**2. Topical photoprotection**

## **2.1. Definition**

There are many methods of sun protection, such as photoprotection by clothing, systemic photoprotection (medicine and dietary supplements) and topical photoprotection, using sun products with a variety of dosage forms.

reduce the number of indices, and the aim of the creation of an index of 50+ concerning all products which have a determined SPF equal to or higher than 60 was to avoid having indices higher than 100 on packaging, as this could have led the consumer to believe that the product

**European regulation American regulation**

Whichever legislation is considered, a limited number of filters are authorized in the formula‐ tion of sun products. In Europe, Appendix VI of the Regulation lists the 26 authorized filters, that is to say 25 organic filters and one screen, titanium dioxide, each one having a maximum concentration of use (% m/m) and perhaps a list of comments which should feature on the packaging. In the USA, the original list was made up of 16 filters (15 filters and 1 screen). In the periodfrom1997 to 2008, 8 filters recognizedsafe andeffective were gradually addedto this list. The FDA gradually authorized a certain number of products which were synthetized and patented in Europe in order to beef up the original list. It should be noted that zinc oxide is not mentionedinAppendixVIoftheRegulation(Table4).Theconcentrationofzincoxideistherefore not limited. This, however, remains theoretical, as the limit is imposed by its dosage form, as in high percentages of concentration, a paste is obtained, which would be difficult to market. Seventeen filters are currently in common between the European and American legislation.

*2.2.3. The combination of different filters or the combination of filters with active ingredients*

European formulators have a great deal of freedom. They can combine as many filters as they want, as long as the combinations are not already patented, of course. They can also combine filters with active ingredients which have a softening, antioxidizing or soothing effect, etc. They have to check that the raw material they want to incorporate is not banned and they must check to see if the material is on a list if regulated ingredients (Appendix III: substances with restricted use in particular). In the USA, combinations with **protectants** are authorized within the limits of the maximum authorized concentrations (Table 5). **A skin protectant drug product is defined as «a drug product that temporarily protects injured or exposed skin or mucous membrane surfaces from harmful or annoying stimuli, and may help provide relief to such**


About Suncare Products http://dx.doi.org/10.5772/55411 131



(2 < SPF < 12)

(12 ≤ SPF < 30)

(SPF ≥ 30)

provided total protection.

**Table 3.** Different categories of sunscreens

*2.2.2. Authorized filters*

**surfaces».**


Different categories of sunscreens

Sun products are used to avoid skin damage due to the sun. These products contain molecules which can work through absorption or by reflecting UV rays [29].

The classification of sun products as either cosmetics, or as over-the-counter medicines, differs according to the health authority governing bodies concerned.

The Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSaPS) [The French Agency for Health Safety and Health Products – equivalent to the FDA – Food and Drugs Administration (USA) and the MHRA (UK) remains cautious, saying that "Sun products are effective in the prevention of actinic erythema" It insists, by saying that their preventive effects concerning photo-ageing and skin cancer is yet to be proved [30]. In France, although the Code de la Santé Publique (Public Health Code), defines cosmetics in a general way, it does not, however, give a specific definition for sun products [31].

In the USA, an over-the-counter sunscreen drug product in a form suitable for topical admin‐ istration is generally recognized as safe and effective and is not misbranded if it meets each condition. Here, we are talking of harmlessness and of efficacy (but without being specific about possible prevention regarding effects of UV radiation) [32]. This notion of harmlessness can be found in the Public Health Code [33], in European directives [34] and more recently in regulation N°1223/2009 [35] which has just been written and whose aim is to suggest a more legible type of legislation bringing together successive directive demands.

#### **2.2. Which regulatory status for sun products?**

#### *2.2.1. Different categories of sun products*

As we mentioned earlier, the status of sun product is not unique and differs from country to country. We will mention more specifically the two main legislations on suncare products, namely the European and American ones. It should be noted that the indices which may appear on the packaging of sun products are not the same for European products as they are for American ones (Table 3). In Europe, all of the products which have an SPF (Sun Protection Factor) lower than 6 are not considered as sun products (compared to 2 according to American legislation). The number of categories is bigger in Europe than in the USA (4 large categories and 8 indices in Europe compared to 3 large categories and an infinite number of indices which could be seen on the packaging in the USA. In Europe, in order to make the consumer's life easier and to avoid swamping them with too many indices, a standard index system on packaging was established. Therefore, on the market, products with indices of 17, 24, 36, 54 etc. cannot be found. The index value is always rounded down. In Europe, the tendency is to reduce the number of indices, and the aim of the creation of an index of 50+ concerning all products which have a determined SPF equal to or higher than 60 was to avoid having indices higher than 100 on packaging, as this could have led the consumer to believe that the product provided total protection.


