7 Exposure and risk assessment

Survey and safety assessment of Chemical substances in artificial nails and nail hardeners

7.1 Exposure and risk assessment for consumers using nail hardeners
7.2 Exposure and risk assessment for consumers using artificial nails

The assessment of exposure to substances in nail hardeners and artificial nails is based on the analysed content of substances in selected products on the Danish market (see part 3) and is performed in accordance with the principles in the EU Technical guidance Document (TGD) (27) and The Scientific Committee for Consumer Products (SCCP) guidelines (28). The internal body dose (Systemic Exposure Dose, SED) is estimated in a worst case scenario for a model person by applying standard parameters from TGD and SCCP. The health risks of exposure to selected substances in nail hardeners and artificial nails are assessed by calculating the margin of safety (MoS). The calculation is based on NOAEL, possibly LOAEL established in the toxicological profiles prepared in this survey and the estimated systemic exposure dose (SED).

The safety assessment (part 6) showed that sensitisation is the critical effect of most of the selected components in the nail products. However, sensitisation of contact allergens are dependent not only on the inherent sensitisation capacity of the chemical, but also on the dose and type of exposure, the amount of allergen per unit area surface of skin, the vehicle and the condition of the skin (29). Establishment of a lower safe threshold concentration for the induction and elicitation of sensitisation may be difficult, particularly for use in regulatory toxicology. A validated method for risk assessment for the sensitisation effect has not yet been established. Therefore the below risk assessment is split in a risk assessment of the systemic effects and a part describing the potential risk of sensitisation.

7.1 Exposure and risk assessment for consumers using nail hardeners

In this survey it was decided to focus on free formaldehyde in the nail hardeners. Other substances could also be interesting from a health perspective. However, it was out of range of this project to cover additional ingredients.

Formaldehyde in nail hardeners may react with proteins on the surface of the nail and thereby be immobilized. Depending on the applied concentration some of the formaldehyde may, however, penetrate the nail plate and reach the tissue under the nail. This may especially be the case if the nail is thin, soft or damaged. Formaldehyde may also reach the skin surrounding the nail if the product is not very carefully smeared on the nail plate. As formaldehyde is volatile at room- and skin temperature and may be inhaled after evaporation from the nail and areas of the skin, it is also relevant to include calculation of inhalation in the systemic dose estimation.

The daily exposure of formaldehyde in nail hardeners has been calculated for a model person of 40 kg. This body weight is based on a conservative approach also including younger girls from 15 years and up in the risk assessment.

The daily exposure was calculated for the highest allowed content of formaldehyde in nail hardeners; 5%. The maximum amount of formaldehyde found in the analysed products was 4.05%.

The following assumptions were used as realistic worst-case scenario:

Weight of person, adult: 40 kg

Number of applications per day: 1/day^[6]

Applied amount per application (10 nails): 0.25 g (28)

Maximum amount of formaldehyde in nail hardeners: 5 %

7.1.1 Risk assessment for systemic effects

It is assessed that the amount of formaldehyde in nail hardeners will either react with proteins on the surface of the nail, reach the skin surrounding the nail or evaporate during the drying process of the nail hardener. It is evaluated that around 25% of the total content of formaldehyde in the product will evaporate during the drying process. The remaining 75% will cover the nail plate and the skin surrounding the nail. The nails approximately amount to maximum 40 cm². The skin surrounding the nails will amount to about 4 cm² (28), corresponding to about 9% of the total area of nail and skin. Therefore it is assumed that 9% of the applied nail hardeners will cover the skin surrounding the nail, and thereby may contribute to the systemic dose.

It is assumed that none of the formaldehyde reacting on the nail plates will contribute to the systemic dose as no specific data for this possible contribution to a systemic dose is known. The possible effects of formaldehyde penetrating the nail are discussed later in the chapter.

Twenty-five percent formaldehyde will evaporate during the drying process. It is assumed that it is released in the close area around the person (1 m³), and that half of it is absorbed via inhalation or dermal absorption.

