海洋生态与环境科学重点实验室知识库

近年非典、禽流感、手足口等众多人畜新型疾病不断出现，与此同时全球人口老龄化程度也在不断加剧，越来越多新型药物活性化合物（PhACs）被加速研发、生产及应用，PhACs的种类和消费量均在逐年快速递增，而其中很大部分PhACs不可避免的将进入环境中。PhACs具有较强生物活性、持久性、生物累积性等特性，可对人类健康和生态环境产生重大影响。PhACs的入海对海洋生态系统产生的影响不可预估，其对海洋环境的影响日益凸显，PhACs已经成为一类具“纯人为影响标志”的新兴海洋有机污染物。目前PhACs对海洋生态系统的潜在生态风险已经引起了国内外学者和国际组织的广泛关注，对海洋环境中PhACs的系统研究具有重要的科学意义和应用价值。本研究选择了受人为活动和自然因素双重影响的典型海湾——胶州湾的海水、沉积物以及大气沉降（降雪）中的158种PhACs作为主要研究对象，系统研究了胶州湾及邻近环境中PhACs的水平与组成、生物地球化学分布特征、来源、污染趋势、环境控制因素以及潜在生态风险。获得了一系列创新的结果和认识：

（1）胶州湾海水、沉积物及邻近环境大气沉降（降雪）中均存在不同水平的PhACs，且其组成差异明显。胶州湾海水中PhACs分布除受化合物自身降解影响外，主要受“来源途径-海水动力过程”的影响，属被动扩散分布模式。沉积物中PhACs分布主要受 “来源途径-海水动力过程-沉积物组成”的影响，即被动扩散-主动吸附相结合的复合分布模式。

通过高分辨质谱大通量筛查和三重四级杆质谱分析，在海水中共检出36种目标PhACs，其中17种是在海水中第一次报道；在降雪中共检出38种目标PhACs，均为降雪、积雪中的第一次报道，本研究也是关于积雪PhACs污染的第一次报道；在胶州湾沉积物中共检出25种目标PhACs，其中10种是在海洋沉积物中第一次被发现。

不同海洋环境中PhACs的组成由于药物本身的性质、用途和用量而差异较大。胶州湾沉积物中PhACs浓度为3.62-21.4 ng/g，降雪、海水中PhACs浓度分别为52.8-1616 ng/L和23.6-217 ng/L。海水中主要为为金刚烷胺（24.7 ng/L）、林可霉素（8.55 ng/L）、酮基布洛芬（8.30 ng/L）和四环素（7.48 ng/L）；降雪融水中主要为四环素（125.8 ng/L）、3-去乙酰基头孢噻肟（17.7 ng/L）、罗硝唑（8.79 ng/L）和醋酸曲安西龙双（2.84 ng/L）；沉积物中主要为酮基布洛芬（2.49 ng/g）、土霉素（1.00 ng/g）和罗红霉素（0.97 ng/g）。虽然不同环境中PhACs的组成差异明显，但抗生素均为占比最大的种类，且这些抗生素类药物都是我国临床医疗和畜禽养殖常用药物，与我国的PhACs的生产和使用特点基本一致。

胶州湾PhACs海水及沉积物水平分布总体呈现湾内从东向西逐渐减少，湾内高于湾外的特征，且PhACs的总浓度的等值线均几乎与海岸线平行。胶州湾西部PhACs含量（平均值：38.4 ng/L；5.06 ng/g）明显低于受人为活动影响严重的东部（平均值：116 ng/L；14.2 ng/g）。

海水中PhACs浓度与营养盐呈正相关，且两者分布高度相似（相关因子r值均在0.9以上），其中磷酸盐还与16种PhACs残留呈现显著正相关（P<0.01），说明它们有相似来源。PhACs浓度与盐度呈负相关，盐度越低说明陆源淡水输入量越大，但此时海水中PhACs浓度反而越高。表明PhACs在海水中的分布属于被水动力过程控制的被动单一扩散分布模式。

