The U.S. sunscreen industry has been in limbo for nearly 3 decades awaiting action from the U.S. Food and Drug Administration regarding testing protocols that would better standardize the way in which sunscreens are tested and rated for their efficacy in blocking UVA. As it is now, when you read a sunscreen label there is no way to quantify how effective a product is at shielding UVA. No currently approved testing method exists for supporting UVA claims. The consequences of not having this information are increasingly important as the evidence about UVA’s destructive capabilities mounts.
So what is being done about this lack of testing protocols with regard to UVA, and how will proposed changes affect the way in which we all use sunscreens for protection? This article will explore these questions and more. But first, a quick review of why we all need more protection from UVA.
What Is UVA and Why Is It Important?
The ultraviolet spectrum extends from 290 to 400 nanometers. The ultraviolet (UV) spectrum is sandwiched between X-radiation and visible light, and the solar UV spectrum is divided into the UVB region from 290 nm to 320 nm and the UVA region from 320 nm to 400 nm. The UVA region is further divided into UVAI from 340 nm to 400 nm and UVAII from 320 nm to 340 nm.
Wavelengths in the UVB region are about a thousand times more effective at producing sunburn than those in the UVA region, and until recently UVA was considered to be relatively safe “tanning” radiation and few sunscreens provided significant UVA protection
However, UVA accounts for as much as 95% of solar radiation, penetrates the skin deeper than UVB, and contributes to photoaging, carcinogenicity, and immunosuppression.1
While UVB is associated with direct damage to DNA, UVA is associated with indirect damage mediated by free radical formation and damage to cellular membranes.2
As long ago as 1991, Diffey advanced the idea that human UV protection should be “balanced,” that is, about the same across the UV spectrum. This was based on the fact that we evolved under a forest canopy that provided approximately equal protection at all wavelengths.3 Today, there is evidence suggesting that energy from different wavelengths switches on (and off) a wide variety of genes, and that selectively filtering one set of wavelengths can have unintended consequences.4
No one can argue against the necessity of protection against sunburn and even subthreshold levels of erythemogenic radiation, or dispute the role of UVB in producing non-melanoma skin cancer.5 However, the roles of UVB and UVA in malignant melanoma are blurred, with contradictory findings.6 These factors argue in favor of higher levels of “broad-spectrum” protection, with UVA protection factors at least one-third of the SPF.7
How the FDA Categorizes Sunscreens
FDA considers sunscreen products to be over-the-counter (OTC) drugs. As OTC drugs, sunscreen ingredients, formula testing and finished product labeling are regulated under a monograph.8 The original proposed sunscreen monograph was published in 1978, but since the monograph was never finalized, the U.S. sunscreen industry has been awaiting the new regulations for almost 30 years.
During that time, evidence of the need for improved UVA protection has mounted, and Europe and Japan have developed sensible and rational testing procedures and labeling for UVA protection claims, in addition to a wide variety of approved broad-spectrum sunscreen ingredients.9,10 During this same time, UVA protection labeling in the United States has been limited to terms such as “UVA/UVB protection” or “Broad-Spectrum Protection,” based on the presence of certain ingredients that are relatively weak UVA absorbers.
It gets worse: The only truly effective UVA absorber available for general use in the United States is avobenzone, and even avobenzone wasn’t approved until 1997. Besides that, avobenzone is not inherently photostable, and heroic formulation man-euvers are required to make it so. The situation has been, as a senior executive of a large French cosmetics company remarked in the late nineties, “an embarrassment.”
Now it appears that the landscape is about to change significantly, and for the good of the public, as well as the industry. In August of 2007, the FDA published the long-awaited “Proposed Amendment of the Final Sunscreen Monograph.”11 The proposed amendment contains an in-vitro test based on spectrophotometric measurements of product UVA transmittance and a test on human volunteer subjects based on protection against pigmentation responses induced by UVA radiation.
The prescribed in-vitro test yields the ratio of long-wavelength UVA absorbance to total UV absorbance, while the in-vivo test yields a UVA protection factor analogous to SPF, based on a tanning response primarily arising from short-wavelength UVA. The proposed amendment also addresses photostability by including a pre-irradiation step in the spectrophotometric method.
Besides testing methodologies, the proposal includes some innovative labeling provisions, guaranteed to impress our European friends — and a few gaffes for their amusement (more on that, later). Some important provisions of the proposal include the following.
Key Provisions Related to UVA Protection
• Categories of UVA Protection
The proposed amendment contains an in-vitro test based on measurements of UVA transmittance by products applied to quartz plates and an in-vivo test on human volunteer subjects based on protection against pigmentation responses produced by UVA radiation.
The prescribed in-vitro test yields the ratio of UVAI (340 nm to 400 nm) absorbance to total UV absorbance (290 nm to 400 nm), while the in-vivo test yields a UVA protection factor analogous to SPF, based on a pigmentation response primarily arising from UVAII (320 nm to 340 nm).
• Photostability
The FDA addressed photostability of sunscreens by including a pre-irradiation step in the above in-vitro method for evaluating UVA protection.
