloss up their hooves, moisturize, and seal it all in from the elements. Of course, antifungals can be incorporated if you are pursuing the drug route for this item.

We can spend all day discussing formulation. I will pop a few other ideas into your head on this that might be more entailed, niche, or surround the needs one might have because of pets. For our fancy pups and horses out there, pet hairspray or hair coloring is popular in the realm of animal showcases. I just recall in The Wizard of Oz how the horses were different colors. Ear rinses and wound care are important within the realm of animal care; however, most of this does tread into the medicinal application. For our pals that stay inside, odors can persist from various circumstances, cage cleaners, urine/pet mess cleaners, and air fresheners come in handy. Keep in mind pet-friendly ingredients!

Here’s a little helpful list to leave off with when formulating grooming aid products for U.S. commerce. These are a few questions to send your vendor or investigate on your end:

Is this item on TSCA inventory? Is this item safe for use on (animal you are formulating for)? Does this material fall within (the pH range of the animal you are formulating for)? Does this item have any affiliation with toxicity, allergy, or other concerns (for the animal you are formulating for)? Are these ingredients affiliated with any FDA or EPA registration? Does this raw material have any glaring regulatory issues on a state level?

All in all, formulating grooming aids for pets is satisfying because you are helping pets actualize their best selves so they can have the most positive experiences with their family and loved ones. A healthy and happy pet is so wonderful! There are so many types of products that can be made to help pets or issues surrounding them. Understanding the special regulations surrounding grooming aids will help keep your formulations compliant. Having a baseline understanding of formulating all things personal care can give you an edge in formulating for pet care. Now go out there and make the most PAWpular formulas on the market!

(1)Pet Grooming Product Market Size | Industry Report, 2019-2025. www.grandviewresearch.com. https://www.grandviewresearch.com/industry-analysis/pet-grooming-products-market.

‌(2)Sec. 653.100 Animal Grooming Aids Compliance Policy Guide Guidance for FDA Staff. https://www.fda.gov/media/121177/download.

(3)US EPA, O. EPA’s Regulation of Flea and Tick Products. www.epa.gov. https://www.epa.gov/pets/epas-regulation-flea-and-tick-products.

(4)US EPA. Summary of the Toxic Substances Control Act | US EPA. US EPA. https://www.epa.gov/laws-regulations/summary-toxic-substances-control-act.

(5)US EPA, O. How to Access the TSCA Inventory. www.epa.gov. https://www.epa.gov/tsca-inventory/how-access-tsca-inventory.

(6)US EPA, O. About the TSCA Chemical Substance Inventory. US EPA. https://www.epa.gov/tsca-inventory/about-tsca-chemical-substance-inventory.

(7)Matousek, J. L.; Campbell, K. L.; Kakoma, I.; Solter, P. F.; Schaeffer, D. J. Evaluation of the Effect of PH on in Vitro Growth of Malassezia Pachydermatis. Canadian Journal of Veterinary Research 2003, 67 (1).

(8)Table 5 . Skin pH in different regions in cats. ResearchGate. https://www.researchgate.net/figure/Skin-pH-in-different-regions-in-cats_tbl3_49731296 (accessed 2024-09-29).

(9)Let Your Horse Shine Bright. FEI.org. https://www.fei.org/stories/lifestyle/health-fitness/let-your-horse-shine-bright-cavalor#:~:text=The%20pH%20of%20your%20horse (accessed 2024-09-29).

‌(10)Proksch, E. PH in Nature, Humans and Skin. The Journal of Dermatology 2018, 45 (9), 1044–1052. https://doi.org/10.1111/1346-8138.14489.

ABOUT THE AUTHOR

Amanda Rountree
IKI Manufacturing

Amanda Rountree is a Senior Manager of Product Development at IKI Manufacturing. She has been in the cosmetic industry for seven years. Her primary R&D expertise is centered around aerosol and liquid development of personal care and household products. She has made everything from laundry detergent, eyelash serum, peel-off masks, and hairspray. Amanda’s favorite aspect is innovative product development and helping craft an exciting marketing story for a successful product launch. She has always been passionate about science and knew she would be a cosmetic chemist since high school. This led her to pursue her Bachelor’s in Chemistry at North Central College. As a student, Amanda became involved with the Midwest Chapter of the Society of Cosmetic Chemists. She has served as Hospitality Chair in 2019, Secretary in 2020, Bylaws Chair in 2021, Chair-Elect in 2022, Chair in 2023, and Teamworks Chair in 2024. Amanda has championed better connections within the Midwest Chapter by branching outside of the Illinois/Chicagoland area and incorporating Wisconsin and Indiana for exciting events. She is also involved as a board member of the Southern Aerosol Technical Association (SATA) and serves as an active speaker at industry conferences. Her educational message spreads beyond the industry, as she recently spoke at an a Household & Commercial Products Association (HCPA) event to Federal legislators regarding research and development.

Formulating Toothpaste
Author: Hani Fares, Ph. D.

Most personal care formulators are familiar with skin, hair and make-up formulations. Oral care formulation has always been a distant cousin.  The ingredient listing on the back of the carton seems very familiar, but the technology is quite distinct.  In this article, I will try to explain certain elements to simplify the development process of toothpaste formulations.

In the United States, toothpaste is considered an over-the counter dosage form that falls under the anticaries drug products monographs. In fact, the monograph defines dentifrices as “an abrasive-containing dosage form for delivering anticaries drug to the teeth”¹.  Interestingly enough, there are two key messages in this definition: the first one is that dentifrices must contain abrasives, and the second is that they should deliver actives to teeth. As such, dentifrices do not have to be gels or pastes, they could be powders.  In fact, tablets were introduced recently as alternatives to traditional paste.  However, pastes and gels are the most common forms used by consumers.

There are three anticaries actives approved for use in dentifrices, namely sodium fluoride, sodium monofluorophosphate (naMFP), and stannous fluoride.  One thing to note is that the source of fluoride used must be paired with the recommended abrasive.  For example, sodium fluoride and stannous fluoride toothpastes are typically paired with silica abrasives and naMFP is typically paired with calcium carbonate or dicalcium phosphate.  The idea of pairing actives with abrasives is based on relating these dentifrices to the original clinical studies conducted on such combinations.

In addition to pairing abrasives and actives, several tests must be performed on any newly launched toothpaste. The first test is a biological animal caries reduction test. This test must be paired with either Enamel Solubility Reduction (ESR) or Fluoride Enamel Uptake (FU). However, since there has been a lot of pressure on reducing animal testing, companies have been using other methodologies² that showed equivalence to animal testing. Manufacturers are also required to generate data on free fluoride in the dentifrice.  Such data is typically generated based on accelerated stability protocols before launch and can be substituted with real-time data once the product is launched.

