Species difference in toxicokinetics and safety assessment of senecionine N-oxide in a UDP-glucuronosyltransferase 1A4 humanized mouse model.

Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins, and herbs containing PAs are of high concern. PAs are normally found in tertiary amines and N-oxide forms (PA N-oxides), yet the latter are less evaluated for their toxicokinetics. As a continuation of our investigation into the safety assessment of PA-containing herbal medicines, the toxicity and toxicokinetic characteristics of senecionine N-oxide (a representative toxic PA N-oxide) were investigated by using the UDP-glucuronosyltransferase 1A4 humanized mouse model (hUGT1A4 mouse model) and compared with those in wild-type mice simultaneously. Results show that the toxicity caused by senecionine N-oxide exposure was evidently decreased in hUGT1A4 mice as approved by pathology and biochemistry assays. In addition, a N-glucuronidation conjugate was exclusively found in hUGT1A4 mice but not in wild-type (WT) mice. In vitro studies proved that senecionine N-oxide initially reduced to the corresponding tertiary amine alkaloid (senecionine) and then underwent N-glucuronidation via human UGT1A4. The variation in toxicokinetic characteristics was also observed between hUGT1A4 mice and WT mice with a notably enhanced clearance of senecionine N-oxide and senecionine, and accordingly less formation of pyrrole-protein adducts in hUGT1A4 mice, which finally led to the detoxification of senecionine N-oxide exposure in hUGT1A4 mice. Our results provided the first in vivo toxicity data and toxicokinetic characteristics of senecionine N-oxide in a humanized animal model and revealed that human UGT1A4 plays an important role in the detoxification of senecionine N-oxide.

Pollution levels and health risk assessment of potentially toxic metals of size-segregated particulate matter in rural residential areas of high lung cancer incidence in Fuyuan, China.

The highest incidence and mortality rate of lung cancer in rural area of Fuyuan has been a research hotspot, and the pathogenesis is still unclear. Therefore, atmospheric particulate matters (APMs) samples were collected between 18 February and 01 March 2017, exploring water-soluble potentially toxic metals (WSPTMs) and water-soluble inorganic ionic species (WSIIs) levels, size distribution, sources, acidity and alkalinity, and potential carcinogenic and non-carcinogenic risks, hoping to provide scientific basic data to solve this problem. In our study, the average ratio of nitrate ion (NO3-)/sulfate ion (SO42-) within PM1.1, PM1.1-2.0, PM2.0-3.3, PM3.3-7.0, and PM>7.0 were 0.22, 0.18, 0.15, 0.34 and 0.36, respectively, that revealed that combustion sources contributed to PM were more significant. The anions in equilibrium (ANE) / cations in equilibrium (CAE) < 1 for all samples within PM1.1, PM2.0-3.3, PM3.3-7.0 indicate that the APMs were alkaline, but PM1.1-2.0 particulate matter shows weak acidity. SO42- prefers to combine with NH4+ to form (NH4)2SO4, which hinders the formation of NH4NO3, the remaining SO42- and NO3- to neutralize the K+, KNO3 was formed at all particulate, however, K2SO4 can only be formed in PM<3.3. Arsenic (As) and Selenium (Se) were identified as the most enriched WSPTMs in all PM sizes, predominantly from anthropogenic emissions, were suggested that coal combustion is a significant source of PM-bound WSPTMs. Total WSPTMs exhibited high total carcinogenic risks (TCR) values (9.98 × 10-6, 1.06 × 10-5, and 1.19 × 10-5 for girls, boys and adults, respectively) in the smaller particles (< 1.1 µm). Se was considered as the major contributor (63.60%) to carcinogenic risk (CR) in PM2.0 and had an inverse relationship with PM size that should be of prime concern.

Pollution characteristics and risk assessment of potentially toxic elements of fine street dust during COVID-19 lockdown in Bangladesh.

Due to the COVID-19 pandemic, Bangladesh government took the measure like partial lockdown (PL) and complete lockdown (CL) to curb the spread. These measures gave a chance for environmental restoration. In this study, street dust samples were collected during PL and CL from four main urban land use categories in Dhaka city, such as industrial area (IA), commercial area (CA), public facilities area (PFA), and residential area (RA). Ten potentially toxic elements (Cr, Mn, Zn, Fe, Pb, Cu, Co, Ni, As, and Cd) in fine street dust particles (diameter < 20 µm) were determined following aqua-regia digestion and measured by inductively coupled plasma mass spectrometry (ICP-MS) to evaluate distribution, pollution sources, and potential risks to ecological systems and human health. Results showed that during PL, the concentrations of toxic elements in the dust were higher than that of CL. Cd and Fe were lowest and highest in concentration with 1.56 to 41,970 µg/g and 0.82 to 39,330 µg/g in partial and complete lockdown period respectively. All toxic elements were detected at high levels above background values where Fe with the highest and Cd with lowest concentrations, respectively. By land use, the levels of toxic elements pollution followed IA > PFA > RA > CA. Correlation analysis (CA), principal component analysis (PCA), and hierarchal cluster analysis (HCA) revealed that the sources of these analyzed toxic elements were mainly from anthropogenic which are related to industrial and vehicular or traffic emissions. Enrichment factor (EF), geoaccumulation index (Igeo), contamination factor (CF), and pollution load index (PLI) also suggested that the dust was more polluted during PL. Exposure of toxic elements to human was mainly via skin contact followed by ingestion and inhalation. Hazard quotient (HQ) values were < 1 except for Mn through dermal contact at all sites during partial and complete lockdown, similar to hazard index (HI), while Cr further showed high non-carcinogenic risks to children. Generally, children HI values were about 5-6 times higher than those of adults, suggesting a greater vulnerability of children to the health concerns caused by toxic elements in street dust. Carcinogenic risk (CR) values via ingestion pathway indicated all elements (except Pb) had significant health effect, while CR value by inhalation results showed no significant health effect. Cumulative carcinogenic risk (CCR) value had significant health effect except Pb in all land use categories. CCR values decreased during CL and reached at acceptable limit for most of the cases. This research provides a message to the local governments and environmental authorities to have a complete assessment of toxic elements in the street dust of Dhaka megacity in order to assuring public health safety and ecological sustainability.

Water Footprint Allocation under Equity and Efficiency Considerations: A Case Study of the Yangtze River Economic Belt in China.

From a water footprint perspective, this paper adopts Gross Domestic Product (GDP) as the influencing factor to construct a lexicographical optimization framework for optimizing water resources allocation under equity and efficiency considerations. This approach consists of a lexicographic allocation of water footprints (LAWF) model and an input-output capacity of water footprints (IOWF) model. The proposed methodology is then applied to allocate water resources in the Yangtze River Economic Belt (YREB) by employing the 2013 cross-sectional data in the area. The results show that: (1) The LAWF scheme signifies reductions in water footprints in each of the YREB administrative units, thereby significantly strengthening their IOWFs. (2) IOWFs are affected by industrial attributes and natural endowments, and the impact tends to vary across different industries and regions. (3) Policy suggestions are proposed to effectively enhance the IOWFs of the weakest industries across the three YREB regions to exploit their natural endowments.