• UVA Labeling
Proposed UVA labeling consists of four progressive categories, denoted as low, medium, high, and highest protection, based on both the in-vitro and in-vivo tests.
Table 1 (above) denotes the four-star rating system that will be applied to the sunscreen products and will be a useful tool for consumers for understanding how well a sunscreen protects against UV.
In-vitro Test for UVA Protection
The proposed in-vitro test requires applying 2 mg/cm2 of product on a quartz plate, irradiating with a specified UV dose from a solar simulator and then measuring the fraction of the applied UV dose transmitted through the sunscreen film at 5 nm wavelength intervals from 290 nm to 400 nm. The specified irradiation UV dose is based on two-thirds of the label SPF, and is measured in MEDs (minimal erythema dose), where one MED is the UV dose required to produce a mild sunburn on “typical” fair skin. For example, if the label SPF is 15, the irradiation dose in MEDs is two-thirds times 15, or 10 MEDs.
Continuing on, the fraction of the applied UV dose transmitted through a sunscreen film is known as the transmittance. Finally the absorbance at each wavelength is given by the equation below:
Absorbance = -log (transmittance)
The absorbance spectrum is a useful graphic for understanding how well a sunscreen protects at each wavelength. (See Figure 1, below.)
The proposed index of UVA protection is the ratio of the average absorbance in the UVAI region (340 nm to 400 nm) to the average total UV absorbance (290 nm to 400 nm).
The proposed UVA protection rating categories based on UVAI/UVA ratio are shown in Table 2, below.
For Sunscreen A shown in Figure 1, below, the average absorbance in the UVAI region is 0.82 and the average total UV absorbance is 1.22. The ratio of UVAI absorbance to total UV absorbance is 0.672. Thus Sunscreen A shown in Figure 1 would be rated in the “Medium” category.
Consider the absorbance spectrum of Sunscreen B shown in Figure 2, below.
For Sunscreen B the average absorbance in the UVAI region is 0.965 and the average total UV absorbance is 1.167. The ratio of UVAI absorbance to total UV absorbance is 0.827. Thus Sunscreen B would be rated in the “High” category. Other spectroradiometric ratios are used around the world, but this one is special, as discussed later.
Now, let’s consider the in-vivo test on human subjects.
The In-Vivo Test for UVA protection
The proposed in-vivo test is based on a method published by the Japan Cosmetic Industry Association in 1995.12 Briefly, the FDA version involves exposing a panel of 20 moderately pigmented human volunteers to a series of five ascending UVA doses and evaluating the tanning response 3 to 24 hours later.
Unprotected sites and sites protected with the sunscreen are exposed, and the protection factor is computed as the ratio of the lowest UVA dose that produces a mild, transient tanning response in the sunscreen-protected site to that in the unprotected site. The mean ratio (protection factor) for the panel is adjusted by the one-sided 95% confidence interval (to yield the lowest statistically predicted value for 95% of the “normal” population), and categories based on the adjusted mean protection factor are defined as follows:
Adjusted PF < 2: No rating
Adjusted PF 2 to < 4: Low
Adjusted PF 4 to < 8: Medium
Adjusted PF 8 to < 12: High
Adjusted PF 12 or more: Highest
The tanning response is called persistent pigment darkening (PPD) because it doesn’t fade as rapidly as the immediate pigment response, which disappears within a few minutes, and it isn’t true tanning, which develops over several days. Persistent pigment darkening was selected because it can be produced with relatively small UVA doses, and it has a reliable dose response curve. Persistent pigment darkening is produced more strongly by UVAII wavelengths, and the effectiveness of longer wavelengths gradually decreases, as shown in Figure 3, above.
In reality, the PPD response is artificial, since its wavelength dependence is unrelated to any form of UV damage, and the response is exhibited only by pigmented individuals who have the least need for UV protection.
But use of the PPD response to measure UVA protection accomplishes two things: It provides a means for assessing protection, primarily from UVAII, and it involves the “competence” of the sunscreen film on actual human skin, as opposed to the spectrophotometric test on artificial substrates. If the sunscreen product is labeled as water resistant or very water resistant, the proposal requires that the PPD test be performed after 40 or 80 minutes of water immersion — further testing the integrity of the film.
Final UVA Protection Labeling
The spectrophotometric test and the in-vivo test are designed to be performed in tandem. Then the final product labeling is based on the lower rating of the two, in the form of stars. One star denotes “low UVA protection,” two stars denote “medium UVA protection,” three equate “high UVA protection” and four represent “highest UVA protection.” A rating in the highest category is difficult, if not impossible, to achieve using active ingredients currently approved by the FDA for use in the United States.
A Few Words About Photostability
Sunscreen ingredients protect by absorbing UV energy. The basic laws of thermodynamics dictate that absorbed energy must be dissipated in some way. The usual and ideal case is that energy absorbed by sunscreens on the skin is radiated back into the environment as heat. However, a few sunscreen ingredients tend to dissipate energy by breaking down chemically during this process and losing their UV absorbing properties.
