渤海贝类中麻痹性贝毒的源头解析、形成机制及风险评估

As the most lethal biotoxins among phycotoxins, Paralytic Shellfish Toxins（PSTs）can be accumulated in shellfish, and pose serious public health, and even death threat to consumer, which made it have become a serious food safety issue of common concern to the world. In China, the serious existing of PSTs have bring huge impassive impact on shellfish aquaculture, not only made consumers poisoning frequently, also lead to shellfish products suffered 19 years of international technical barriers, and the latter just be being partially lifted in 2016. However, the poisoning event caused by PSTs in mussels from Bohai in May 2016, have revealed the absence of control technology of shellfish toxins in our country. The fundamental reason for this status is that we still do not certify the original resource of shellfish toxins, do not know the occurrence rules of shellfish toxins, do not understand the degree of risk, as well as do not know the critical control point, which leading to the inability to establish scientific regulatory measures. By the theory of hazard analysis and critical control point(HACCP), we focus on the aquaculture area near Qinhuangdao where is the spot for the mussel causing poisoning incident. In this project, we firstly investigate the residues of PSTs in shellfish samples, as well as the diversity of harmful algae and their cyst, to identify the external pathways of PSTs from its producers to shellfish. Then, the accumulation, distribution and biotransformation of PSTs in shellfish tissues will be conducted by exposure experiments, followed by the analysis of metabolic group and transcript group together, which will realize the relationship of metabolite and control gene during PSTs metabolic process, to explain the endogenous processes and regulatory mechanisms of risk formation of PSTs in shellfish. By comprehensive consideration of the database of CAC\FDA\EFSA, an integrated probabilistic risk assessment model will be developed to evaluate the dietary cumulative exposures to these PSTs due to shellfish consumption, combined with PSTs residue levels in main cities around Bohai Sea. Both variation and uncertainty in the exposure and effect assessment will be included and dealt with separately in a probabilistic way. Cumulative risk assessment(CRA) enables us to assess whether risks are caused by exposure to a number of PSTs at low levels, or whether some specific components of PSTs contribute disproportionately to a cumulative risk. We will finally determine the target species should be monitored during the shellfish aquaculture process in this area. By this project, we will further understand the residue level, original resource, occurrence mechanism, risk level and key control points of PSTs in Bohai sea, especially in the shellfish aquaculture area near Qinhuangdao. Our work will provide some scientific support for the construction of regional monitoring program in this area, to ensure the consumer health and the sustainable development of shellfish aquaculture.

麻痹性贝毒(PSTs)是已知危害最严重的藻毒素，也是世界共同关注的重大食品安全问题。PSTs严重威胁我国贝类产业发展，不仅多次导致消费者中毒，更是国际壁垒重要限制目标。2016年渤海贻贝中毒事件的发生，凸显我国贝类毒素管控能力严重不足。根本原因在于不认识其源头、不了解其机制、不明确其风险、不清楚关键控制点，从而缺乏相应科学措施所致。基于HACCP理论，本项目以渤海贻贝中毒事件源头海域为目标，综合分析该海域PSTs污染状况及产毒藻/孢囊演替规律，识别贝类中PSTs污染的外源途径；研究主产贝类中PSTs蓄积、分布及转化过程，解析代谢组和转录组关联信息，阐释PSTs风险形成的内源过程及调控机制；最后，进行贝类中PSTs污染风险评估，完成主因子风险排序。项目将明确渤海贝类增殖区PSTs形成机制、风险水平及关键控制点，为构建区域性监控计划提供科学依据，对于确保消费者健康和贝类产业发展具有积极意义。

本项目以我国贻贝中毒高发区-秦皇岛山海关区为重点研究对象，进行了来源识别、调控机制和风险评估三个层次的研究。其中（1）该海域PSTs风险具有稳定的发生规律，每年3-5月份为风险高发期；该海域贝类中PSTs具体风险表征组成为C和GTX类毒素，不同贝类中风险大小顺序为虾夷扇贝>贻贝>栉孔扇贝>牡蛎>海湾扇贝；该海域PSTs风险主要肇事产毒甲藻为链状亚历山大藻（Alexandrium catenella），表层沉积物中存在大量包囊；水体温度为该产毒藻最重要的环境驱动因子，监测水体温度可有效预测A. catenella风险的发生。（2）贻贝对PSTs具有较强的蓄积能力，其平均蓄积和消除速率分别达到0.42和0.17 mg STX.2HCl eq/kg/day；内脏团代谢PSTs过程中，快速代谢和慢速代谢阶段分别有8131和7894个差异表达基因，涉及MAPK、Ras、TNF、PI3K-AKT、NF-kappaB和AMPK共6个通路，其中以MAPK通路为主；生物转化主要发生在C和GTX同系物之间，同时出现低毒→高毒、高毒→低毒转化的方式，但终端风险整体增强。（3）构建了贻贝中PSTs风险评估技术模型，评估发现我国近海贻贝中PSTs风险最大，主要风险组分为C1&2和GTX1-4，膳食风险最大的为2-7岁儿童及65岁以上老人，男性风险则普遍高于女性。本课题目前发表学术论文11篇，其中SCI4篇；授权国家发明专利2项。授权国家发明专利2件，软件著作权2件；获得中国水产科学研究院科技进步三等奖1项（排名1），山东省和青岛市科技进步三等奖各1项（排名5和2）；提交技术报告和社情民意3条，被中央统战部《零讯》、全国政协等采用。参加国内外学术交流会议10人次，做学术报告8次；培养硕士研究生4名，2名顺利毕业获得硕士学位，2名在读。