Dentifrice manufacturers have been quite active in going beyond just the anticaries and antiplaque claims that they can achieve with a traditional fluoride toothpaste.  Generating additional claims and benefits to consumers has led to formulating new premium toothpastes.  One area of premiumization was to launch antigingivitis toothpastes.  Such toothpaste will fall under the antigingivitis/antiplaque monograph³. These dentifrices are formulated with stannous fluoride as the active ingredient and silica as the abrasive.  In addition to all the tests described in the fluoride monograph, these must be tested in vitro for their antimicrobial activity against plaque organisms commonly associated with gingivitis.  These tests must include MIC assays, 30-second kill-time studies and plaque biofilm assays .  In addition, these products must demonstrate activity ex-vivo using a Plaque Glycolysis and Regrowth Model (PGRM)⁴. Companies seeking the antigingivitis claim outside of the monograph must go through the New Drug Application (NDA) process.  One well-known example is “Colgate Total,” which used Triclosan as the antimicrobial and PVM/MA Copolymer (commercially known as Gantrez™) as the polymeric delivery system for the oral cavity.  The NDA process is quite long and expensive but typically allows certain exclusivities to the marketing company.

Another area that has gained a lot of popularity in dentifrices is whitening.  Claiming to whiten teeth is generally a cosmetic claim, though many companies conduct consumer studies to measure the whitening effect of their toothpaste on panelists.  Whitening teeth involves removing extrinsic stains or bleaching extrinsic/intrinsic stains.  Removing extrinsic stains has been achieved by using sodium hexametaphosphate.  Other types of phosphates have been used as well but are not as efficacious. Hydrogen peroxide is the most widely used form of peroxide used in toothpaste to bleach intrinsic and extrinsic stains.  That is due to its acceptable taste and its availability in a complex form with PVP which makes it quite stable for a longer time.  Other forms of peroxide like urea peroxide are used as well but are not very popular. Whitening toothpastes are typically anhydrous formulations due to the instabilities of sodium hexametaphosphate and hydrogen peroxide in the presence of water.  These formulations require a special type of thickener and do have a unique mouthfeel.

Another area of interest to consumers is treating sensitive teeth with toothpaste.  This area is covered by a monograph as well and the two actives allowed are potassium nitrate and stannous fluoride.  Potassium nitrate is typically formulated in silica/sodium fluoride base.

As you can see, there are some intricacies in formulating toothpaste but at the end of the day, it all comes down to consumer experiences and product performance. A skilled formulator is always capable of marrying all the ingredients in a formulation to deliver a delightful experience and a great mouthfeel.  Formulation has always been a blend of science and art, and many dentifrices are able to provide this great consumer experience. I hope I have shed some light onto the world of formulating formulation-let’s go create new formulations!

References

1. Federal register, Vol 60, No 194, 21CFR 310.
2. Featherstone, J., Stookey, G., Kaminski. M., and Faller, R. Recommendation for non-animal alternative to rat carries testing, Am J. Dent., 5 (2011) 289-294.
3. Federal register, Vol 68, No 103, 21CFR356
4. White, D., Cox, E., Liang, N., Macksood, D., and Bacca, L., A new Plaque Glycolysis and regrowth Method (PGRM) for the in vivo determination of antimicrobial dentifrice/rinse efficacy towards the inhibition of plaque growth and metabolism – method development, validation and initial activity screens., J. Clin. Dent. 6 (1995) 59-70.

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 Global Lead 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.

Regulatory Considerations Regarding Sunscreen Actives

Yun Shao
Kobo Products, Inc.
June 2024

Summer is here, and it is time to enjoy outdoor activities and the beautiful landscape with friends and family. However, the Sun is bright and scorching, making the weather hot and the use of sunscreen essential. Sunscreen, sunscreen, sunscreen!

When developing sunscreen products, it is crucial to focus not only on performance and aesthetics to meet consumer expectations but also on regulatory compliance. Sunscreen products are regulated worldwide and are classified as drugs by the FDA. For the US market both the manufacturers of sunscreen products and the actives (considered as Active pharmaceutical ingredients (APIs)) used in these products must comply with FDA requirements, including registration and listing, as well as adherence to ICH Q7A Current Good Manufacturing Practices.

In terms of quality control, all sunscreen actives must meet the United States Pharmacopeia (USP) specifications mandated by the FDA in its sunscreen monograph.¹ However, there can be some confusion regarding the specific details of these requirements.

National Drug Code (NDC)

The NDC, or National Drug Code, is a unique 10-digit, 3-segment number that serves as a universal product identifier for human drugs in the United States. This code is present on all nonprescription (OTC) and prescription medication packages and inserts in the US. Most formulators know that an NDC is required for a finished sunscreen product. But what about the sunscreen actives used in the formulation?

An NDC is not typically required for an API (Active Pharmaceutical Ingredient) used solely as a raw material in the manufacturing of drug products. However, some sunscreen actives in raw material form are listed in the NDC database due to voluntary actions by their suppliers. This practice is common for suppliers who import sunscreen actives into the US to facilitate customs clearance.

USP specification

To ensure compliance, a sunscreen active must be tested against its USP monograph and complies with all specifications. This testing is straightforward for organic sunscreen actives because they are often supplied as pure compounds. You can take a sample, follow the USP test methods, and conduct the tests. However, it is more complicated for inorganic UV filters such as titanium dioxide (TiO₂) and zinc oxide (ZnO).

Most commercial grades of TiO₂ and ZnO used in sunscreen applications have exceedingly small particle sizes and large surface areas. Consequently, they are highly photoactive and can catalyze the oxidation of organic compounds in sunscreen formulations or potentially molecules in the stratum corneum. To mitigate this, especially for TiO₂, surface treatment with inorganic compounds like alumina and/or silica, and organic compounds such as stearic acid or silicones, is common.

As a result, the commercial TiO₂/ZnO powders available to formulators are always a mixture of the active compound and the coating materials. The actives cannot be separated from the coating materials, and the powder, if tested as is, cannot meet USP specifications. USP verification or certification can only be performed by the manufacturer, as they have access to the actives prior to the surface treatment. It is common to see a statement in the Certificate of Analysis (CofA) indicating that the active prior to surface treatment is USP grade, or a separate section in the CofA showing the test results of the active prior to surface treatment.

Due to their large surface area, both attenuation grade TiO₂/ZnO have much moisture absorbed on their surfaces. In the USP specifications for TiO₂, the loss on ignition is set to be less than 13% for the attenuated grade (micronized or nano) TiO₂. However, for ZnO, the specification for loss on ignition is less than 1%. There is no provision for micronized or nano zinc oxide. Therefore, to meet these specifications, the powder needs to be dried before the loss on ignition test.