In the SPF test on human volunteer subjects, a typical photolabile sunscreen has an original SPF higher than its label value, but during UV exposure to artificial UV from a solar simulating xenon arc lamp, the SPF decreases. The net ratio of transmitted to applied UV dose is the measured SPF value used for labeling. However, in full-spectrum outdoor sunlight exposures of sunscreen users, the SPF of a photolabile sunscreen starts out high, but may drop more precipitously, and the net protection may not be commensurate with the labeled SPF value.13
The most notoriously offending ingredient is avobenzone, particularly in combination with octinoxate. Avobenzone may be stabilized, however, by incorporating other ingredients that assist in the process of absorbing and releasing UV energy without chemical breakdown.14 The leading sunscreen manufacturers have adopted various photostabilizing strategies, beginning by scrupulously avoiding the combination of avobenzone and octinoxate.
What’s Impressive About the FDA’s Proposal?
What is impressive is that the proposal requires a spectrophotometric test that is rigorous; it also addresses the issue of photostability and yields a UVA protection index that has a very high dynamic range. (There is a 200-fold range of possible values of the UVAI/UV ratio.) With its high dynamic range, the UVAI/UV ratio is the most highly discriminating of all UVA rating systems in general use. 15
It may be possible to achieve an adjusted protection factor greater than 12 in the human in-vivo test, but the lower rating of the two tests must be used in final labeling. Achieving the “highest” rating in the spectrophotometric test is difficult, if not impossible, using ingredients that are available today in the United States. Thus FDA has established a global benchmark for UVA protection — and a challenge to formulators.
What Were the Gaffes?
Now to address the aforementioned gaffes in FDA’s proposal. For the in-vitro test, the agency specified application of 2 mg/cm2 of product (the same amount used in the human SPF and PPD tests) to a quartz plate with undefined roughness values. Although the pre-irradiation dose is based on SPF, the measured SPF of a film applied at 2 mg/cm2 to a typical quartz plate is ridiculously high, so pre-irradiation with a UV dose based on SPF is meaningless.
Moreover, the specified solar-simulating light source does not contain enough power at short-UV wavelengths to permit accurate transmittance measurements through a film of that thickness. The Europeans have solved that problem by using thinner films on well-characterized plexiglass plates and a light source with a more “flat” spectrum.16
However, the lower application amount specified by the Europeans may not permit accurate assessment of photostability. If the final FDA monograph specifies an appropriate substrate that replicates the roughness of human skin and a reasonable UV source for measuring transmittance, those flaws may not be “gaffes,” after all. In fact, they may permit more reliance on in-vitro testing and reduced UV exposure of human volunteers.
What’s Next?
The FDA solicited comments on its proposed amendment from interested parties and the public until Dec. 26, 2007. According to an FDA spokesperson, thousands of comments were received. The FDA is now reviewing the comments, and the timetable is unclear for releasing the final FDA sunscreen monograph.
Furthermore, FDA is reviewing five applications for U.S. marketing of UVA and UVB sunscreen ingredients currently marketed in Europe and elsewhere, and approvals of two are expected by year end. Both are broad-spectrum absorbers that are inherently photostable and could permit development of photostable products in the United States, with ratings in the “highest” category.10
At the end of the day, the proposed monograph amendment of 2007 represents long-needed progress in UVA testing and labeling in the United States, with the end result being better protection from UVA radiation for everyone.
The U.S. sunscreen industry has been in limbo for nearly 3 decades awaiting action from the U.S. Food and Drug Administration regarding testing protocols that would better standardize the way in which sunscreens are tested and rated for their efficacy in blocking UVA. As it is now, when you read a sunscreen label there is no way to quantify how effective a product is at shielding UVA. No currently approved testing method exists for supporting UVA claims. The consequences of not having this information are increasingly important as the evidence about UVA’s destructive capabilities mounts.
So what is being done about this lack of testing protocols with regard to UVA, and how will proposed changes affect the way in which we all use sunscreens for protection? This article will explore these questions and more. But first, a quick review of why we all need more protection from UVA.
What Is UVA and Why Is It Important?
The ultraviolet spectrum extends from 290 to 400 nanometers. The ultraviolet (UV) spectrum is sandwiched between X-radiation and visible light, and the solar UV spectrum is divided into the UVB region from 290 nm to 320 nm and the UVA region from 320 nm to 400 nm. The UVA region is further divided into UVAI from 340 nm to 400 nm and UVAII from 320 nm to 340 nm.
