苯并[a]芘在栉孔扇贝（Chlamys farreri）体内的毒代与毒效动力学研究
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摘要
近年来,随着海上石油和轮船运输业的发展以及工业、生活污水的大量排放,海洋环境中多环芳烃化合物(polycyclic aromatic hydrocarbon, PAHs)的污染日益加重,16种PAHs已经成为海洋环境中必须监测的污染物,其中苯并[a]芘(BaP)属致癌性最强的PAHs之一。栉孔扇贝(Chlamys farreri)是我国北方近海重要的经济贝类。本论文以BaP作为PAHs的代表物,通过实验室实验和自然海区取样的方法,采用现代分析技术,研究了BaP在栉孔扇贝体内的毒代与毒效动力学规律,并建立了栉孔扇贝对BaP的生理毒代与毒效动力学模型(PBTK-TD model),在水产品安全、海洋生物保护和环境监测等领域具有指导意义。
1.苯并[a]芘在栉孔扇贝体内累积和消除规律的研究
本部分设置4个BaP染毒浓度,研究了BaP在栉孔扇贝组织中(包括软体部、鳃丝、血淋巴、消化盲囊和闭壳肌)累积和消除规律,结果显示BaP污染对栉孔扇贝体内BaP含量影响显著(P<0.05):扇贝血淋巴中BaP含量在染毒开始后就迅速升高并一直维持在较高的水平,各处理组之间无显著差异(P>0.05),结束曝污后只有0.05μg/L处理组血淋巴BaP含量在消除实验后期略微下降;扇贝其它组织BaP含量受水体中BaP浓度影响显著,同一组织不同曝污浓度以及相同曝污浓度不同组织中的BaP含量都有显著差异(P<0.05),各组织所有处理组BaP含量随时间均呈双峰变化,表现为染毒初期各组织中BaP含量迅速上升,紧接着小幅下降,之后又累积升高,在消除实验开始后,各组织中BaP含量迅速回落,之后趋于平缓,但实验结束时扇贝体内BaP含量还是维持在较高水平,各组织中BaP消除率与组织中脂肪含量负相关。可见栉孔扇贝对环境中BaP具有很强的富集能力,组织中BaP累积量具有明显的时间剂量效应。
2.苯并[a]芘在栉孔扇贝体内生理毒代动力学模型的研究
根据栉孔扇贝生理特征和BaP转运规律,构建了用于BaP在栉孔扇贝体内代谢动力学研究的生理模型。研究了不同曝污浓度下BaP在栉孔扇贝软体部、鳃丝、消化盲囊和闭壳肌中的毒代动力学规律:BaP在栉孔扇贝0.05μ/L处理组的软体部、鳃丝和闭壳肌,0.5μ/L处理组的软体部和闭壳肌以及5μ/L处理组的闭壳肌中符合一室开放模型,其它各组均符合二室开放模型;消除实验期间扇贝对BaP的消除动力学均符合二室开放模型。研究发现BaP能在扇贝体内快速累积,但消除半衰期较长,代谢排出速度较慢,根据实验所获得的毒代动力学参数可预测栉孔扇贝体内BaP的分布以及各组织中含量的经时变化规律,建立了BaP在栉孔扇贝体内的生理毒代动力学模型。
3.苯并[a]芘在栉孔扇贝体内的毒代-毒效动力学模型研究
本研究在栉孔扇贝对BaP生理毒代动力学研究的基础上,将毒性效应指标引入,研究了栉孔扇贝鳃丝和消化盲囊芳烃羟化酶(AHH)、脂质过氧化(MDA)、单细胞凝胶电泳和蛋白质羰基化水平等毒理指标的动力学规律,并将BaP在栉孔扇贝鳃丝和消化盲囊中的毒代和毒效动力学有机结合,探讨了BaP在栉孔扇贝组织中的生理毒代-毒效动力学模型(PBTK-TD model),发现组织中BaP含量与毒效指标表现出很好的时间和剂量同步行,剂量关系多符合一元三次方程关系,且相关性良好,可见栉孔扇贝鳃丝和消化盲囊中的毒性效应指标能在一定程度上指示组织中BaP的含量,BaP含量也能反应BaP对扇贝的损伤程度,这在水产品安全、海洋生物及海洋环境的保护具有一定的指导意义。
4.青岛近海栉孔扇贝体内苯并[a]芘累积与毒性效应的野外调查
本文选择了青岛近海3个取样位点(红石崖、太平角和8号码头)分别于2007年4月30日和7月30日取各海区表层海水和栉孔扇贝各组织测定了BaP含量,并分析了BaP对扇贝鳃丝和消耗盲囊毒性效应。结果显示两个时间所取三个位点海水中BaP的含量大小均为:8号码头>太平角>红石崖(P<0.05),并且7月30日所取的样品中BaP含量均高于4月30日所取的样品(P<0.05);分析扇贝体内累积量,发现鳃丝和软体部对水体中BaP污染较敏感,与水体中BaP浓度成正相关,且不同取样点差异显著(P<0.05),其它组织除8号码头消化盲囊中BaP含量较其它海区高外,均无显著差异(P>0.05);研究毒性效应得出以下结论:鳃丝和消化盲囊单细胞凝胶电泳与蛋白质羰基化含量对BaP污染较敏感,不同取样位点差异显著(P<0.05),拖尾率和蛋白质羰基化含量均与海水BaP浓度呈正相关,而AHH活力和MDA含量仅表现为8号码头扇贝鳃丝高于另外两个位点,其它均无显著差异(P>0.05)
Recently, because of development of maritime petroleum, marine traffic and industry sewerage discharge, polycyclic aromatic hydrocarbon (PAHs) pollution became seriously. 16 kinds of PAHs became priority organic pollutants. Benzo[a]pyrene (BaP) is one of the most carcinogenic PAHs. Chlamys farreri is important economy bivalve cultured bu float valve in northern coast of China. We adopted laboratory study and sea area sampling, study the toxicokinetics and toxicodynamic of BaP in C. farrery,and a physiologically based toxicokinetic and toxicodynamic(PBTK-TD)model was developed for BaP in scallop (Chlamys farreri).What can be used in security of aquatic food, protection of halobios and oceanic environment.
1. Research on bioaccumulation and elimination of benzo[a]pyrene in tissues of scallop (Chlamys farreri)
