Abstract
This study aimed to assess two novel 5-arylideneimidazolidine-2,4-dione (hydantoin) derivatives (JH3 and JH10) demonstrating photoprotective activity using the reconstructed human skin model EpiskinTM. The skin permeability, irritation, and phototoxicity of the compounds was evaluated in vitro. Moreover, the in vitro genotoxicity and human metabolism of both compounds was studied. For skin permeation and irritation experiments, the test compounds were incorporated into a formulation. It was shown that JH3 and JH10 display no skin irritation and no phototoxicity. Both compounds did not markedly enhance the frequency of micronuclei in CHO-K1 cells in the micronucleus assay. Preliminary in vitro studies with liver microsomes demonstrated that hydrolysis appears to constitute their important metabolic pathway. EpiskinTM permeability experiments showed that JH3 permeability was lower than or close to currently used UV filters, whereas JH10 had the potential to permeate the skin. Therefore, a restriction of this compound permeability should be obtained by choosing the right vehicle or by optimizing it, which should be addressed in future studies.
Highlights
Reasonable ultraviolet (UV) radiation exposure has beneficial effects for human health, overexposure is a main risk factor for the development of both acute effects as well as chronic outcomes [1–3]
Measurement of the Il-1α confirmed these results, as its level reached a maximal value of 31 pg/mL and corresponded to the release observed in non-irradiated tissue (Figure 4). These results demonstrated the absence of phototoxic potential for test compounds in our test conditions
The present study showed that both JH3 and JH10 were degraded in human liver microsomes (HLMs), resulting in very short in vitro microsomal half-lives (t1/2∼5 min) and subsequently high in vitro Clint (>172 μL/mg min)
Summary
Reasonable ultraviolet (UV) radiation exposure has beneficial effects for human health (e.g., vitamin D synthesis in the skin), overexposure is a main risk factor for the development of both acute effects as well as chronic outcomes [1–3]. As frequent and repeated application on large skin areas is recommended, even low penetration rates may lead to a significant amount of sunscreen entering the body and appearing in the systemic circulation. This was observed in the case of several frequently used UV filters such as benzophenone-3 (BP3), 3-(4-methylbenzylidene) camphor (4MBC), and octylmethoxycinnamate (OMC) [7–9]. Another limitation of agents allowed for photoprotection is their potential to induce contact and photocontact allergies or phototoxic effects [10,11]. Molecules 2022, 27, x FOR PEEcRoRnEsViIdEWering the aforementioned facts, there remains a justified need for th2eodf 2e3velopment of Molecules 2022, 27, x FOR PEEnReRwEV,IeEWffective UV filters with improved human and environmental safet2y.of 23
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