Wavelengths in the UVB region are about a thousand times more effective at producing sunburn than those in the UVA region, and until recently UVA was considered to be relatively safe “tanning” radiation and few sunscreens provided significant UVA protection
However, UVA accounts for as much as 95% of solar radiation, penetrates the skin deeper than UVB, and contributes to photoaging, carcinogenicity, and immunosuppression.1
While UVB is associated with direct damage to DNA, UVA is associated with indirect damage mediated by free radical formation and damage to cellular membranes.2
As long ago as 1991, Diffey advanced the idea that human UV protection should be “balanced,” that is, about the same across the UV spectrum. This was based on the fact that we evolved under a forest canopy that provided approximately equal protection at all wavelengths.3 Today, there is evidence suggesting that energy from different wavelengths switches on (and off) a wide variety of genes, and that selectively filtering one set of wavelengths can have unintended consequences.4
No one can argue against the necessity of protection against sunburn and even subthreshold levels of erythemogenic radiation, or dispute the role of UVB in producing non-melanoma skin cancer.5 However, the roles of UVB and UVA in malignant melanoma are blurred, with contradictory findings.6 These factors argue in favor of higher levels of “broad-spectrum” protection, with UVA protection factors at least one-third of the SPF.7
How the FDA Categorizes Sunscreens
FDA considers sunscreen products to be over-the-counter (OTC) drugs. As OTC drugs, sunscreen ingredients, formula testing and finished product labeling are regulated under a monograph.8 The original proposed sunscreen monograph was published in 1978, but since the monograph was never finalized, the U.S. sunscreen industry has been awaiting the new regulations for almost 30 years.
During that time, evidence of the need for improved UVA protection has mounted, and Europe and Japan have developed sensible and rational testing procedures and labeling for UVA protection claims, in addition to a wide variety of approved broad-spectrum sunscreen ingredients.9,10 During this same time, UVA protection labeling in the United States has been limited to terms such as “UVA/UVB protection” or “Broad-Spectrum Protection,” based on the presence of certain ingredients that are relatively weak UVA absorbers.
It gets worse: The only truly effective UVA absorber available for general use in the United States is avobenzone, and even avobenzone wasn’t approved until 1997. Besides that, avobenzone is not inherently photostable, and heroic formulation man-euvers are required to make it so. The situation has been, as a senior executive of a large French cosmetics company remarked in the late nineties, “an embarrassment.”
Now it appears that the landscape is about to change significantly, and for the good of the public, as well as the industry. In August of 2007, the FDA published the long-awaited “Proposed Amendment of the Final Sunscreen Monograph.”11 The proposed amendment contains an in-vitro test based on spectrophotometric measurements of product UVA transmittance and a test on human volunteer subjects based on protection against pigmentation responses induced by UVA radiation.
The prescribed in-vitro test yields the ratio of long-wavelength UVA absorbance to total UV absorbance, while the in-vivo test yields a UVA protection factor analogous to SPF, based on a tanning response primarily arising from short-wavelength UVA. The proposed amendment also addresses photostability by including a pre-irradiation step in the spectrophotometric method.
Besides testing methodologies, the proposal includes some innovative labeling provisions, guaranteed to impress our European friends — and a few gaffes for their amusement (more on that, later). Some important provisions of the proposal include the following.
Key Provisions Related to UVA Protection
• Categories of UVA Protection
The proposed amendment contains an in-vitro test based on measurements of UVA transmittance by products applied to quartz plates and an in-vivo test on human volunteer subjects based on protection against pigmentation responses produced by UVA radiation.
The prescribed in-vitro test yields the ratio of UVAI (340 nm to 400 nm) absorbance to total UV absorbance (290 nm to 400 nm), while the in-vivo test yields a UVA protection factor analogous to SPF, based on a pigmentation response primarily arising from UVAII (320 nm to 340 nm).
• Photostability
The FDA addressed photostability of sunscreens by including a pre-irradiation step in the above in-vitro method for evaluating UVA protection.
• UVA Labeling
Proposed UVA labeling consists of four progressive categories, denoted as low, medium, high, and highest protection, based on both the in-vitro and in-vivo tests.
Table 1 (above) denotes the four-star rating system that will be applied to the sunscreen products and will be a useful tool for consumers for understanding how well a sunscreen protects against UV.
In-vitro Test for UVA Protection
The proposed in-vitro test requires applying 2 mg/cm2 of product on a quartz plate, irradiating with a specified UV dose from a solar simulator and then measuring the fraction of the applied UV dose transmitted through the sunscreen film at 5 nm wavelength intervals from 290 nm to 400 nm. The specified irradiation UV dose is based on two-thirds of the label SPF, and is measured in MEDs (minimal erythema dose), where one MED is the UV dose required to produce a mild sunburn on “typical” fair skin. For example, if the label SPF is 15, the irradiation dose in MEDs is two-thirds times 15, or 10 MEDs.
Continuing on, the fraction of the applied UV dose transmitted through a sunscreen film is known as the transmittance. Finally the absorbance at each wavelength is given by the equation below:
Absorbance = -log (transmittance)
The absorbance spectrum is a useful graphic for understanding how well a sunscreen protects at each wavelength. (See Figure 1, below.)
The proposed index of UVA protection is the ratio of the average absorbance in the UVAI region (340 nm to 400 nm) to the average total UV absorbance (290 nm to 400 nm).
The proposed UVA protection rating categories based on UVAI/UVA ratio are shown in Table 2, below.
For Sunscreen A shown in Figure 1, below, the average absorbance in the UVAI region is 0.82 and the average total UV absorbance is 1.22. The ratio of UVAI absorbance to total UV absorbance is 0.672. Thus Sunscreen A shown in Figure 1 would be rated in the “Medium” category.