In the experiment, 4 treatments were set up to investigate bioaccumulation and elimination of benzo[a]pyrene (BaP) in tissues (including soamtic tissue, gill,haemolymph, digestive gland and adductor muscle) of scallop (Chlamys farreri). The results suggested that BaP exposure had significant effects on BaP content in tissues of scallop (P<0.05). In haemolymph, there were no obvious difference of B[a]P content among all treatments (P<0.05). BaP content increased rapidly at the beginning of exposure and maintained at a high level during the experiment. After exposure cessation, B[a]P content in haemolymph descended appreciably at the late elimination experiment only in 0.05μg/L treatment. While BaP content in other tissues was affected markedly by BaP concentration of exposure water (P<0.05). There were marked difference of BaP content among the same tissue in different treatments, and the same situation were seen in different tissues treated with the same treatment. The change of BaP content of each tissue in all treatments exposure showed two peaks, that was at the beginning of exposure, BaP content in tissues rised rapidly, and then descended appreciably, but increased afterwards. At the initiation of elimination experiment, BaP content in tissues dropped swiftly and then became stabilization, which stayed at a high level at the end of the whole experiment. The elimination rate of BaP in all tissues showed negative relation with the lipid content in corresponding tissues. What can be concluded is that the ability of bioaccumulation of BaP in scallop is mighty and the cumulative content shows time response.
2. A physiologically based toxicokinetic model for benzo[a]pyrene in Chlamys farreri
The Physiologically Based Toxicokinetic Model for Benzo [a] Pyrene (BaP) in Chlamys farreri physiological characteristic of C. farreri and transfer rule of BaP. This article mainly research about the toxicokinetics of BaP in somatic tissue , gill , digstive gland and adductor muscle : There are lots of deals present themselves as One-compartment Model , such as somatic tissue , gill and adductor muscle dealed with 0.05μg/L and 0.5μg/L , others are accord with Two-compartment Modle ; They are tally with Two-compartment Modle during the eliminate period . We can conclude from this experiment that BaP have the ability of accumulate in Chlamys farreri quickly , but the half life of elimination is to long , and the rate of metabolize is comparatively slow . The parameters of poison metabolize conclude from this experiment can forecast the distribution of BaP in Chlamys farreri and the change rule of content in different tissue , so the concise PBTK model came into being .
3. A Toxicokinetic and toxicodynamic models for benzo[a]pyrene in Chlamys farreri
Based on PBTK model for BaP in, this study we import toxicological index in gill and digestive gland: included AHH, MDA, single cell gel electrophoresis (SCGE) assay and oxidative carbonyl protein, a physiologically based toxicokinetic and toxicodynami(cPBTK-TD)model was developed for BaP in scallop (Chlamys farreri). We found that, BaP content and toxicological index in gill and digestive gland showed time and dose correlativity, accorded with cubic equation. What can be conclude is that the toxicological index in gill and digestive gland of scallop can reflect the BaP content in scallop tissue, whereas the component of BaP in tissue can direct the damage degree. It is very important for security of aquatic food, protection of halobios and sea environment.