Therefore, calculating the systemic exposure dose (SED) only includes the part constituting the skin surrounding the nail (9%) and half the part evaporating during the drying process; 12.5% of the total amount contained in the product. In total 21.5% of the total content of formaldehyde will contribute to a systemic dose.

Daily exposure_{inhalation+dermal}, formaldehyde:

The daily exposure dose (SED) of formaldehyde in nail hardeners is calculated as mg per kg bodyweight per day (mg/kg bw/day) for the model person.

Normally, a cosmetic product with a margin of safety (MoS) of more than 100 is considered to be a product exposing the user to an acceptable (minimum) health risk (28). When calculating the margin of safety, a safety factor of 10 for extrapolation of data from animals to humans and a safety factor of 10 for particularly sensitive human individuals are taken into account.

Based on the demonstrated NOAEL values for systemic effects of formaldehyde (15 mg/kg bw/day), a margin of safety is calculated for the maximum allowed concentrations of formaldehyde in nail hardeners; 5% (table 7-1).

Table 7.1 The systemic exposure dose (SED) and NOAELs for formaldehyde are used to calculate the margin of safety.

Substance	NO(A)EL (mg/kg bw/d)	Daily dose, adult, 40 kg (SED) (mg/kg bw/d)	MoS
Formaldehyde	15^a	0,067	224

^a Based on systemic effects other than cancer

The calculated margin of safety for formaldehyde in nail hardeners is larger than 100, which indicates an acceptable health risk in relation to systemic effects and the scenario described above.

A critical effect of formaldehyde is its possible potential as carcinogen. The carcinogenic potential of formaldehyde is observed in humans after inhalation of large concentrations in the working environment (2).

The threshold limiting value (TLV) of formaldehyde is 0.4 mg/m³. The threshold limiting value of 0.4 mg/m³ is based on the concentration in the working environment for a working day of 8 hours corresponding to a total concentration of 3.2 mg/m³.

It is assumed that 25 percent of the formaldehyde contained in the nail hardener will evaporate during the drying process. It is further assumed that it is released in the close area around the person (» 1 m³). This corresponds to a concentration in the close area of the person of 3.125 mg/m³ in a short period of time each time the nail hardener is used. The use of nail hardeners’ during one year is maximum 124 times (see appendix 10.1) giving a daily mean exposure of 1.06 mg/m³ (3 times lower than the total threshold value) indicating that the life-time risk of cancer by using nail hardener is negligible. However sensitive persons may experience irritation of the nasal cavity and the upper respiratory tract during the short time of use (½ hour) of nail hardeners as the short-term concentration during use is higher than the threshold limiting value.

7.1.2 Risk assessment for sensitisation

Based on published literature the most critical effect of nail hardeners are sensitisation. However, it is difficult to establish a lower limit for this effect. Thus the above exposure scenario did not include this effect. One of the effects observed after use of nail hardeners are dermatitis at sites distant from the fingers, commonly eyelids, around the mouth and chins, sides of the neck, and on the genitalia (30),(31). However, effects directly at or around the finger nails are also observed (30). Depending on the concentration of applied formaldehyde and the physiological condition of the nail, some formaldehyde may penetrate the nail plate and come into contact with the underlying tissue. So far there have not been any scientific studies that have identified the amount of formaldehyde penetrating the nail under different conditions. Therefore, there are no quantitative estimates on how much formaldehyde there will be present at the underlying tissue after application of nail hardener. The possible effects may be irritation of the tissue under the nail and possible allergic reactions.

Formaldehyde has both a irritating and sensitisation potential. With standard patch tests protocols it has been observed that formaldehyde concentrations of 2% and higher may produce skin irritation and sensitisation in non-sensitised individuals (7). Allergic reactions to formaldehyde concentrations of 1% has also been observed in patients with skin problems (7). Based on Local Lymph Node assays (LLNA) induction of sensitisation was observed at formaldehyde concentration from 0.4 to 0.96% (9),(12).