Zinc Oxide Type

There are three USP monographs related ZnO:

1. Zinc Oxide
2. Zinc Oxide Neutral
3. Zinc Oxide Powder

These monographs specify different purity requirements, with Zinc Oxide having the most stringent criteria. Only USP Zinc Oxide is listed in the FDA sunscreen monograph.¹ While the Zinc Oxide Neutral monograph mentions labeling it for use in sunscreen, its purity level is too low for this purpose. Zinc Oxide Powder also has different, typically lower, purity requirements compared to USP Zinc Oxide. Therefore, it is important to use USP Zinc Oxide for sunscreen formulations to meet FDA standards.

Assaying The Actives

When assaying active ingredients in sunscreen formulations, the method chosen should align with the assay’s purpose. If the goal is to certify compliance of a RM with the United States Pharmacopeia (USP), a USP method must be adopted. However, once an active ingredient is incorporated into a sunscreen formulation or undergoes surface treatment (as is the case with TiO₂ and ZnO), the mixture is no longer considered a USP active. In such cases, the purpose of the assay is to analyze the active ingredient level, not its USP compliance. Therefore, any effective and validated analytical method can be used.

Organic sunscreen actives are often assayed using gas chromatography. The USP method can also be applied to assaying the raw material (RM) as well as the sunscreen composition. For inorganic UV filters, various methods can be used for assaying the treated powder or finished sunscreen products. These methods include X-ray Fluorescence (XRF), titration, Atomic Absorption Spectroscopy (AAS), Ion Chromatography (IC), and Inductively Coupled Plasma Mass Spectrometry (ICP-MS).

All except the titration method offer high sensitivity and are originally designed for trace metal analysis. Each method has specific pitfalls related to interferences, sample preparation, and operational complexity. It is crucial to fully validate the selected method for each type of sample. Subsequently, managing the analytical workload can be a significant challenge for companies with diverse sunscreen product lines. Each sunscreen formulation may require a specific test protocol and validation to eradicate or minimize the potential matrix effect of different formulations on the test result. Therefore, it is necessary for companies to have a well-organized and efficient analytical testing process to ensure compliance with regulations and maintain product quality across their range of sunscreen products.

Active vs. Non-active TiO₂

The distinction between active and non-active TiO₂ can be particularly confusing in color cosmetics with SPF, where both pigmentary and attenuation-grade TiO₂ are utilized. While assaying and reporting the total TiO₂ content is straightforward, the level can fluctuate among different shades, especially when the range of shades is very wide. This variability makes it challenging to determine the suitable active level for labeling purposes.

To address this issue, there is a practice to report only the level of attenuation-grade TiO₂ content. However, this approach can also be complex, as it requires assaying the intermediate product in the production process. This datapoint is then used in the calculation of the final active content, adding to the intricacy of the process.

Environmental Concern

As we all know, the use of oxybenzone and octinoxate in sunscreens has been banned in Hawaii, Key West in Florida, Palau, the U.S. Virgin Islands, Aruba, Bonaire, and Mexico due to their toxicity towards coral reefs. This has reduced the number of sunscreen actives available for formulation in sunscreen products in the US. As a result, the use of TiO₂ and especially ZnO has dramatically increased.

It is interesting to note that ZnO is considered aqua toxic by the EPA and ECHA. According to DOT regulations, a pictogram indicating this aqua toxicity must be included in the SDS and on the shipping label. Nonetheless, studies have shown that the level of ZnO introduced into seawater from sunscreen use by consumers is extremely low. ²   It is well below the Predicted No Effect Concentration of Zn²⁺ and Most Sensitive Observed Effect Levels. ^3,4 Therefore, the use of zinc oxide as a sunscreen active is considered safe for marine species and ZnO sunscreen can be claimed as reef safe.

On the other hand, TiO₂ is insoluble in water and has no toxicity towards any species. Its safety towards coral reefs was suggested by Corinaldesi in comparison to ZnO. ³ Of course, nano TiO₂ is photo-catalytical under UV exposure if uncoated. However, with proper coating, the photocatalytic activity is suppressed, making TiO₂ environmentally friendly. It could be the best sunscreen active from an environmental perspective.

However, TiO₂ has a higher refractive index and often leaves a white cast on the skin if not formulated properly, which presents a significant challenge to formulators. Despite its environmental advantages, it has not been as widely considered for sunscreen formulations as zinc oxide in recent years.

In conclusion, navigating the regulatory landscape and environmental considerations for sunscreen actives is complex. Manufacturers must balance regulatory compliance, environmental safety, and formulation challenges to develop effective and safe sunscreen products.

References:

1. Federal Register / Vol. 64, No. 98 / Friday, May 21, 1999 /Rules and Regulations: Sunscreen Drug Products For Over–The-Counter Human Use; Final Monograph.
2. Antonio Tovar-Sa´nchezet al., Sunscreen Products as Emerging Pollutants to Coastal Waters, PLOS ONE, June 2013, Volume 8, Issue 6, e65451.
3. C Corinaldesi, Impact of inorganic UV filters contained in sunscreen products on tropical stony corals (Acropora spp.), Sci Total Enviro., 2018 Oct 1:637-638:1279-1285.
4. Ingo B. Miller, Toxic effects of UV filters from sunscreens on coral reef revisited: regulatory aspects for “reef safe” products, Environ Sci Eur (2021) 33:74.
5. Andreas P. Gondikas et al., Release of TiO₂ Nanoparticles from Sunscreens into Surface Waters: A One-Year Survey at the Old Danube Recreational Lake; Sci. Technol.2014, 48, 10, 5415–5422.

ABOUT THE AUTHOR

Dr. Yun Shao joined Kobo Products Inc. in 1996 and currently serves as the Senior Vice President of R&D. With over 20 years of experience, he is a seasoned expert in inorganic sunscreen technology, micro TiO₂ and ZnO development, pigment surface treatment, dispersion technology, specialty cosmetic ingredients, color cosmetics, and global cosmetic ingredient regulations.

Dr. Shao has shared his work at prestigious scientific meetings, including the IFSCC Congress, SCC Annual Scientific Meeting, and FLSCC Sunscreen Symposium. He holds nine patents and has co-authored several book chapters and technical papers on surface treatment and inorganic sunscreen formulations.

Dr. Shao earned his Ph.D. in Polymer Chemistry from Rensselaer Polytechnic Institute and his B.S. in Applied Chemistry from the University of Science and Technology of China. He is a member of the Society of Cosmetic Chemists and a founding member of the Chinese American Cosmetic Professional Association.

