What's in Your Sunscreen, Part 2: Major Sunscreen Ingredients, FDA Approved or Toxic Substances?

Sunscreen has long been a cornerstone of public health recommendations for preventing sunburn, premature skin aging, and skin cancer. In the United States, sunscreen ingredients are regulated by the Food and Drug Administration (FDA) as over-the-counter (OTC) drug products. For decades, several active ingredients in sunscreens—particularly organic ("chemical") UV filters—have been marketed under the assumption that they are “generally recognized as safe and effective” (GRASE). However, two studies published in the Journal of the American Medical Association (JAMA) prompted a significant shift in how these ingredients are assessed.

JAMA Clinical Trials Show Higher than Expected Systemic Absorption

In 2019 (1) and 2020 (2), two randomized clinical trials conducted by FDA scientists and published in JAMA raised important questions about systemic exposure to sunscreen active ingredients. These studies found that when sunscreen products were applied under conditions that reflect typical use (and in some cases, maximal use), several active ingredients (ALL of the most common organic filter) —such as oxybenzone, avobenzone, octocrylene, homoslate, octisalate, and octinoxate—were absorbed through the skin and detected in the bloodstream at levels exceeding 0.5 ng/mL. This threshold is significant because it is the FDA’s benchmark for requiring additional safety data, such as toxicology and carcinogenicity studies.

In response, the FDA issued a proposed administrative order in 2021 that reclassified all of said commonly used chemical UV filters as “not GRASE due to insufficient data.” Only two active ingredients, zinc oxide and titanium dioxide, were affirmed as GRASE based on existing safety data.

GRASE Classification: 1999 Final Order vs 2021 Proposed Order

Items in bold are those discussed in the prior post, "Whats in Your Sunscreen? Part 1: The Most Common UV Filters

Category	Final Order (1999)	Proposed Order (2021)
GRASE (Generally Recognized As Safe and Effective)	Aminobenzoic acid (PABA), Avobenzone, Cinoxate, Dioxybenzone, Ensulizole, Homosalate, Meradimate, Octinoxate, Octisalate, Octocrylene, Oxybenzone, Padimate O, Sulisobenzone, Titanium dioxide, Trolamine salicylate, Zinc oxide	Titanium dioxide, Zinc oxide
Not GRASE (Due to Safety Concerns)	(None – all were considered GRASE)	Aminobenzoic acid (PABA), Trolamine salicylate
Not GRASE (Due to Insufficient Data)	(None – all were considered GRASE)	Avobenzone, Cinoxate, Dioxybenzone, Ensulizole, Homosalate, Meradimate, Octinoxate, Octisalate, Octocrylene, Oxybenzone, Padimate O, Sulisobenzone

FDA "GRASE" Period

The detection of these ingredients in plasma does not directly confirm nor is meant to imply harm. The clinical significance of this absorption remains unknown: these trials did not study the effect of this systemic absorption, only that it is higher than expected. However, the FDA concluded that more rigorous data are necessary to fully evaluate the long-term safety of these ingredients. The agency clarified that this reclassification was not a ban, but rather a call for manufacturers to generate and submit more safety data to support continued OTC marketing without an approved new drug application. However, it has been nearly 5 years and there has not been any new clarification or update from the FDA.

This reclassification is especially relevant in the context of a broader trend in public health recommendations: as encouragement towards more frequent sunscreen use becomes stronger—particularly daily application and application from early childhood onward—the safety evaluation of its ingredients is increasingly impactful. The FDA’s cautious approach is designed not to alarm consumers, but it's hard to resist making a conclusion that if these are NOT generally recognized as safe and effective, then we should regard them as potentially harmful.

What Do I Do With This Information?

The FDA and dermatologists continue to underscore the protective benefits of sunscreen. The risks associated with UV radiation—sunburn, skin cancer, and photoaging—are well-established and can be reduced through appropriate sun protection strategies.

As a dermatologist, I’ve chosen to limit my family's use of organic (chemical) sunscreens due to lingering questions about their systemic effects. More importantly, there are plenty of effective alternatives for sun protection: mineral-based sunscreens containing zinc oxide or titanium dioxide, seeking shade, wearing sun-protective clothing, and avoiding outdoor activities during peak UV hours.

That said, if the choice is between prolonged unprotected sun exposure or using a chemical sunscreen, I will choose the latter. We know that excessive sun exposure causes harm, while the potential risks of chemical sunscreens remain uncertain. In that situation, I opt for the more probable benefit.

Dr. Ryan M. Trowbridge, MD, MS, MA

Harvard-Trained, Board-Certified Dermatologist and DermMythBuster

P.S. Have you come across any new or conflicting research on this topic? Please share—I’d love to explore it further with you!

For medical consultations with me, visit Bridge-Derm.com.

References

1. Matta MK, Zusterzeel R, Pilli NR, et al. Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial. JAMA. 2019;321(21):2082-2091. doi:10.1001/jama.2019.5586

2. Matta MK, Florian J, Zusterzeel R, et al. Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial [published correction appears in JAMA. 2020 Mar 17;323(11):1098. doi: 10.1001/jama.2020.1950.]. JAMA. 2020;323(3):256-267. doi:10.1001/jama.2019.20747

3. U.S. Food and Drug Administration. Final Administrative Order OTC000006: Over-the-Counter Monograph M020: Sunscreen Drug Products for Over-the-Counter Human Use. Published September 24, 2021. Accessed March 29, 2025. https://www.accessdata.fda.gov/scripts/cder/omuf/index.cfm

4. U.S. Food and Drug Administration. Proposed Order OTC000008: Amending Over-the-Counter Monograph M020: Sunscreen Drug Products for OTC Human Use. Published September 24, 2021. Accessed March 29, 2025. https://www.accessdata.fda.gov/scripts/cder/omuf/index.cfm