Relationship between sensitive skin and sleep disorders, fatigue, dust, sweating, food, tobacco consumption or female hormonal changes: Results from a worldwide survey of 10 743 individuals.

BACKGROUND: Sensitive skin is related to environmental factors. OBJECTIVES: We aimed to investigate the roles of poorly known associated and triggering factors on sensitive skin in a large global population. METHODS: A survey was administrated to a representative sample of the adult population aged 18-75 years in five different countries (Brazil, China, France Russia, and the United States). All participants answered a web-based questionnaire on sociodemographic characteristics, sensitive skin and environmental factors. RESULTS: Among the 10 743 included individuals (5285 men and 5458 women), 48.2% declared that they had sensitive skin. The group with sensitive skin reported significant increases in fatigue, dust or sweating and to a lesser extent food or tobacco consumption. The members of this group also declared that they experienced more sleep disorders than individuals without sensitive skin. Sensitive skin was very frequent in pregnant women, women with painful menstruations or women using contraceptive pills. CONCLUSIONS: This large cohort study identified new factors, including female hormonal status, fatigue, sleep disorders and food, associated with sensitive skin. These associations suggest that sensitive skin is not restricted to an epidermal disorder but may be included in a larger context. The identified factors are potential upstream drivers of neurogenic inflammation in sensitive skin.

Triggering factors in sensitive skin from the worldwide patients' point of view: a systematic literature review and meta-analysis.

Sensitive skin (SS) is a syndrome defined by the occurrence of unpleasant sensations in response to stimuli that normally should not provoke such sensations. In most patients, symptoms occur within 1 h following exposure to trigger factors and may persist for minutes or even hours. Numerous triggering factors (physical, chemical or psychological) are suspected and described in articles. The aim of this article was to perform a systematic literature review to collect data on the triggering factors involved in SS and to then perform a meta-analysis. Thirteen studies were included in the systematic literature review. Subjects were classified into groups, SS or no sensitive skin (NSS), and triggering factors were researched through responses to different questions. SS could be triggered by numerous factors. The most important triggering factor was cosmetics, with an odds ratio (OR) equal to 7.12 [3.98-12.72]. Other triggering factors were physical (variations in temperature, cold, heat, wind, sun, air conditioning, wet air and dry air), chemical (water and pollution) or psychological (emotional) factors. After cosmetics, the most important factors were wet air, OR 3.83 [2.48-5.91]; air conditioning, OR 3.60 [2.11-6.14]; heat, OR 3.5 [2.69-4.63]; and water, OR 3.46 [2.56-4.77].

Qualitative and quantitative composition of essential oils: A literature-based database on contact allergens used for safety assessment.

The risks related to the use of essential oils are difficult to ascertain at present, due in part to the large number of different oils available on the market, making it difficult for the risk assessor. Essential oils may contain skin allergens in significant amounts, and could thus pose a risk to the consumer. The aim of our study was to collect as much qualitative and quantitative data as possible on allergens present in essential oils. 11 types of essential oils, with 25 respective subspecies, were taken into account based on a previous survey. Based on the literature, 517 dosages were recorded from 112 publications, providing precious information for probabilistic exposure assessment purposes. 22 substances recognized as established allergens were found in the essential oils we included. Of these, 11 are also found in cosmetics as fragrance components. These results are of major importance regarding co-exposure to fragrance allergens. Moreover, this could lead to regulatory measures for essential oils in the future, as it is the case for cosmetic products, in order to better protect consumers against skin allergy.

Usage patterns of aromatherapy among the French general population: A descriptive study focusing on dermal exposure.

Although likely benefits of aromatherapy are well documented, little is known about essential oils consumption and exposure to molecules present in the oils. The aim of our study was to determine usage patterns of 12 types of essential oils among a quite large panel, sorted per sex and quintile of age from birth to 70. A survey was conducted in September 2014 among 1507 French individuals, selected to build a representative panel of the general population. The key point of our study, apart from the fact that it has never been done among general population, was the focus on dermal exposure. Information about types of essential oils used, skin areas exposed, frequencies and quantities were collected. Our work revealed that some sub-populations could be significantly exposed to molecules of toxicological concern, especially in terms of skin sensitization. This work is the first step to assess human exposure to these molecules, and will help safety authorities and risk managers to protect the population.

