Systemic absorption of sunscreen after topical application
Cameron G J Hayden, Michael S Roberts, Heather A E Benson
Sunscreens are widely used to avoid sunburn, photoageing, and skin cancer, and to minimise various photosensitivities and phototoxicities.
However, sunscreen products are only routinely tested for their ability to delay the onset of erythema (sunburn) in skin exposed to ultraviolet (UV) radiation.
Regulatory agencies differ in the requirements for the approval of sunscreening agents. In the USA, sunscreens are regarded as drugs1 whereas in Europe they are termed cosmetics. It is often assumed that little or none of a topically applied substance is absorbed into the systemic circulation.
We show that substantial amounts of an applied sunscreen, oxybenzone, are absorbed and subsequently excreted in human urine.
Oxybenzone has low acute toxicity in animal studies2 yet little is known about its chronic toxicity and disposition after topical application in people. Oxybenzone is a benzophenone derivative commonly used throughout the world to make sun-products with especially high sun protection factors (SPF).
It belongs to a small group of UVA blocking agents that include methyl anthranilate and butylmethoxydibenzoyl-methane, which is the UVA sunscreen of choice in Europe.
Oxybenzone recovered in urine as unchanged oxybenzone and metabolites after topical application of commercially available SPF 15+ sunscreen to nine human volunteers
1 m2 is approximately 60% of an adult's total skin surface area (1·7 m2).
The study was approved by the University of Queensland Medical Ethics Committee and informed consent was obtained from all volunteers.
A group of healthy human volunteers (mean 29 [SE 1·8] years, n=9) were instructed to apply a commercially available SPF15+ sunscreen product to the entire surface of their forearms generously but realistically compared with their normal sun protection behaviour.
In practice 13·0 (1·00) g of sunscreen product was applied to a surface area of 1051 (60·8) cm2. The formulation remained unoccluded for 12 h before being removed with soap and water.
The sunscreen product was a lotion containing oxybenzone 6% (w/v), octyl methoxycinnamate 7·5% (w/v), octyl salicylate 5% (w/v) and octocrylene 7% (w/v), all being chemical sunscreening agents.
The volunteers collected urine just before application and for 48 h after application, recording the time and volume of each sample. Exercise, sunlight, alcohol, caffeine, and other drugs were avoided for the duration of the study. The urine samples were immediately frozen until analysis by high performance liquid chromatography with UV absorption detection (287 nm).
The urine was treated with b-glucuronidase HP-2 enzyme before injecting on to a C-18 Novapak column (Waters) with a mobile phase of acetonitrile and aqueous 0·05% trifluoroacetic acid (50:50% v/v). Sunscreen products and solutions have been assayed previously.3
... significant amounts of oxybenzone penetrate the epidermal barrier, a finding consistent with in-vitro4 and animal5 research.
Analysis of the urine using ß-glucuronidase suggests that oxybenzone and its metabolites (2,3,4-trihydroxy-benzophenone and 2,4-dihydroxy-benzophenone) undergo extensive conjugation in the body. It is estimated that the actual amount absorbed from the applied formulation over a 10-h period was between 1 and 2% of the applied amount contained in the product.
The application density of the sunscreen formulation used in this study (12·4 mg/cm2) was six times that used for routine SPF assessment (2 mg/cm2) but was deemed to be appropriate by the volunteers. In addition, sunscreens are recommended to be reapplied frequently throughout the day therefore the daily amount used in practice is likely to exceed 2 mg/cm2.
Over the period of application only 1-2% of sunscreen in the applied product was absorbed, therefore the sunscreen content of the topical product was relatively unchanged over the period of application. It is likely that given the apparent small depletion of sunscreen in the applied formulation on the skin, a similar amount would have been absorbed if a product application density of 2 mg/cm2 had been used.
However, had there been substantial depletion of sunscreen in the product (ie, greater than 10%) over the period of application the density of product applied to the skin would have been critical.
Our results suggest that sunscreens should not be the sole method of sun protection.
It would be prudent not to apply oxybenzone to large surface areas of skin for extended and repeated periods of time, unless no alternative protection is available.
There may be an additional concern for young children who have less well-developed processes of elimination, and have a larger surface area per body weight than adults, with respect to systemic availability of a topically applied dose.
We acknowledge the support of the Queensland Cancer Fund and the NH&MRC (Australia), the technical assistance of N V Hoffmann, and the time given by the volunteers.
1 USA Food and Drug Administration. Sunscreen drug products for over the counter human use: tentative final monograph. Fed Reg 1993; 58: 28194302. [PubMed]
2 Cosmetic Ingredient Review. Final report on the safety of benzophenone-1, -3, -4, -5, -9, and -11. J Am Coll Toxicol 1983; 2: 3577. [PubMed]
3 Jiang R, Hayden CGJ, Prankerd RP, Robers MS, Benson HAE. High performance liquid chromatographic assay for common sunscreening agents in cosmetic products, bovine serum albumin solution and human plasma. J Chromatogr B 1996; 682: 13745. [PubMed]
4 Treffel P, Gabard B. Skin penetration and sun protection factor of ultra-violet filters from two vehicles. Pharm Res 1996; 13: 77074. [PubMed]
5 Okereke CS, Abdel-Rhaman MS, Friedman MA. Disposition of benzophenone-3 after dermal administration in male rats. Toxicol Lett 1994; 73: 11322. [PubMed]
School of Pharmacy (H A E Benson), and Department of Medicine, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia 4072
The Lancet Volume 350, Number 9081 20 September 1997
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