Health risk assessment of heavy metal(loid)s in road dust via dermal exposure pathway from a low latitude plateau provincial capital city: The importance of toxicological verification.

The human health risk assessment through the dermal exposure of metal (loid)s in dust from low latitude and high geological background plateau cities was largely unknown. In this study, the road dust samples were harvested from a typical low-latitude plateau provincial capital city Kunming, Southwest China. The total concentration and dermal bioaccessibility of heavy metal (loid)s in road dust were determined, and their health risks as well as cytotoxicity on human skin keratinocytes were also assessed. The average concentrations of As (28.5 mg/kg), Cd (2.65 mg/kg), Mn (671 mg/kg), and Zn (511 mg/kg) exceeded the soil background values. Arsenic had the highest bioaccessibility after 2 h (3.79%), 8 h (4.24%), and 24 h (16.6%) extraction. The dermal pathway when bioaccessibility is considered has a higher hazard quotient than the conventional method using total metal(loid)s in the dust. In addition, toxicological verification suggested that the dust extracts suppressed the cell viability, increased the reactive oxygen species (ROS) level and DNA damage, and eventually activated the mitochondria-mediated apoptosis pathway, evidenced by the upregulation of Caspase-3/9, Bax, and Bak-1. Cadmium was positively correlated with the mRNA expression of Bax. Taken together, our data indicated that both dermal bioaccessibility and cytotoxicity should be considered for accurate human skin health risk assessment of heavy metal(loid)s in road dust, which may provide new insight for accurate human health risk assessment and environmental management.

Experimental study on the probabilities of kinked arches and kinked arch locations in ore passes under the influences of multiple factors.

A smooth shaft production process is important to ensure the safe and efficient development of mineral resources. Due to the influence of ore rock and the mismatch between rock size and ore pass design, an arching phenomenon occurs frequently during actual ore pass release, stagnating production. Therefore, an ore pass release simulator with a freely variable ore pass angle and height is designed and used to conduct a four-factor, five-level orthogonal ore pass release experiment. An analysis is performed to determine the influence of four factors-ore particle size, ore moisture, ore pass inclination and slip height-on the probability of ore pass arching; from there, an ore pass arching probability equation is constructed and the characteristics of the ore pass arching location are clarified, effectively predicting the probability of ore pass arching and providing an effective basis for handling arching events within an applicable range. This analysis effectively predicts the probability of ore pass arch within the applicable range, and provides an effective basis for handling ore pass arch events.

Effects of TCPP and TCEP exposure on human corneal epithelial cells: Oxidative damage, cell cycle arrest, and pyroptosis.

Tris(2-chloroisopropyl) phosphate (TCPP) and Tris(2-chloroethyl) phosphate (TCEP) are the widely used organophosphorus flame retardants indoors and easily accessible to the eyes as the common adhesive components of dust and particle matter, however, hardly any evidence has demonstrated their corneal toxicity. In this study, the adverse effects of TCPP, TCEP, and TCPP + TCEP exposure on human corneal epithelial cells (HCECs) were investigated. The cell viability and morphology, intracellular reactive oxygen species (ROS), cell cycle, and the expressions of cell cycle and pyroptosis-related genes were assessed to explain the underlying mechanisms. Compared to individual exposure, co-exposure to TCPP20+TCEP20 showed higher cytotoxicity with a sharp decrease of >30% in viability and more serious oxidative damage by increasing ROS production to 110.92% compared to the control group. Furthermore, the cell cycle arrested at the S phase (36.20%) was observed after combined treatment, evidenced by the upregulation of cyclin D1, CDK2, CDK4, CDK6, p21, and p27. Interestingly, pyroptosis-related genes GSDMD, Caspase-1, NLRP3, IL-1ß, IL-18, NLRP1, and NLRC4 expressions were promoted with cell swelling and glowing morphology. Oxidative stress and cell cycle arrest probably acted as a key role in TCPP20+TCEP20-induced cytotoxicity and pyroptosis in HCECs. Our results suggested that TCPP20+TCEP20 co-exposure induced severer corneal damage, further illustrating its significance in estimating indoor health hazards to humans.

The spatial distribution, health risk, and cytotoxicity of metal(loid)s in contaminated field soils: The role of Cd in human gastric cells damage.

