The development of a hybrid fish gill cell-polymer PAMPA assay system to replace bioconcentration factor tests for highly hydrophobic compounds

开发混合鱼鳃细胞聚合物 PAMPA 检测系统，以取代高疏水性化合物的生物浓缩因子测试

• 批准号: 260617395
• 负责人: Dr. Sabine Schnell
• 金额: --
• 依托单位: Diabetes and Nutritional Sciences
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/260617395?language=en
• 关键词: development; hybrid; fish; gill; cell

In recent decades, the worldwide outburst in technological and industrial advancements has greatly increased the use of chemicals as well as the concerns for the environment and health. Regarding the aquatic environment, the accumulation of chemicals in fish and other aquatic organisms has been a significant concern to industry, government regulators, the academic community, and the general public for a long time. Evaluations of persistent, bioaccumulative and toxic (PBT) properties of chemicals are necessary in order to provide protection to aquatic wildlife from harmful effects of pollutants on human health. The information on bioaccumulation of chemicals is an important requirement for environmental risk assessment and for regulatory regimes such as the EU regulation No. 1907/2006 concerning the Registration, Evaluation, Authorization, and restriction of Chemicals (REACH). As part of REACH it is most likely that many chemicals produced will need to be tested for their potential to bioaccumulate. Bioaccumulation studies investigate the enrichment of chemicals in living organism, usually distinguishing between the uptake of chemicals from the diet and direct accumulation from the water (bioconcentration) by fish. These studies using fish are carried out based on the technical guideline such as the Organisation for Economic and Co-operation Development (OECD) 305 Bioaccumulation in Fish: Aqueous and Dietary Exposure. For aqueous OECD 305 test 80 fish per compound are routinely used and for the dietary tests up to 230 fish. There are over 3000 chemicals that require further testing as part of REACH legislation, which will mean the use of up to 242,000 fish for toxicology testing. There is a worldwide desire to reduce numbers of animals used in environmental risk assessment, thus an active research agenda exists to identify relevant alternatives to whole animal toxicity testing. The current project will evaluate a system that does not use animals as a replacement for fish bioconcentration studies. More specifically, we will focus on a specific group of chemicals that are poorly water-soluble because there are a number of scientific issues associated with developing alternative test methods for this class of compounds. Previous systems that use artificial membranes show encouraging results for predicting bioconcentration of fairly water soluble compounds. However, these systems do not incorporate a biologically active epithelium and thus may not accurately predict bioconcentration. The current study overcomes this by combining fish gill cell cultures with features of previous methodologies using artificial membranes. The study will compare uptake and elimination of compounds by two gill cell culture models; a primary Fish Gill cell Culture System (FIGCS) and a cell line RTgill-W1. Data will be used to generate predictive models and the results will be compared to known whole fish bioconcentration factor values as a means of validation.

近几十年来，世界范围内技术和工业进步的爆发大大增加了化学品的使用以及对环境和健康的关注。关于水环境，化学品在鱼类和其他水生生物中的积累长期以来一直是工业界、政府监管机构、学术界和公众的重要关注。为了保护水生野生动物免受污染物对人类健康的有害影响，有必要对化学品的持久性、生物累积性和毒性进行评估。关于化学品生物蓄积性的信息是环境风险评估和监管制度的一项重要要求，如欧盟关于化学品注册、评估、授权和限制的第1907/2006号条例。作为REACH的一部分，很可能需要对生产的许多化学品进行生物累积潜力测试。生物蓄积性研究调查化学品在生物体内的富集情况，通常区分鱼类从食物中摄取的化学品和从水中直接蓄积的化学品（生物蓄积）。这些使用鱼类的研究是根据技术准则进行的，例如经济与合作发展组织（经合组织）305号文件《鱼类的生物累积性：水和饮食接触》。对于水性OECD 305试验，每种化合物通常使用80条鱼，对于膳食试验，最多使用230条鱼。作为REACH法规的一部分，有超过3000种化学品需要进一步测试，这意味着将使用多达242，000条鱼进行毒理学测试。全世界都希望减少环境风险评估中使用的动物数量，因此存在一个积极的研究议程，以确定整个动物毒性试验的相关替代方案。目前的项目将评估一个不使用动物替代鱼类生物浓缩研究的系统。更具体地说，我们将重点关注一组特定的水溶性差的化学品，因为有一些科学问题与开发这类化合物的替代测试方法有关。以前使用人工膜的系统在预测相当水溶性化合物的生物浓缩方面显示出令人鼓舞的结果。然而，这些系统不包含生物活性上皮，因此可能无法准确预测生物浓缩。当前的研究通过将鱼鳃细胞培养与之前使用人工膜的方法的特征相结合来克服这一点。该研究将通过两种鳃细胞培养模型比较化合物的吸收和消除;原代鱼鳃细胞培养系统（FIGCS）和细胞系RTgill-W1。数据将用于生成预测模型，并将结果与已知的整鱼生物浓缩系数值进行比较，作为验证手段。