#### **Table 3.** Different categories of sunscreens

#### *2.2.2. Authorized filters*

**2. Topical photoprotection**

products with a variety of dosage forms.

which can work through absorption or by reflecting UV rays [29].

according to the health authority governing bodies concerned.

however, give a specific definition for sun products [31].

**2.2. Which regulatory status for sun products?**

*2.2.1. Different categories of sun products*

There are many methods of sun protection, such as photoprotection by clothing, systemic photoprotection (medicine and dietary supplements) and topical photoprotection, using sun

Sun products are used to avoid skin damage due to the sun. These products contain molecules

The classification of sun products as either cosmetics, or as over-the-counter medicines, differs

The Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSaPS) [The French Agency for Health Safety and Health Products – equivalent to the FDA – Food and Drugs Administration (USA) and the MHRA (UK) remains cautious, saying that "Sun products are effective in the prevention of actinic erythema" It insists, by saying that their preventive effects concerning photo-ageing and skin cancer is yet to be proved [30]. In France, although the Code de la Santé Publique (Public Health Code), defines cosmetics in a general way, it does not,

In the USA, an over-the-counter sunscreen drug product in a form suitable for topical admin‐ istration is generally recognized as safe and effective and is not misbranded if it meets each condition. Here, we are talking of harmlessness and of efficacy (but without being specific about possible prevention regarding effects of UV radiation) [32]. This notion of harmlessness can be found in the Public Health Code [33], in European directives [34] and more recently in regulation N°1223/2009 [35] which has just been written and whose aim is to suggest a more

As we mentioned earlier, the status of sun product is not unique and differs from country to country. We will mention more specifically the two main legislations on suncare products, namely the European and American ones. It should be noted that the indices which may appear on the packaging of sun products are not the same for European products as they are for American ones (Table 3). In Europe, all of the products which have an SPF (Sun Protection Factor) lower than 6 are not considered as sun products (compared to 2 according to American legislation). The number of categories is bigger in Europe than in the USA (4 large categories and 8 indices in Europe compared to 3 large categories and an infinite number of indices which could be seen on the packaging in the USA. In Europe, in order to make the consumer's life easier and to avoid swamping them with too many indices, a standard index system on packaging was established. Therefore, on the market, products with indices of 17, 24, 36, 54 etc. cannot be found. The index value is always rounded down. In Europe, the tendency is to

legible type of legislation bringing together successive directive demands.

**2.1. Definition**

130 Highlights in Skin Cancer

Whichever legislation is considered, a limited number of filters are authorized in the formula‐ tion of sun products. In Europe, Appendix VI of the Regulation lists the 26 authorized filters, that is to say 25 organic filters and one screen, titanium dioxide, each one having a maximum concentration of use (% m/m) and perhaps a list of comments which should feature on the packaging. In the USA, the original list was made up of 16 filters (15 filters and 1 screen). In the periodfrom1997 to 2008, 8 filters recognizedsafe andeffective were gradually addedto this list. The FDA gradually authorized a certain number of products which were synthetized and patented in Europe in order to beef up the original list. It should be noted that zinc oxide is not mentionedinAppendixVIoftheRegulation(Table4).Theconcentrationofzincoxideistherefore not limited. This, however, remains theoretical, as the limit is imposed by its dosage form, as in high percentages of concentration, a paste is obtained, which would be difficult to market. Seventeen filters are currently in common between the European and American legislation.