The spatial distribution and pollution level of heavy metal(loid)s in soil (0-6 m) from a typical industrial region in Jiangmen City, Southeast China was investigated. Their bioaccessibility, health risk, and human gastric cytotoxicity in topsoil were also evaluated using an in vitro digestion/human cell model. The average concentrations of Cd (87.52 mg/kg), Co (106.9 mg/kg), and Ni (1007 mg/kg) exceeded the risk screening values. The distribution profiles of metal(loid)s showed a downward migration trend to reach a depth of 2 m. The highest contamination was found in topsoil (0-0.5 m), with the concentrations of As, Cd, Co, and Ni being 46.98, 348.28, 317.44, and 2395.60 mg/kg, respectively, while Cd showed the highest bioaccessibility in the gastric phase (72.80 %), followed by Co (21.08 %), Ni (18.27 %), and As (5.26 %) and unacceptable carcinogenic risk. Moreover, the gastric digesta of topsoil suppressed the cell viability and triggered cell apoptosis, evidenced by disruption of mitochondrial transmembrane potential and increase of Cytochrome c (Cyt c) and Caspases 3/9 mRNA expression. Bioaccessible Cd in topsoil was responsible for those adverse effects. Our data suggest the importance to reduce Cd in the soil to decrease its adverse impacts on the human stomach.

Dermal bioaccessibility and cytotoxicity of heavy metals in urban soils from a typical plateau city: Implication for human health.

The dermal exposure of heavy metals in contaminated urban soils poses huge environmental health risks globally. However, their dermal bioaccessibility and adverse effects on human skin cells were not fully understood. In this study, we measured the total and dermal bioaccessibility of Cr, As, Cd, Pb, and Cu in four selected urban soil samples from Kunming, Yunnan, China, and evaluated the cellular responses of these bioaccessible extracts on human keratinocytes (HaCaT). Among all the metals, only As in Soil-3 (S3) exceeded Chinese risk screening and Yunnan background values at 38.2 mg/kg. The average concentrations of Cr, As, Cd, Pb, and Cu in all soil samples were 47.79, 15.50, 3.11, 104.27, and 180.29 mg/kg respectively. Although relatively high concentrations of heavy metals were detected in soil samples, the highest dermal bioaccessibility of Cd was 3.57% with others' being lower than 1%. The bioaccessible dermal-absorbed doses (DADs) of Cr, As, Cd, Pb, and Cu from soils reflected acceptable health risks since all DADs were below the corresponding derived dermal reference values. However, the toxic data showed the extracts of S3 and S4 presented certain cytotoxicity in HaCaT cells, indicating the existing models based on dermal bioaccessibility and DADs may be not accurate enough to assess their human health risk. Taken together, the human health risk assessment should be modified by taking their skin cytotoxicity into account.

Effects of soil-extractable metals Cd and Ni from an e-waste dismantling site on human colonic epithelial cells Caco-2: Mechanisms and implications.

E-wastes release toxic metals including Cd, Cu, Ni, Pb and Zn into nearby soils during dismantling process. However, their adverse effects and the associated mechanisms on human intestinal epithelium are poorly understood. In this study, their toxic effects on human colonic epithelial cells Caco-2 and the underlying mechanisms were assessed basing on three soils from Wenling e-waste dismantling site. Since soil-extractable metals are more available for gastrointestinal absorption, we used phosphate buffer saline solution to extract metals at solid to liquid ratio of 1:2. Among metals, total Cd and Ni exceeded the risk screening values in three soils, being 3.8-8.8 and 42.4-155 mg/kg. Furthermore, high extractable-metals at 5.9, 1.9, and 0.87 mg/kg Cd (20-67%) and 4.6, 6.4, and 12.4 mg/kg Ni (3.6-29%) were observed for Soil-1, -2 and -3, respectively. All three extracts triggered cytotoxicity, with Soil-2 showing the strongest inhibition of cell viability. Higher production of reactive oxygen species and stronger inhibition of antioxidant enzymes SOD1 and CAT were observed in Soil-2 and -3. Upregulation of proinflammatory mediators (IL-1ß, IL-8 and TNF-α) and apoptosis-regulatory genes (GADD45α, Caspase-3, and Caspase-8) were observed. Our data suggest that soil extracts induced cytotoxicity, oxidative damage, inflammatory response, and cell apoptosis in Caco-2 cells, indicating soil ingestion from e-waste dismantling site may adversely impact human health.