Consider the absorbance spectrum of Sunscreen B shown in Figure 2, below.
For Sunscreen B the average absorbance in the UVAI region is 0.965 and the average total UV absorbance is 1.167. The ratio of UVAI absorbance to total UV absorbance is 0.827. Thus Sunscreen B would be rated in the “High” category. Other spectroradiometric ratios are used around the world, but this one is special, as discussed later.
Now, let’s consider the in-vivo test on human subjects.
The In-Vivo Test for UVA protection
The proposed in-vivo test is based on a method published by the Japan Cosmetic Industry Association in 1995.12 Briefly, the FDA version involves exposing a panel of 20 moderately pigmented human volunteers to a series of five ascending UVA doses and evaluating the tanning response 3 to 24 hours later.
Unprotected sites and sites protected with the sunscreen are exposed, and the protection factor is computed as the ratio of the lowest UVA dose that produces a mild, transient tanning response in the sunscreen-protected site to that in the unprotected site. The mean ratio (protection factor) for the panel is adjusted by the one-sided 95% confidence interval (to yield the lowest statistically predicted value for 95% of the “normal” population), and categories based on the adjusted mean protection factor are defined as follows:
Adjusted PF < 2: No rating
Adjusted PF 2 to < 4: Low
Adjusted PF 4 to < 8: Medium
Adjusted PF 8 to < 12: High
Adjusted PF 12 or more: Highest
The tanning response is called persistent pigment darkening (PPD) because it doesn’t fade as rapidly as the immediate pigment response, which disappears within a few minutes, and it isn’t true tanning, which develops over several days. Persistent pigment darkening was selected because it can be produced with relatively small UVA doses, and it has a reliable dose response curve. Persistent pigment darkening is produced more strongly by UVAII wavelengths, and the effectiveness of longer wavelengths gradually decreases, as shown in Figure 3, above.
In reality, the PPD response is artificial, since its wavelength dependence is unrelated to any form of UV damage, and the response is exhibited only by pigmented individuals who have the least need for UV protection.
But use of the PPD response to measure UVA protection accomplishes two things: It provides a means for assessing protection, primarily from UVAII, and it involves the “competence” of the sunscreen film on actual human skin, as opposed to the spectrophotometric test on artificial substrates. If the sunscreen product is labeled as water resistant or very water resistant, the proposal requires that the PPD test be performed after 40 or 80 minutes of water immersion — further testing the integrity of the film.
Final UVA Protection Labeling
The spectrophotometric test and the in-vivo test are designed to be performed in tandem. Then the final product labeling is based on the lower rating of the two, in the form of stars. One star denotes “low UVA protection,” two stars denote “medium UVA protection,” three equate “high UVA protection” and four represent “highest UVA protection.” A rating in the highest category is difficult, if not impossible, to achieve using active ingredients currently approved by the FDA for use in the United States.
A Few Words About Photostability
Sunscreen ingredients protect by absorbing UV energy. The basic laws of thermodynamics dictate that absorbed energy must be dissipated in some way. The usual and ideal case is that energy absorbed by sunscreens on the skin is radiated back into the environment as heat. However, a few sunscreen ingredients tend to dissipate energy by breaking down chemically during this process and losing their UV absorbing properties.
In the SPF test on human volunteer subjects, a typical photolabile sunscreen has an original SPF higher than its label value, but during UV exposure to artificial UV from a solar simulating xenon arc lamp, the SPF decreases. The net ratio of transmitted to applied UV dose is the measured SPF value used for labeling. However, in full-spectrum outdoor sunlight exposures of sunscreen users, the SPF of a photolabile sunscreen starts out high, but may drop more precipitously, and the net protection may not be commensurate with the labeled SPF value.13
The most notoriously offending ingredient is avobenzone, particularly in combination with octinoxate. Avobenzone may be stabilized, however, by incorporating other ingredients that assist in the process of absorbing and releasing UV energy without chemical breakdown.14 The leading sunscreen manufacturers have adopted various photostabilizing strategies, beginning by scrupulously avoiding the combination of avobenzone and octinoxate.
What’s Impressive About the FDA’s Proposal?
What is impressive is that the proposal requires a spectrophotometric test that is rigorous; it also addresses the issue of photostability and yields a UVA protection index that has a very high dynamic range. (There is a 200-fold range of possible values of the UVAI/UV ratio.) With its high dynamic range, the UVAI/UV ratio is the most highly discriminating of all UVA rating systems in general use. 15
It may be possible to achieve an adjusted protection factor greater than 12 in the human in-vivo test, but the lower rating of the two tests must be used in final labeling. Achieving the “highest” rating in the spectrophotometric test is difficult, if not impossible, using ingredients that are available today in the United States. Thus FDA has established a global benchmark for UVA protection — and a challenge to formulators.
What Were the Gaffes?