#### *2.2.3. The combination of different filters or the combination of filters with active ingredients*

European formulators have a great deal of freedom. They can combine as many filters as they want, as long as the combinations are not already patented, of course. They can also combine filters with active ingredients which have a softening, antioxidizing or soothing effect, etc. They have to check that the raw material they want to incorporate is not banned and they must check to see if the material is on a list if regulated ingredients (Appendix III: substances with restricted use in particular). In the USA, combinations with **protectants** are authorized within the limits of the maximum authorized concentrations (Table 5). **A skin protectant drug product is defined as «a drug product that temporarily protects injured or exposed skin or mucous membrane surfaces from harmful or annoying stimuli, and may help provide relief to such surfaces».**


**US Europe**

/

About Suncare Products http://dx.doi.org/10.5772/55411 133

/

1 - Allantoin 0.5 – 2% / 2 - Cocoa butter 50 – 100% / 3 - Cod liver oil 5 – 13.56% / 4 - Dimethicone 1 à 30% / 5 - Glycerin 20 – 45% / 6 - Hard fat 50 – 100% / 7 - Lanolin 12.5 – 50% /

9 - Petrolatum 30% / 10 - White petrolatum 30% / 11 - Aluminium hydroxyde gel 0.15 – 5% Annex III 12 - Calamine 1 - 25% / 13 - Kaolin 4 – 20% /

18 - Topical starch 10 – 98% / 19 - Sodium bicarbonate / /

Three ingredient groups in US : group 1 [1 to 10] – group 2 [11 to 16] and group 3 [17]

combined with glycerine, but not with aluminium hydroxide gel.

**Table 5.** Comparative regulation of ingredients called « protectants » in US

50% 30 – 35% in combination with colloidal oatmeal

14 - Zinc acetate 0.1 – 2% Annex Colorant (CI 77950) 15 - Zinc carbonate 0.2 – 2% Annex III ( 1% expressed in Zinc) 16 - Zinc oxide 1 – 25% Annex Colorant (CI 77947)

> 0.007% minimum 0.003% minimum in combination with mineral oil

The active ingredients in each of these groups can be combined only with the other active ingredients in the same group. Active ingredients in different groups cannot be used in the same drug product. For example, cocoa butter can be

The comments which must be included on the packaging are presented in Table 6. The same concern for public health governs the labelling rules, no matter which legislation is concerned. It is a pity that at present, on the packaging of European sun products, there is no clear reference to the size of the recommended dose of the product which should be applied on the skin. This lack is currently being studied, and it has to be said that having directions on the packaging

8 - Mineral oil

17 - Colloidal oatmeal

*2.2.4. Labelling rules*

**Table 4.** Authorized UV-filters in Europe and in US


Three ingredient groups in US : group 1 [1 to 10] – group 2 [11 to 16] and group 3 [17]

The active ingredients in each of these groups can be combined only with the other active ingredients in the same group. Active ingredients in different groups cannot be used in the same drug product. For example, cocoa butter can be combined with glycerine, but not with aluminium hydroxide gel.

**Table 5.** Comparative regulation of ingredients called « protectants » in US

#### *2.2.4. Labelling rules*

**INCI name/American name (trade name)**

132 Highlights in Skin Cancer

Camphor benzalkonium methosulfate (Mexoryl SO®

Homosalate (Eusolex HMS, Néohélipan HMS, Parsol

Phenylbenzimidazole sulfonic acid, Ensulizole (Eusolex

Butylmethoxydibenzoylmethane (Eusolex 9020, Parsol

Octocrylene (Uvinul N539T, Eusolex OCR, Parsol 340,

Polyacrylamidomethylbenzylidene camphor (Mexoryl

Ethyl hexyl methoxycinnamate, Octinoxate (Uvinul MC 80, Eusolex 2292, Parsol MCX, Néohéliopan AV)

Isoamyl p-methoxycinnamate, Amiloxate (Néohéliopan

4 -methylbenzylidene camphor, Enzacamene (Eusolex

Ethylhexylsalicylate, Octisalate (Eusolex OS, Néohéliopan

Methylene bis-benzotriazolyl tetramethylbutylphenol,

Disodium phenyl dibenzimidazole tetrasulfonate

Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine,

Diethylamino hydroxybenzoyl hexyl benzoate

**Table 4.** Authorized UV-filters in Europe and in US

6300, Néohéliopan MBC, Parsol 5000)

OS, Dermoblock OS)

Bisoctrizole (Tinosorb M)

(Uvinul A+)

(Néohéliopan AP)

Bemotrizinal (Tinosorb S)

