Due to the complexity of the skin, it has been difficult for scientists to answer questions related to dermal absorption. There is no debate about whether or not topical substances can be absorbed into the bloodstream. This is a known fact, as topical treatments are used as a vehicle to transport drugs and other substances into the body's systemic circulation.¹ The concern is if skin care and cosmetics are able to be absorbed into the bloodstream, and if so, to what degree and to what effect?

To answer this question, a deep look into the cosmetics industry is necessary. While many factors determine whether or not a chemical or substance will pass through the several layers and enzymes that exist before reaching the bloodstream, one thing is certain. Historically, the cosmetics industry uses chemicals that have the ability to do so. Moreover, the greater concern is that unsuspecting ingredients have a tendency to be contaminated with toxic chemicals as a byproduct of the manufacturing process, and many of these contaminants are able to be absorbed into the bloodstream. Some popular contaminants include, but are not limited to, 1,4-dioxane, nitrosamines, ethylene oxide, and formaldehyde. Despite research affirming the highly toxic effects of these chemicals, they are still pervasive in the cosmetics industry due to a lack of federal regulations. This has left the practitioner and consumer in charge of determining what is safe to apply and what is best to avoid. A major first step in the right direction is to evaluate the potential threats and gain an overall understanding of the mechanisms involved in the study of dermal absorption, also known as penetration.

Because of the several, and often unrelated, variables that govern absorption into the bloodstream, the rate and quantity are not constants that can be quantified for the general population. There are both internal and external factors that affect dermal absorption; however, research tends to combine these into one list of variables. When broken down, it clarifies the complexity of how substances are able to penetrate the upper layers of the skin and, ultimately, reach systemic circulation and the lymphatic system. Dermal penetration of a substance depends on a number of elements, including: the physicochemical properties of a chemical, such as molecular weight, charge, and concentration; the area and duration of exposure; the formulation or vehicle of the substance; and the potential interactions among other present substances. Then there are physiological and biological factors affecting penetration. The condition and integrity of the stratum corneum, for example, highly determines the rate of dermal absorption. Aside from this, the site of the body, the thickness of the epidermis, temperature, and local blood flow also plays a role.²

To complicate matters is the very complex field of skin permeation studies. Only recently have researchers realized that past and present procedures for measuring skin absorption may be deemed invalid due to the complexity of replicating human skin under its living, unique biological conditions. Most dermal absorption studies are based on animal data, which researchers now understand that the metabolic environment of human skin is vastly different from one person to another, let alone a different species.³ Most accurately stated by Dr. Thomas Hudson when discussing research studies, he affirmed, “Research is an approximation of reality – it isn’t reality itself. Reality has too many variables. No research study can control them all.” Yet, this is the only quantifiable data available to reach conclusions about the mechanisms and effects of concerning topics such as dermal absorption.

Stepping back from the seemingly complex web of compounding factors, perhaps a better approach to understanding the likelihood of potentially harmful substances entering the bloodstream is to understand the concepts of biotransformation and bioaccumulation. Although, at first, it may seem that these are two additional factors determining the fate of chemicals in the body, when viewed from a holistic perspective, a clearer picture of potential vulnerability comes into focus. Seen from a bigger picture, biotransformation is the process by which a chemical alters through a series of reactions in the body. Bioaccumulation refers to the buildup of toxins in the body because they are accumulated at a rate faster than they are metabolized.⁴ Arguably, biotransformation and bioaccumulation are, more often than not, the hidden factors that determine dermal absorption. There is still much to be learned regarding the various interactions that occur between compounds, especially in the presence or absence of others. Biotransformation is probably the least predictable factor in dermal absorption due to the vast array of variables present among different individuals and their respective environments. When coupled with the risk of bioaccumulation, relying solely on research studies become unadvisable, and here is why. In a healthy ecosystem and environment, bioaccumulation should not be a concern for many chemicals present in the cosmetics industry; however, due to the increasing exposure of these chemicals from other modern industries – such as agricultural, pharmaceutical, and textiles – a person’s toxic load becomes heavier over the course of time. Phthalates are an excellent example of this.

Phthalates have traditionally not been considered bioaccumulative; however, recent research indicates that long-term exposure is rejecting that notion. As increased levels of phthalates are now widespread throughout many industries – including packaging, children’s toys, and previously mentioned agriculture, pharmaceuticals, and textiles, to name a few – humans are constantly exposed to it. Among these industries, personal care (which includes cosmetics), ranks high at the top. Disturbingly, infants, children, and teenagers are the most susceptible to phthalate toxicity due to their developing skin.⁵ There is sufficient evidence that phthalates cause endocrine disruption, as well as developmental and reproductive toxicity. Phthalates are frequently used in scented products, however they are rarely found on labels because they are included in the ubiquitous term “fragrance.”⁶ The chemical composition of the ingredient, fragrance, is not required to be disclosed on labels and can be considered a “proprietary blend” by companies wishing to not reveal their chosen chemicals.