4. Bioaccumulation and toxicological effects of benzo[a]prrene in Chlamys farreri from offing of Qingdao
Sub-surface seawater and scallop (Chlamys farreri) samples at 3 sites(include Honsshiya, Taipingjiao and No.8 dock) in the sea area of the Qingdao in Apr. 30 and Jul. 30 of 2007, Benzo[a]Pyrene (BaP) content of seawater and tissue of scallop, toxicological index of gill and digestive gland were analyzed. As a result, the BaP in seawater is NO.8 dock > Taipingjiao > Hongshiya(P<0.05), in individual site April < July. Compare content of BaP in seawater and scallop tissue, a good correlation is observed between sea water and partial scallop tissue(gill and somatic tissue) (P<0.05), there is no significant difference between other tissue of scallop sampled from different sea areas.The frequencies of comet cells and oxidative carbonyl protein content in scallop tissue (gill and smatic tissue) were obtained as follows, No.8 dock > Taipingjiao > Hongshiya(P<0.05), AHH activity and MDA content had no significant difference, except the gill of scallop simpled from No.8 dock is higher than others.
1.苯并[a]芘在栉孔扇贝体内累积和消除规律的研究
本部分设置4个BaP染毒浓度,研究了BaP在栉孔扇贝组织中(包括软体部、鳃丝、血淋巴、消化盲囊和闭壳肌)累积和消除规律,结果显示BaP污染对栉孔扇贝体内BaP含量影响显著(P<0.05):扇贝血淋巴中BaP含量在染毒开始后就迅速升高并一直维持在较高的水平,各处理组之间无显著差异(P>0.05),结束曝污后只有0.05μg/L处理组血淋巴BaP含量在消除实验后期略微下降;扇贝其它组织BaP含量受水体中BaP浓度影响显著,同一组织不同曝污浓度以及相同曝污浓度不同组织中的BaP含量都有显著差异(P<0.05),各组织所有处理组BaP含量随时间均呈双峰变化,表现为染毒初期各组织中BaP含量迅速上升,紧接着小幅下降,之后又累积升高,在消除实验开始后,各组织中BaP含量迅速回落,之后趋于平缓,但实验结束时扇贝体内BaP含量还是维持在较高水平,各组织中BaP消除率与组织中脂肪含量负相关。可见栉孔扇贝对环境中BaP具有很强的富集能力,组织中BaP累积量具有明显的时间剂量效应。
2.苯并[a]芘在栉孔扇贝体内生理毒代动力学模型的研究
根据栉孔扇贝生理特征和BaP转运规律,构建了用于BaP在栉孔扇贝体内代谢动力学研究的生理模型。研究了不同曝污浓度下BaP在栉孔扇贝软体部、鳃丝、消化盲囊和闭壳肌中的毒代动力学规律:BaP在栉孔扇贝0.05μ/L处理组的软体部、鳃丝和闭壳肌,0.5μ/L处理组的软体部和闭壳肌以及5μ/L处理组的闭壳肌中符合一室开放模型,其它各组均符合二室开放模型;消除实验期间扇贝对BaP的消除动力学均符合二室开放模型。研究发现BaP能在扇贝体内快速累积,但消除半衰期较长,代谢排出速度较慢,根据实验所获得的毒代动力学参数可预测栉孔扇贝体内BaP的分布以及各组织中含量的经时变化规律,建立了BaP在栉孔扇贝体内的生理毒代动力学模型。
3.苯并[a]芘在栉孔扇贝体内的毒代-毒效动力学模型研究
本研究在栉孔扇贝对BaP生理毒代动力学研究的基础上,将毒性效应指标引入,研究了栉孔扇贝鳃丝和消化盲囊芳烃羟化酶(AHH)、脂质过氧化(MDA)、单细胞凝胶电泳和蛋白质羰基化水平等毒理指标的动力学规律,并将BaP在栉孔扇贝鳃丝和消化盲囊中的毒代和毒效动力学有机结合,探讨了BaP在栉孔扇贝组织中的生理毒代-毒效动力学模型(PBTK-TD model),发现组织中BaP含量与毒效指标表现出很好的时间和剂量同步行,剂量关系多符合一元三次方程关系,且相关性良好,可见栉孔扇贝鳃丝和消化盲囊中的毒性效应指标能在一定程度上指示组织中BaP的含量,BaP含量也能反应BaP对扇贝的损伤程度,这在水产品安全、海洋生物及海洋环境的保护具有一定的指导意义。
4.青岛近海栉孔扇贝体内苯并[a]芘累积与毒性效应的野外调查
本文选择了青岛近海3个取样位点(红石崖、太平角和8号码头)分别于2007年4月30日和7月30日取各海区表层海水和栉孔扇贝各组织测定了BaP含量,并分析了BaP对扇贝鳃丝和消耗盲囊毒性效应。结果显示两个时间所取三个位点海水中BaP的含量大小均为:8号码头>太平角>红石崖(P<0.05),并且7月30日所取的样品中BaP含量均高于4月30日所取的样品(P<0.05);分析扇贝体内累积量,发现鳃丝和软体部对水体中BaP污染较敏感,与水体中BaP浓度成正相关,且不同取样点差异显著(P<0.05),其它组织除8号码头消化盲囊中BaP含量较其它海区高外,均无显著差异(P>0.05);研究毒性效应得出以下结论:鳃丝和消化盲囊单细胞凝胶电泳与蛋白质羰基化含量对BaP污染较敏感,不同取样位点差异显著(P<0.05),拖尾率和蛋白质羰基化含量均与海水BaP浓度呈正相关,而AHH活力和MDA含量仅表现为8号码头扇贝鳃丝高于另外两个位点,其它均无显著差异(P>0.05)
Recently, because of development of maritime petroleum, marine traffic and industry sewerage discharge, polycyclic aromatic hydrocarbon (PAHs) pollution became seriously. 16 kinds of PAHs became priority organic pollutants. Benzo[a]pyrene (BaP) is one of the most carcinogenic PAHs. Chlamys farreri is important economy bivalve cultured bu float valve in northern coast of China. We adopted laboratory study and sea area sampling, study the toxicokinetics and toxicodynamic of BaP in C. farrery,and a physiologically based toxicokinetic and toxicodynamic(PBTK-TD)model was developed for BaP in scallop (Chlamys farreri).What can be used in security of aquatic food, protection of halobios and oceanic environment.
1. Research on bioaccumulation and elimination of benzo[a]pyrene in tissues of scallop (Chlamys farreri)
