Post-fertilization 2-ethylhexyl-4-methoxycinnamate (EHMC) exposure affects axonal growth, muscle fiber length, and motor behavior in zebrafish embryos.

Organic UV filters, which are often found in the environment, have been the focus of much public health concern. 2-ethylhexyl-4-methoxycinnamate (EHMC) is one of the most common organic UV filters present in the environment. However, few studies have investigated its developmental neurotoxic (DNT) effects and the underlying molecular mechanisms. In the present study, zebrafish embryos were exposed to low concentration of EHMC (0, 0.01, 0.1, 1 mg/L) in static water starting from 6 h post-fertilization (hpf). Results showed that EHMC exposure caused a reduction in somite count at 13 hpf, a diminishment in head-trunk angle at 30 hpf, a delay in hatching at 48 hpf, and a decrease in head depth and head length at both 30 and 48 hpf. Additionally, EHMC led to abnormal motor behaviors at various developmental stages including altered spontaneous movement at both 23 and 24 hpf, and decreased touch response at 30 hpf. Consistent with these morphological changes and motor behavior deficits, EHMC inhibited axonal growth of primary motor neurons at 30 and 48 hpf, and yielded subtle changes in muscle fiber length at 48 hpf, suggesting the functional relevance of structural changes. Moreover, EHMC exposure induced excessive cell apoptosis in the head and spinal cord regions, increased the production of reactive oxygen species (ROS) and malondialdehyde (MDA), and reduced the level of glutathione (GSH). Defects of lateral line system neuromasts were also observed, but no structural deformity of blood vessels was seen in developing zebrafish. Abnormal expression of axonal growth-related genes (gap43, mbp, shha, and α1-tubulin) and apoptosis-related genes (bax/bcl-2 and caspase-3) revealed potential molecular mechanisms regarding the defective motor behaviors and aberrant phenotype. In summary, our findings indicate that EHMC induced developmental neurotoxicity in zebrafish, making it essential to assess its risks and provide warnings regarding EHMC exposure.

Effects associated with exposure to the emerging contaminant octyl-methoxycinnamate (a UV-B filter) in the aquatic environment: a review.

Given the increasing concern surrounding ultraviolet (UV) radiation-induced skin damage, there has been a rise in demand for UV filters. Currently, UV-filters are considered emerging contaminants. The extensive production and use of UV filters have led to their widespread release into the aquatic environment. Thus, there is growing concern that UV filters may bioaccumulate and exhibit persistent properties within the environment, raising several safety health concerns. Octyl-methoxycinnamate (OMC) is extensively employed as a UV-B filter in the cosmetic industry. While initially designed to mitigate the adverse photobiological effects attributed to UV radiation, the safety of OMC has been questioned with some studies reporting toxic effects on environment. The aim of this review to provide an overview of the scientific information regarding the most widely used organic UV-filter (OMC), and its effects on biodiversity and aquatic environment.

Disrupting effects of the emerging contaminant octylmethoxycinnamate (OMC) on human umbilical artery relaxation.

Cardiovascular diseases (CVD) represent the number one cause of death worldwide. The vascular endothelium may play a role in the pathophysiology of CVD diseases. Octylmethoxycinnamate (OMC) is a UV-B filter (CAS number: 5466-77-3) widely used worldwide in numerous personal care products, including sunscreens, daily creams, and makeup. This UV-B filter is considered an endocrine disruptor. Therefore, this investigation aimed to evaluate the direct effects of OMC in human umbilical arteries (HUAs) with endothelium and the possible mechanisms involved in the response. The results demonstrated that OMC exerts a rapid (non-genomic) and endothelium-dependent arterial relaxant effect on HUAs previously contracted with serotonin (5-HT) and Histamine (His). On the other hand, when HUAs were contracted with potassium chloride (KCl), the relaxing effect was only observed in HUAs without endothelium, and it appeared to be inhibited in HUAs with endothelium. Thus, the vasorelaxant effect of OMC depends on the endothelium and depends on the contractile agent used, suggesting that OMC may act through different signaling pathways. Furthermore, computational modulation studies, corroborated the binding of OMC to all the proteins under investigation (eNOS, COX-2, ET-1, and TxA2), with higher affinity for COX-2. In summary, the vascular effect of OMC may involve activating different pathways, i.e., acting through the NO pathway, COX pathway, or activating the endothelin-1 pathway.

