*2.4.2.2. Definition of SPF*

An individual Sun Protection Factor (SPFi ) value for a product is defined as the ratio of the MED on product protected skin (MEDp) to the MED on unprotected skin (MEDu) of the same subject:

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

The SPF for the product is the arithmetic mean of all valid individual obtained from all subjects in the test, expressed to one decimal place.

#### *2.4.2.3. Information concerning the volunteers*

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, we can determine the ITA (Individual Typological Angle) which is proportional to the degree of pigmentation of the skin. The darker the skin, the smaller the angle [45, 46]. However, it is regrettable that the minimum number of subjects required by the Colipa in order to obtain valid results is only 10. The FDA demands double that number, which seems more reasonable. No notion of latent period between the tests is mentioned by the FDA. It is a pity that the presence of nevi is not totally unacceptable in the US, indeed, the link between multiple nevi and melanomas is a well-established fact. The risk of developing a melanoma for a person with multiple nevi, that is to say between 100 and 120, is 7 times higher than for someone who only has a few nevi (between 0 and 15) [47, 48, 49]. It would be interesting, therefore, to limit the tests to subjects with a low number of nevi. It also seems absurd to find references to people with phototype I skin, as these subjects are at risk of developing skin cancer [50]. It therefore appears useless to subject them to UV irradiation, whether it be natural or artificial.

A test will be considered as valid if "confidence limits (95% Confidence Interval) for the mean SPF should fall within the range of ± 17% of the mean SPF". In the case of a high level of uncertainty, the subject(s) having generated over-large standard deviation are excluded from

The irradiation sites are similar whether it be for the Colipa or the FDA: between the scapula line and the waist. The minimum surface area required according to the FDA is one of 50cm² for an area, and of 4 to 5 cm² for a subsite area. For the Colipa, the minimum area for a product

and the maximum shall be 60 cm2

The Colipa specifies that the quantity of the product applied on the skin before spreading should be 2 mg/cm2 ± 2.5% (the sensitivity of the scales should be at least 0.0001 g, ie. with at least 4 decimal places). The product should be applied with a finger-cot and can be deposited with a syringe for liquid products, or for products which can be made into liquids after being warmed slightly. The Colipa states a quantity of 15 drops of the product for 30 cm2 in order to obtain a homogenous distribution of the product. The application time is also measured and should be between 20 and 50 seconds according to the surface area in question. The products

The Colipa makes a clarification regarding the proximity of the test sites: there must be a

A variable latent period is respected between application and irradiation: 15 minutes (FDA)

The lack of information concerning the quantity of the product present on the skin after spreading is also regrettable. No *in vivo* method states the quantity of the product which remains on the finger-cot, a quantity which varies according to the nature of the product which is applied (a product which is either fluid or pasty, with either sticky or, on the contrary, film-

The conditions of temperature of the room in which the tests are carried out are drawn up by the Colipa. It is recommended to use rooms with air-conditioning. However, the temperature

The characteristics in terms of quality of emitted UV rays, of total irradiance and the uniformity of the beam are similar in Europe to the United States. The characteristics are the following: a solar simulator used for determining the SPF of a sunscreen product should be filtered so that it provides a continuous emission spectrum from 290 to 400 nm similar to sunlight at sea level from the sun at a zenith. No emission fluctuations should be seen through time and the

minimum distance of 1 cm between the borders of adjacent product application sites.

.

(this dose is universally recognized).

About Suncare Products http://dx.doi.org/10.5772/55411 139

the study.

*2.4.2.4.1. Test area*

*2.4.2.4. The conditions of the test*

application site shall be 30 cm2

are applied in a randomized way.

or 15 to 30 minutes (Colipa).

range is quite wide (18 to 26°C).

*2.4.2.4.2. The characteristics of the lamp used*

forming ingredients).

The dose of the product applied on the skin is **2 mg/cm**<sup>2</sup>


**Table 7.** Characteristics of the panel

A test will be considered as valid if "confidence limits (95% Confidence Interval) for the mean SPF should fall within the range of ± 17% of the mean SPF". In the case of a high level of uncertainty, the subject(s) having generated over-large standard deviation are excluded from the study.