Aggregate exposure to common fragrance compounds: Comparison of the contribution of essential oils and cosmetics using probabilistic methods and the example of limonene.

The knowledge of aggregate exposure to different types of products is paramount in the risk assessment. The aim of this study was to compare the relative contribution of essential oils compared to cosmetics on the daily dermal exposure to limonene, an ubiquitous fragrance compound that can be an allergen depending on its degree of oxidation. Aggregate daily exposure to limonene was calculated among a panel of French volunteers using both essential oils and cosmetics, for 4 different specific zones, i.e. face and neck, chest, upper limbs and lower limbs. Calculations were made using a probabilistic Monte Carlo method and sensitivity analysis. The main strength of this work was the inclusion of essential oils in addition to cosmetics in the model. For the first time, the generated data could be used to compare the contribution of these two products in dermal exposure. Essential oils appear to be significant contributors to exposure to limonene particularly for the face. This work is a first step that will permit to determine the exposure to other fragrance compounds with sensitizing potential. These data will be useful for risk managers to consider the inclusion of essential oils in the overall burden of this pathology.

Consumption of cosmetic products by the French population. Third part: Product exposure amount.

A recent study in France provided valuable data on the frequency and amount of use of cosmetic products (Ficheux et al., 2015, 2016a). The aim of the present study was to generate Product Exposure Amount data, i.e. the amounts of cosmetics applied to the skin among the French population using the raw data collected during the previous enquiry. These data are useful to derive Consumer exposure level data which are paramount for skin sensitization risk assessments. Exposure data were generated for 69 different cosmetics, classified as products for the hair, face, buccal hygiene, hands, feet, body, shaving and depilation, sunscreens as well as products specifically intended for babies. Exposure was calculated using a probabilistic Monte Carlo method. The main strength of this work was the break-down of data by age and sex. The results showed that some data used by the International Fragrance Association in skin sensitization risk assessments, in particular facial care products and deodorants, could be unsuitable for the protection of French consumers. For the first time, data were also generated for products intended for babies' nappy area. These data will be useful for the implementation of the Quantitative Risk Assessment for skin sensitization among the French population.

Adequacy of the default values for skin surface area used for risk assessment and French anthropometric data by a probabilistic approach.

The notes of guidance for the testing of cosmetic ingredients and their safety evaluation by the Scientific Committee on Consumer Safety (SCCS) is a document dedicated to ensuring the safety of European consumers. This contains useful data for risk assessment such as default values for Skin Surface Area (SSA). A more in-depth study of anthropometric data across Europe reveals considerable variations. The default SSA value was derived from a study on the Dutch population, which is known to be one of the tallest nations in the World. This value could be inadequate for shorter populations of Europe. Data were collected in a survey on cosmetic consumption in France. Probabilistic treatment of these data and analysis of the case of methylisothiazolinone, a sensitizer recently evaluated by a deterministic approach submitted to SCCS, suggest that the default value for SSA used in the quantitative risk assessment might not be relevant for a significant share of the French female population. Others female populations of Southern Europe may also be excluded. This is of importance given that some studies show an increasing risk of developping skin sensitization among women. The disparities in anthropometric data across Europe should be taken into consideration.

Probabilistic exposure assessment of sun care products.

The aim of this study has been to assess the consumption and the exposure to 6 types of sun care products: sunscreen cream, sunscreen milk, sunscreen spray, sunscreen stick, moisturizing cream with SPF and after-sun milk. Consumption data were obtained from 75 clinical safety studies conducted on 3001 subjects: 371 children aged 3-9, 149 children aged 10-14 and 2481 adults aged more than 15. Exposure was assessed using a probabilistic method. Strength of the study include stratification of consumption and exposure data according to sex and age, as well as other important points such as the galenic form, the site of application and the value of the sun protection factor.