Now to address the aforementioned gaffes in FDA’s proposal. For the in-vitro test, the agency specified application of 2 mg/cm2 of product (the same amount used in the human SPF and PPD tests) to a quartz plate with undefined roughness values. Although the pre-irradiation dose is based on SPF, the measured SPF of a film applied at 2 mg/cm2 to a typical quartz plate is ridiculously high, so pre-irradiation with a UV dose based on SPF is meaningless.
Moreover, the specified solar-simulating light source does not contain enough power at short-UV wavelengths to permit accurate transmittance measurements through a film of that thickness. The Europeans have solved that problem by using thinner films on well-characterized plexiglass plates and a light source with a more “flat” spectrum.16
However, the lower application amount specified by the Europeans may not permit accurate assessment of photostability. If the final FDA monograph specifies an appropriate substrate that replicates the roughness of human skin and a reasonable UV source for measuring transmittance, those flaws may not be “gaffes,” after all. In fact, they may permit more reliance on in-vitro testing and reduced UV exposure of human volunteers.
What’s Next?
The FDA solicited comments on its proposed amendment from interested parties and the public until Dec. 26, 2007. According to an FDA spokesperson, thousands of comments were received. The FDA is now reviewing the comments, and the timetable is unclear for releasing the final FDA sunscreen monograph.
Furthermore, FDA is reviewing five applications for U.S. marketing of UVA and UVB sunscreen ingredients currently marketed in Europe and elsewhere, and approvals of two are expected by year end. Both are broad-spectrum absorbers that are inherently photostable and could permit development of photostable products in the United States, with ratings in the “highest” category.10
At the end of the day, the proposed monograph amendment of 2007 represents long-needed progress in UVA testing and labeling in the United States, with the end result being better protection from UVA radiation for everyone.
The U.S. sunscreen industry has been in limbo for nearly 3 decades awaiting action from the U.S. Food and Drug Administration regarding testing protocols that would better standardize the way in which sunscreens are tested and rated for their efficacy in blocking UVA. As it is now, when you read a sunscreen label there is no way to quantify how effective a product is at shielding UVA. No currently approved testing method exists for supporting UVA claims. The consequences of not having this information are increasingly important as the evidence about UVA’s destructive capabilities mounts.
So what is being done about this lack of testing protocols with regard to UVA, and how will proposed changes affect the way in which we all use sunscreens for protection? This article will explore these questions and more. But first, a quick review of why we all need more protection from UVA.
What Is UVA and Why Is It Important?
The ultraviolet spectrum extends from 290 to 400 nanometers. The ultraviolet (UV) spectrum is sandwiched between X-radiation and visible light, and the solar UV spectrum is divided into the UVB region from 290 nm to 320 nm and the UVA region from 320 nm to 400 nm. The UVA region is further divided into UVAI from 340 nm to 400 nm and UVAII from 320 nm to 340 nm.
Wavelengths in the UVB region are about a thousand times more effective at producing sunburn than those in the UVA region, and until recently UVA was considered to be relatively safe “tanning” radiation and few sunscreens provided significant UVA protection
However, UVA accounts for as much as 95% of solar radiation, penetrates the skin deeper than UVB, and contributes to photoaging, carcinogenicity, and immunosuppression.1
While UVB is associated with direct damage to DNA, UVA is associated with indirect damage mediated by free radical formation and damage to cellular membranes.2
As long ago as 1991, Diffey advanced the idea that human UV protection should be “balanced,” that is, about the same across the UV spectrum. This was based on the fact that we evolved under a forest canopy that provided approximately equal protection at all wavelengths.3 Today, there is evidence suggesting that energy from different wavelengths switches on (and off) a wide variety of genes, and that selectively filtering one set of wavelengths can have unintended consequences.4
No one can argue against the necessity of protection against sunburn and even subthreshold levels of erythemogenic radiation, or dispute the role of UVB in producing non-melanoma skin cancer.5 However, the roles of UVB and UVA in malignant melanoma are blurred, with contradictory findings.6 These factors argue in favor of higher levels of “broad-spectrum” protection, with UVA protection factors at least one-third of the SPF.7
How the FDA Categorizes Sunscreens
FDA considers sunscreen products to be over-the-counter (OTC) drugs. As OTC drugs, sunscreen ingredients, formula testing and finished product labeling are regulated under a monograph.8 The original proposed sunscreen monograph was published in 1978, but since the monograph was never finalized, the U.S. sunscreen industry has been awaiting the new regulations for almost 30 years.
During that time, evidence of the need for improved UVA protection has mounted, and Europe and Japan have developed sensible and rational testing procedures and labeling for UVA protection claims, in addition to a wide variety of approved broad-spectrum sunscreen ingredients.9,10 During this same time, UVA protection labeling in the United States has been limited to terms such as “UVA/UVB protection” or “Broad-Spectrum Protection,” based on the presence of certain ingredients that are relatively weak UVA absorbers.
It gets worse: The only truly effective UVA absorber available for general use in the United States is avobenzone, and even avobenzone wasn’t approved until 1997. Besides that, avobenzone is not inherently photostable, and heroic formulation man-euvers are required to make it so. The situation has been, as a senior executive of a large French cosmetics company remarked in the late nineties, “an embarrassment.”