Drometrizole trisiloxane (Mexoryl XL) 15%

Terephtalydene dicamphor sulfonic acid, Ecamsule

232, Parsol HS, Néohéliopan Hydro USP)

HMS)

(Mexoryl SX)

Néohéliopan 303 USP)

178)

SW)

E1000)

**Cmax authorized (Europe)**

10% (in acid form)

10% (in acid form)

10% (in acid form)

) 6% /

10% 15%

5% 3%

6% /

10% 7.5%

10% 10%

4% 4%

5% 5%

10% 10%

10% 10%

10% /

8% (in acid form) 4%

Aminobenzoic acid / 15% Cinoxate / 3% Dioxybenzone / 3% Meradimate / 5% Trolamine salicylate / 12% Zinc oxide / 25%

Oxybenzone (Eusolex 4360, Uvinul M40) 10% 6%

Benzylidene camphor sulfonic acid (Mexoryl SL) 6% (in acid form) /

PEG-25 PABA (Uvinul P25) 10% /

Octyl triazone (Uvinul T150) 5% 5%

Diethylhexylbutamidotriazone (Uvasorb HEB) 10% 3%

3-benzylidene camphor (Unisol S22) 2% /

Octyl dimethyl PABA, Padimate O (Eusolex 6007) 8% 8% Benzophenone-4 et 5 , Sulisobenzone (Uvinul MS40) 5% (in acid form) 10%

Polysilicone 15 (Parsol SLX) 10% / Titanium dioxide 25% 25%

**Cmax authorized (US)**

10%

10%

/

The comments which must be included on the packaging are presented in Table 6. The same concern for public health governs the labelling rules, no matter which legislation is concerned. It is a pity that at present, on the packaging of European sun products, there is no clear reference to the size of the recommended dose of the product which should be applied on the skin. This lack is currently being studied, and it has to be said that having directions on the packaging as to how much of the product should be used would be very useful, as it is known that consumers do not use as much of the product as they should, on average 4 times less [36]. It is known that the effect is linked to the dose. A good initiative of the Colipa should be noted concerning sun protection cosmetics: this committee has in fact created a logo (Figure 1) which reminds us that the product in question provides protection against UVA rays. A ratio of UVA efficacy/UVB efficacy equal to or lower than 3 was imposed in order to avoid products which only protect against UVB rays.

**Figure 1.** UVA logo

**2.3. Dosage forms**

emulsion stabilizer [38].

*2.3.1. Liquid forms: Sun oils and waters*

*2.2.5. Procedures to be followed*

ecamsule, avobenzone and octocrylene.

In Europe, it is just necessary to draw up a file on cosmetics which should remain relatively short. This is only consulted by authorized personnel from the authorities which are concerned (AFSSaPS or the Répression des Fraudes [Fraud Prevention]) in case of inspection. The status of an over-the-counter medicine is very restricting as solid clinical studies must back up the request for such a status. As an example, we can look at the Anthélios SX® product by the Laboratoires La Roche Posay whose sale is now authorized in the USA following FDA approval. The file was backed up by 28 clinical studies including 2500 patients from 6 months to 65 years of age. It can be said, therefore, that sun products destined for the American market are ones which have sufficient hindsight in Europe (enough time has lapsed to enable clinical studies to be compiled). What is more, very few active ingredients are present in the formula:

About Suncare Products http://dx.doi.org/10.5772/55411 135

Sun products come in different dosage forms: liquid forms (oils), thick pasty forms (emulsions which are referred to as milks or creams according to the texture) and solid forms (sticks). The most interesting forms are the systems which contain 2 phases enabling hydro- and liposoluble filters to be incorporated together. The role of the excipient is a minor one, and will have little influence on the SPF measured. However, it will have an important role to play in terms of how the product is spread [36], in terms of its substantivity (a sun product must stay on the surface and the phenomenon of transdermal penetration must be reduced to as little as possible) [37]. Pickering emulsions are interesting as their formula contains titanium dioxide which not only carries out the role of an active sun-protection ingredient but also that of an

Oils and waters are single-phase systems and are forms which provide minimal sun protection. Generally, they are composed of thermal water to which a hydrophilic filter is added. As for