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.

Ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane: Toxicological effects on marine biota and human concerns.

Ethylhexyl methoxycinnamate (EHMC) (CAS number: 5466-77-3) and butyl methoxydibenzoylmethane (BMDM) (CAS number: 70356-09-1) are important sunscreens. However, frequent application of large amounts of these compounds may reflect serious environmental impact, once it enters the environment through indirect release via wastewater treatment or immediate release during water activities. In this article, we reviewed the toxicological effects of EHMC and BMDM on aquatic ecosystems and the human consequences. According to the literature, EHMC and BMDM have been detected in water samples and sediments worldwide. Consequently, these compounds are also present in several marine organisms like fish, invertebrates, coral reefs, marine mammals, and other species, due to its bioaccumulation potential. Studies show that these chemicals are capable of damaging the aquatic beings in different ways. Further, bioaccumulation studies have shown that EHMC biomagnifies through trophic levels, which makes human seafood consumption a concern because the higher position in the trophic chain, the more elevate levels of ultraviolet (UV) filters are detected, and it is established that EHMC present adverse effects on the human organism. In contrast, there are no studies on the BMDM bioaccumulation and biomagnification potential. Different strategies can be adopted to avoid the damage caused by sunscreens in the environment and human organism. Two of them include the use of natural photoprotectors, such as polyphenols, in association with UV filters in sunscreens and the development of new and safer UV filters. Overall, this review shows the importance of studying the impacts of sunscreens in nature and developing safer sunscreens and formulations to safeguard marine fauna, ecosystems, and humans.

Chitosan - Rosmarinic acid conjugates with antioxidant, anti-inflammatory and photoprotective properties.

Rosmarinic acid is an attractive candidate for skin applications because of its antioxidant, anti-inflammatory, and photoprotective functions, however, its poor bioavailability hampers its therapeutic outcome. In this context, synthesis of polymer conjugates is an alternative to enlarge its applications. This work describes the synthesis of novel water-soluble chitosan - rosmarinic acid conjugates (CSRA) that have great potential for skin applications. Chitosan was functionalized with different contents of rosmarinic acid as confirmed by ATR-FTIR, 1H NMR and UV spectroscopies. CSRA conjugates presented three-fold radical scavenger capacity compared to the free phenolic compound. Films were prepared by solvent-casting procedure and the biological activity of the lixiviates was studied in vitro. Results revealed that lixiviates reduced activation of inflamed macrophages, improved antibacterial capacity against E. coli with respect to native chitosan and free rosmarinic acid, and also attenuated UVB-induced cellular damage and reactive oxygen species production in fibroblasts and keratinocytes.

A species specific metabolism leading to male rat reprotoxicity of Cyclamen aldehyde: in vivo and in vitro evaluation.

Cyclamen aldehyde (CA; 3-(4-isopropylphenyl)-2-methylpropanal) is a widely used fragrance material. Repeated dose studies in rats revealed adverse effects on sperm maturation. Here we review all the mechanistic and in vivo evidence, to determine relevancy to human health. The effect on spermatogenesis appears to be linked to the metabolite p-isopropyl-benzoic acid (p-iPBA). Studies in rat, rabbit and human suspended hepatocytes indicated species differences with p-iPBA detected in rat hepatocytes only. In plated rat hepatocytes, p-iPBA is conjugated to Coenzyme A (CoA) and p-iPBA-CoA accumulates to stable levels over 22 h. In vitro accumulation of CoA conjugates is a metabolic hallmark correlated to male rat reproductive toxicity for related compounds. p-iPBA-CoA is formed in vivo in liver and testes of rats dosed with CA. In plated rabbit and human hepatocytes p-iPBA-CoA doesn't accumulate. Correlating to this lack of metabolite accumulation, no effects of CA on spermatogenesis were observed in a rabbit in vivo study. A species specific metabolic fate linked to CA toxicity in male rats is postulated which appears not relevant to the rabbit as non-responder species. Lack of accumulation of p-iPBA-CoA in human hepatocytes indicates that like rabbits, humans are unlikely to be vulnerable to p-iPBA hepatic and testicular toxicity.