Now it appears that the landscape is about to change significantly, and for the good of the public, as well as the industry. In August of 2007, the FDA published the long-awaited “Proposed Amendment of the Final Sunscreen Monograph.”11 The proposed amendment contains an in-vitro test based on spectrophotometric measurements of product UVA transmittance and a test on human volunteer subjects based on protection against pigmentation responses induced by UVA radiation.
The prescribed in-vitro test yields the ratio of long-wavelength UVA absorbance to total UV absorbance, while the in-vivo test yields a UVA protection factor analogous to SPF, based on a tanning response primarily arising from short-wavelength UVA. The proposed amendment also addresses photostability by including a pre-irradiation step in the spectrophotometric method.
Besides testing methodologies, the proposal includes some innovative labeling provisions, guaranteed to impress our European friends — and a few gaffes for their amusement (more on that, later). Some important provisions of the proposal include the following.
Key Provisions Related to UVA Protection
• Categories of UVA Protection
The proposed amendment contains an in-vitro test based on measurements of UVA transmittance by products applied to quartz plates and an in-vivo test on human volunteer subjects based on protection against pigmentation responses produced by UVA radiation.
The prescribed in-vitro test yields the ratio of UVAI (340 nm to 400 nm) absorbance to total UV absorbance (290 nm to 400 nm), while the in-vivo test yields a UVA protection factor analogous to SPF, based on a pigmentation response primarily arising from UVAII (320 nm to 340 nm).
• Photostability
The FDA addressed photostability of sunscreens by including a pre-irradiation step in the above in-vitro method for evaluating UVA protection.
• UVA Labeling
Proposed UVA labeling consists of four progressive categories, denoted as low, medium, high, and highest protection, based on both the in-vitro and in-vivo tests.
Table 1 (above) denotes the four-star rating system that will be applied to the sunscreen products and will be a useful tool for consumers for understanding how well a sunscreen protects against UV.
In-vitro Test for UVA Protection
The proposed in-vitro test requires applying 2 mg/cm2 of product on a quartz plate, irradiating with a specified UV dose from a solar simulator and then measuring the fraction of the applied UV dose transmitted through the sunscreen film at 5 nm wavelength intervals from 290 nm to 400 nm. The specified irradiation UV dose is based on two-thirds of the label SPF, and is measured in MEDs (minimal erythema dose), where one MED is the UV dose required to produce a mild sunburn on “typical” fair skin. For example, if the label SPF is 15, the irradiation dose in MEDs is two-thirds times 15, or 10 MEDs.
Continuing on, the fraction of the applied UV dose transmitted through a sunscreen film is known as the transmittance. Finally the absorbance at each wavelength is given by the equation below:
Absorbance = -log (transmittance)
The absorbance spectrum is a useful graphic for understanding how well a sunscreen protects at each wavelength. (See Figure 1, below.)
The proposed index of UVA protection is the ratio of the average absorbance in the UVAI region (340 nm to 400 nm) to the average total UV absorbance (290 nm to 400 nm).
The proposed UVA protection rating categories based on UVAI/UVA ratio are shown in Table 2, below.
For Sunscreen A shown in Figure 1, below, the average absorbance in the UVAI region is 0.82 and the average total UV absorbance is 1.22. The ratio of UVAI absorbance to total UV absorbance is 0.672. Thus Sunscreen A shown in Figure 1 would be rated in the “Medium” category.
Consider the absorbance spectrum of Sunscreen B shown in Figure 2, below.
For Sunscreen B the average absorbance in the UVAI region is 0.965 and the average total UV absorbance is 1.167. The ratio of UVAI absorbance to total UV absorbance is 0.827. Thus Sunscreen B would be rated in the “High” category. Other spectroradiometric ratios are used around the world, but this one is special, as discussed later.
Now, let’s consider the in-vivo test on human subjects.
The In-Vivo Test for UVA protection
The proposed in-vivo test is based on a method published by the Japan Cosmetic Industry Association in 1995.12 Briefly, the FDA version involves exposing a panel of 20 moderately pigmented human volunteers to a series of five ascending UVA doses and evaluating the tanning response 3 to 24 hours later.
Unprotected sites and sites protected with the sunscreen are exposed, and the protection factor is computed as the ratio of the lowest UVA dose that produces a mild, transient tanning response in the sunscreen-protected site to that in the unprotected site. The mean ratio (protection factor) for the panel is adjusted by the one-sided 95% confidence interval (to yield the lowest statistically predicted value for 95% of the “normal” population), and categories based on the adjusted mean protection factor are defined as follows:
Adjusted PF < 2: No rating
Adjusted PF 2 to < 4: Low
Adjusted PF 4 to < 8: Medium
Adjusted PF 8 to < 12: High
Adjusted PF 12 or more: Highest
The tanning response is called persistent pigment darkening (PPD) because it doesn’t fade as rapidly as the immediate pigment response, which disappears within a few minutes, and it isn’t true tanning, which develops over several days. Persistent pigment darkening was selected because it can be produced with relatively small UVA doses, and it has a reliable dose response curve. Persistent pigment darkening is produced more strongly by UVAII wavelengths, and the effectiveness of longer wavelengths gradually decreases, as shown in Figure 3, above.