Gut Microbial Metabolites of Dietary Polyphenols and Their Skin Health Benefits

Author:
Hang Ma, Ph.D.
Research Unit for Nutraceutical and Cosmeceutical Applications (RUNCA), Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island

Imagine your gastrointestinal tract as a sophisticated biochemical laboratory, where the vast community of gut microbes metabolizes polyphenols— plant-derived compounds widely found in fruits, vegetables, coffees, and teas. Through complex enzymatic processes, these microbes break down polyphenols into a variety of smaller, bioactive compounds known as polyphenol microbial metabolites (PMMs). These metabolites are important to overall human health: they enhance antioxidant defenses, modulate inflammatory responses, and may even alleviate diseases.

Figure 1. Illustration of gut microbial biotransformation of dietary polyphenols to their metabolites.

A fun fact about PMMs: they can act like a natural “skincare” from within your body!

Here are some common PMMs you can intake from your foods and their potential skin-beneficial effects:

1. Urolithins: They are PMMs derived from ellagitannins and ellagic acid found in various fruits (e.g. pomegranate) and nuts. They have been studied for anti-cancer and neuroprotective effects. For instance, urolithin A (UA) is reported to be safe and can improve mitochondrial and cellular health in humans [1]. In addition, UA can exert anti-aging effects on human skin fibroblasts [2] and protect skin cells from UVA-induced cellular damage [3].
2. Equol: This compound is produced from the isoflavonoid daidzein found in soy and other legumes. It exerts estrogenic activity and has been studied for its potential benefits in alleviating menopausal symptoms and reducing bone loss. A microarray/protein-based study showed that equol and its isomers protect human skin cells by modulating the expression of aging and inflammatory genes [4].
3. Enterolactone and enterodiol: These are PMMs produced from the microbial fermentation of lignans, a group of unique phytochemicals found in flaxseeds, sesame seeds, maple syrup extract, and other plant sources. These metabolites have been linked to potential benefits in reducing the risk of hormone-related cancers [5].
4. Hydroxyphenylvalerolactones: These PMMs are formed from the breakdown of tea flavonoids (known as catechins) and are thought to contribute to the health benefits of tea. Human clinical studies showed that green tea catechin metabolites including hydroxyphenylvalerolactones can be detected in the skin tissue with skin protective effects against UV-induced inflammation [6].
5. Simple phenols: These compounds include tyrosol and hydroxytyrosol, which are PMMs of olive and jasmine phenolics, such as oleuropein. A reported study showed that hydroxytyrosol and its parent compound oleuropein are skin permeable and they can inhibit elastase and collagenase (enzymes that cause skin wrinkles) as well as protect skin cells in a synergistic manner [7].

PMMs hold significant promise for skin health. Partially, this is due to their promising biological effects such as antioxidant properties. PMMs can protect the skin from premature aging by neutralizing harmful free radicals. Additionally, their anti-inflammatory capabilities may soothe irritated skin, reducing redness and swelling associated with conditions like acne, eczema, and psoriasis. Some of these metabolites also exhibit antimicrobial properties that can prevent skin infections by inhibiting the growth of pathogens. Beyond these benefits, phenolic metabolites enhance the skin’s barrier function, improving its natural defenses and moisture retention. Incorporating phenolic-rich foods into one’s diet can support the production of these beneficial metabolites, potentially enhancing skin health from within. For example, a recent randomized double-blind placebo-controlled clinical study showed that a pomegranate supplement (i.e. Pomella^®) can promote skin health and beauty from within properties by improving biomarkers that are associated with visible wrinkles and moisture in a healthy population. Interestingly, polyphenols in pomegranate and their PMMs are thought to exert synergistic influence on both gut and skin microbiomes [8].

Although the potential of PMMs in skincare is promising, several challenges hinder their application and effectiveness. First, the variability in individual gut microbiota composition means that not everyone produces these beneficial metabolites at the same levels. Additionally, the complexity of accurately studying these metabolites in skin tissue remains challenging. These factors add layers to the barrier of developing PMMs-based topical skincare products. Research and development efforts are directed to effectively deliver these compounds to the skin and to ensure the stability and absorption of PMMs. Lastly, regulatory hurdles related to proving the health claims of such products can slow down their introduction to the market.

The future of utilizing PMMs in skincare is an exciting frontier with immense potential. Efforts are needed to advance our understanding of how these compounds interact with the skin’s microbiome and cellular structures, aiming to enhance their bioavailability and stability for effective topical applications. Collaborative research from all angles including microbiology, dermatology, and cosmetic science is crucial to developing new skincare formulations that harness these promising PMMs. Additionally, the industry is expected to innovate with sustainable and scientifically-backed products that leverage the health-promoting potential of PMMs.

References

1. Andreux, Pénélope A., et al. “The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.” Nature Metabolism 1.6 (2019): 595-603.
2. Liu, Chun-feng, et al. “Antiaging effects of urolithin A on replicative senescent human skin fibroblasts.” Rejuvenation Research 22.3 (2019): 191-200.
3. Liu, Wenjie, et al. “Urolithin A protects human dermal fibroblasts from UVA-induced photoaging through NRF2 activation and mitophagy.” Journal of Photochemistry and Photobiology B: Biology 232 (2022): 112462.
4. Lephart, Edwin D. “Protective effects of equol and their polyphenolic isomers against dermal aging: microarray/protein evidence with clinical implications and unique delivery into human skin.” Pharmaceutical Biology 51.11 (2013): 1393-1400.
5. Adlercreutz, Herman. “Lignans and human health.” Critical reviews in clinical laboratory sciences 44.5-6 (2007): 483-525.
6. Rhodes, Lesley E., et al. “Oral green tea catechin metabolites are incorporated into human skin and protect against UV radiation-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-hydroxyeicosatetraenoic acid.” British Journal of Nutrition 110.5 (2013): 891-900.
7. Li, Huifang, et al. “Dietary polyphenol oleuropein and its metabolite hydroxytyrosol are moderate skin permeable elastase and collagenase inhibitors with synergistic cellular antioxidant effects in human skin fibroblasts.” International Journal of Food Sciences and Nutrition 73.4 (2022): 460-470.
8. Chakkalakal, Mincy, et al. “Prospective randomized double-blind placebo-controlled study of oral pomegranate extract on skin wrinkles, biophysical features, and the gut-skin axis.” Journal of Clinical Medicine 11.22 (2022): 6724.

The acceleration of climate change driven events is creating an increasing pressure on the environment and living organisms that depend upon it with consequences that will be hard to fix or reverse in the future. Every living organism that is exposed to environmental changes is impacted. We need to understand the scenario to put in place effective actions to mitigate the changes that will affect the environment we know and the way we source natural ingredients for cosmetic use. The call for action is now.

