Why Only 2 Sunscreen Filters Have FDA GRASE Status

The 2019 JAMA Study That Changed Everything

In May 2019, the FDA published a landmark study in JAMA. Researchers applied sunscreen to participants under "maximal use conditions" (covering 75% of body surface, 4 times daily for 4 days) and measured plasma concentrations.

The results:

Systemic Absorption (Matta et al., 2019)

UV Filter	Max Plasma Concentration	FDA Threshold
Avobenzone	1.8-4.3 ng/mL	0.5 ng/mL
Oxybenzone (BP-3)	169.3-209.6 ng/mL
Octocrylene	2.9-7.8 ng/mL
Ecamsule	1.5 ng/mL

All four exceeded the 0.5 ng/mL threshold that triggers requirements for nonclinical toxicology studies.

Oxybenzone reached 209.6 ng/mL - over 400 times the FDA threshold. This doesn't mean it's dangerous, but it does mean the FDA requires additional safety data before confirming GRASE (Generally Recognized As Safe and Effective) status.

GRASE Categories Explained

GRASE

Zinc Oxide, Titanium Dioxide

Safe and effective. Minimal systemic absorption.

Non-GRASE

PABA, Trolamine Salicylate

Not safe or effective. Banned from OTC sunscreens.

Category III

12 chemical filters including oxybenzone, avobenzone, octinoxate, homosalate, octocrylene

Insufficient data. More studies needed before GRASE determination.

The Physical vs. Chemical Divide

Why did zinc oxide and titanium dioxide get GRASE status while chemical filters didn't? The answer is penetration:

According to Smijs and Pavel (2011), the most cited study on this topic:

TiO₂ and ZnO nanoparticles accumulate in stratum corneum furrows and follicle openings
No significant penetration past the stratum corneum on intact skin
ZnO occasionally detected in viable epidermis during long-term exposure - but not systemically
Surface coatings (silica, alumina) reduce any ROS generation concerns

In contrast, chemical filters are designed to absorb UV by penetrating into the skin - which means they also absorb into the bloodstream.

Oxybenzone: The Most Controversial Filter

Oxybenzone (benzophenone-3) gets the most scrutiny for several reasons:

Highest systemic absorption: 209.6 ng/mL max plasma concentration
Endocrine disruption concerns: A 2025 review found associations with reduced testosterone in adolescent males, altered thyroid hormones in pregnant women
Environmental impact: Banned in Hawaii and Key West for coral reef toxicity

The EU responded by reducing the maximum allowed concentration from 6% to 2.2% in body products (2022). But the FDA still hasn't made a final GRASE determination.

Important Context

The JAMA study authors explicitly stated: "These findings do not indicate that individuals should refrain from the use of sunscreen."

Systemic absorption doesn't automatically mean harm. It means we need more data to understand the implications. Sun protection remains critical for skin cancer prevention.

EU vs. US: The Regulatory Gap

Here's a frustrating reality for US consumers:

Aspect	FDA (US)	EU
Classification	OTC Drug	Cosmetic
Approved UV filters	16 (only 2 GRASE)	30+
New filter approval time	10+ years (NDA required)	2-5 years (SCCS opinion)
Last new filter approved	2016 (ecamsule via NDA)	Ongoing

Because the FDA classifies sunscreens as drugs, new UV filters require either an NDA (New Drug Application) or inclusion in the OTC monograph - both lengthy processes. Europe classifies them as cosmetics, allowing faster approval of modern filters with better UVA protection and cosmetic elegance.

What About Nanoparticles?

Zinc oxide and titanium dioxide in nano form (<100nm) eliminate the white cast of traditional mineral sunscreens. Safety data shows:

Most nanoparticles remain confined to the stratum corneum (Ferraris 2021)
Only particles smaller than 10nm showed limited penetration to viable epidermis
Co-exposure of ZnO and TiO₂ actually reduces toxicity through antagonistic effects (Liang 2022)
Surface coatings are critical for minimizing ROS generation

The EU requires [nano] labeling when these ingredients are in nanoparticle form. They're prohibited in spray products due to inhalation concerns - not dermal safety.

Practical Recommendations

Evidence-Based Choices

Mineral sunscreens (ZnO/TiO₂) have the strongest safety profile - FDA GRASE, minimal absorption, broad spectrum when combined.
Chemical filters are not proven unsafe - they just lack complete safety data. Millions use them daily without documented harm.
Avoid oxybenzone if concerned about endocrine effects - it has the highest absorption and most inconclusive associations.
Reef-safe = mineral filters - Hawaii and Key West bans target oxybenzone and octinoxate specifically.
Any sunscreen beats no sunscreen - the skin cancer protection benefit is well-established.

The Bottom Line

Zinc oxide and titanium dioxide are FDA GRASE because they don't significantly penetrate past the skin's outer layer. Chemical filters do penetrate - and until we have comprehensive toxicology data, they remain in regulatory limbo (Category III).

This doesn't mean chemical sunscreens are dangerous. It means the science is incomplete. If you want the most conservative choice based on current evidence, mineral sunscreens are it.

References

Matta MK, et al. (2019). Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients. JAMA. DOI: 10.1001/jama.2019.5586
Smijs TG, Pavel S (2011). Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness. Nanotechnology, Science and Applications. DOI: 10.2147/NSA.S19419
Sabzevari N, et al. (2021). Sunscreens: UV Filters to Protect Us. International Journal of Women's Dermatology. DOI: 10.1016/j.ijwd.2020.05.017
Suh S, et al. (2020). The Banned Sunscreen Ingredients and Their Impact on Human Health. International Journal of Dermatology. DOI: 10.1111/ijd.14824
Jaskulak M, et al. (2025). Endocrine and Reproductive Health Considerations of Sunscreen UV Filters. Current Opinion in Endocrine and Metabolic Research. DOI: 10.1016/j.coemr.2025.100555