In reality, the PPD response is artificial, since its wavelength dependence is unrelated to any form of UV damage, and the response is exhibited only by pigmented individuals who have the least need for UV protection.
But use of the PPD response to measure UVA protection accomplishes two things: It provides a means for assessing protection, primarily from UVAII, and it involves the “competence” of the sunscreen film on actual human skin, as opposed to the spectrophotometric test on artificial substrates. If the sunscreen product is labeled as water resistant or very water resistant, the proposal requires that the PPD test be performed after 40 or 80 minutes of water immersion — further testing the integrity of the film.
Final UVA Protection Labeling
The spectrophotometric test and the in-vivo test are designed to be performed in tandem. Then the final product labeling is based on the lower rating of the two, in the form of stars. One star denotes “low UVA protection,” two stars denote “medium UVA protection,” three equate “high UVA protection” and four represent “highest UVA protection.” A rating in the highest category is difficult, if not impossible, to achieve using active ingredients currently approved by the FDA for use in the United States.
A Few Words About Photostability
Sunscreen ingredients protect by absorbing UV energy. The basic laws of thermodynamics dictate that absorbed energy must be dissipated in some way. The usual and ideal case is that energy absorbed by sunscreens on the skin is radiated back into the environment as heat. However, a few sunscreen ingredients tend to dissipate energy by breaking down chemically during this process and losing their UV absorbing properties.
In the SPF test on human volunteer subjects, a typical photolabile sunscreen has an original SPF higher than its label value, but during UV exposure to artificial UV from a solar simulating xenon arc lamp, the SPF decreases. The net ratio of transmitted to applied UV dose is the measured SPF value used for labeling. However, in full-spectrum outdoor sunlight exposures of sunscreen users, the SPF of a photolabile sunscreen starts out high, but may drop more precipitously, and the net protection may not be commensurate with the labeled SPF value.13
The most notoriously offending ingredient is avobenzone, particularly in combination with octinoxate. Avobenzone may be stabilized, however, by incorporating other ingredients that assist in the process of absorbing and releasing UV energy without chemical breakdown.14 The leading sunscreen manufacturers have adopted various photostabilizing strategies, beginning by scrupulously avoiding the combination of avobenzone and octinoxate.
What’s Impressive About the FDA’s Proposal?
What is impressive is that the proposal requires a spectrophotometric test that is rigorous; it also addresses the issue of photostability and yields a UVA protection index that has a very high dynamic range. (There is a 200-fold range of possible values of the UVAI/UV ratio.) With its high dynamic range, the UVAI/UV ratio is the most highly discriminating of all UVA rating systems in general use. 15
It may be possible to achieve an adjusted protection factor greater than 12 in the human in-vivo test, but the lower rating of the two tests must be used in final labeling. Achieving the “highest” rating in the spectrophotometric test is difficult, if not impossible, using ingredients that are available today in the United States. Thus FDA has established a global benchmark for UVA protection — and a challenge to formulators.
What Were the Gaffes?
Now to address the aforementioned gaffes in FDA’s proposal. For the in-vitro test, the agency specified application of 2 mg/cm2 of product (the same amount used in the human SPF and PPD tests) to a quartz plate with undefined roughness values. Although the pre-irradiation dose is based on SPF, the measured SPF of a film applied at 2 mg/cm2 to a typical quartz plate is ridiculously high, so pre-irradiation with a UV dose based on SPF is meaningless.
Moreover, the specified solar-simulating light source does not contain enough power at short-UV wavelengths to permit accurate transmittance measurements through a film of that thickness. The Europeans have solved that problem by using thinner films on well-characterized plexiglass plates and a light source with a more “flat” spectrum.16
However, the lower application amount specified by the Europeans may not permit accurate assessment of photostability. If the final FDA monograph specifies an appropriate substrate that replicates the roughness of human skin and a reasonable UV source for measuring transmittance, those flaws may not be “gaffes,” after all. In fact, they may permit more reliance on in-vitro testing and reduced UV exposure of human volunteers.
What’s Next?
The FDA solicited comments on its proposed amendment from interested parties and the public until Dec. 26, 2007. According to an FDA spokesperson, thousands of comments were received. The FDA is now reviewing the comments, and the timetable is unclear for releasing the final FDA sunscreen monograph.
Furthermore, FDA is reviewing five applications for U.S. marketing of UVA and UVB sunscreen ingredients currently marketed in Europe and elsewhere, and approvals of two are expected by year end. Both are broad-spectrum absorbers that are inherently photostable and could permit development of photostable products in the United States, with ratings in the “highest” category.10
At the end of the day, the proposed monograph amendment of 2007 represents long-needed progress in UVA testing and labeling in the United States, with the end result being better protection from UVA radiation for everyone.