In the experiment, 4 treatments were set up to investigate bioaccumulation and elimination of benzo[a]pyrene (BaP) in tissues (including soamtic tissue, gill,haemolymph, digestive gland and adductor muscle) of scallop (Chlamys farreri). The results suggested that BaP exposure had significant effects on BaP content in tissues of scallop (P<0.05). In haemolymph, there were no obvious difference of B[a]P content among all treatments (P<0.05). BaP content increased rapidly at the beginning of exposure and maintained at a high level during the experiment. After exposure cessation, B[a]P content in haemolymph descended appreciably at the late elimination experiment only in 0.05μg/L treatment. While BaP content in other tissues was affected markedly by BaP concentration of exposure water (P<0.05). There were marked difference of BaP content among the same tissue in different treatments, and the same situation were seen in different tissues treated with the same treatment. The change of BaP content of each tissue in all treatments exposure showed two peaks, that was at the beginning of exposure, BaP content in tissues rised rapidly, and then descended appreciably, but increased afterwards. At the initiation of elimination experiment, BaP content in tissues dropped swiftly and then became stabilization, which stayed at a high level at the end of the whole experiment. The elimination rate of BaP in all tissues showed negative relation with the lipid content in corresponding tissues. What can be concluded is that the ability of bioaccumulation of BaP in scallop is mighty and the cumulative content shows time response.
2. A physiologically based toxicokinetic model for benzo[a]pyrene in Chlamys farreri
The Physiologically Based Toxicokinetic Model for Benzo [a] Pyrene (BaP) in Chlamys farreri physiological characteristic of C. farreri and transfer rule of BaP. This article mainly research about the toxicokinetics of BaP in somatic tissue , gill , digstive gland and adductor muscle : There are lots of deals present themselves as One-compartment Model , such as somatic tissue , gill and adductor muscle dealed with 0.05μg/L and 0.5μg/L , others are accord with Two-compartment Modle ; They are tally with Two-compartment Modle during the eliminate period . We can conclude from this experiment that BaP have the ability of accumulate in Chlamys farreri quickly , but the half life of elimination is to long , and the rate of metabolize is comparatively slow . The parameters of poison metabolize conclude from this experiment can forecast the distribution of BaP in Chlamys farreri and the change rule of content in different tissue , so the concise PBTK model came into being .
3. A Toxicokinetic and toxicodynamic models for benzo[a]pyrene in Chlamys farreri
Based on PBTK model for BaP in, this study we import toxicological index in gill and digestive gland: included AHH, MDA, single cell gel electrophoresis (SCGE) assay and oxidative carbonyl protein, a physiologically based toxicokinetic and toxicodynami(cPBTK-TD)model was developed for BaP in scallop (Chlamys farreri). We found that, BaP content and toxicological index in gill and digestive gland showed time and dose correlativity, accorded with cubic equation. What can be conclude is that the toxicological index in gill and digestive gland of scallop can reflect the BaP content in scallop tissue, whereas the component of BaP in tissue can direct the damage degree. It is very important for security of aquatic food, protection of halobios and sea environment.
