This study aimed to examine the incidence of cosmetic dermatitis in 2019 to identify cosmetic allergens. We performed a 48-hour closed patch test on the backs of patients who came to our hospital on suspicion of cosmetic dermatitis. Patch testing was performed with each patient’s own cosmetics, the Japanese baseline series, cosmetic allergens from AMED (Chief researcher Kayoko Matsunaga), and hair care products. Patch test result was judged according to the International Contact Dermatitis Research Group (ICDRG) Recommendations. A reaction stronger than or equal to (+) at 72 h or 7 days after application was regarded as a positive reaction. 263 cosmetics products were tested on 54 patients with suspected cosmetic dermatitis. Of these, 6 patients showed positive reactions with total of 7 cosmetic products. Skin whitening cosmetics were the most frequent causative cosmetic allergens in 2019, although the most frequent patch test positive products (a reaction stronger than or equal to ?+) in the last 20 years were shampoo, rinse and washing soap (31%～50%).

In the study of photoaging, sun exposure is a target of interest. We can see there are specific changes in photoaging skin. In our previous study, using normal human dermal fibroblasts (NHDF) aged by repeated passage, UVA irradiation against NHDF caused also calcium accumulation and calcification as well as protein carbonylation induced from oxidative damage. Furthermore, we reported that the expression of PiT-1 and OPN, which are well known as osteogenesis markers of human aortic smooth muscle cells, increased in UVA-irradiated NHDF. In this study, we observed the dermis of several sections of human skin tissue that were chronically exposed to the sun and those that were not. As a result, the expression of protein carbonylation due to oxidative stress appeared universally in human dermis chronically exposed to the sun. In addition, the expression of the type I collagen and osteopontin as osteogenic markers were different in skin sections between chronically and non-chronically exposed to the sun. Furthermore, uniform calcium-ions accumulation and local calcification in the dermis were prominent only in aged human dermis among the human skin chronically exposed to the sun. Next, we observed two kinds of skin tissue, which were the back of the hand and the buttock; both obtained from the same human, age 46 years. As a result, it was suggested that there is calcium-ions accumulation in the dermis of the back of the hand that was exposed chronically to the sun.

From these results, it was suggested as a possibility that chronic sun exposure induces calcium-ions accumulation and chronological aging accelerates calcification in the human dermis.

Recently, multiple in vitro skin sensitization tests have been listed in the Organisation for Economic Co-operation and Development (OECD) guidelines. The threshold of toxicological concern (TTC) is a threshold for human exposure when chemicals do not show any obvious adverse effects at lower doses. In this study, we aimed to develop a quantitative prediction model using an in vitro/in silico dataset and to establish a TTC concept for skin sensitization. The EC3 value, the endpoint of the local lymph node assay (LLNA), was used as the objective variable and data on 120 substances were extracted from the dataset published by Cosmetics Europe. In vitro tests (DPRA, KeratinoSens™ and h-CLAT) data and physico-chemical properties were used as explanatory variables. A quantitative prediction model for EC3 was developed using support vector regression (SVR), a machine learning approach. Predicted EC3 values were used to establish no expected sensitization induction level (NESIL), and the acceptable exposure level (AEL) for each chemical was calculated by dividing NESIL by the sensitization assessment factor (SAF). Then, by fitting the gamma distribution of AELs using a negative log (10) scale, the 95th and 99th percentile probability were calculated as the dermal sensitization threshold (DST) value. Finally, the conversion of the DST to the threshold concentration of a women’s face cream was performed as an example of the application of this concept.

This prediction model was validated by a three-fold cross-validation, and the accuracy of prediction of potency class in five categories was 45.8%. Assuming 20% of all chemicals are skin sensitizers, the DST (μg/cm²) for women’s face cream was 0.129 (99th percentile) and 3.99 (95th percentile). Furthermore, the threshold concentration of this type of products was 0.008% (for DST 99th percentile) and 0.26% (for DST 95th percentile). The TTC concept for skin sensitization can be applied as a non-animal approach in evaluating the safety profile of cosmetic ingredients.

Human skin consists of 2 kinds of barrier systems such as stratum corneum barrier and tight junction barrier in stratum granulosum. Stratum corneum barrier protects against the entry of harmful substances such as chemicals and microbes into the skin (outside to inside barrier), and it prevents excessive water loss from skin (inside to outside barrier). Activation of keratinocytes produce alarmin such as IL-33, TSLP and IL-25, and induce Th2 dominant inflammation. Th2 cells release Th2-cytokines such as IL-4, IL-13 and IL-31, and induce itch.