Global Warming
We exist in a thin layer of the atmosphere, 7 miles above sea level. Life has been preserved for thousands of years with the right conditions of temperature and air, mostly nitrogen and oxygen, but also greenhouse gases such as methane, nitrous oxide and carbon dioxide that released in the atmosphere contributed to stabilize the right temperature for living organisms. However, since the industrial revolution in the late 1800s, increasing burning of coal, oil, and natural gas, has caused more carbon dioxide to be released in the atmosphere, eventually trapping the heat, with the consequence of increasing its temperature, a process referred as global warming. Extreme weather has also triggered melting of glaciers, ice caps and contributed to sea level rise. In the US, greenhouse gas emissions linked to global warming, have been associated with transportation, electricity production, industry, residential/commercial heating, and agriculture practices.1

Climate Change and its Effect on Plant Growth
A plant needs water, air, sunlight, optimal temperature, and the right soil to properly grow. Climate change is affecting all the above, except for sunlight.

With most of the water being saltwater from the ocean, only 3% is fresh (glaciers, groundwater, lakes, rivers, etc.). A warmer climate is causing an increased water evaporation, eventually trapped in the atmosphere. Cycles of rain are altered; dry areas are getting drier and wet areas wetter. Plants would find it difficult to adapt to these changes and in dry areas, farmers would need more and more ground water to sustain irrigation.

With carbon dioxide increasing in the atmosphere, plants are growing faster, but weeds also, with the difficulty to control them. Plant-feeding insects are proliferating due to the decrease in plant nutritional value and increase in sugar content when plants are grown under a higher carbon dioxide atmosphere. This decrease in nutritional value is a concern for the human diet but also for other uses (such as cosmetics and supplements and their ingredients quality). Plants contain less protein, zinc, iron, and vitamins, especially B vitamins.2,3

Temperature changes during nighttime or daytime alter the normal growth of the plant and its reproductive stage. With increased heat some plants grow faster, and farmers would need to manage irrigation, planting, harvesting, etc., but extreme heat would harm plants, especially during pollination, and the yield would decrease dramatically. Many plants like winter exposure and warmer winter will also reduce yield or select out many plant varieties. In general, because of increasing heat, the plant cultivation geographical map is shifting, moving northern.

Finally, climate change is also affecting the quality of the soil, so essential for life development. A healthy soil is a living system that sustains plants, animals, and humans.4 It contains billions of bacteria, fungi, nematodes, insects, spiders, and many other organisms interacting together and with the plant’s roots. Soil contains organic matter, often derived from living organisms but also from plant decay (humus). This organic matter is vital for life, it absorbs water optimally. The symbiosis between the soil and the plant’s root is very important, and it helps keep the plant healthy. The quality of the soil translates in the quality of the plant and its products, the massive cleaning of forest for land cultivation is depleting the soil and carbon is released in the atmosphere instead of being kept in the soil.

Some examples of Plants disruption
Many plants providing ingredients for our cosmetic products grow in coastal zones, such as 70% of coconuts trees. These zones are threatened by rising seas. Moreover, scientist studying coconuts plants have shown a negative impact on growth by rising temperatures.5 The cultivation and yield of Lavender, Jasmine, and Rose, in Grasse, France, have been seriously affected recently by more extreme weather, including droughts.6 These plants are essential to produce essential oils for the fragrance industry. Medicinal plants are more and more popular in our industry due to a wellness push. Many species of medicinal plants grow on mountains and many of them are difficult to cultivate. Warmer temperatures are threatening most species, pushing species to adapt and grow to higher altitudes to remain viable with species not able to adapt and possibly to disappear.7 Basic life is changing in the ocean, too. Phytoplankton and Algae are declining due to a warmer ocean and efficiency in photosynthesis is affected.8 With declining fishing and algae availability in the arctic sea due to climate change effect on temperature and on El Nino driving stream, global sourcing of omega-3 has been challenged with main production shifting to indoor algae cultivation and fermentation.9

Conclusions
Climate change is real and we, as an industry, need to work with our suppliers to sustain our ingredients sourcing. Development of climate change resistant species, vertical and cellular farming to balance the pressure on cultivation and wild picking, and finally optimization of plant usage by improved extraction and process methodology, are urgently needed to reduce the demand on classical supply chain and implement a more sustainable use of resources.

References
1. Sources of Greenhouse Gas Emissions. EPA, 2015
2. Samuel S et al. Increasing CO2 threatens human nutrition. Nature 510 (7503):139-42, 2014
3. Chunwu Zhu, et al. Carbon dioxide levels this century will alter the protein, micronutrients, and vitamin content of rice grains with potential health consequences for the poorest rice-dependent countries. Science Advances 4(5); 2, 2018
4. Soil Health. USDA, 2019
5. Sunoy J, et al. Impact of climate change on plantation crops: coconuts. In Impact of Climate Change on Plantation Crops, ed. KB Hebbar et al., 2017
6. Quito A. The top luxury company in the world is fighting to save the flowers that go into its perfume. Quartz, 2019
7. Das M, et al. Impact of climate change on medicinal and aromatic plants: review. Indian J Agric Sci 86: 1375-82, 2016
8. Roxy MK, et al. A reduction in marine primary productivity driven by rapid warming over the tropical Indian ocean. Geophysical Research Letters 43(2): 826, 2016
9. Cheung W, et al. Climate change exacerbates nutrient disparities from seafood. Nature Climate Change 13: 1242-49, 2023

About the Author

Giorgio Dell’Acqua is passionate about the environment and sustainability. He has given many lectures in the past on sustainable supply chain, natural ingredients and upcycling as well as publishing several articles for the industry on this topic (see below for references). Giorgio is currently Chief Science Officer at Nutrafol, a company specialized in natural based supplements and topicals for healthy hair and scalp. 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 20+ 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. He has helped bring 200+ successful active ingredients and finished products to market, has authored more than 90 publications in medicine and cosmetic science, and he holds 2 patents. Giorgio is also on the executive board of the US Society of Cosmetic Chemists (SCC) as its 2024 secretary, he is the chair for the NYSCC outreach committee and he is a member of the NYSCC Scientific Committee.