4. Bioaccumulation and toxicological effects of benzo[a]prrene in Chlamys farreri from offing of Qingdao
Sub-surface seawater and scallop (Chlamys farreri) samples at 3 sites(include Honsshiya, Taipingjiao and No.8 dock) in the sea area of the Qingdao in Apr. 30 and Jul. 30 of 2007, Benzo[a]Pyrene (BaP) content of seawater and tissue of scallop, toxicological index of gill and digestive gland were analyzed. As a result, the BaP in seawater is NO.8 dock > Taipingjiao > Hongshiya(P<0.05), in individual site April < July. Compare content of BaP in seawater and scallop tissue, a good correlation is observed between sea water and partial scallop tissue(gill and somatic tissue) (P<0.05), there is no significant difference between other tissue of scallop sampled from different sea areas.The frequencies of comet cells and oxidative carbonyl protein content in scallop tissue (gill and smatic tissue) were obtained as follows, No.8 dock > Taipingjiao > Hongshiya(P<0.05), AHH activity and MDA content had no significant difference, except the gill of scallop simpled from No.8 dock is higher than others.
引文
[1]. 2003年青岛市海洋环境质量公报
[2]. 2004年青岛市海洋环境质量公报
[3]. 2005年青岛市海洋环境质量公报
[4].白东鲁,陈凯先.药物化学进展[M].北京:化学工业出版社, 2005.
[5].陈大健,王加才,张萍等.氟苯尼考对鲫鱼CYP2E1活性影响的药代动力学评价.中国兽医科学2007, 37(03):269-273
[6].陈海刚,李兆利,徐韵,等.五氯酚钠对鲤鱼肾细胞DNA损伤的体内和体外研究.环境与健康杂志, 2006, 23(6): 515-517.
[7].陈杭,王选,王强力.药动学模型生理化的研究进展.中国药学杂志, 2007, 42(18): 1364-1367.
[8].丛绍强,阴冠程,张永波,董燕霞.PK-PD结合模型在药学研究中的应用.社区医学杂志, 2005, 2(2): 39-40
[9].丁莉.现代药理学研究的新课题――PK-PD结合模型.湖北中医杂志, 2006, 28(7): 51-52.
[10].方展强,杨丽华.重金属在鲫幼鱼组织中的积累与分布[J].水利渔业, 2004, 24(6): 135-138
[11].房文红,邵锦华,施兆鸿,等.斑节对虾血淋巴中诺氟沙星含量测定及药代动力学[J].水生生物学报, 2003, 27(1):13-17.
[12].冯涛,郑微云,洪万树等.苯并(a)芘对大弹涂鱼肝脏芳烃羟化酶活性的影响[J].水产学报,2001,25(2):156-160.
[13].郝琨,柳晓泉,王广基.临床前毒代动力学研究进展[J].中国药科大学学报, 2004,35(3): 195-199.
[14].胡炅,陈汇.药物代谢动力学在药物研究中的应用与进展(上)[J].中国药师, 2007, 10, 654-658.
[15].姬汴生,张银娣.美多洛尔药动学药效学结合模型的研究[J].河南医科大学学报, 1995, 30(1): 34-36.
[16].吉云秀,邵秘华.多环芳烃的污染及其生物修复[J].交通环保,2003, 24(5): 33-37.
[17].贾晓平,林钦.广东沿海养殖牡蛎石油污染研究报告[R].南海水产研究所, 1990.
[18].贾晓平.紫贻贝(Mytilus edulis)软组织中石油烃化合物释放的大力学研究.海洋环境科学, 1989, 8(3): 1-9.
[19].简纪常,吴灶和,陈刚.恩诺沙星在眼斑拟石首鱼体内的药物代谢动力学.找个兽医学报, 2005, 25(2):195-197.
[20].孔繁翔.环境生物学[M].北京:高等教育出版社, 2000,38-56.
[21].郎佩珍,王毅,杨波,王宁,于瑞莲,龙凤山.鲤鱼对硝基苯的生物积累、消除与代谢研究[J].环境科学学报, 1997, 17(2): 213-219.
[22].林建清.生物标志物法研究多环芳烃对海水养殖鱼类的毒性效应(博士学位论文).厦门:厦门大学.2002
[23].林琳.高效液相色谱法分析海水中多环芳烃(PAHs).浙江海洋学院学报(自然科学版), 2002, 21(3): 252-254.
[24].刘国安,金凤玲.单细胞凝胶电泳--一个极有希望应用于临床诊断的技术.国外医学临床生物化学与检验学分册, 2003, 24(2): 117-121.