UV-B filter octylmethoxycinnamate impaired the main vasorelaxant mechanism of human umbilical artery.

Personal care products (PCPs) are a group of diverse substances widely used daily for health, beauty, and cleanliness. More than 90% of all PCPs contain the UV-B filter octylmethoxycinnamate (OMC) as a protective function, however, their safety has recently been questioned. The purpose of the present work was to understand how the long-term exposure of UV-filter OMC, used daily by pregnant women, disrupts their vascular homeostasis, altering vascular responses of proteins and channels involved in contractile processes. The long-term effects of 24 h of exposure to OMC (1, 10, and 50 µmol/L) were evaluated on contractile responses of human umbilical arteries (HUA) to serotonin and potassium chloride. Since OMC altered vascular homeostasis of arteries, its vascular mode of action was explored in more detail through the analysis of the activity of cGMP and Ca2+-channels, two pathways involved in their relaxation and contraction, respectively. Our findings showed that long-term exposure of UV-filter OMC impaired the main vasorelaxant mechanism of HUA, once OMC altered the vasorelaxant response pattern of sodium nitroprusside and nifedipine. Results also showed that long-term exposure to OMC induced a decreased vasorelaxation response on HUA due to an interference with the NO/sGC/cGMP/PKG pathway. Moreover, OMC seems to modulate the L-type Ca2+ channels, the BKCa 1.1 α-subunit channels, and the PKG. Overall, since OMC compromises the vascular homeostasis of pregnant women it can be an inductor of pregnancy hypertensive disorders.

The biological activity of the organic UV filter ethylhexyl methoxycinnamate in rainbow trout (Oncorhynchus mykiss).

UV filters are able to enter the aquatic environment and negatively affect non-target organisms. The aim of this study was to evaluate subchronic exposure to ethylhexyl methoxycinnamate (EHMC) in rainbow trout. The tested EHMC concentrations of 6.9 (low), 96.0 (medium) and 395.6 µg/kg (high) were used. The lowest concentration was based on environmentally relevant concentrations. The higher concentrations were chosen as a multiple of the lowest one to determine the dose-response relationship. EHMC was incorporated into feed pellets. The experiment was conducted for six weeks in a semi-static system. Haematological, biochemical and oxidative stress indices were determined at the end of the experiment and supplemented by histological examination. Significant changes were proven at medium and high concentrations of EHMC. Specifically, increases of glucose, lactate and decrease of albumin and total protein in plasma indicate a stress ethology. Moreover, a decrease of plasma cholesterol, triacylglycerols and ammonia were observed even in the experimental group exposed to the lowest concentration of EHMC, perceived as an environmentally relevant concentration. The ferric reducing ability of plasma was decreased in all tested concentrations. Exposure to the highest concentration of EHMC resulted in a decrease in leukocyte counts. Increased activity of glutathione peroxidase in liver was recorded for the medium and the highest concentration of EHMC. The level of the thiobarbituric acid reactive substances in kidney was elevated for the highest concentration. Decrease of the activity of glutathione-S-transferase in gills for medium concentration of EHMC was registered. Histopathological examination revealed massive destruction of hepatic parenchyma at the highest concentration of EHMC. All these results support the finding of a stress load on the fish organism. In summary, although subchronic exposure to EHMC had no effect on behaviour, mortality or feed intake, this exposure resulted in the alteration of saccharide, lipid and protein metabolism and weakened antioxidant capacity.