References (sustainability)

Han M, Dell’Acqua G. Exploring extremophiles: a novel and sustainable path for innovation in the cosmetic industry. Cosmetiscope 30(2): 1-7, 2024
Dell’Acqua G. Green isn’t enough. Social Progress is the next chapter for naturals. Cosmet. Toil. (Cover page article), 134(7): 28-40, 2019
Dell’Acqua G. Recycling natural by-products from food and agriculture waste into powerful active ingredients for cosmetic applications. H&PC Today 13(3): 16-19, 2018
Dell’Acqua G. Sustainable product development. CTSCC Nutmeg Newsletter 35(3): 7-11, 2018
Dell’Acqua G. Communities under the forest – Can we separate humans from trees? NYSCC Cosmetiscope, 24(2): 15-16, 2018
Dell’Acqua G. Garbage to glamour: recycling food by-products for skin care. Cosmet. Toil. (Cover page article), 132(2): 28-37, 2017
Dell’Acqua G. The challenges of sustainable development. NYSCC Cosmetiscope 23(2):1-6, 2017
Dell’Acqua G. Sustainable ingredients with scientific edge. Midwest SCC Scoop 47(6):7-11, 2015
Dell’Acqua G, Calloni G. Sustainable ingredients and innovation in cosmetics. Cosmet. Toil., 128(8): 528-536, 2013

Defining beauty is a complex and multifaceted task that can be accomplished both topically and from within. Beauty is one of those feel-good life deliverables that both gives and receives, making it a personalized priority for all of us.

Beauty is a matter of interpretation, appreciation, and commitment. It all starts with a strong dedication and willingness to pursue practices that feed overall wellness persistently. Beauty is intricately linked to health, with factors such as restful sleep, regular exercise, and a balanced diet playing pivotal roles in maintaining radiant skin, bright eyes, and lustrous hair and nails.

As time passes, aging becomes a concern for many people, prompting changes in the way we view our routines, diet, and abilities. The use of topical products is first line defense and a natural progression towards influencing the rate at which you age as it hits on many sensorial notes both on a neural level and through repetitive muscle entrainment, making it easy to create a positive habit toward maintaining your health. The downside is that topical products typically work on or underneath the superficial surface of skin and hair. The epidermis, and the hair cuticle, respectively, are designed by nature to keep things out in an environment that is constantly changing. All of this is a good thing. From a product development perspective, it becomes a never-ending effort to correct and maintain your skin and hair without adding to the everyday stress of imbalance that already exists.

One of the overlooked functions of skin is that it acts as an excretory organ, much of what goes on inside your body has a direct effect on how your skin functions and ultimately looks. Furthermore, being the largest organ, it is privileged with miles of vessels moving nutrients and metabolites of every category to all parts of our skin, hair, and nails. Because of this nutrient flow, many of these nutrients and by-products of their metabolism find their way to the surface of the skin acting in concert with the skin’s topical biochemistry and microbial ecology, influencing immune learning and defense. As all of this occurs, your gut health, mental health, sleep patterns and attitudes are being transmitted through your skin in both acute and long-term ways. Like growth rings on a tree, your skin, hair, and nails, reflect a moment in time and the conditions within that moment.  If beauty is what we seek, I suggest blending all the possibilities there are into the best possible moment in time.

Taking a new perspective on empowering beauty is leveraging the wonders of a comprehensive approach to both topical care and support from within.

Beauty-from-within supplements are becoming more popular amongst consumers. It is one of the fastest-growing categories in the nutraceuticals industry with an above average CAGR.

Internally supporting beauty is a strategy that can address skin and hair at almost every level, leading to lasting results and a more consistent routine resulting in less overall stress.  This integrated approach, focusing on creating a positive feedback loop of promoting overall health and wellness, can lead to healthier, more radiant skin, brighter eyes, and lustrous hair. This exponentially grows the possibilities of intervention in terms of product development and gives the consumer a sense of control over their aging process and creating enduring foundational results with significant benefits over a single armed beauty approach.

Under this approach, beauty is linked to overall wellness, lifestyle, diet, exercise, sleep, and stress management, which become additional targets to support through dietary supplementation and lifestyle changes.

I encourage you to visit the events page on the NYSCC website and register for the “Beauty from Within: Next Level Beauty Care & Wellness Strategies” event being held at the Pleasantdale Chateau in West Orange, NJ on March 26th. There is a great line up of speakers that will explore and inspire all the wonders of beauty from both sides. I look forward to seeing you there.

Author Bio:

Michael Anthonavage serves as the VP of Innovation at Vitaquest International, dedicated to expanding the supplement market footprint and ensuring their customers gain a competitive edge. With expertise in bringing new technologies to market, championing innovation and growth for all areas of health and nutrition as well as many aspects of skin and haircare product development.  Michael is a seasoned skin biologist, research scientist, educator, and a member of the scientific advisory board for the New York Society of Cosmetic Chemists for the past 5 years.

Here’s a hot flash you may not have heard before.  You’re not aging.  You’re rusting. As we get older, we start to face a complexion that looks duller, dingy, cloudier, less luminous. And more unevenly discolored.  The reason?  Iron is the most abundant transition metal in human body and the best-known driving force behind oxygen free radical formation through Fenton and Haber-Weiss reactions (Pierre and Fontecave 1999). Yes, the irony of iron is that iron is the element essential for building strong structures and machines but can also be the cause of their deterioration through rust. Oxidative damage a.k.a. – rusting is due to two distinct but surprisingly related functions: the build-up of iron in the skin as we get older coupled with a slowing of the skin’s natural exfoliation process. These result in iron staying in the skin for 56 days instead of 28 days as skin turnover time (Weintraub et al. 1965).

Here’s another conundrum.  In pre-menopause, excess iron in the body and skin is eliminated two ways: through monthly menstruation and through exfoliation. When menstruation ceases, iron levels can surge. Excess iron in the body is common with the onset of menopause.  In fact, iron can accumulate in the skin and is clinically shown to increase by as much as +42% pre through post menopause (Pelle et al. 2013). This excess iron is normally eliminated through menstruation as well as natural exfoliation.  The cessation of menstruation coupled with the deceleration of exfoliation limits the capacity to remove excess iron from the skin.

When body iron storage increases, skin too is exposed to higher levels of iron, which in turn can cause oxidative damage as the excess iron reacts with UVA. The result: skin aging and photoaging is accelerated. For example, ferritin is the iron storage protein for excess iron with a capacity of binding up to 4,500 atoms of iron per ferritin. It consists of heavy (H) and light (L) chain subunits. It was shown that ferritin can be immediately degraded by UVA doses of 100 and 250 kJ/m², releasing large amounts of iron for Fenton and Haber-Weiss reactions, producing oxygen free radicals (Pourzand et al. 1999). In a cell culture model mimicking menopausal conditions, increased iron and UVA were found to significantly increase an enzyme called collagenase-1 (Jian et al. 2011). Increased activity of collagenase-1 increases collagen degradation, causing wrinkles initially and skin thinning when we get older.

Like rust on metal, higher levels of iron when exposed to UV radiation, blue light, air pollutants and irritants from other sources results in increased oxidative damage in skin.  If you’ve ever seen a rusty bicycle, you know the corrosive damage the environment has on metal.  Oxidative stress begets skin-aging yellowing, dullness, dark spots and discolorations as well as wrinkles, loss of elasticity and other signs of aging.

