Toxicity and ecological risk assessment for two AhR agonistic pesticides mepanipyrim and cyprodinil and their metabolites.

Mepanipyrim and cyprodinil are widely used to control and/or prevent fungal diseases in fruit culture. They are frequently detected in the aquatic environment and some food commodities. Different from TCDD, mepanipyrim and cyprodinil are more easily metabolised in the environments. However, the risk of their metabolites to the ecological environment is unclear and needs to be further confirmed. In this study, we investigated the temporal pattern of mepanipyrim- and cyprodinil-induced CYP1A and AhR2 expression and EROD enzyme activity at different time frames during zebrafish embryonic and larval development. Then, we assessed the ecological risk of mepanipyrim, cyprodinil, and their metabolites to aquatic organisms. Our results showed that mepanipyrim and cyprodinil exposure could increase the expression level of cyp1a and ahr2 genes and EROD activity by a dynamic pattern in different developmental stages of zebrafish. Besides, their several metabolites showed strong AhR agonistic activity. Importantly, these metabolites could cause potential ecological risks to aquatic organisms and should be paid more attention to. Our results would provide an important reference value for environmental pollution control and the use management of mepanipyrim and cyprodinil.

Developmental toxicity and neurotoxicity assessment of R-, S-, and RS-propylene glycol enantiomers in zebrafish (Danio rerio) larvae.

Propylene glycol (PG) is widely used in the foods, pharmaceuticals, oil industry, animal feed, cosmetics and other industries. Because of the existence of a chiral carbon center, PG forms R (Rectus)- and S (Sinister)-enantiomers. Currently, the toxicity study of its R-, S-enantiomers is still very scarce. In this study, we have assessed the developmental toxicity and neurotoxicity of the R-, S-, and RS-PG enantiomers in zebrafish larvae. We found that exposure to R-, S-, and RS-PG enantiomers did not significantly affect the basic developmental endpoints of embryos or larvae (i.e., embryonic movement, hatching, mortality, malformation, heartbeat, body length), indicating that R-, S-, and RS-PG exposures did not exhibit the basic developmental toxicity in zebrafish larvae. The toxicity of three enantiomers was lower than that of ethanol, and there was no significant difference between them. However, R-, S-, and RS-PG exposures with high doses could significantly change the eye diameter and locomotor activity of larval zebrafish, indicating that R-, S-, and RS-PG enantiomers of high doses could potentially exhibit the neurotoxicity and ocular developmental toxicity in zebrafish larvae. Therefore, the potential neurotoxicity and ocular developmental toxicity of R-, S-, and RS-PG enantiomers for infants and toddlers should be considered.

RNA m6A Modification Alteration by Black Phosphorus Quantum Dots Regulates Cell Ferroptosis: Implications for Nanotoxicological Assessment.

Nanosafety is a major concern for nanotechnology development. Evaluation of the transcriptome and the DNA methylome is proposed for nanosafety assessments. RNA m6A modification plays a crucial role in development, disease, and cell fate determination through regulating RNA stability and decay. Here, since black phosphorus quantum dots (BPQDs), among many other types of QDs, increase the global m6A level and decrease the demethylase ALKBH5 level in lung cells, the epitranscriptome is taken into consideration for the first time to evaluate nanosafety. Both the transcriptome and m6A epitranscriptome analyses show that BPQDs alter many biological processes, such as the response to selenium ions and the lipoxygenase pathway, indicating possible ferroptosis activation. The results further show that BPQDs cause lipid peroxidation, mitochondrial dysfunction, and iron overload. Recognition of these modified mRNAs by YTHDF2 leads to mRNAs' decay and eventually ferroptosis. This study shows that RNA m6A modification not only is a more sophisticated indicator for nanosafety assessment but also provides novel insight into the role of RNA m6A in regulating BPQD-induced ferroptosis, which may be broadly applicable to understanding the functions of RNA m6A under stress.