Pollution characteristics and human health risks of PM2.5-bound heavy metals: a 3-year observation in Suzhou, China.

This study aimed to analyze the temporal trends, pollution levels, and health risks associated with eleven PM2.5-bound heavy metals (Sb, Al, As, Hg, Cd, Cr, Mn, Ni, Pb, Se and Tl). A total of 504 PM2.5 samples were collected in Suzhou from January 2019 to December 2021. The pollution levels were estimated based on enrichment factors (EFs) which can be used to calculate the enrichment of heavy metals in PM2.5 and determine whether the concentrations of PM2.5-bound heavy metals are influenced by the crustal or anthropogenic sources, and the health risk of PM2.5-bound heavy metals via inhalation was assessed following US EPA's Risk Assessment Guidance for Superfund (RAGS). The annual average concentration of PM2.5 was 46.76 µg m-3, which was higher than the WHO recommended limit of 5 µg m-3. The average of the sum of eleven PM2.5-bound heavy metals was 180.61 ng m-3, dominated by Al, Mn, and Pb. The concentration of PM2.5 in 2020 was significantly lower than that in 2019 and 2021. The PM2.5 and PM2.5-bound heavy metal concentrations in winter and spring were significantly higher than those in autumn and summer. The EF of As, Cr, Cd, Hg, Ni, Pb, Sb, Mn, Se, and Tl was higher than 10, indicating they were mainly from anthropogenic sources. Exposure to a single non-carcinogenic heavy metal via inhalation was unlikely to cause non-carcinogenic effects (HQ < 1), but the integrated non-carcinogenic risks should be taken seriously (HI > 1). The cumulative carcinogenic risks from the carcinogenic elements were exceeding the lower limit (1 × 10-6) of the acceptable risk range. The carcinogenic risks of As and Cr(VI) contributed 60.98% and 26.77%, respectively, which were regarded as two key carcinogenic risk factors. Overall, the government policies and countermeasures for the PM2.5 pollution control should be performed not only based on the PM2.5 concentration but also based on the PM2.5-bound heavy metals and their health risks for the local residents.

The essential role of CYP2E1 in metabolism and hepatotoxicity of N,N-dimethylformamide using a novel Cyp2e1 knockout mouse model and a population study.

N,N-Dimethylformamide (DMF) is a widespread contaminant of leather factories and their surrounding environment. There is a lack of direct in vivo evidence supporting CYP2E1 as a primary enzyme responsible for DMF metabolism and hepatotoxicity. In this study, a novel Cyp2e1 knockout (KO) mouse model was generated and used to assess whether DMF metabolism and hepatotoxicity is CYP2E1 dependent using an acute toxicity protocol with a single dose of 1500 mg DMF/kg. An epidemiological study in 698 DMF-exposed workers and 188 non-DMF-exposed controls was conducted to investigate the associations between functional polymorphisms of CYP2E1 (rs6413432/rs2031920) and DMF metabolite (N-methylcarbmoylated-hemoglobin [NMHb]). We successfully established Cyp2e1 KO mice with evidence from DNA sequence analysis, which showed 1-bp insertion at 65 bp (C) site of Cyp2e1 Exon 1. In addition, western blot and in vivo pharmacokinetic study also showed a complete absence of CYP2E1 protein and a 92% and 88% reduction in CYP2E1 activity among males and females, respectively. DMF metabolism as evidenced by increased blood NMHb, and hepatotoxicity as evidenced by elevated liver/body weight ratio, activity of liver enzymes and massive liver necrosis were detected in wild-type (WT) mice but were completely abrogated in KO mice, strongly supporting a CYP2E1-dependent pattern of DMF metabolism and hepatotoxicity. Moreover, variant allele of CYP2E1-rs6413432 was also significantly associated with higher NMHb levels in DMF-exposed workers (P = 0.045). The increase of glucose-regulated protein 94 detected in WT mice but not in KO mice suggested CYP2E1-dependent endoplasmic reticulum stress may be a key mechanism underlying DMF-induced hepatotoxicity.