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Pesticides commonly occur as mixtures in an aqueous environment, causing deleterious effects on human health and the environment. However, the mechanism underlying the combined effects on aqueous organisms remains largely unknown, especially at low concentrations. In the current study, we inspected the interactive toxicity of tebuconazole (TEB), a triazole fungicide, and bifenthrin (BIF), a pyrethroid insecticide, to zebrafish (Danio rerio) using various toxicological assays. Our data revealed that the 96 h-LC 50 (lethal concentration 50) values of BIF to fish at different life periods (embryonic, larval, juvenile, and adult periods) ranged from 0.013 (0.011–0.016) to 0.41 (0.35–0.48) mg a.i. L−1, which were lower than that of TEB ranging from 1.1 (0.88–1.3) to 4.8 (4.1–5.7) mg a.i. L−1. Combination of TEB and BIF induced synergetic acute toxicity to embryonic fish. Activities of T-SOD, POD, and GST were distinctly altered in most individual and joint administrations. Expressions of 16 genes associated with oxidative stress, cellular apoptosis, immune system, and endocrine system at the mRNA level were evaluated, and the information revealed that embryonic zebrafish were impacted by both individual compounds and their combinations. Six genes (cas9 , P53 , gr , TRα, IL-8, and cxcl-clc) exhibited greater changes when exposed to pesticide mixtures. Therefore, the joint effects induced by the pesticides at low concentrations should be considered in the risk assessment of mixtures and regulated as priorities for mixture risk management in the aqueous ecosystem. More research is needed to identify the threshold concentrations of the realistic pesticide mixtures above which synergistic interactions occur. [Display omitted] • Bifenthrin exhibited higher acute toxic effects than tebuconazole on the zebrafish. • Co-exposure of tebuconazole and bifenthrin elicited synergistic acute responses. • Synergistic oxidative stress, apoptosis and endocrine disrupting effects were observed. • Immune gene expressions (IL-8 and cxcl-clc) were significantly altered in mixtures. • Identification of single pesticides involved in synergism can benefit risk precautions. [ABSTRACT FROM AUTHOR]

The natural co-occurrence of multiple mycotoxins has been reported in cereals and cereal products worldwide. Even though the dietary exposure to mycotoxins constitutes a serious human health, most reports are limited to the toxic effect of individual mycotoxins. The purpose of the present study was to assess the combined toxic effects of zearalenone (ZEN) and fumonisin B1 (FB1) and the potential interaction of their mixture on zebrafish (Danio rerio) embryos. Our results showed that ZEN possessed the higher toxicity to embryonic zebrafish (7-day LC 50 value of 0.78 mg a.i. L−1) compared with FB1 (7-day LC 50 value of 227.7 mg a.i. L−1). The combination of ZEN and FB1 exerted an additive effect on zebrafish embryos. Meanwhile, the activities of antioxidant CAT, caspase-3, and detoxification enzyme CYP450, as well as the expressions of six genes (Mn-sod , cas9 , bax , cc-chem , ERα , and crh) associated with oxidative stress, cellular apoptosis, immune system, and endocrine system were prominently altered in the mixture exposure compared with the corresponding single treatment group of ZEN or FB1. Taken together, the regulatory standards of mycotoxins in food and feed should be updated based on the mixture effects of mycotoxins, and there is an increased need on effective detoxification methods for controlling and reducing the toxicity of multiple mycotoxins in animal feed and throughout the food supply chain. [Display omitted] • The natural co-occurrence of multiple mycotoxins is common in worldwide cereals. • Co-exposure of zearalenone and fumonisin B1 exhibited additive acute response. • Combined effects related to biochemical index changes were observed in the mixture. • Gene expression altered for oxidative stress, apoptosis, immune and endocrine system. • Regulatory standards of mycotoxins should take the mixture effects into account. [ABSTRACT FROM AUTHOR]

Abstract: DNA damage caused by low dosage of avermectin was evaluated in hemocytes of silkworm (Bombyx mori) using the alkaline single-cell gel electrophoresis (SCGE). The fourth instar larvae of silkworm were exposed to avermectin by oral feeding with mulberry leaves treated on the three different concentrations. The hemocytes were collected at day 1, 3, 5, 7, 9 for assessment of DNA damage with tail DNA percent. Results showed that there was positive correlation between avermectin concentration and DNA damage in three tested treatments. The maximum value of tail DNA percent was observed at the third day, followed by a gradual non-linear decline. For better understanding the results of SCGE at transcription level, differentially expressed genes (DEGs) were explored in hemocytes of silkworm exposed to avermectin (1.0μg/l) using annealing control primer (ACP)-based PCR. 15 DEGs were screened and sequenced, among which 10 genes were up-regulated, 5 genes were down-regulated. These genes were related with DNA damage or DNA damage repair of hemocytes. [Copyright &y& Elsevier]