[25].刘凌云,郑光美.普通动物学[M],北京:高等教育出版社, 1997, 198-219
[26].刘彦,李健,王群,刘淇.鳗弧菌感染牙鲆药物代谢动力学模型的初步建立[J].海洋水产研究, 2007, 28(2): 76-83.
[27].罗松柏,何绍雄.生理要带动力学模型的进展与应用.药学学报, 1997, 32(2): 151-160.
[28].骆苑蓉,胡忠,郑天凌,黄栩.红树林沉积物中的微生物对苯并[a]芘的降解研究[J].厦门大学学报(自然科学版),2005,44:75-79.
[29].丘耀文,周俊良, Maskaoui K.,等.大亚湾海域水体和沉积物中多环芳烃分布及其生态危害评价.热带海洋学报, 2007,4, 72-80.
[30].田蕴,郑天凌,王新红,骆苑蓉.厦门马銮湾养殖海区多环芳烃的污染特征.海洋环境科学, 2003, 22(1): 29-33.
[31].王广基,刘晓东,柳晓泉等.药物代谢动力学[M].化学工业出版社, 2005.
[32].王佳山,仲兆庆,王福寿.PAH的危害及产生的途径[J].山东环境,2001,2:41-43.
[33].王群,李健,孙修涛.呋喃唑酮在黑鲷体内的代谢动力学和残留研究[J].青岛海洋大学学报, 2002 ,32(增) :45-49.
[34].王群,孙修涛,刘德月.土霉素在黑鲷体内的药物代谢动力学研究.海洋水产研究, 2001, 22(1): 42-47.
[35].徐凤山.中国海双壳类软体动物[M].北京:科学出版社,1997 (3):68-70.
[36].徐楠,王春霞,呼世斌等.五种多环芳烃化合物对鲤鱼肝微粒体芳烃羟化酶的诱导[J].中国环境监测,2000,16(6):9-12
[37].徐维海,林黎明,朱校斌,王新亭.四环素类抗菌药物在吉富罗非鱼体内的代谢动力学研究.水产科学, 2004, 23(3): 1-3.
[38].薛良义,李卢,周济胜.硝基苯和氯苯对鲫鱼血细胞DNA损伤的研究.水利渔业, 2005, 25(3): 8-9.
[39].薛焰,郭立玮,袁红宇,等.药理效应法测定超细粉马钱子和普通粉马钱子的药动学参数[J].南京中医药大学学报, 2002, 18(2):94-95.
[40].杨红梅,王浩,刘艳琴,殷晓燕.高效液相色谱法测定肉类食品中苯并芘残留的研究[J].食品研究与开发, 2006, 27(10): 124-126.
[41].杨先乐,湛嘉,胡鲲.氯霉素在尼罗罗非鱼血浆中的药代动力学研究.水产学报, 2005, 29(1):60-65.
[42].杨永亮,麦碧娴,潘静.胶州湾表层沉积物中多环芳烃的分布及来源.海洋环境科学. 2003, 22(4): 38-43.
[43].袁彦华,孙连军,郭秀兰等.多环芳烃化合物环境污染研究.环境与健康杂志, 2002(10): 72-73.
[44].郑丙辉,孟伟.环境污染物对水生生物产生氧化压力的分子生物标志物[J].生态学报, 2007, 27(1): 180-188.
[45].中国食品工业标准汇编(肉、禽、蛋及其制品卷,第二版)[M].北京:中国标准出版社, 2003. 476.
[46].朱必凤,邓少平,林志红.芳烃羟化酶与鲫鱼组织富集多环芳烃和代谢释放的关系.中国环境科学. 1996, 16(1): 38-41.
[47].朱靳良,邓丽霞,李芳红等.用单细胞凝胶电泳检测砷、汞、铅致DNA损伤的研究[J].卫生毒理学杂志. 1998, 12(3): 141-145.
[48]. Abbas R., Hayton W. L.. A Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Paraoxon in Rainbow Trout[J]. Toxicology and applied pharmacology, 1997, 145(1) : 192-201.
[49]. Abbas R., Hayton W.. Gas chromatographic determination of parathion and paraoxon in fish plasma and tissues[J] . J Anal Toxicol , 1996 ,20 (3) :151-154.
[50]. Abedini S., Namdari R., Law F. C. P.. Comparative pharmacokinetics and bioavailability of oxytetracycline in rainbow trout and Chinook salmon[J]. Aquaculture, 1998, 162 (1) : 23-32.
[51]. Avci A.,Kacmaz M., Durak I.. Peroxidation in muscle and liver tissues from fish in a contaminated river due to a petroleum refinery industry.Ecotoxicology and Environmental Safety, 2005,60:101-105.