Barrier damages caused by environmental and genetic factors induce dry skin, alloknesis (sensitive skin) and intractable itch. Th2 cell-dominant immune responses and an elongation of nerve fibers into the epidermis causes an intractable itch which is resistant to the traditional treatments of itch. In this paper, an interaction between barrier dysfunction and intractable itch was discussed.

Skin located on the outside of the human body functions as a barrier against foreign environmental stimuli. Thus, considering the functions of skin, it responds by adapting to stresses from the environment in order to maintain homeostasis of the body. As an example, skin pigmentation caused by sun exposure is one of the skin’s responses to avoid damage caused by UV light. However, foreign environmental stimuli beyond the ability of the skin to adapt to can lead to worse conditions. Most foreign environmental stimuli generate oxidative stress in skin resident cells due to the unexpected production of reactive oxygen species (ROS). In other words, adaptations to foreign environmental stimuli might be to overcome the damage initiated by oxidative stress. Recently, it was proposed that the Exposome, which is the sum of factors the body is exposed to endogenously and exogenously from birth until death, initiates and promotes skin aging. Therefore, it is thought that optimal adaptation to environmental changes will maintain healthy skin and prevent skin aging. I introduce evidence that foreign environmental stimuli such as sunlight and low humidity are generators of ROS in the skin based on the results of our in vitro study.

Immune system is regulated by not only genetic background but also environmental factors including diets. Accumulating evidence indicates that ω3 fatty acids exert anti-inflammatory properties and recent advances in the metabolome analysis revealed that fatty acid metabolism plays a key role in the regulation of skin allergic inflammation. We found that fatty acid metabolism varies among tissues. For example, 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) and 12-hydroxyeicosapentaenoic acid (12-HEPE) were generated from eicosapentaenoic acid in the gut and skin, respectively when mice were maintained on a diet containing linseed oil which is high in ω3 α-linolenic acid. In addition, both 17,18-EpETE and 12-HEPE ameliorated contact hypersensitivity by inhibiting neutrophil infiltration through different mechanisms. 17,18-EpETE acted directly on neutrophils to block pseudopod formation in a GPR40-dependent manner, while 12-HEPE acted on keratinocytes to suppress chemokine production for neutrophil recruitment in an RXRα-dependent manner. We further found that maternal intake of linseed oil ameliorated skin allergic inflammation in their pups, which was mediated by breast milk containing 14-hydroxydocosapentaenoic acid (14-HDPA). In pups, 14-HDPA induced the expression of TNF super family, TRAIL, on plasmacytoid dendritic cells and consequently inhibited inflammatory cytokine production from T cells. As another example, when mice were maintained on a diet containing coconut oil which has little amounts of essential fatty acids, mead acid was uniquely produced from oleic acid, which in turn ameliorated contact hypersensitivity through the inhibition of neutrophil pseudopod formation, leukotriene B₄ production and increment of vascular permeability. These results demonstrate that the fatty acid composition and metabolism are a critical determinant of beneficial effects of dietary lipids on the control of skin allergic inflammation.

In the past few years, the temperature in Japan has exceeded 40 degrees Celsius, and it has become a life-threatening situation that goes beyond skin health. While there has been no precipitation for a long time, there are many “highest observation history” phenomena, and abnormal weather such as severe flood damage is occurring frequently. The pandemic of the new coronavirus is partly related to deforestation due to population growth, and there is a possibility that permafrost will thaw due to global warming and past and unknown viruses will appear.

The warning has been done for quite long, but economic development has been prioritized and it has reached a crisis. Regarding global warming, the Kyoto Protocol was adopted at COP3 in 1997, and the Paris Agreement was agreed at COP21 in 2015. Regarding ozone depletion, the Montreal Protocol was adopted in 1987 and came into effect in 1989 faster than global warming. The production of CFCs decreased, and ozone depletion was suppressed. However, due to the increasing scattering of aerosols, the ultraviolet rays on the surface of the earth have stopped falling. In this way, the material cycle is interrelated, and it is necessary to understand the whole picture, not to solve it by reducing one substance.

In 1972, the United Nations Environment Program was established after the United Nations Conference on the Human Environment. In addition to the activities such as the international treaties mentioned above, SDGs consisting of 17 goals and 169 targets were adopted at the 2015 UN Summit. I hope “Healthy planet Healthy people” will be realized by thinking that “the surface of the earth is the skin and the atmosphere is the scent” and acting quantitatively, concretely and promptly at each level of individuals, groups, organizations, regions, countries, and the world.