Evaluation of in vitro toxicity information for zebrafish as a promising alternative for chemical hazard and risk assessment.

In vitro assays are widely proposed as a test alternative to traditional in vivo standard acute and chronic toxicity tests. However, whether toxicity information derived from in vitro assays instead of in vivo tests could provide sufficient protection (e.g., 95 % of protection) for chemical risks remain evaluated. To investigate the feasibility of zebrafish (Danio rerio) cell-based in vitro test method as a test alternative, we comprehensively compared sensitivity differences among endpoints, among test methods (in vitro, FET and in vivo), and between zebrafish and rat (Rattus norvegicus), respectively using chemical toxicity distribution (CTD) approach. For each test method involved, sublethal endpoints were more sensitive than lethal endpoints for both zebrafish and rat, respectively. Biochemistry (zebrafish in vitro), development (zebrafish in vivo and FET), physiology (rat in vitro) and development (rat in vivo) were the most sensitive endpoints for each test method. Nonetheless, zebrafish FET test was the least sensitive one compared to its in vivo and in vitro tests for either lethal or sublethal responses. Comparatively, rat in vitro tests considering cell viability and physiology endpoints were more sensitive than rat in vivo test. Zebrafish was found to be more sensitive than rat regardless of in vivo or in vitro tests for each pairwise endpoint of concern. Those findings indicate that zebrafish in vitro test is a feasible test alternative to zebrafish in vivo and FET test and traditional mammalian test. It is suggesting that zebrafish in vitro test can be optimized by choosing more sensitive endpoints, such as biochemistry to provide sufficient protection for zebrafish in vivo test and to establish applications of zebrafish in vitro test in future risk assessment. Our findings are vital for evaluating and further application of in vitro toxicity toxicity information as an alternative for chemical hazard and risk assessment.

Deriving freshwater guideline values for neonicotinoid insecticides: Implications for water quality guidelines and ecological risk assessment.

The increased use of neonicotinoid insecticides in aquatic environments poses a significant threat to non-target freshwater species. However, the existing water quality guidelines (WQGs) for neonicotinoids mainly focus on imidacloprid, and only a few authoritative institutions have established WQGs for other neonicotinoids. There is a critical need to develop WQGs and conduct ecological risk assessment (ERA) of different neonicotinoids in global freshwater environments. In this study, we derived interim acute and chronic guideline values and acute-to-chronic ratios (ACRs) for six neonicotinoids based on publicly available acute and chronic toxicity data. The exposure concentrations of neonicotinoids were obtained from published literature worldwide, and ERA was conducted for neonicotinoids in global freshwater ecosystems using a tiered approach. The derived chronic guideline values (95% confidence interval (CI), ng/L) were 0.63 (0.02-5.47) for thiacloprid (the lowest) and 16.4 for dinotefuran (the highest). The identified ACRs (95% CI) ranged from 90.9 (47.0-180) to 957 (102-3350), which can be used to extrapolate scarce chronic data from the acute data. Neonicotinoid concentrations in global freshwater were predicted from 10.6 (6.88-23.4) (thiacloprid) to 339 (211-786) ng/L (thiamethoxam). The estimated risk quotients ranged from 3.23 (dinotefuran) to 21.73 (thiacloprid), and the probability of exceeding WQGs ranged from 27.1% (dinotefuran) to 77.1% (thiacloprid). The ERA results indicated that the six neonicotinoids posed negligible acute risks but high chronic risks to global freshwater ecosystems, especially acetamiprid (65.8%) and thiacloprid (28.1%). The key findings of this study provide critical scientific information regarding the ecological risks of long-term neonicotinoid exposure and key insights for policy development and water quality control.