[52]. Barron M. G., Schultz M. A., Hayton W. L.. Presystemic branchial metabolism limits di-2-ethylhexyl phthalate accumulation in fish [J] . Toxicol Appl Pharmacol , 1989, 98 :49 - 57.
[53]. Barron M. G., Tarr B. D., Hayton W. L.. Temperature dependence of di-2-ethylhexyl phthalate pharmacokinetics in rainbow trout [J] .Toxicol Appl Pharmacol , 1987 ,88, 305-312.
[54]. Barron M. G.., Plakas S. M., Wilga P. C.. Chlorpyrifos pharmacokinetics and metabolism following intravascular and dietary administration in channel catfish[J] . Toxicol Appl Pharmacol , 1991 ,108 (3) : 474-482.
[55]. Baumann P. C., W. D. Smith and M. Ribick. Hepatic tumorrares and polynuclear aromatic hydrocarbon levels in two populatins of brown bull-head (Ictalurus nebulosus). In M. Cooke, A .J. Dennis and G. L .F ischer, eds., Polynuclear Aromat ic Hydrocarbons: Physical Biological Chemisry [M ]. Battelle Press, Columbus, OH, 1981.93-102.
[56]. Boehm P. D., Quinn J.G... The persistence of chronically accumulated hydrocarbons in the hardshell clam Mercenaria mercenaria[J]. MarineBiology,1977,44:227-233
[57]. Bogaards J. J. P., Freidig A. P., van Bladeren P. J.. Prediction of isoprene diepoxide levels in vivo in mouse, rat and man using enzyme kinetic data in vitro and physiologically-based pharmacokinetic modeling Chemico-Biological Interactions. 2001, 138, 247-265.
[58]. Bolger M., Carrington C.. Hazard and risk assessment of crud oil in subsistence seafood samples from Prince William Sound: lessens learned from the ExxonValdez[A]. In L. Jay Fielde al. (eds.). Evaluating and communicating Subsistence Seafoo Safetyina Cross-Cultural Contex: Lessons Learned from the Exxon Valdez Oil Spill. Pensacola: Society of Enviromental Toxicology and Chemistry,1999: 195-204.
[59]. Bradford M. M.. Arapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding[J]. Anal Biochem, 1976,72:248-254
[60]. Bucheli T D, Font K. Induction of cytochrome P450 as a biomarker for environmental contamination in aquatic ecosystems [J]. Grit Rev Enviro Sci Techn.1995, 25(3):201-268.
[61]. Bungay P. M., Dedrick R. L., Guarino A. M.. Pharmacokinetic modeling of the dogfish shark ( Squalus acanthias ) : distribution and urinary and biliary excretion of phenol red and its glucuronide[J] . J Pharmcok Biopharm, 1976, 4 :377-388.
[62]. C.Cossu, A.Doyotte, M.C.Jacquin, et al. Glutathione reductase, selenium-deoendent glutathione peroxidase glutathione levels, and lipid peroxidation in freshwater bivalves, Unio tomidus, as biomarkers of aquactic contamination in field studies. Ecotoxicology and Environmental Safety.1997(38):122-131.
[63]. Cavalieri E L, Rogan E G. Central role of radical cations in metabolic activation of polycyclicaromatic hydrocarbons. Xenobiotica, 1995, 25 (7), 677-688.
[64]. Cederberg J., Basu S., Eriksson U. J.. Increased rate of lipid peroxidation and protein carbonylation in experimental diabetic pregnancy[J] . Diabetologia , 2001 , 44 (6) :766-774.
[65]. Chou B. Y. H., Liao C, M., Lin M, C., Cheng H. H.. Toxicokinetics/toxicodynamics of arsenic for farmed juvenile milkfish Chanos chanos and human consumption risk in BFD-endemic area of Taiwan. Environment International, 2006,32,545-553.
[66]. Clark K. J. . Temperature and species comparisons of benzocaine pharmacokinetics , metabolism and physiologically based pharmacokinetic model within Channel catfish , Ictalurus punctatus, and YellowPerch , Perca flavescens [J] . Dissertation Abstracts International Part B : Science and Engineering. 2000, 60(8): 3880.
[67]. Company R., Serafim A., Cosson C., et al. Effect of cadmium, copper and mercury on antioxidant enzyme activities and lipid peroxidation in the gills of the hydrothermal vent mussel Bathymodiolus azoricus.Marine Environmental Research, 2004, 58:377-381.
[68]. Della-Rocca G., Zaghini A., Magni A.. Pharmacokinetics of amoxicillin in sea bream ( Sparus aurata) after oral and intravenous administrations. 1 : comparation of serum concentrations evaluated with two different analytical methods [J] . Boll Soc Ital Patol Ittica, 1998 ,10 (24) :45-50.
