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首页> 外文期刊>Toxicology and Applied Pharmacology >Assessing interactions of binary mixtures of Penicillium mycotoxins (PMs) by using a bovine macrophage cell line (BoMacs)
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Assessing interactions of binary mixtures of Penicillium mycotoxins (PMs) by using a bovine macrophage cell line (BoMacs)

机译：使用牛巨噬细胞系（Bomacs）评估青霉素霉菌毒素（PMS）二元混合物的相互作用

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摘要

Penicillium mycotoxins (PMs) are toxic contaminants commonly found as mixtures in animal feed. Therefore, it is important to investigate potential joint toxicity of PM mixtures. In the present study, we assessed the joint effect of binary combinations of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA) and penicillic acid (PA) using independent action (IA) and concentration addition (CA) concepts. Previously published toxicity data (i.e. IC25; PM concentration that inhibited bovine macrophage (BoMacs) proliferation by 25%) were initially analyzed, and both concepts agreed that OTA + PA demonstrated synergism (p < 0.05), while PAT + PA showed antagonism (p < 0.05). When a follow-up dilution study was carried out using binary combinations of PMs at three different dilution levels (i.e. IC25, 0.5 * IC25, 025 * IC25), only the mixture of CIT + OTA at 0.5 * IC25 was determined to have synergism by both IA and CA concepts with Model Deviation Ratios (MDRs; the ratio of predicted versus observed effect concentrations) of 1.4 and 1.7, respectively. The joint effect of OTA + MPA, OTA + PA and CIT + PAT complied with the IA concept, while CIT + PA, PAT + MPA and PAT + PA were better predicted with the CA over the IA concept The present study suggests to test both IA and CA concepts using multiple doses when assessing risk of mycotoxin mixtures if the mode of action is unknown. In addition, the study showed that the tested PMs could be predicted by IA or CA within an approximate two -fold certainty, raising the possibility for a joint risk assessment of mycotoxins in food and feed. (C) 2017 Elsevier Inc. All rights reserved.
机译：青霉毒素（PMs）是动物饲料中常见的有毒污染物。因此，研究PM混合物的潜在联合毒性非常重要。在本研究中，我们使用独立作用（IA）和浓度加成（CA）概念评估了以下PM的二元组合的联合效应：桔霉素（CIT）、赭曲霉毒素A（OTA）、棒曲霉素（PAT）、霉酚酸（MPA）和青霉酸（PA）。对之前公布的毒性数据（即IC25；抑制牛巨噬细胞（BoMacs）增殖25%的PM浓度）进行了初步分析，两个概念一致认为OTA+PA表现出协同作用（p<0.05），而PAT+PA表现出拮抗作用（p<0.05）。当在三种不同稀释水平（即IC25、0.5*IC25、025*IC25）下使用PM的二元组合进行后续稀释研究时，通过IA和CA概念，仅0.5*IC25下的CIT+OTA混合物被确定具有协同作用，模型偏差比（MDR；预测效应浓度与观察效应浓度之比）分别为1.4和1.7。OTA+MPA、OTA+PA和CIT+PAT的联合效应符合IA概念，而CIT+PA、PAT+MPA和PAT+PA在CA概念上的预测更好。本研究建议，在评估真菌毒素混合物的风险时，如果作用方式未知，使用多剂量测试IA和CA概念。此外，该研究表明，IA或CA可以在大约两倍的确定性内预测经检测的PM，从而提高了食品和饲料中真菌毒素联合风险评估的可能性。（C） 2017爱思唯尔公司版权所有。

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