#### *2.4.2.4. The conditions of the test*

#### *2.4.2.4.1. Test area*

we can determine the ITA (Individual Typological Angle) which is proportional to the degree of pigmentation of the skin. The darker the skin, the smaller the angle [45, 46]. However, it is regrettable that the minimum number of subjects required by the Colipa in order to obtain valid results is only 10. The FDA demands double that number, which seems more reasonable. No notion of latent period between the tests is mentioned by the FDA. It is a pity that the presence of nevi is not totally unacceptable in the US, indeed, the link between multiple nevi and melanomas is a well-established fact. The risk of developing a melanoma for a person with multiple nevi, that is to say between 100 and 120, is 7 times higher than for someone who only has a few nevi (between 0 and 15) [47, 48, 49]. It would be interesting, therefore, to limit the tests to subjects with a low number of nevi. It also seems absurd to find references to people with phototype I skin, as these subjects are at risk of developing skin cancer [50]. It therefore

appears useless to subject them to UV irradiation, whether it be natural or artificial.


I – always burns easily; never tans (sensitive) II – Always burns easily; tans minimally (sensitive) III – Burns moderately; tans gradually (light

(Skin type and Sunburn and tanning history based on first 30 to 45 minutes sun exposure after a winter season of no sun exposure)




III using the following guidelines :

of abnormal response to the sun)

brown) (normal)

data for analysis) - maximum 25

**Colipa FDA**






Written consent - Informed, written (signature) consent - Legally effective written informed consent



Phototype - Phototype I, II or III according to Fitzpatrick

methods


beds


Medical characteristics

138 Highlights in Skin Cancer

Number of volunteers

Frequency of participation in

**Table 7.** Characteristics of the panel

tests

The irradiation sites are similar whether it be for the Colipa or the FDA: between the scapula line and the waist. The minimum surface area required according to the FDA is one of 50cm² for an area, and of 4 to 5 cm² for a subsite area. For the Colipa, the minimum area for a product application site shall be 30 cm2 and the maximum shall be 60 cm2 .

The dose of the product applied on the skin is **2 mg/cm**<sup>2</sup> (this dose is universally recognized). The Colipa specifies that the quantity of the product applied on the skin before spreading should be 2 mg/cm2 ± 2.5% (the sensitivity of the scales should be at least 0.0001 g, ie. with at least 4 decimal places). The product should be applied with a finger-cot and can be deposited with a syringe for liquid products, or for products which can be made into liquids after being warmed slightly. The Colipa states a quantity of 15 drops of the product for 30 cm2 in order to obtain a homogenous distribution of the product. The application time is also measured and should be between 20 and 50 seconds according to the surface area in question. The products are applied in a randomized way.

The Colipa makes a clarification regarding the proximity of the test sites: there must be a minimum distance of 1 cm between the borders of adjacent product application sites.

A variable latent period is respected between application and irradiation: 15 minutes (FDA) or 15 to 30 minutes (Colipa).

The lack of information concerning the quantity of the product present on the skin after spreading is also regrettable. No *in vivo* method states the quantity of the product which remains on the finger-cot, a quantity which varies according to the nature of the product which is applied (a product which is either fluid or pasty, with either sticky or, on the contrary, filmforming ingredients).

The conditions of temperature of the room in which the tests are carried out are drawn up by the Colipa. It is recommended to use rooms with air-conditioning. However, the temperature range is quite wide (18 to 26°C).

#### *2.4.2.4.2. The characteristics of the lamp used*

The characteristics in terms of quality of emitted UV rays, of total irradiance and the uniformity of the beam are similar in Europe to the United States. The characteristics are the following: a solar simulator used for determining the SPF of a sunscreen product should be filtered so that it provides a continuous emission spectrum from 290 to 400 nm similar to sunlight at sea level from the sun at a zenith. No emission fluctuations should be seen through time and the intensity of irradiation should be as uniform as possible. The material should be subjected to frequent radiometric controls.

