2-Azahypoxanthine (AHX) and imidazole-4-carboxamide (ICA) are fairy-ring causing compounds from a mushroom-forming fungus, Lepista sordida, and 2-aza-8-oxohypoxanthine (AOH) is a metabolite of AHX in plants. However, the safety of AOH had not yet been elucidated. In this study, we focused on AOH and performed safety evaluations of the compound using in vitro and human patch tests for cosmetic applications. In the Ames test, AOH was not mutagenic to any of the test bacterial strains (> 5000 μg/plate). In vitro skin irritation and skin sensitization studies using reconstructed human epidermis and peptides that contained lysine and cysteine showed that AOH was not a skin irritant (cell viability > 50%) and did not exhibit skin sensitization. This compound also did not exhibit cytotoxicity under ultraviolet- or sham-irradiation in the alternative phototoxicity test using BALB/c 3T3 cells (mean photo effect < 0.1) and no skin reaction was observed in the patch test on human skin. Thus, we concluded that AOH is safe as a cosmetic ingredient. This is the first study in which safety evaluation tests were performed on AOH.

Artisanal and Small Scale Gold Mining (ASGM) contributes as the biggest source of mercury (Hg) emission in Southeast Asian countries including Indonesia. Rice paddies are the most impacted agriculture area caused by Hg emission from ASGM sewage water. It may pose to health risk effect to humans due to the consumption of the rice as the staple food. This study was aimed to evaluate the Hg accumulation in rice and health effect to residents in Lebaksitu ASGM area by analysis of total mercury (THg) and methylmercury (MeHg) in hair. Two villages were selected in this study, Hg hotspot village (Lebak-1) and low Hg exposure village (Lebak-2). The THg concentration in rice ranged from 9.1-115 µg/kg with an average of 32.2 µg/kg. MeHg concentration in rice constituted 14.7-81.8% of the THg. Rice in Lebak-1 had higher THg and MeHg concentrations than those in Lebak-2. The mean THg and MeHg concentration in hair were 3.2 mg/kg and 1.78 mg/kg, respectively. Residents in Lebak-1 had significantly higher THg and MeHg in hair than those collected from Lebak-2. The MeHg ratio to THg in hair varied widely ranged from 15.68-92.43%. There was a significant correlation between high intake of MeHg from rice and the accumulation of MeHg in the hair. It was concluded that rice is the potential source of MeHg exposure to humans through daily consumption in rice consumer countries.

We investigated the potential toxicity of gum ghatti, which is added to food for emulsifying, thickening, and stabilizing, after 4 weeks of repeated oral administration at a dose of 8000 mg/kg/day to male and female SD rats. Although food consumption was significantly reduced in males in the gum ghatti group compared with those in the distilled water group from Day 18 onwards, the change was minor, there was no pathological evidence of digestive tract abnormalities, and there were no significant changes in body weight; therefore, the change in food consumption was judged to be of no toxicological significance. Hematology and blood biochemistry revealed statistically significant differences in some parameters between the gum ghatti group and the distilled water group. These changes were all within the normal range of physiological variation and therefore were not considered to represent the effects of gum ghatti. In addition, general signs, body weight, and pathology showed no changes in either sex attributable to gum ghatti. Thus, all changes observed were of no toxicological significance and within the normal range of physiological variation, suggesting gum ghatti has no toxic effects in rats.

Nucleolin (NCL) is an abundant DNA-, RNA-, and protein-binding protein that is expressed ubiquitously in eukaryotic cells, implicating it in many cellular functions such as gene silencing, senescence, cytokinesis, and proliferation. NCL is also involved in angiogenesis events including vascular endothelial cell migration and proliferation. We previously found that lead, an environmental pollutant with vascular toxicity, inhibits the repair process of injured vascular endothelium via suppression of cell proliferation as a result of a lower proliferative response of cells to endogenous fibroblast growth factor-2. The present study investigated the expression of NCL in proliferating bovine aortic vascular endothelial cells and the role of NCL in proliferation of the cells in the presence or absence of lead. We found that the expression of NCL protein was independent of cell density. Both siRNA-mediated NCL knockdown and an anti-NCL-neutralizing antibody inhibited the proliferation of vascular endothelial cells without non-specific cell damage, indicating that NCL was involved in endothelial cell proliferation. However, lead significantly inhibited the proliferation of vascular endothelial cells without changing the expression level of NCL. Therefore, NCL may positively regulate spontaneous proliferation, but is not involved in the inhibition of proliferation by lead in vascular endothelial cells.

We previously reported that continuous exposure to α-glycosyl isoquercitrin (AGIQ) from the fetal stage to adulthood facilitates fear-extinction learning in rats. The present study investigated the combined effect of continuous exposure to AGIQ with voluntary exercise or environmental enrichment on learning and behaviors in rats. For this purpose, maternal Long-Evans rats were either untreated or treated with 0.5% AGIQ in basal diet from gestational day 6 to day 21 post-delivery. Offspring in both groups were weaned on postnatal day 21 and reared thereafter either in a standard cage, a wheel cage or an environmental enrichment cage until the end of the experiment with or without exposure to AGIQ. Fear memory, locomotor activity and anxiety-like behavior in open field test, spatial memory and nonspatial memory were assessed in adulthood. Environmental enrichment without AGIQ exposure, as well as AGIQ exposure in standard cage, showed a tendency for facilitation of fear-extinction learning. However, exposure to AGIQ and environmental enrichment did not act synergistically. Voluntary exercise only decreased the total distance traveled in the open field test in the condition with or without AGIQ exposure, suggesting induction of anxiety-like behavior. Body weight from lactation period to adulthood, body and brain weights at the end of the experiment did not change by exposure to AGIQ under any cage condition. Therefore, there was no beneficial or detrimental effect of voluntary exercise and environment enrichment on the outcome of behavior or general conditions by continuous AGIQ exposure from the fetal stage.