With that said, exploration of other common ingredients used in cosmetics that pose a serious concern is needed. This is especially relevant where the effects of biotransformation and bioaccumulation are concerned. The National Toxicology Program, an interagency program under the U.S. Department of Human Health and Services, released a report in 2012 on the effects of two forms of vitamin A, retinoic acid and retinyl palmitate, in the presence of sunlight. The study suggested that when exposed to sunlight, vitamin A may increase the development of skin tumors and legions.⁶ The trouble with this is that vitamin A is found in approximately 15 percent of sunscreens and moisturizers with SPF.⁷ This may seem like a low figure until the following statement is considered. It may take no more than nine minutes of daily sun exposure over the course of a year while using topical products containing vitamin A to accelerate the development of skin tumors.⁸ This is, of course, based off animal data, but the point is to illustrate the fact that only recently have researchers begun to understand that external factors, such as the sun, may change how a substance transforms biologically. The key to take away is that many studies are still being conducted to fully understand how biotransformation occurs between molecules and enzymes.

Propylene glycol, another frequently used ingredient in skin care formulations, is used to enhance ingredient absorption. This may be good news when the goal is antioxidant permeation into the skin, as it is known to dissolve lipophilic molecules; however, it does not discriminate, so when used with potentially toxic chemicals, the likelihood of dermal absorption increases. As an example, retinol (a major form of vitamin A) is a lipophilic molecule and should not permeate the stratum corneum; however, researchers hypothesize that through a series of steps, the aliphatic chain of retinol has the ability to insert itself within the aliphatic chains of the stratum corneum and allow for faster transport. Studies show that retinol does indeed penetrate the dermis, interfering with cellular signaling, and potentially causing mutations at very low doses.⁹ When used in a skin care formulation that also contains propylene glycol, there is a basis for major concern. This leads the conversation to an equally menacing ingredient, hydroquinone.

Hydroquinone is a popular skin lightener used by many professional skin care companies. It not only penetrates the skin, it is a heavy-weight when it comes to the hazards it poses to human health. Hydroquinone is both a toxic ingredient and a contaminant found in other ingredients. Studies have confirmed that it causes organ system toxicity in humans and also causes destruction of red blood cells. What is more is that it is known to cause toxic effects at low doses.¹⁰ There are other more dire concerns regarding this chemical; however, since they are based on other animal studies, it is best to accept its potential hazard considering that numerous studies are still being conducted to determine its effects on humans, other species, and the environment.

The European Union’s Scientific Committee on Consumer Safety recently illustrated from several clinical investigations that phenoxyethanol, another common ingredient used in cosmetics, can penetrate the bloodstream, and in some cases, dermal exposure results in higher retained concentrations in the bloodstream than when ingested.¹¹ Similar to phenoxyethanol, hydrocarbon contaminates in mineral oil were once thought to not be resorbed by the body, but then studies began to point to higher concentrations being accumulated over time. According to a study conducted in 2011 with 142 female participants, results indicated that older women had greater concentrations of mineral oil saturated hydrocarbons (MOSH) in their fat tissue and suggested that cosmetics may be a source of relevant contamination.¹² More recent studies conducted in 2017 strongly affirm that there is a need to develop better cosmetic market monitoring and detection techniques to make sure contaminants are not present in consumer products. They also suggested that due to the potential health hazards that these contaminants pose, further toxicity and epidemiological studies need to be conducted regarding bioaccumulation.^{13, 14}

Polyacrylamide, a common stabilizer and binder in lotion formulas, is well-known to contain acrylamide, as this is its synthetic polymer. Acrylamide is not only bioaccumulative, but it is considered a human carcinogen by several global, scientific, and government agencies. Following dermal exposure, it can cause systemic effects, including reproductive and neuro-toxicity.¹⁵ The scientific data regarding polyacrylamide is well established compared to other ingredients; however, since cosmetics are not subject to premarket approval in the United States, cosmetic companies are predominantly responsible for the safety of their products. The obvious issue with that is that unless companies make a concerted effort to understand the toxicological effects of their chosen ingredients and deeply research their physiochemical properties in relation to how they might interact with other ingredients and the environment, then little can be done to regulate the industry. It is then up to the consumer to ensure the safety of the products they purchase.