Sometimes, we speak in terms of SED (Standard Erythema Dose) which corresponds to the efficient erythemogenic exposure. For human beings, an SED corresponds to an exposure of

SED) according to the phototypes (as the Caucasian type includes phototypes which differ as much as phototypes I and IV) [51]. We can speak indifferently either in terms of dose or time.

Although the protocol of determining the SPF is very clearly defined, both in Europe and in America, this is not the case concerning the UVA protection factor [52]. The two most fre‐ quently used methods are the IPD (Immediate Pigment Darkening) and PPD (Persistent Pigment Darkening) methods. Since 2007, taking the UVA protection in a sunscreen into account has become a necessity in Europe, with the establishing of 5 categories corresponding

These methods are based on the evaluation of the Meirowski phenomenon consecutive to the action of UVA rays. To do this, a halide lamp or a xenon arc lamp equipped with UVB filters is used. The subjects who are recruited have phototypes III and IV because they are likely to develop a tan in the evening. If the reading takes place at a maximum of 2 hours after irradi‐ ation, we refer to the IPD (immediate pigment darkening) method. If the reading is taken later,

There is no official method in this field. All the methods which are proposed are spectropho‐ tometric methods based on the Beer Lambert law which links the absorbance of a sample to its concentration of active molecules. The principal of determining the SPF *in vitro* is based on measuring the transmittance of a sun product applied on various kinds of support. In the 1980's, Sayre and Agin studied different spectral light sources enabling them to correlate the results obtained respectively by *in vitro* and *in vivo* methods [58]. The first trials were carried

we can refer to it as the PPD (persistant pigment darkening) method [54, 55, 56].

(or 1.5 SED) and 600 j/m2

(or 6.0

141

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

. Caucasian subjects have an MED of between 150 j/m2

*2.4.2.5. Determining the UVA protection factor (UVA-FP)*

to no, low, medium, high and highest UVA protection [53].

100 j/m2

or :

*2.4.2.5.1. Introduction*

*2.4.2.5.2.- IPD and PPD methods*

The UVA-PF is defined according to:

*2.4.3.1. Determining the SPF in vitro*

UVA-PF = MIPDDprotected skin / DMIPDDunprotected skin

UVA-PF = MPPDDprotected skin / MPPDDunprotected skin

with MIPDD, Minimum Immediate Pigment Darkening Dose

with MPPDD, the Minimal Persistent Pigment Darkening Dose.

*2.4.3. In vitro methods of determining the efficacy of sun products*

The source of illumination should be either a tungsten light bulb or a warm white fluorescent light bulb that provides a level of illumination at the test site within the range of 450 to 550 lux (FDA) or a xenon arc solar simulator with a filtering system.

#### *2.4.2.4.3. Determining the MED in practice*

A series of UV radiation exposures expressed as joules per square meter is administered to the each subject with an accurately-calibrated solar simulator.

A Colipa – FDA comparison is presented in Table 8. The FDA suggests some examples for SPF from 8 to 15.


**Table 8.** MED determination

For a product with an SPF of 8, given that the MED must correspond to the dose or to the median time, it will be surrounded with values obtained according to a geometric sequence at a rate of 1.25:

0.64 x MED – 0.80 x MED – 1 MED – 1.25 Med – 1.56 MED

Furthermore, 2 doses placed symmetrically in relation to the median dose are added, here:

0.9 x MED and 1.10 x MED

Sometimes, we speak in terms of SED (Standard Erythema Dose) which corresponds to the efficient erythemogenic exposure. For human beings, an SED corresponds to an exposure of 100 j/m2 . Caucasian subjects have an MED of between 150 j/m2 (or 1.5 SED) and 600 j/m2 (or 6.0 SED) according to the phototypes (as the Caucasian type includes phototypes which differ as much as phototypes I and IV) [51]. We can speak indifferently either in terms of dose or time.

#### *2.4.2.5. Determining the UVA protection factor (UVA-FP)*