Soil heavy metal pollution and food safety in China: Effects, sources and removing technology.

Soil plays a fundamental role in food safety and the adverse effects of contaminants like heavy metal (loid)s on crop quality have threatened human health. Therefore, it is important to focus on the food safety and agricultural soil pollution by heavy metals, especially for China where the demand for food production is increasing. This review comprehensively introduced the current status of agricultural soil pollution by heavy metals in China, analyzed the main sources of contaminants, including the applications of pesticides and fertilizers, atmospheric deposition related to vehicle emissions and coal combustion, sewage irrigation and mining. Food safety and agricultural soil pollution by heavy metals, the removal technologies for soil remediation such as soil amendments, phytoremediation and foliar sprays were also introduced. The review can provide significant insights for policymakers, environmental engineers, and agro-technicians regarding soil contamination control and management strategies and technologies.

Mechanisms of Cd and Cu induced toxicity in human gastric epithelial cells: Oxidative stress, cell cycle arrest and apoptosis.

Cadmium (Cd) and copper (Cu) are widely present in foods. However, their adverse effects on human gastric epithelium are not fully understood. Here, human gastric epithelial cells (SGC-7901) were employed to study the toxicity and associated mechanisms of Cd + Cu co-exposure. Their effects on cell viability, morphology, oxidative damage, cell cycle, apoptosis, and the mRNA levels of antioxidases and cell cycle regulatory genes were investigated. Co-exposure to Cd (5 µM)/Cu (10 µM) induced >40% cell viability loss, whereas little effect on cell viability at <10 µM Cd or 40 µM Cu. Compared to individual exposure, co-exposure induced greater oxidative damage by elevating ROS (3.5 folds), malondialdehyde (2.3 folds) and expression of SOD1 and HO-1 besides inhibiting CAT, GPX1 and Nrf2. A marked S cell-cycle arrest was observed in co-exposure, evidenced by more cells staying in the S phase (36%), up-regulation of cyclins-dependent kinase (CDK4) and CDKs inhibitor (p21) and down-regulation of CDK2, CDK6 and p27. Furthermore, higher apoptosis (22%) with floated and round cells occurred in co-exposure group. Our data implicate the cytotoxicity of Cd + Cu co-exposure was higher than individual exposure, and individual assessment would underestimate their potential health risk. Oxidative stress and cell cycle arrest possibly played a role in Cd + Cu induced toxicity and apoptosis in SGC-7901 cells. Our data suggest the importance to reduce Cd in foods to decrease its adverse impacts on human digestive system.

Comparative Study of Traditional Ablative CO2 Laser-Assisted Topical Antifungal with only Topical Antifungal for Treating Onychomycosis: A Multicenter Study.

BACKGROUND: The predominance of onychomycosis has been increasing recently. New medications and treatment modalities are being researched for better saturation of the antifungal agents through the nail plate topically because of the low resilience of some patients for the oral antifungal agents. Treatment of onychomycosis, mainly moderate to severe, can be very challenging, expensive, and time consuming. OBJECTIVE: The objective of this clinical trial is to compare the efficacy and safety of a manually operated ablative CO2 laser combined with a topical antifungal agent in patients with onychomycosis. STUDY DESIGN: We conducted an open-label controlled prospective study of 160 eligible patients randomized into control and treatment groups with a 1:1 allocation in the department of dermatology in five different hospitals in Shanghai. It was a 6-month study where both groups were treated with a topical antifungal agent, with the treatment group also receiving ablation by the traditional CO2 laser once a month for the first 3 months. RESULTS: The clinical efficacy and mycological cure rate were significantly higher (p < 0.001) for the treatment group. Three (3.75%) patients from the control group and 18 (25%) patients from the treatment group achieved complete nail clearance along with negative potassium hydroxide and negative culture (primary endpoint) results at 24 weeks. Mycological clearance with at least moderate nail clearance (secondary endpoint) for the treatment group was also significantly higher (p < 0.001) for the laser treatment group. The laser treatment was mildly painful but tolerable by the patients. No drug interactions for both groups were encountered. CONCLUSIONS: The ablative CO2 laser is a primitive yet effective modality to be considered for the delivery of topical antifungal agents for the management of mild-to-severe onychomycosis. The laser has good tolerance in patients and is a common equipment found in most dermatology units even those without the latest medical technology.