There are several more potentially hazardous chemicals being used by the cosmetics industry, and disturbingly, companies are more focused on the short-term, external benefits of their formulations rather than on both the short-term and long-term health effects of their use. Therefore, as a professional and a consumer, the ideal approach is to use the precautionary principle when it comes to choosing skin care and cosmetic products. Become familiar with the most common hazardous chemicals that are used in the cosmetics industry and vet skin care brands prior to using them on clients. This is especially important for teenagers, as it is not only a wise choice, but a responsible one. Clients are generally less aware than professionals regarding industry safety and standards and, therefore, turn to professionals to guide them in making important decisions regarding their health. The best approach is to become knowledgeable in the ever-evolving landscape of cosmetic formulations so that well-researched products and protocols are positioned to provide healthy choices during and after treatment.

References

1. Heylings, J.R. (2015). Toxicity Endpoints & Tests: Dermal Penetration | AltTox.org. [online] http://alttox.org/mapp/toxicity-endpoints-tests/dermal-penetration/ [Accessed 9 Aug. 2017].

2. Kielhorn, J. et al. (2006). Environmental Health Criteria 235: Dermal Absorption. World Health Organization.

3. Jepps, O. G., Dancik, Y., Anissimov, Y. G., & Roberts, M. S. (2013). Modeling the human skin barrier—Towards a better understanding of dermal absorption. Advanced drug delivery reviews, 65(2), 152-168.

4. Elahian, F., Reiisi, S., Shahidi, A., & Mirzaei, S. A. (2017). High-throughput bioaccumulation, biotransformation, and production of silver and selenium nanoparticles using genetically engineered Pichia pastoris. Nanomedicine: Nanotechnology, Biology and Medicine, 13(3), 853-861.

5. Pan, T. et al. (2014). Dermal toxicity elicited by phthalates: Evaluation of skin absorption, immunohistology, and functional proteomics. Food and Chemical Toxicology, 65, 105–114.

6. Campaign for Safe Cosmetics. (2017). Phthalates. | Safecosmetics.org. [online] http://www.safecosmetics.org/get-the-facts/chemicals-of-concern/phthalates/ [Accessed 10 Aug. 2017]

7. National Institutes of Health (2012). Photococarcinogenisis Study of Retinoic Acid and Retinyl Palmitate. [online] https://ntp.niehs.nih.gov/ntp/htdocs/lt_rpts/tr568_508.pdf

8. Environmental Working Group. (2017). The Problem with Vitamin A | ewg.org. [online] http://www.ewg.org/sunscreen/report/the-problem-with-vitamin-a/#.WZMqPHd95E6 [Accessed 9 Aug. 2017].

9. Abla, M. and Banga, A.K. (2012). Quantification of skin penetration of antioxidants of varying lipophilicity. International Journal of Cosmetic Science, 35, 19–26.

10. Environmental Working Group. (2017). Hydroquinone | Skin Deep Cosmetics Database. [online] https://www.ewg.org/skindeep/ingredient/703041/HYDROQUINONE/#.WZOoz1

GGPIU [Accessed 10 Aug. 2017].

11. European Union. (2016) Final version of the opinion on Phenoxyethanol. Scientific Committee on Consumer Safety (SCCS) [European Commission Report]. https://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_195.pdf [Accessed 10 Aug. 2017].

12. Concin, N. et al. (2011). Evidence for cosmetics as a source of mineral oil contamination in women. Journal of Women’s Health, Nov; 20(11):1713-1719

13. Barp, L., Biedermann, M., Grob, K., Blas-Y-Estrada, F., Nygaard, U. C., Alexander, J., & Cravedi, J. P. (2017). Accumulation of mineral oil saturated hydrocarbons (MOSH) in female Fischer 344 rats: comparison with human data and consequences for risk assessment. Science of The Total Environment, 575, 1263-1278.

14. Lachenmeier, D. W. et al. (2017). Evaluation of mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH) in pure mineral hydrocarbon-based cosmetics and cosmetic raw materials using 1H NMR spectroscopy. F1000Research, 6, 682. http://doi.org/10.12688/f1000research.11534.1

15. Centers for Disease Control and Prevention. (2011). NIOSH Skin Notation Profiles Acrylamide. [online] https://www.cdc.gov/niosh/docs/2011-139/pdfs/2011-139.pdf

Melissa Montalvo is a biomedical engineer, lean consultant, and co-founder of Pink Horizons Botanical Skin Care, a Green America certified company that formulates toxin-free, high-performance products for health practitioners and the end-consumer. She and her team work closely with socially responsible organizations such as the Environmental Working Group and Breast Cancer Action to educate the community on holistic living and sustainable business practices. pinkhorizons.com