Until now, antioxidants have been the only defense to attempt to neutralize oxidants after they are formed. Chelation can be used to sequester “free” iron, but it cannot compete to take away from iron in ferritin. The antioxidant and chelation approaches are retroactive and often too late (Table 1). They can only battle the symptoms, but they do not treat the underlying cause.

Table 1. Mode of actions of antioxidants, chelation, and de-ironizing inducer (DII) *

*: The skin is subject to a constant onslaught of free radicals catalyzed by iron-mediated Fenton and Haber-Weiss reactions.

A novel class of actives termed De-ironizing Inducers Technology (DII®) can do what no free-radical neutralizing antioxidant or chelation can do. It reduces iron in ferritin before it is converted to skin-damaging free radicals.  The patented DII® features 3-o-ethyl-ascorbic acid and pearl powder in the right ratios to effectively reduce iron in skin (US Patent 10792240). Research shows that when either alone or when too much of one exists without the other, iron reduction cannot be accomplished.  Ascorbic acid, also known as vitamin C helps release iron deposits from ferritin. Pearl Powder, a soft form of calcium carbonate, absorbs the released iron ions by exchanging them with calcium ions and, thus, removes skin-rusting iron deposits (Figure 1). These two previously incompatible ingredients work in unison to help prevent oxidative stress from forming in the first place, rather than attempting to neutralize free radicals after they appear as most antioxidants do. Without the need to fight free radicals, skin-rejuvenating Hyaluronic Acid plus Tetrapeptide-11 repair previous damage done and the goes one step further to help rebuild collagen, clarity, elasticity and tone / skin’s health and appearance.

Your skin glows with good health. And rust is history!

It is important to note that, while this discovery is made using menopausal model, the DII® is applicable to all ages. Estrogen peaks at age 25 and iron starts to increase from the same age. While estrogen sharply decreases during the menopausal transition period, iron dramatically increases during the same period. DII® may be more age defying in young women but more disrupting with higher success rate in older women. Man starts to accumulate iron from the 20s to the 30s and skin pigmentation is higher in man than in woman (Rahrovan et al. 2018). As a result, DII® is also applicable to man.

References:

Jian J, Pelle E, Yang Q, Pernodet N, Maes D, Huang X. (2011). Iron sensitizes keratinocytes and fibroblasts to uva-mediated matrix metalloproteinase-1 through tnf-alpha and erk activation. Exp Dermatol 20:249-254. https://www.ncbi.nlm.nih.gov/pubmed/20701626

Pelle E, Jian J, Zhang Q, Muizzuddin N, Yang Q, Dai J, et al. (2013). Menopause increases the iron storage protein ferritin in skin. J Cosmet Sci 64:175-179. https://www.ncbi.nlm.nih.gov/pubmed/23752032

Pierre JL, Fontecave M. (1999). Iron and activated oxygen species in biology: The basic chemistry. Biometals 12:195-199. https://www.ncbi.nlm.nih.gov/pubmed/10581682

Pourzand C, Watkin RD, Brown JE, Tyrrell RM. (1999). Ultraviolet a radiation induces immediate release of iron in human primary skin fibroblasts: The role of ferritin. Proc Natl Acad Sci U S A 96:6751-6756. https://www.ncbi.nlm.nih.gov/pubmed/10359784

Rahrovan S, Fanian F, Mehryan P, Humbert P, Firooz A. (2018). Male versus female skin: What dermatologists and cosmeticians should know. Int J Womens Dermatol 4:122-130. https://www.ncbi.nlm.nih.gov/pubmed/30175213

About the Author

Biography: Xi Huang has investigated iron’s role in diseases for more than three decades and is credited in more than 90 peer-reviewed publications, many of which demonstrate that excess iron is an important risk factor in women’s health. Dr. Huang was a faculty member at New York UniversitySchool of Medicine and his research laboratory has shown that iron accumulation due to the cessation of menstruation in postmenopausal women contributes to osteoporosis and skin aging. Dr. Huang is the founder and president of FE:I Beauty Tech, the parent company of i-On Skincare (www.ionskincare.com). Dr. Huang received his Ph.D. and M.S. in Toxicology and Applied Pharmacology from the Université Denis Diderot – Paris VII and received his undergraduate degree from China Agricultural University.

Coloring agents are essential components of certain cosmetic products, especially color cosmetic formulations. Most cosmetic colorants are synthetic and are regulated globally.  In the US, they are regulated by FDA with monographs for each and all located in Title 21 of the Code of Federal regulations, Parts 73 and 74. In the EU, allowed cosmetic colorants are listed in Annex IV, Regulation 1223/2009/EC on Cosmetic Products, as corrected by Corrigendum to Commission Regulation (EU) 2021/850, 17 June 2021. Many colorants on that list are also used in food and have corresponding E (Europe) numbers such as E-171 for TiO₂ and E-172 for iron oxides. In such cases, the specifications for food colorants are used for cosmetic application.  Therefore, it is common to see a note in technical datasheet for a cosmetic colorant stating it complies with the 21CFR and E number (like E-172 for iron oxides) specifications.

Although many of us formulate with colorants frequently, we seem to need help on gaining complete clarity on certain aspects of them. In this blog, we will go over some fundamentals and a few common confusions about certain pigments.  Let’s first start with some terms that we often hear.

Dye:  It is a material that imparts a color and is soluble in the vehicle or substrate in which it is dispersed.

Pigment:  It is a material that is insoluble in the vehicle or substrate in which it is dispersed. True pigments are colorants completely insoluble based on their chemical structure and constituent groups. They typically do not contain the normal substitution groups that promote water solubility, such as sulfonates (-SO₃), carboxylic acid (-COOH) or hydroxyl groups (-OH). Hence, there is no bleeding in hydrous systems. There are only two examples of true pigments used in cosmetics:  D&C Red No. 30 and D&C Red No. 36.

For leave-on cosmetic applications, pigments instead of dyes are often used because dyes are hard to remove after use, thus, stain the skin. Dyes are more commonly used in rinse-off products such as shampoo and mouth rinse. Now let’s go a little further:

Toner:  It is a pigment that is produced by precipitating a water-soluble dye as a metal salt. Typical metals used for this precipitation are sodium, calcium, barium and strontium. e.g., D&C Red 7 Ca Salt. (be aware that it is not a lake)

Lake:  It is a pigment produced by absorbing a water-soluble dye or a primary toner onto an insoluble substrate. All the lakes are pigments.

