Human health risk assessment of cinnamate UV absorbers: In vitro and in silico investigations.

Organic UV absorbers (UVAs) are contaminants of emerging concern. Environmental persistence and potential toxicological enrichment studies of UVAs have attracted international concern. It is important to study the toxicity mechanism of UVAs. This study is the first to report the toxicological mechanism of two cinnamate UV absorbers (CUVAs), 2-ethyl 4-methoxycinnamate (OMC) and isoamyl 4-methoxycinnamate (IMC) based on cellular models and molecular models. Cellular models demonstrated that the CUVAs-induced apoptosis might be associated with cellular mitochondrial damage pathways. The results of molecular models showed that OMC and IMC could affect the binding between major proteins and enzymes in the mitochondrial damage pathway and contaminants, ultimately leading to apoptosis. The cellular-molecular models showed that IMC and OMC have dose-effect relationships on cytotoxicity. The composite model is more informative than a single model. This study further indicate that UVAs causes toxicology effects that have implications for the environment and human health.

Synthesis of zanthoxylamide protoalkaloids and their in silico ADME-Tox screening and in vivo toxicity assessment in zebrafish embryos.

Inspired by the simple and attractive structure of zanthoxylamide protoalkaloids: armatamide, rubecenamide, lemairamin, rubemamine and zanthosine; isolated from plants of the genus Zanthoxylum. We report the synthesis of a series of 29 substituted N-phenylethyl cinnamamides through the direct amidation of a variety of cinnamic acids with a broad range of phenylethylamines promoted by tris-(2,2,2-trifluoroethyl) borate (B(OCH2CF3)3) in excellent yields and under mild reaction conditions. Then, the toxicological profile of the prepared compounds was studied through in silico computational methods, analyzing eight toxicity risks (hepatotoxicity, mutagenic, carcinogenicity, tumorigenic, immunotoxicity, cytotoxicity, irritant and reproductive effects) and two toxicity targets (AOFA and PGH1), while the acute toxicity toward zebrafish embryos (96 hpf-LC50, 50% lethal concentration) was also determined in the present study. From the results of the toxicity tests, we concluded that zanthoxylamide protoalkaloids can be classified as slightly toxic compounds, with a LC50 values around 217 µM that gave an understanding of their toxicity on living organisms and their possible environmental impact.

Safety assessment and toxicological profiling of a novel combinational sunprotective dermal formulation containing melatonin and pumpkin seed oil.

Ultraviolet (UV) radiation exposure has been known to cause irreparable damages to human skin. The daunting risk of UV radiation exposure faced by military personnel led to the development of a sunscreen formulation which has superior sun protection factor combined with the ability to counteract reactive oxygen species. The present work deals with the preclinical safety evaluation of the sunscreen formulation comprising of four US FDA approved UV filters; namely avobenzone, octinoxate, oxybenzone, titanium dioxide along with melatonin and pumpkin seed oil, via OECD protocols of assessing acute oral and dermal toxicity; skin sensitizing; skin irritating; ocular irritating and genotoxic potential. Both oral and dermal LD50 values were found to be ˃2000 mg/kg body weight in adult Wistar albino rats using acute dermal and oral toxicity tests. The sunscreen formulation was found to be non-sensitizing to the skin of guinea pigs and non-irritating to both skin and eyes of rabbits. The sunscreen formulation was also found to be non-mutagenic which was affirmed by a battery of genotoxicity and muagenicity assays. The results obtained from this preclinical study indicated that the sunscreen formulation is non toxic and safe in animal models. This study along with additional preclinical evaluations may serve as a basis for considering the formulation as a potential candidate for further trials to establish its efficacy, tolerability and applicability.