**Table 6.** Labelling of sunscreens

**Figure 1.** UVA logo

as to how much of the product should be used would be very useful, as it is known that consumers do not use as much of the product as they should, on average 4 times less [36]. It is known that the effect is linked to the dose. A good initiative of the Colipa should be noted concerning sun protection cosmetics: this committee has in fact created a logo (Figure 1) which reminds us that the product in question provides protection against UVA rays. A ratio of UVA efficacy/UVB efficacy equal to or lower than 3 was imposed in order to avoid products which

**EU Europe**

SPF : 6 – 10 Low protection SPF : 15 – 20 – 15 Moderate protection SPF : 30 – 50 High protection SPF : 50+

Very high protection

/

Water resistant Very water resistant

No sun exposure before 36 months

« provides minimum » « minimal » or « minimum » « protection against » « sunburn » or « sunburn and tanning » or "for skin that sunburns

12 ≤ SPF ‹ 30 : « provides moderate » or "moderate" « protection against » « sunburn » or « sunburn and tanning » or "for skin that sunburns

SPF ≥ 30 : « provides high » or "high » « protection against » « sunburn » or « sunburn and tanning » or "for skin

eyes. Rinse with water to remove" "Sto use and ask a doctor if rash or irritation developps and lasts"

activity in the water or sweating or

« retains SPF after 40 minutes of activity in the water or sweating or

or « smoothly » or « evenly » ""reapply as needed or after towel drying, swimming, or sweating or

highly sensitive sunburn"

only protect against UVB rays.

134 Highlights in Skin Cancer

Categories of sunscreens 2 ‹ SPF ≤ 12 : « provides minimal » or

minimally"

easily"

Warnings "When using this product keep out of

Particular allegations « retains SPF after 40 minutes of

perspiring »

perspiring"

perspiring"

ask a doctor »

Quantity to apply « apply » « liberally » or « generously »

Cas of childrens « children under 6 months of age :

**Table 6.** Labelling of sunscreens

#### *2.2.5. Procedures to be followed*

In Europe, it is just necessary to draw up a file on cosmetics which should remain relatively short. This is only consulted by authorized personnel from the authorities which are concerned (AFSSaPS or the Répression des Fraudes [Fraud Prevention]) in case of inspection. The status of an over-the-counter medicine is very restricting as solid clinical studies must back up the request for such a status. As an example, we can look at the Anthélios SX® product by the Laboratoires La Roche Posay whose sale is now authorized in the USA following FDA approval. The file was backed up by 28 clinical studies including 2500 patients from 6 months to 65 years of age. It can be said, therefore, that sun products destined for the American market are ones which have sufficient hindsight in Europe (enough time has lapsed to enable clinical studies to be compiled). What is more, very few active ingredients are present in the formula: ecamsule, avobenzone and octocrylene.

#### **2.3. Dosage forms**

Sun products come in different dosage forms: liquid forms (oils), thick pasty forms (emulsions which are referred to as milks or creams according to the texture) and solid forms (sticks). The most interesting forms are the systems which contain 2 phases enabling hydro- and liposoluble filters to be incorporated together. The role of the excipient is a minor one, and will have little influence on the SPF measured. However, it will have an important role to play in terms of how the product is spread [36], in terms of its substantivity (a sun product must stay on the surface and the phenomenon of transdermal penetration must be reduced to as little as possible) [37]. Pickering emulsions are interesting as their formula contains titanium dioxide which not only carries out the role of an active sun-protection ingredient but also that of an emulsion stabilizer [38].

#### *2.3.1. Liquid forms: Sun oils and waters*

Oils and waters are single-phase systems and are forms which provide minimal sun protection. Generally, they are composed of thermal water to which a hydrophilic filter is added. As for sun oils, they are generally composed of a vegetal oil, such as monoi, for example, or coconut or sesame oil, to which one or more lipophilic filters is added.

marketing of a certain number of products containing sun filters (such as benzyl salicylate) [40] and claiming to prevent sunburn, without being able to evaluate precisely the level of efficacy. At this time, the product Ambre solaire® by the chemist Eugène Schueller could be found on the market. At the time, no particular attention was paid to the molecules used and a certain number of ingredients used were likely to cause what Freund defined for the first time as Berloque Dermatitis [41]. From the end of the Second World War, the number of companies involved in the field of sun protection (Coppertone, Piz Buin, etc.) increased, and more and more knowledge was gained about efficacy. Some errors were committed, however, such as the Bergasol products (in the 1970's) which were formulated with bergapten, which is a molecule with photosensitizing properties which are nowadays well-known [42]. The efficacy indicators which were initially very low, defined by Blum et al in 1945 [43], gradually increased,