Exposure assessment of family cosmetic products dedicated to babies, children and adults.

Very few consumption and exposure data is available for family cosmetic products. The aim of the present study was to assess the consumption and the exposure to family cosmetic products used by babies, children and adults. 10 categories of products were studied: shampoo, shower gel, solid soap, cleansing lotion, emollient foam, emollient bath, cream, milk, balm and lip balm. Consumption data were obtained from 2994 participants (789 babies aged 0-3 years, 837 children aged 4-12 years and 1368 adults aged more than 18 years) included in 87 clinical safety studies. Exposure was performed using a probabilistic method. The implementation of consumption and exposure assessment by age has strengthened this work, as consumption and mainly exposure differences were shown. In fact, babies were always the most exposed to family products, followed by children and adults. These original data will be useful for safety assessors and safety agencies in order to protect consumers.

Influence of the container on the consumption of cosmetic products.

The container, also known as primary package or inner package, could be defined as the packaging designed to come into direct contact with the cosmetic product. To author's knowledge, no study was available regarding the effect of the primary package on the consumption of cosmetic products. The aim of the study was to assess the impact of the container on the consumption of three cosmetic products widely used, i.e. shampoo, shower gel and emollient cream. The three products were contained in a tube with a flip top cap and in a bottle with a pump. The study was conducted on 221 French adults: 108 women and 113 men. Results showed that the consumption of each cosmetic product was slightly higher when the product was packaged in tube with a flip top cap than in bottle with a pump. The difference of consumption could vary from 5 % to 23 % when calculated with mean values. This information could be interesting for safety evaluators, safety agencies and commercial services of cosmetic manufacturers.

Probabilistic assessment of exposure to hair cosmetic products by the French population.

Cosmetic exposure data are limited in Europe and especially in France. The aim of this study was to assess the exposure to hair cosmetics using recent consumption data (percentage of users, frequency of use and amount per use) generated for the French population (Ficheux et al., 2015, 2016). Exposure was assessed using a probabilistic method for eleven hair products: liquid shampoo, dry shampoo, conditioner, hair mask, hair serum, hair oil, styling lacquer, styling gel, styling foam, styling wax and styling spray. Exposure was assessed by sex and by age classes in adults and children. Pregnant women were also studied. For liquid shampoo, conditioner and some styling products (gel, lacquer and foam), the levels of exposure were higher than the values currently used by the Scientific Committee on Consumer Safety (SCCS). Exposure values found for styling wax and styling spray were lower than SCCS values. Exposure was assessed for the first time for dry shampoo, hair mask, hair serum and hair oil products. These new French exposure values will be useful for safety assessors and for safety agencies in order to protect the general population and these at-risk populations.

Probabilistic assessment of exposure to cosmetic products by French children aged 0-3 years.

Very few exposure data are available for children in Europe and worldwide. The aim of this study was to assess the exposure to cosmetic products used on children aged 0-3 years using recent consumption data generated for the French population. Exposure was assessed using a probabilistic method for 24 products including cleanser, skin care, fragrance, solar and bottom products. The exposure data obtained in this study for children aged 0-3 years were higher than the values fixed by the SCCS for all common products: liquid shampoo, face moisturizer cream, toothpaste, shower gel and body moisturizer cream. Exposure was assessed for the first time for many products such as sunscreens, Eau de toilette and massage products. These new French exposure values will be useful for safety assessors and for safety agencies.

Exposure of hairdressers to the main cosmetics used in hairdressing salons in France: A preliminary study.