A large range of human patch tests has been performed with formaldehyde during the last 30 years. Based on the large amount of data it was suggested that a dermal allergic response to formaldehyde concentrations below 0.025 – 0.05% is rare in formaldehyde-sensitised subjects (7).

This indicates that the legal amount of 5% formaldehyde in nail hardeners adds a risk of sensitisation to the users. Based on the data presented in the safety assessment a maximum allowable amount of formaldehyde of 0.01% in nail hardeners would be considered safe for both non-sensitive and formaldehyde-sensitised subjects, while a higher concentration may be considered safe for non-sensitized individuals. The scientific committee on consumer products (SCCP) has recently been requested for an opinion on formaldehyde in cosmetic products including the use in nail hardener products. This opinion may help establish a safe concentration for induction of formaldehyde allergy under this specific exposure.

As described before, the sensitisation of contact allergens are dependent not only on the inherent sensitisation capacity of the chemical, but also on the dose and type of exposure, the amount of allergen per unit area surface of skin, the vehicle and the condition of the skin. Such data has not been evaluated in this project. However, it may be argued that a higher concentration of formaldehyde than 0.01% in nail hardeners may be safe based on the limited exposure of the skin during normal use of the products. The legal amount of formaldehyde as a preservative in cosmetics is 0.2%. The opinion from SCCP may clarify if a higher concentration than this can be considered safe in nail hardener products. Furthermore, a warning on the products may help protecting formaldehyde-sensitised individuals. The products could be labelled with the warning ‘contains more than 0.05% formaldehyde’.

7.1.3 Overall discussion on nail hardeners’

The risk assessment of formaldehyde in nail hardeners shows that the allowable concentration of free formaldehyde in nail hardeners gives no health concerns regarding systemic effects of formaldehyde. However, the legal allowable amount of formaldehyde seems high regarding the sensitisation potential of the substance. To avoid unacceptable numbers of induction of allergic reactions and elicitation in already sensitised individuals to this kind of products a lower concentration may be argued. Based on the data presented in the safety assessment a maximum concentration of 0.01% formaldehyde in nail hardeners would be regarded as safe for all kind of users. A higher concentration limit can be argued if the purpose is to protect non-sensitised individuals.

Several products were found to contain much lower levels of formaldehyde (< 1 %) than the allowed 5 %. This shows that it is possible to produce nail hardeners with lower levels of formaldehyde. Other kinds of substances with a hardening effect in the products are, however, not covered by his safety assessment. It can not be excluded that they also may pose a risk for the users.

During use of the product it is further recommend that it should take place in rooms with well airing minimising the exposure via inhalation and thereby the risk of irritation of the air ways. Furthermore, the users should be very carefully when they apply nail hardeners at the nail plate to avoid skin contact.

7.2 Exposure and risk assessment for consumers using artificial nails

The safety assessment of the selected 4 acrylates showed that the critical effect of the substances is their potential to cause sensitisation or/and irritation. Limited data was found describing systemic effects.

Substances in artificial nails may be absorbed through the skin surrounding the nail when/if the material is in contact with the skin. Some of the substances in the products are volatile at room- and skin temperature and may be inhaled after evaporation from the nail and areas of the skin. Therefore, it may be relevant to include calculation of inhalation in the dose estimation. During the preparation of the nail, one should file the nail into shape. By that procedure, fine dust from the nail may expose the user further for different chemicals. This exposure is not included in the scenarios as it is evaluated to be most important for the safety of the nail technician, which is not included in the project.

The user may also bite or suck their fingers and thereby expose them self via the oral route. However, in this risk assessment the focus was the dermal exposure as this exposure route is evaluated to constitute the largest contribution to possible risks for the users.