Currently, whatever the country, protocols can be found which have similar conditions (type

The FDA defines the MED as the "the quantity of erythema-effective energy (expressed as joules per square meter) required to produce the first perceptible, redness reaction with clearly

The Colipa [44] gives its own definition, a precision of time, as we know that sunburn is likely to develop over a 24-hour period: "The Minimal Erythema Dose in human skin is defined as the lowest UV dose that produces the first perceptible unambiguous erythema with defined

MED on product protected skin (MEDp) to the MED on unprotected skin (MEDu) of the same

The SPF for the product is the arithmetic mean of all valid individual obtained from all subjects

The comparative elements between the Colipa and the FDA concerning the subjects selected are presented in Table 7. As we can notice, the selection conditions are very similar. In Europe, the selection of subjects is made following the visual determining of the phototype of the subjects and by questioning or by instrumental methods using a chromameter which converts the colours into a digital code comprising 3 coordinates (Lab system). Using these coordinates,

) value for a product is defined as the ratio of the

About Suncare Products http://dx.doi.org/10.5772/55411 137

borders appearing over most of the field of UV exposure, 16 to 24 hours".

eventually reaching the values of 50+ which we know today.

of panel, mass of the product applied, type of lamp used, etc.).

*2.4.2. In vivo methods of determination*

*2.4.2.1. Definition of the MED*

defined borders".

*2.4.2.2. Definition of SPF*

subject:

An individual Sun Protection Factor (SPFi

in the test, expressed to one decimal place.

*2.4.2.3. Information concerning the volunteers*

SPF = MEDp (protected skin) / MEDu (unprotected skin)

#### *2.3.2. Paste forms: Gels and emulsions*

Gels, often called "sun jellies", are forms which are not very photoprotective. These are aqueous or hydroalcoholic phases (the latter being quite incompatible with exposure to the sun!) which are thickened using a derivative of cellulose (carboxymethyl cellulose, for example) or a derivative of carboxyvinylic acid and incorporating a hydrophilic filter.

As for emulsions, they are the most commonly used dosage forms in the field of topical photoprotection. According to their viscosity and therefore their use limited to small surface areas (the face for example), or adapted to large areas (the whole body), they are referred to either as milks or creams. Whichever they may be, these forms provide a wide range of SPF values, going up to 50+. As they are two phase systems, (containing a hydrophilic phase and a lipophilic phase), they offer the great advantage of enabling all sorts of combinations of filters (hydro- and lipophilic ones) to which screens (such as zinc oxide and titanium dioxide) can be added. Lipophilic aqueous emulsions (W/O) are to be preferred due to their water-resistant character.

#### *2.3.3. Solid forms: Sticks*

The stick is a highly photoprotective cosmetic form which is adapted for application on small surface areas, obviously for the lips, and also for the sides of the nose, for example. A stick is made up of a mixture of waxes (animal wax, such as bees' wax, or vegetable waxes such as carnauba wax) which act as a "spine" for the finished product and give it its hardness, fats (vaseline, shea butter, etc.) and oils (sweet almond, jojoba, etc.). Lipophilic filters and screens are then incorporated into this mixture.

#### **2.4. Determining the efficacy**

#### *2.4.1. Efficacy indicators: SPF and UVA-PF*

In France, article L 5131-6 of the Public Health Code states that " a cosmetic product can only be put onto the market free of charge or against payment if the manufacturer, or their repre‐ sentative, or the person for whom the cosmetic product is made […], effectively makes available to the controlling authorities […] proof of the effects that it is claimed to have, when it is warranted by the nature of the effect or of the product". As for over-the-counter products, clinical trials must have been carried out, of course, in order for the product to be able to be put onto the market, as in this case, it is a medicine.