In recent years, more attention has been given to chemical exposure in hairdressers. This increasing interest is largely due to the various respiratory and skin symptoms observed in hairdressers. According to these symptoms, hairdressers are in contact with various sources of exposure. Particularly in France, little information is available to assess professional exposure of hairdressers. In order to gather information to assess exposure in hairdressers, 11 hairdressing salons were visited. All the salons were located in Brest City (France). Preferentially, small hairdressing salons were visited. Observations were performed to obtain salon characteristics and to record workers' practices. Calculations revealed that in the worst-case scenario, dermal professional exposure reaches 14.68 and 13.67 mg/kg/day for hair coloring and highlighting mixtures, respectively. Inhalation exposure represents 14.2 and 18.1 mg/kg/day for hair coloring and highlighting mixtures, respectively. These exposure values represent baseline values for exposure of French hairdressers working in small hairdressing salons.

Consumption of hair dye products by the French women population: Usage pattern and exposure assessment.

Only few published data are available in the literature about consumption and exposure, for hair dye products. The aim of this study was to assess the use of 10 different hair dye products in French Women with a focus on consumption of hair dye in different places of use (at home and at the hairdressers) in order to assess the corresponding dermal exposures. The assessment was performed on a total of 4237 women older than 15 years old, thanks to three national web surveys. The percentage of hair dye users among the French women population was about 64%.The mean frequency of use ranged between 2.23 and 14.22 times per year depending on the studied product and age category of women. This study provided the first data available for exposure to hair dye products with mean exposures ranging between 1.48 and 6.49 mg/kg bw/day depending on the product studied and age category of women. Moreover, consumption data obtained in this study might be useful to perform safety assessment of hair dye products thanks to the knowledge of the age categories of the population having the highest percentage of users and/or frequency of use.

Consumption of cosmetic products by the French population second part: Amount data.

The aim of the study was to assess the amount per use of cosmetic products consumed at home by the adult, child and baby French population. 1078 men and women participated in the study which was performed in four cities of France. This enquiry was performed on 106 cosmetics including general hygiene, skin care, hair care, hair styling, make-up, fragrances, solar, shaving and depilatory, and baby products. Coupled to frequency data previously obtained (Ficheux et al., 2015), these amounts per use data will be used in order to assess the exposure to cosmetics by the French population. These current exposure values could be useful for safety assessors and for safety agencies.

Consumption of cosmetic products by the French population. First part: frequency data.

The aim of this study was to assess the percentage of users, the frequency of use and the number of cosmetic products consumed at home by the French population. The evaluation was performed for adult, child and baby consumers. Pregnant women were also taken into account in this work. All in all, 141 products cosmetics including general hygiene, skin care, hair care, hair styling, make-up, fragrances, solar, shaving and depilatory products were studied. The strengths of the study were the separation of data by sex and by age groups, the consideration of a priori at risk subpopulations and the consideration of a large number of cosmetic products. These current consumption data could be useful for safety assessors and for safety agencies in order to protect the general population and these at risk subpopulations.

Exposure method development for risk assessment to cosmetic products using a standard composition.

In a risk assessment of cosmetic products, it is necessary to know both qualitative and quantitative compositions. Currently, European Regulation No. 1223/2009 requires the industries to provide ingredient lists for finished cosmetic products but not their concentrations. Ingredient concentrations are available in few bibliographic references but in an incomplete and approximate way. In this study, we propose a method to qualitatively and quantitatively estimate the composition of a cosmetic product. This method has the advantages of being applicable to all cosmetic products and supplying concentration data for all ingredients. The results obtained seem quite fair compared to literature data. Applied to nail polish as an example, this method can be used to assess exposure per ingredient according to the Monte Carlo probabilistic method. It should be promising to assess the consumer risk to cosmetic product compositions.

Probabilistic assessment of exposure to nail cosmetics in French consumers.