The exposure of the substances in artificial nails depends on which system is used. Exposure has been calculated for a model person of 40 kg to include younger girls. The model person uses two different artificial nail systems; acrylic artificial nails (liquid and powder) or gel nails. Artificial nails are added on the nails maximum every second month. But as the largest exposure happens the day of fixing the artificial nails an acute scenario is described for that day; independent of the long-term exposure.

7.2.1 Risk assessment for systemic effects – artificial acrylic nails

Acrylates

2-Hydroxyethyl acrylate, 2-hydroxypropyl methacrylate and ethylene dimethacrylate were found in artificial acrylic nails products.

The nails approximately amount to maximum 40 cm². The skin surrounding the nails will amount to about 4 cm² (28), corresponding to about 9% of the total area of nail and skin. Therefore, it is assumed that 9% of the applied nail product will cover the skin surrounding the nail, and thereby may contribute to the systemic dose.

The following assumptions were used as realistic worst-case scenario:

Weight of person, adult: 40 kg

Applied amount per application (liquid): 2 ml » 2 g

Content in product (maximum): 15% » 150 g/kg product

Percent of product reaching the skin: 9%

Absorption: 100%

It is further assumed that a negligible amount of acrylate penetrate the nail.

Using the described assumptions a daily exposure would be:

Daily exposure_dermal, ethylene dimethacrylate:

NOAELS for systemic effects were only found for 2 of the 3 acrylates (table 7.2).

Table 7.2 The systemic exposure dose (SED) and NOAELs for acrylates found in artificial acrylic nails are used to calculate the margin of safety (MoS).

Substance	NO(A)EL (mg/kg bw/d)	Maximum amount in product (%)	Daily dose, adult, 40 kg (SED) (mg/kg bw/d)	MoS
2-Hydroxyethyl acrylate	131	0.03	0.001	131,000
2-Hydroxypropyl methacrylate	1000	10.25	0.46	2,174
Ethylene dimethacrylate	-	15	0.675	-

Based on this scenario and the NOAELS found for the acrylates it clearly shows that the substances will pose no health risk for the users of artificial acrylic nails concerning systemic effects. For ethylene dimethacrylate no NOAEL was identified. However, with the calculated exposure, it is evaluated that the risk of systemic effects is negligible.

7.2.2 Risk assessment for systemic effects – artificial gel nails

The realistic worst-case exposure scenario for a model person using the gel nail system was based on the following assumptions:

Weight of person, adult: 40 kg

Applied amount per application (gel) 3 g

Content in product (Gel): 8.25% » 82.5 g/kg product

Percent of product reaching the skin: 9%

Absorption: 100%

It is further assumed that a negligible amount of acrylate penetrate the nail.

As for the artificial acrylic nail system it is assumed that 9% of the applied nail product will cover the skin surrounding the nail, and thereby may contribute to the systemic dose.

Daily exposure_dermal, 2-hydroxyethyl acrylate:

Table 7.3 The systemic exposure dose (SED) and NOAELs for acrylates found in gel nails products are used to calculate the margin of safety (MoS).

Substance	NO(A)EL (mg/kg bw/d)	Maximum amount in product (%)	Daily dose, adult, 40 kg (SED) (mg/kg bw/d)	MoS
2-Hydroxyethyl acrylate	131	8.25	0.56	234
2-Hydroxypropyl acrylate	7^A	0.865	0.06	116
2-Hydroxypropyl methacrylate	1000	1.45	0.1	10,000
Ethylene dimethacrylate	-	0.041	0.003	-

^A LOAEC

As for the acrylic nail system, the gel nails pose no health risks for the users concerning systemic effects of the substances.

7.2.3 Risk assessment for sensitisation – artificial nails

This survey of artificial nails has shown that the products contain a large range of substances; ex. different acrylates (chapter 4). Thus, a comprehensive risk assessment of the products is difficult to perform as not all the ingredients are known. The critical effect of many acrylates is their sensitisation potential, for which a lower safe exposure dose is complex to establish. Furthermore, literature shows that many acrylates cross-react with other acrylates making the safety assessment more complex (21,32).