F, D and C codes in the names of a colorant stands for its approved use in Food, Drug and Cosmetics. A colorant must meet its purities requirements to ensure its safety. FDA separates color additives into two categories:

1. Colorant subject to certification: they are derived primarily from petroleum and are known as coal-tar Most synthetic, organic colorants fall in this category. They must be batch certified by the FDA. They are further divided into two categories:
2. Certifiable Primary Colors: They are pure color which contain no extenders or diluents. They have color names and numbers assigned such as FD&C Yellow 5, D&C Red 6 and Ext. D&C Violet 2.
3. Certifiable Color Lakes: Lakes follow the same restrictions as the primary colors with the additional rule that they must have the name of the precipitating metal and the word “lake”. An example would be FD&C Yellow 5 Al Lake.
4. Colorant exempt from certification: These are natural organic colorants and synthetic inorganics obtained largely from mineral, plant, or animal sources. Although batch certification is not required, purity must be tested by the manufacturer to meet FDA specifications. Examples are Titanium dioxide and Iron oxides.

Now that we have gone over the general terms and regulatory aspects of colorants, let’s look at common ambiguities about a few specific pigments:

1. Rutile and anatase

First, they both are TiO₂, but refer to two crystalline structures. It is like using Coke or Pepsi to represent carbonated soft drinks. Anatase is slightly softer and less abrasive than rutile. This makes little difference to the skin feel but can make a big difference in TiO₂ production process.  Rutile is so abrasive that it can wear out the equipment that processes hundred to thousands of tons per campaign. Consequently, rutile is often surface treated with alumina to extend the useful life of the equipment in addition to provide other benefits.

Rutile has a slightly higher refractive index than anatase, and thus, it can scatter light more effectively. So, does it mean that Rutile is more opaque? Not quite. Opacity is the result of scattering which depends as much on the size and size distribution of the pigment particles as on its refractive index. In reality, it is rare to find a rutile and an anatase that have the same particle size, let alone size distribution. Therefore, being rutile or anatase does not necessarily indicate a higher or lower opacity.

Commercial anatase is usually made to have a small primary particle size, in a range of about 140 – 170 nm. That of rutile is often bigger, roughly 170 – 250 nm.  Due to its smaller size, anatase scatters blue light slightly more, and thus, imparts a blueish undertone.  This is the reason that anatase is often said to be bluer than rutile.

Lastly, the production processes, chloride and sulphate, are often brought into discussion about TiO₂.  In Chloride process, TiCl₄ is vaporized and burnt into rutile.  In sulphate process, Ti(SO₄)₂ is neutralized with base to generate anatase. If aluminum salt is used as the inducer, rutile TiO₂ can also be made via the sulphate process. TiO₂ made from a Chloride process often has a lower level of contaminants, which translates into high purity and clean color. This had been indeed the case in the past, but not so much anymore since the sulphate process technology has been greatly improved over the years.

1. Carbon black

 Carbon black can be made via several processes. In the US, carbon black as a cosmetic color additive is called D&C Black No. 2, a high-purity carbon black prepared by the oil furnace process.¹ It is manufactured by the combustion of aromatic petroleum oil feedstock and consists essentially of pure carbon, formed as aggregated fine particles with a surface area range of 200 to 260 m²/g.

JSCI monograph requires Carbon black to be obtained by incomplete combustion of natural gas or liquid hydrocarbon. Such carbon black is often called channel black and is not approved by the FDA.  This, unfortunately, adds unnecessary complexity to formulating for the global market.

2. Chromium oxide and Chromium hydroxide green

Hexavalent Chromium (Cr⁶⁺) is known to be carcinogenic, thus, it should not be present or at a very low level in cosmetics products. However, its presence is unavoidable due to the chemistry and manufacturing process. For both pigments, the FDA set a limit of 2% NaOH extract, not more than 0.1% as Cr₂O₃ (based on sample weight). ² This limit is equivalent to 684 or 513 ppm maximum Hexavalent Chromium, respectively. The actual level of Cr⁶⁺ in a commercial grade needs to be tested for calculating the final level in a finished formulation.

3. Mica and Pearlescent pigments

A common restriction people often talk about is the size limit of 150 mm. Mica is an approved colorant for drug use, and the FDA has imposed a size limit on it.  Mica can also be used as a colorant for cosmetic applications for which the FDA does not list any size limit in the monograph. Moreover, mica can be used in cosmetics as filler, a category that the FDA does not regulate with specific requirements.

Efforts have been made to list Mica-based pearlescent pigments as approved colorants for cosmetic purposes, but this has not happened yet. as of now, such pigments have been approved as colorants only for drug use, and the corresponding specifications require that the mica meets the colorant specifications for drug use.  This is likely the reason that we hear the 150-mm size limit in our industry.  As mentioned above, mica-based pigments are not approved colorants for cosmetic use. Consequently, the composition has to be expressed as a mixture of individual components such as, for instance, mica and titanium dioxide. Each of these ingredients needs to meet the corresponding FDA specification if applicable.  The size limit on mica for drug use may not be observed.

4. Zinc oxide

Zinc oxide is a long approved cosmetic colorant, though its use as opacificer in cosmetics is limited. That main reason is that its opacity is much lower than TiO₂ due to its lower refractive index (2 vs. 2.7).  Roughly 3 times more ZnO is needed to achieve the same degree of opacity of TiO₂. Moreover, ZnO is slightly soluble in water, resulting in the pH of formulations containing ZnO to be above 7.5.

As of August 7, 2022, the use of TiO₂ as food colorant has been banned in the EU, directly affecting its use in lip and oral products. Respirable TiO₂ is considered carcinogenic, according to Proposition 65 of the state of California, affecting the use of TiO₂ in some powder and spray formulations. TiO₂ is difficult to replace because of its unique performance and inertness. In light of the regulatory restriction, ZnO with the right size and high opacity has gained attention recently, especially for anhydrous formulations.

5. Red 6 lake and red 7 lake in Japan

Most FDA approved colorants can be used in Japan. Red 6 lake, widely used in lip products, is a notable exception. The reason is that Red 6 lake is Red 6 Barium salt laked on barium sulfate, but Red 6 Barium salt is not an approved colorant in Japan. On the other hand, Red 7 lake is Red 6 Calcium salt laked on barium sulfate but Red 6 Calcium salt is approved in Japan.  In the case that the shade cannot be achieved without Red 6, Red 6 sodium salt can be used. However, it must be noted that red 6 sodium salt is water soluble, which is opposite to Red 6 lake.

Currently, the FDA has approved 64 color additives for cosmetic use, each of which has its merits and drawbacks due to their unique chemistry and production process.³ The knowledge is important not only for formulating the right color shade, but also for troubleshooting instability and especially, regulatory compliance. The author hopes that this blog will contribute to your learning of cosmetic colorants.

References:

1. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-74/subpart-C/section-74.2052
2. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-C/section-73.2327
3. https://www.fda.gov/industry/color-additive-inventories/summary-color-additives-use-united-states-foods-drugs-cosmetics-and-medical-devices#table3A