The aim of this study was to assess probabilistic exposure to nail cosmetics in French consumers. The exposure assessment was performed with base coat, polish, top coat and remover. This work was done for adult and child consumers. Dermal, inhalation and oral routes were taken into account for varnishes. Exposure evaluation was performed for the inhalation route with polish remover. The main route of exposure to varnishes was the ungual route. Inhalation was the secondary route of exposure, followed by dermal and oral routes. Polish contributed most to exposure, regardless of the route of exposure. For this nail product, P50 and P95 values by ungual route were respectively equal to 1.74 mg(kg bw week)(-1) and 8.55 mg(kg bw week)(-1) for women aged 18-34 years. Exposure to polish by inhalation route was equal to 0.70 mg(kg bw week)(-1) (P50) and 5.27 mg(kg bw week)(-1) (P95). P50 and P95 values by inhalation route were respectively equal to 0.08 mg(kg bw week)(-1) and 1.14 mg(kg bw week)(-1) for consumers aged 18-34 years exposed to polish remover. This work provided current exposure data for nail cosmetics, and a basis for future toxicological studies of the uptake of substances contained in nail cosmetics in order to assess systemic exposure.

Effects of beauvericin, enniatin b and moniliformin on human dendritic cells and macrophages: an in vitro study.

The aim of this study was to assess the in vitro effects of emerging mycotoxins beauvericin, enniatin B and moniliformin on human dendritic cells and macrophages. Beauvericin and enniatin B were cytotoxic on these cells. IC50 were equal to 1.0 µM, 2.9 µM and 2.5 µM beauvericin for immature dendritic cells, mature dendritic cells and macrophages, respectively. IC50 were equal to 1.6 µM, 2.6 µM and 2.5 µM for immature dendritic cells, mature dendritic cells and macrophages exposed to enniatin B, respectively. Effects on the differentiation process of monocytes into macrophages or into immature dendritic cells as well as effects on dendritic cells maturation have been studied. The differentiation process of monocytes into immature dendritic cells was not disturbed in the presence of beauvericin. Dendritic cells exposed to beauvericin during the maturation process presented a decrease of CCR7 expression and an increase of IL-10 secretion. Monocytes exposed to beauvericin during the differentiation process into macrophages presented a decrease of endocytosis ability. The differentiation process of monocytes into immature dendritic cells was not disturbed in the presence of enniatin B. Dendritic cells exposed to enniatin B during the maturation process presented a decrease of expression of the maturation makers CD80, CD86 and CCR7 and an increase of IL-10 secretion. Monocytes exposed to enniatin B during the differentiation process into macrophages presented a decrease of endocytosis ability and an increase of CD71. CD1a expression and endocytosis capacity were decreased on immature dendritic cells exposed to moniliformin. Monocytes-derived macrophages exposed to moniliformin during the differentiation process presented a decrease of endocytosis ability, and a decrease of CD71 and HLA-DR expression. According to these results, immunological disorders could be observed on human after ingestion of these alimentary toxins.

Co-exposure of Fusarium mycotoxins: in vitro myelotoxicity assessment on human hematopoietic progenitors.

Mycotoxins such as beauvericin (BEA), deoxynivalenol (DON), enniatin B (ENB), fumonisin B1 (FB1), T-2 toxin and zearalenone (ZEA) can co-occur in food commodities. This aim of this study was to assess the myelotoxicity of these mycotoxins in couple using in vitro human granulo-monocytic (Colony Forming Unit-Granulocyte and Macrophage, CFU-GM) hematopoietic progenitors. Clonogenic assays have been performed in the presence of the following couples of fusariotoxins: DON + BEA, DON + FB1, DON + T-2, DON + ZEA, T-2 + ZEA and BEA + ENB. Co-exposure of human CFU-GM to DON + BEA resulted in synergic myelotoxic effects. The combination of DON + T-2 presented additive or synergic myelotoxic effects. The couples DON + ZEA, T-2 + ZEA and BEA + ENB had additive myelotoxic effects, while the combination of DON + FB1 showed antagonist myelotoxic effects. These in vitro results suggested that the simultaneous presence of mycotoxins in food commodities and diet may be more myelotoxic than the presence of one mycotoxin alone. Diminution of hematopoietic progenitors could give rise to a decrease number of mature blood cells, inducing agranulocytosis and/or thrombocytopenia and in severe cases aplastic anemia.