Literature shows that sensitisation is a health problem for the users of artificial nails (20,21,33,34,35). The data from the literature is based on human patch tests performed with already sensitised persons, and not test of the induction of allergic reaction in healthy persons. The literature shows that the allergic lesions due to artificial nails are classically around the nails, but are also seen spread to the face and eyelids (31). Allergic reactions may occur 2 to 4 months, and even as long as 16 months after the application. The first indication is an itch in the nail bed. Paronychia, which is usually present in allergic reactions, is associated with excruciating pain in the nail area, and sometimes with paresthesia. The nail bed, thickened, and there is usually onycholysis. The natural nail plate becomes thinner, split and sometimes discoloured. It takes several months for the nail to return to normal. Permanent nail loss is rare (30).

Artificial acrylic nails

The acrylic artificial nail system consists of a liquid and a powder. 2-Hydroxypropyl methacrylate and ethylene dimethacrylate was found in the liquid used to develop the acrylic artificial nail. Five different liquids contained the two acrylates in concentrations from 0.89 to 15% (table 4.3). The maximum amount found was 10.25% for 2-hydroxypropyl methacrylate and 15% for ethylene dimethacrylate. The powder contained none of the analysed acrylates.

Based on human patch tests and animal studies the two acrylates are evaluated as weak sensitisers in a concentration of 2%. However, in these products up to 15% of one acrylate has been observed. The substances potential to elicitate sensitisation in minimum 13% of the tested persons, when tested in a concentration of 2% indicates that concentrations of 10-15% may pose a significant risk of sensitisation.

It is evaluated that the risk can be minimised by avoiding skin contact. The very central point is not by accident to smear the product outside the nail, and thereby avoid contact with the surrounding skin. By avoiding skin contact it is evaluated that the risk of sensitisation is considerably lowered.

Artificial gel nails

The gel nail system is based on one product (a gel) that is smeared on the nail like nail polish about ten times after each other. 2-Hydroxyethyl acrylate was found in 6 out of 7 analysed gel nail products in concentrations from 3.05 to 8.25 %. 2-Hydroxypropyl acrylate was found in 4 out of 7 products, but in lower concentrations; from 0.041 to 0.865. Ethylene dimethacrylate was found in very low concentrations in 4 products, while 2-hydroypropyl methacrylate only was found in 1 product in a concentration of 1.45% (table 4.2). 2-Hydroxyethyl acrylate is clearly the most frequent substance of the analysed acrylates in gel nails.

Based on human patch tests and animal studies 2-hydroxyethyl acrylate and 2-hydroxypropyl acrylate are evaluated as moderate sensitisers. The two acrylates is found to elicitate allergic reactions in a considerable number of humans (> 8% of acrylate-sensitised subjects) in a concentration of 0.1%. The acrylates are evaluated to have a higher potential as sensitisers than the methacrylates found in acrylic nails. This indicates that the use of gel nails may pose a higher risk of sensitisation than acrylic nails.

7.2.4 Overall discussion on artificial nails

It was shown in the risk assessment that use of artificial nails will pose no risk of systemic effects. However, the assessments showed that the amounts of acrylates in the products are important for the health risks of the user regarding the sensitisation potential. This survey only handled a few acrylates. It is evaluated that the products may contain a large spectrum of other acrylates as well (see table 4.4 – 4.5) with the same or even larger potential of contact allergy. The survey further showed that the potential risk of contact allergy seems higher for the gel nail system than for the acrylic artificial nails (liquid and powder) based on the content of acrylates in the products.

Footnotes

^[6] From the instruction of use the following use of product is recommended: Apply one layer on the first day and a second layer on the second day. On the third day remove both layers. Repeat the steps for 14 days. After this 14-day treatment the product should only be used 1-2 times peer week. The 14-day treatment should not be repeated more than 1-2 times a year.