#### *2.4.1.1. A few words about sun protection factor*

The Sun Protection Factor (SPF) is a factor which indicates the efficacy of a sun product regarding erythema, as UVB rays are 1000 times more erythemogenic than UVA rays [39]. If we briefly recount the history of sun products, everything started in the 1930's with the marketing of a certain number of products containing sun filters (such as benzyl salicylate) [40] and claiming to prevent sunburn, without being able to evaluate precisely the level of efficacy. At this time, the product Ambre solaire® by the chemist Eugène Schueller could be found on the market. At the time, no particular attention was paid to the molecules used and a certain number of ingredients used were likely to cause what Freund defined for the first time as Berloque Dermatitis [41]. From the end of the Second World War, the number of companies involved in the field of sun protection (Coppertone, Piz Buin, etc.) increased, and more and more knowledge was gained about efficacy. Some errors were committed, however, such as the Bergasol products (in the 1970's) which were formulated with bergapten, which is a molecule with photosensitizing properties which are nowadays well-known [42]. The efficacy indicators which were initially very low, defined by Blum et al in 1945 [43], gradually increased, eventually reaching the values of 50+ which we know today.

### *2.4.2. In vivo methods of determination*

Currently, whatever the country, protocols can be found which have similar conditions (type of panel, mass of the product applied, type of lamp used, etc.).

### *2.4.2.1. Definition of the MED*

sun oils, they are generally composed of a vegetal oil, such as monoi, for example, or coconut

Gels, often called "sun jellies", are forms which are not very photoprotective. These are aqueous or hydroalcoholic phases (the latter being quite incompatible with exposure to the sun!) which are thickened using a derivative of cellulose (carboxymethyl cellulose, for example) or a

As for emulsions, they are the most commonly used dosage forms in the field of topical photoprotection. According to their viscosity and therefore their use limited to small surface areas (the face for example), or adapted to large areas (the whole body), they are referred to either as milks or creams. Whichever they may be, these forms provide a wide range of SPF values, going up to 50+. As they are two phase systems, (containing a hydrophilic phase and a lipophilic phase), they offer the great advantage of enabling all sorts of combinations of filters (hydro- and lipophilic ones) to which screens (such as zinc oxide and titanium dioxide) can be added. Lipophilic aqueous emulsions (W/O) are to be preferred due to their water-resistant

The stick is a highly photoprotective cosmetic form which is adapted for application on small surface areas, obviously for the lips, and also for the sides of the nose, for example. A stick is made up of a mixture of waxes (animal wax, such as bees' wax, or vegetable waxes such as carnauba wax) which act as a "spine" for the finished product and give it its hardness, fats (vaseline, shea butter, etc.) and oils (sweet almond, jojoba, etc.). Lipophilic filters and screens

In France, article L 5131-6 of the Public Health Code states that " a cosmetic product can only be put onto the market free of charge or against payment if the manufacturer, or their repre‐ sentative, or the person for whom the cosmetic product is made […], effectively makes available to the controlling authorities […] proof of the effects that it is claimed to have, when it is warranted by the nature of the effect or of the product". As for over-the-counter products, clinical trials must have been carried out, of course, in order for the product to be able to be

The Sun Protection Factor (SPF) is a factor which indicates the efficacy of a sun product regarding erythema, as UVB rays are 1000 times more erythemogenic than UVA rays [39]. If we briefly recount the history of sun products, everything started in the 1930's with the

or sesame oil, to which one or more lipophilic filters is added.

derivative of carboxyvinylic acid and incorporating a hydrophilic filter.

*2.3.2. Paste forms: Gels and emulsions*

136 Highlights in Skin Cancer

character.

*2.3.3. Solid forms: Sticks*

are then incorporated into this mixture.

*2.4.1. Efficacy indicators: SPF and UVA-PF*

put onto the market, as in this case, it is a medicine.

*2.4.1.1. A few words about sun protection factor*

**2.4. Determining the efficacy**

The FDA defines the MED as the "the quantity of erythema-effective energy (expressed as joules per square meter) required to produce the first perceptible, redness reaction with clearly defined borders".

The Colipa [44] gives its own definition, a precision of time, as we know that sunburn is likely to develop over a 24-hour period: "The Minimal Erythema Dose in human skin is defined as the lowest UV dose that produces the first perceptible unambiguous erythema with defined borders appearing over most of the field of UV exposure, 16 to 24 hours".