对于沉积物来说，PhACs与TOC呈显著正相关（P<0.01，r=0.932），有机质对PhACs污染物吸附起重要作用。PhACs与粘土比例也呈现显著正相关性（P<0.01，r=0.896），沉积物粒径越小，总的表面积越大，吸附作用越强，越有利于PhACs的富集。表明PhACs在沉积物中的分布属于被水动力过程控制的沉积物主动吸附的扩散-吸附分布模式。

（2）陆源输入是胶州湾PhACs的主要来源，其主要来源于东部河流（特别是李村河）的污水排放，大气沉降也是胶州湾PhACs不可忽略的来源；胶州湾PhACs对部分生物类群有潜在生态风险。

通过对胶州湾海水、沉积物中的PhACs与其对应的关键因子（磷酸盐、粪甾醇、盐度等）关系的系统分析得知，胶州湾海水中磷酸盐和PhACs有相似的来源，粪甾醇对胶州湾沉积物中PhACs的来源分布具有重要的指示作用。胶州湾东部河流输入，特别是李村河污水排放是胶州湾PhACs最主要的来源。胶州湾受到人类粪便排放的污染，东部的生活污水、医疗废水可能是胶州湾PhACs的主要源头。

PhACs的传输途径研究表明胶州湾大气沉降（降雪）中除沙丁胺醇、罗硝唑和恶喹酸等少数种类的PhACs与远距离运输有关外，其余大多来自本地污染源排放，本地污染源排放远大于远距离传输的贡献。降雪中人用、兽用和人畜共用药物占总PhACs比例分别为40.1%、46.0%和13.8%，兽药在大气中比例较高可能与动物粪便土壤施放、填埋有关。

胶州湾PhACs对无脊椎动物、藻类、鱼类和高等植物等水生生物产生的影响程度差异较大。海水、沉积物和降雪中PhACs对鱼类和高等植物潜在风险很小（RQ<0.01），但对无脊椎动物和藻类情况不容乐观。四环素、氧氟沙星、林可霉素、红霉素、克林霉素、土霉素、磺胺甲基异噁唑等7种PhACs对胶州湾环境中的无脊椎动物和藻类均有着高等或中等潜在生态风险。

In recent years, a variety of novel zoonotic diseases, such as SARS, avian influenza and HFMD (hand-foot-and-mouth disease), have emerged, and the aging of the global population undergoes constant exacerbation. To face this situation, an increasing number of novel pharmaceutically active compounds (PhACs) are involved in accelerating research and development, production and application. As the types and consumption of PhACs increase each year, most drugs inevitably enter the environment. Their strong bioactivity, persistence and bioaccumulation characterize the drugs to be significantly influential on human health and the ecological environment. The impact of PhACs entering oceans on marine ecosystems is immeasurable, and the different impacts of PhACs on marine environments are also increasingly highlighted. For this reason, PhACs are recognized as an important new type of marine organic pollutant. In the meantime, the potential ecological risks in marine environments, especially offshore environments, and the prevention and control of PhAC pollution have been popular topics that have been increasingly investigated by scholars abroad and at home. Therefore, systematic studies on PhACs in marine environments are of great scientific significance and application value. In this study, the seawater, sediment and atmospheric sedimentation (snow) of Jiaozhou Bay (JZB), a model bay that is influenced by both human activities and natural factors, were selected as the primary study objects. By high throughput screening and the combination of the relationships between PhACs and the relevant environmental factors, a systematic exploration was applied to study the occurrence, biogeochemical distribution characteristics, sources, pollution trends, environmental control factors and potential ecological risks of PhACs in the environment of JZB. A series of new results and understandings have been obtained as follows:

1. In these three media—seawater, sediments and atmospheric sedimentation (snow) of JZB—PhAC contamination was found to different extents, suggesting a wide presence of PhACs in the environment of JZB. The PhAC distribution in the seawater of JZB is mainly guided by a means of “sources and channels—the hydrodynamic process of seawater”, in addition to the self-degradation factors of the compounds. Namely, the distribution of the compounds is formed by a passive diffusion mode. In contrast, in the sediments, the PhAC distribution is regulated and controlled by the path of “sources and channels—hydrodynamic process of seawater-composition of sediments”; that is, the distribution is shaped by a “passive diffusion-active adsorption” composite pattern.

