Genotoxicity, oxidative stress and transcriptomic effects of Nitenpyram on human bone marrow mesenchymal stem cells.

Despite of the global contamination and ubiquitous exposure to nitenpyram (NIT), little knowledge is available on the adverse effects to human health, with some evidence referring to its genotoxic potency to non-target organisms and esophageal squamous papilloma in rats. Human bone marrow mesenchymal stem cells (hBMSCs) was employed as an in vitro model more relevant to humans to assess the potential genotoxicity of NIT and to understand the underlying mechanisms at cellular and molecular levels. Noncytotoxic concentrations of NIT, 50-2500 µg/mL, dose-dependently elevated micronucleus (MN) and nuclear bud (NB) frequencies to 8.7-29‰ and 15-35‰, respectively. Additional metabolism by rat liver S9 fraction decreased chromosome impairment by 27-52% on MN frequencies and 63-76% on NB frequencies. A commercial NIT product, containing 20% of NIT and 60% of pymetrozine, caused higher cytotoxicity and chromosome impairment in comparison with NIT alone. Expressions of genes responses to DNA damage, ATM, ATR, p53, p21, Bax, H2AX, and GADD45A were disturbed by NIT treatment. Reactive oxygen species (ROS) amount and superoxide dismutase (SOD) activity were enhanced by NIT. Comet assay showed that lower concentrations of NIT, 12.5-100 µg/mL, induced the DNA damage. Transcriptomic analysis identified 468 differentially expressed genes (p < 0.05, |log2(Foldchange)| ≥ 1), from which 22 pathways were enriched. Multiple affected pathways were related to cancer including viral carcinogenesis and bladder cancer. NIT may produce genotoxicity via inducing oxidative stress and deregulating PI3K/Akt, AMPK and mTOR signaling pathways, associated with carcinogenetic potency. While environmental levels of NIT alone may pose little risk to human health, attention should be paid to the health risk arose from the synergistic or additive effects that may exist among NEOs and other types of pesticides.

Integrated estrogenic effects and semi-volatile organic pollutants profile in secondary and tertiary wastewater treatment effluents in North China.

Endocrine-disrupting effects on aquatic organisms caused by wastewater discharging have raised extensive concerns. However, the efficiency of various wastewater treatment processes to remove estrogenic activity in effluents and the association with organic micropollutants was not well known. We evaluated the estrogenic activity using a well-characterized in vivo bioassay featuring the Chinese rare minnows (Gobiocypris rarus) and analyzed 886 semi-volatile organic compounds (SVOCs) in effluents from four secondary wastewater treatment plants (SWTP A-D) and a tertiary wastewater treatment plant (TTP E) that utilized various common treatment processes in northern China. The final effluents from SWTPs and TTP E all exhibited estrogenic effects, increasing male fish plasma vitellogenin (VTG) contents and estradiol/testosterone (E2/T) ratios. Key regulating genes in the male fish liver including vtg1, vtg3, era, erß, and cyp19a were upregulated. TTP E demonstrated high performance in reducing estrogenic activity in the effluents, with a reduction of 64% in integrative biomarkers of estrogenic response (IBR). UV disinfection at SWTPs removed IBR by 14%- 33%, while ozone disinfection at TTP E did not reduce IBR. Several SVOCs including alkanes, chlorobenzenes, and phthalates, detected at ng/L to µg/L level, significantly correlated with effluent estrogenic activity. Our findings suggest the necessity and the potential means to improve the efficiency of current wastewater treatment approaches to achieve better protection for aquatic organisms against the joint effects of mixtures of various categories of micropollutants in effluents.