The development and application of a novel hazard scoring tool for assessing impacts of cosmetic ingredients on aquatic ecosystems: A case study of rinse-off cosmetics.

The cosmetic industry has been committed to promoting less hazardous products to reduce the environmental impacts of cosmetic ingredients. This requires identifying safer cosmetic ingredients for developing cosmetic formulations that are less harmful to the environment. However, one of the challenges in developing eco-friendly cosmetics relies on integrating all environmental hazard (EH) information of cosmetic ingredients to select the most eco-friendly ones (i.e., ingredients least harmful to the aquatic environment). Thus, we developed a hazard scoring tool (IARA matrix), which integrates data on biodegradation, bioaccumulation, and acute aquatic toxicity, providing a hazard index to classify cosmetic ingredients (raw materials) into categories of EH (low, moderate, high, or very high). The classification of the IARA was based on parameters established by Cradle to Cradle (C2C), the US Environmental Protection Agency (USEPA), and European Regulation 1272/2008, considering the most conservative values of each source. The Leopold matrix was employed as a model for the tool, using a numerical scale from 0 to 6 (lowest to highest EH). According to the IARA, we have successfully demonstrated that ultraviolet (UV) filter ingredients have the highest EH out of 41 cosmetic ingredients commonly used for rinse-off products. In addition to UV filters, triclosan (bactericide) and dimethicone (emollient) presented the second-highest EH for aquatic ecosystems, and humectants presented the lowest hazard index. By applying the IARA in the case study of rinse-off products, we have estimated that the aquatic hazard of cosmetic products can be reduced 46% by identifying less hazardous ingredients and combining them into a cosmetic formulation. In summary, the IARA tool allows the estimation of the EH of cosmetic ingredients, provides safer products, and helps achieve sustainability for cosmetic products. Integr Environ Assess Manag 2023;19:1619-1635. © 2023 SETAC.

Unraveling the molecular and cellular mechanisms of stretch marks.

BACKGROUND: Striae distensae, commonly known as stretch marks, are cutaneous lesions that accompany the hormonal upheavals of the major stages of life: puberty and pregnancy. Stretch marks occur in 90% of women, and they appear as red or purple lines that slowly fade to pale lines on the skin. There have been few studies regarding stretch mark origins, and new preventive and corrective treatments are needed. AIMS: The aim of this work was to understand the primary genes and proteins involved in the regulation of striae compared to normal skin and to identify the differentially expressed genes and biochemical aspects of SA and SR Importantly, this is the first published study to use a molecular high-throughput approach combined with in vivo evaluation. METHODS: In this study, we analyzed the molecular differences between skin with and without stretch marks (rubra [SR] and alba [SA]) of female volunteers using DNA microarray (Whole Human Genome Microarray Kit, 4×44 K, Agilent Technologies) analyses of cutaneous biopsies (2 mm) and in vivo confocal Raman spectroscopy of selected buttock regions, a technique recently introduced as a noninvasive skin evaluation method. RESULTS: We identified gene expression alterations related to ECM, cellular homeostasis, and hormones such as secretoglobulins. Spectral analyses of collagen, fibrillin, and glycosaminoglycans were conducted by Raman spectroscopy at different skin depths. The main differences observed when comparing skin with and without stretch marks were at depths between 75 and 95 µm, corresponding to the dermal-epidermal junction and dermis regions and showing differences between normal skin and stretched skin regarding collagen, collagen hydration, and elastin fibers. CONCLUSION: The results obtained by RNA and protein analyses are complementary and show that significant changes occur in the skin affected by stretch marks. These results suggest new strategies and opportunities to treat this skin disorder and for the development of new and eficiente cosmetic products.

Active ingredients against human epidermal aging.

The decisive role of the epidermis in maintaining body homeostasis prompted studies to evaluate the changes in epidermal structure and functionality over the lifetime. This development, along with the identification of molecular mechanisms of epidermal signaling, maintenance, and differentiation, points to a need for new therapeutic alternatives to treat and prevent skin aging. In addition to recovering age- and sun-compromised functions, proper treatment of the epidermis has important esthetic implications. This study reviews active ingredients capable of counteracting symptoms of epidermal aging, organized according to the regulation of specific age-affected epidermal functions: (1) several compounds, other than retinoids and derivatives, act on the proliferation and differentiation of keratinocytes, supporting the protective barrier against mechanical and chemical insults; (2) natural lipidic compounds, as well as glycerol and urea, are described as agents for maintaining water-ion balance; (3) regulation of immunological pathogen defense can be reinforced by natural extracts and compounds, such as resveratrol; and (4) antioxidant exogenous sources enriched with flavonoids and vitamin C, for example, improve solar radiation protection and epidermal antioxidant activity. The main objective is to provide a functional classification of active ingredients as regulatory elements of epidermal homeostasis, with potential cosmetic and/or dermatological applications.

Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma cell death.

Induction of apoptotic cell death in response to chemotherapy and other external stimuli has proved extremely difficult in melanoma, leading to tumor progression, metastasis formation and resistance to therapy. A promising approach for cancer chemotherapy is the inhibition of proteasomal activity, as the half-life of the majority of cellular proteins is under proteasomal control and inhibitors have been shown to induce cell death programs in a wide variety of tumor cell types. 4-Nerolidylcatechol (4-NC) is a potent antioxidant whose cytotoxic potential has already been demonstrated in melanoma tumor cell lines. Furthermore, 4-NC was able to induce the accumulation of ubiquitinated proteins, including classic targets of this process such as Mcl-1. As shown for other proteasomal inhibitors in melanoma, the cytotoxic action of 4-NC is time-dependent upon the pro-apoptotic protein Noxa, which is able to bind and neutralize Mcl-1. We demonstrate the role of 4-NC as a potent inducer of ROS and p53. The use of an artificial skin model containing melanoma also provided evidence that 4-NC prevented melanoma proliferation in a 3D model that more closely resembles normal human skin.

Artificial skin in perspective: concepts and applications.

Skin, the largest organ of the human body, is organized into an elaborate layered structure consisting mainly of the outermost epidermis and the underlying dermis. A subcutaneous adipose-storing hypodermis layer and various appendages such as hair follicles, sweat glands, sebaceous glands, nerves, lymphatics, and blood vessels are also present in the skin. These multiple components of the skin ensure survival by carrying out critical functions such as protection, thermoregulation, excretion, absorption, metabolic functions, sensation, evaporation management, and aesthetics. The study of how these biological functions are performed is critical to our understanding of basic skin biology such as regulation of pigmentation and wound repair. Impairment of any of these functions may lead to pathogenic alterations, including skin cancers. Therefore, the development of genetically controlled and well characterized skin models can have important implications, not only for scientists and physicians, but also for manufacturers, consumers, governing regulatory boards and animal welfare organizations. As cells making up human skin tissue grow within an organized three-dimensional (3D) matrix surrounded by neighboring cells, standard monolayer (2D) cell cultures do not recapitulate the physiological architecture of the skin. Several types of human skin recombinants, also called artificial skin, that provide this critical 3D structure have now been reconstructed in vitro. This review contemplates the use of these organotypic skin models in different applications, including substitutes to animal testing.