Using high-throughput screening and advanced mass spectrum analysis technology, a total of thirty-six PhACs were detected in seawater, of which seventeen were first reported in seawater; thirty-eight targeted compounds were found in snow, and all of them were disclosed in a scientific journal for the first time, while the study was the first report concerning PhAC contamination in snow; moreover, twenty-five target PhACs were verified in the sediments of JZB, of which ten were discovered for the first time in marine sediments.

Among the three environmental media above, the sediments were found to contain the highest PhAC occurrence concentration, with a value of 3.62-21.4 ng/g, followed by snow and seawater, whose PhAC concentrations were 52.8-1616 ng/L and 23.6-217 ng/L, respectively. The occurrence of different types of PhACs in the marine environment varies greatly depending on the application range, utilization purpose and physicochemical properties of the drug itself. Of the PhACs remaining in the seawater, the preponderant kinds include tetracycline (7.48 ng/L), carprofen (8.30 ng/L), lincomycin (8.55 ng/L) and amantadine (24.7 ng/L). In the snow, the primary kinds were triamcinolone diacetate (2.84 ng/L), ronidazole (8.79 ng/L), desacetylcefotaxime (17.7 ng/L) and tetracycline (125 ng/L). In the sediments, the major PhACs included roxithromycin (0.97 ng/g), oxytetracycline (1.00 ng/g) and ketoprofen (2.49 ng/g). Despite a significant difference in the composition of PhACs in distinct environmental media, antibiotics and hormones generally dominate in environments because they are frequently used in clinical medical care and livestock and poultry farming in China. This result is overall consistent with the characteristics of PhAC production and utilization in China.

The PhAC distribution presents a gradual decrease in density from east to west, where the areas inside the bay have a higher concentration than the areas outside the bay. Meanwhile, the isopleth of the total PhAC concentration appears to be practically parallel to the coastline. In addition, it was noted that the PhAC concentration in western JZB (38.4 ng/L; 5.06 ng/g) was obviously lower than that in eastern JZB (116 ng/L; 14.2 ng/g), where the impact of human activities is severe.

Regarding the seawater environment, PhACs are positively correlated with nutrients, and both display a distribution pattern highly similar to each other (the correlation factors r being larger than 0.9). Of the nutrients, phosphates were proven to exhibit a significantly positive correlation with 16 PhACs (P<0.01). This finding indicates that phosphates may harbor similar sources. The content of PhACs is negatively correlated with salinity. Low salinity signifies a high input volume of fresh water, but the PhAC concentration in seawater increases when the fresh water input increases. The correlation indicates the “single-diffusion” passive mode of the PhAC distribution in seawater, which is managed by the “hydrodynamic process”.

Regarding the sediments, the PhACs here are significantly positively correlated with TOC (P<0.01, r=0.932). Organic matter plays a vital role in adsorbing PhAC contaminants. Similarly, a significantly positive correlation was noted between PhACs and clay (P<0.01, r=0.896). The smaller the diameter of sediment grains is, the larger the total surface area, and the stronger the adsorption action, which is also more favorable for the enrichment of PhACs. The PhAC distribution in sediments shows an active mode of “diffusion-adsorption”, where it is jointly regulated by the “hydrodynamic process” and “sediment adsorption”.

2. Land-based input was identified as the main source of PhACs in the JZB. River input was found to be the major land-based input of the PhACs in this area, which was mainly derived from eastern rivers (the sewage discharge of the Licun River, in particular). Atmospheric sedimentation may also be a non-negligible, important source of the PhACs in JZB. The PhACs were found to harbor potential toxicity risks for some biological groups in JZB.

According to the systematic analyses on the relationship between the PhACs in the JZB seawater and key environmental factors, phosphate was considered a potential indicator to prompt the distribution characteristics of PhAC concentrations in JZB seawaters, while coprostanol was considered a possible indicator of the distribution of the concentration of PhACs in the JZB sediments. The input of rivers in the eastern part of the bay, especially the waste discharge from the Licun River, forms the prime source of PhACs in this region. As the bay has been severely contaminated by human excreta, domestic sewage and medical wastewater from the eastern coastal region are likely to be the main sources of the PhACs in JZB.

The investigation of the PhAC transmission route suggested that in atmospheric sedimentation, in addition to the PhACs of salbutamol, ronidazole, oxolinic acid and a few other kinds that are from remote transmission, most of the PhACs come from local pollutant emissions. In short, for PhACs, the discharge of local contaminants contributes more than remote transmission. Of the PhACs in snow, drugs for humans only, animals only and both humans and animals account for 40.1%, 46.0% and 13.8%, respectively. The high amount of veterinary drugs in the atmosphere may be associated with the persistent landfill deposition of animal droppings.

The impacts of PhACs on aquatic organisms such as invertebrates, algae, fishes and plants in JZB were noted to vary greatly. Though unlikely to bring potential risks to fishes and plants (RQ<0.01), the PhACs in seawater, sediments and atmospheric sedimentation present a much less optimistic picture for invertebrates and algae. Tetracycline, ofloxacin, lincomycin, roxithromycin, clindamycin, oxytetracycline, and sulfamethoxazole posed high or medium risks to invertebrates and algae.

第1章 绪论. 1

1.1 药物活性化合物（PhACs）概况. 1

1.1.1 研究背景. 1

1.1.2 环境中 PhACs的来源. 2

1.1.3 环境中 PhACs的分析方法比较. 5

1.1.4 PhACs在海洋环境中的研究进展和存在的问题. 7

1.2 论文的选题意义及主要研究内容. 9

1.3 研究区域概况及研究方法. 11

1.3.1 研究区域概况. 11

1.3.2 站位设置及采样. 12

1.3.3 分析方法. 15

1.3.4 质量控制（QA/QC）. 25

1.3.5生态风险评估方法. 25

第2章胶州湾海水与沉积物中的药物活性化合物. 27

2.1 胶州湾海水中PhACs的组成与分布. 28

2.1.1 胶州湾海水中PhACs的构成与浓度水平. 28

2.1.2 胶州湾海水中PhACs的分布特征. 33

2.2胶州湾海水中PhACs环境生物地球化学特征. 37

2.2.1 PhACs与海水环境因子的耦合关系. 37

2.2.2 海水中PhACs的生态风险评估. 43

2.3 胶州湾沉积物中PhACs的组成与分布. 45

2.3.1胶州湾沉积物中PhACs的构成与浓度水平. 45

2.3.2 胶州湾沉积物中PhACs的分布特征. 49

2.4 沉积物中PhACs环境生物地球化学特征. 52

2.4.1沉积物中PhACs分布的环境控制因子. 52

2.4.2沉积物中PhACs的来源解析. 58

2.4.3沉积物中PhACs的生态风险评价. 63

2.5本章小节. 65

第3章胶州湾大气沉降（降雪）中的药物活性化合物. 67

3.1 降雪中PhACs的组成特征. 67

3.1.1抗生素. 70

3.1.2  非甾体抗炎药（NSAIDs）. 71

3.1.3 激素. 72

3.1.4. 其它药物. 72

3.2 来源解析. 73

3.2.1 路径来源分析. 73

3.2.2 组成来源解析. 78

3.3生态风险评价. 80

3.4 本章小结. 80

第4章 结论与创新. 82

4.1 结论. 82

4.2 创新点. 85

参考文献. 87

致 谢. 99

作者简历及攻读学位期间发表的学术论文与研究成果    101