[69]. Driscoll S. B. K., Schaffner L. C., Dickhut R. M.. Toxicokinetics of Fluoranthene to the Amphipod, Leptocheirus pkumufosus, in Water-only and Sediment Exposures. Marine Environmental Research, 1998, 45(3): 269-284.
[70]. F.Gagné, C. B., J.Hellou (). Endocrine disruption and health effects of caged mussels,Elliptio complanata, placed downstream from a primary-treated municipal effluent plume for 1 year. Comparative Biochemistry and Physiology, 2004, C , 138: 33-44.
[71]. Galcazzi R., Benet L., Sheiner L. B., Rclationship between the pharmacokinetics and pharmacodynamics of procainamide[J]. Clin Pharmacol Ther, 1976, 20, 278-289.
[72]. GB5009.27- 2003.食品中苯并(a)芘的测定[S].北京:中国标准出版社, 2004.
[73]. GB5009.27- 2003.食品中苯并(a)芘的测定[S].北京:中国标准出版社, 2004.
[74]. GB5009.27- 2003.食品中苯并(a)芘的测定[S].北京:中国标准出版社, 2004.
[75]. Géret F., Jouan A., Bebianno M. J., et al. Influence of metal exposure on metallothionein synthesis and lipid peroxidation in two bivalve mollusks: the oyster (Crassostrea gigas) and the mussel (Mytilus edulis).Aquatic Living Resources, 2002, 15(1): 61-66.
[76]. Goldberg E D. The surveillance of coastal marine waters with bivalves: The mussel watch. In:Analytical Techiques in Environmental Chemistry: Proceedings of the International Congress, Barcelona, Spain, November 1978 (J. Albaigés, Ed.), 373-386.
[77]. H. Skarphéeinsdóttir, G. Ericson, L. Dalla Zuanna, M. Gilek.. Tissue differences, dose-/response relationship and persistence of DNA adducts in blue mussels (Mytilus edulis L.) exposed to benzo[a]pyrene. Aquatic Toxicology 2003, 62, 165-177
[78]. Hattum B. V., Montanes J. F. C.. Toxicokinetics and Bioconcentration of Polycyclic Aromatic Hydrocarbons in Freshwater Isopods. Environ. Sci. Technol. 1999,33,2409-2417.
[79]. Ishizaki T., Hirayama I., Tawara K., et al.. Pharmacokinctics and pharmacodynamics in young normal and elderly hypcrtensive subjects: A study using sotalol as a model drug[J]. J Pharm Exp Ther, 1980, 212, 173-181.
[80]. Jacob J., Karcher W.. Polycyclic aromatic hydrocarbon of environmental and occupational importance[J] . Fresenius Z. Anal. Chem. , 1986 , 323 : 1-10.
[81]. James M. O., Barron M G. Disposition of sulfadimethoxine in the lobster( Homarus americanus) [J] . Vet Hum Toxicol , 1988 , 30 (1 suppl . ) :36-40.
[82]. Kitzman J. V., Holley J. H., Huber W. G.., et al . Pharmacokinetics and metabolism of fenbendazole in channel catfish[J] . Vet Res Commun , 1990 ,14 (3) :217-226.
[83]. Kristine L. Willett, Cody Wilson,Jane Thomsen,et al. Evidence for and against the presence of polynuclear aromatic hydrocarbon and 2,3,7,8-tetrachloro-p-dioxin binding proteins in the marine nussels,Bathymodiolus and Modiolus modiolus. Aquatic Toxicology.1999(48):51-64.
[84]. Labieniec M.. Response of DNA, proteins and membrane bilayer in the digestive gland cells of freshwater mussel Unio tumidus to tannins exposure. Toxicology in Vitro, 2004, 18, 773-781.
[85]. Law R.J., Hellou J. Contamination of fish and shellfish following oil spill incidents[J]. Environmental Geoscience, 1999, 6: 90-98
[86]. Liao C. M., Liang H. M., Chen B. C. et al.. Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan[J]. Environmental Pollution, 2005,135,221–233.
[87]. Liao C. M., Liang H. M., Chen B. C., et al.. Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan. Environmental Pollution, 2005,135,221-233.
[88]. Livingstone D. R., Nasci C, Sole M., et al.. Apparent induction of a cytochrome P450 with immunochemical similarities to CYPIA in digestive gland of the mussel (Mytilus galloprovincialis L) with exposure to 2,2,’3,4,4,’5’-hexachlorobiphenyl and A rochlor 1254, Aquat Toxicol, 1997,38, 205-224.
[89]. M. Ferreira , P. M.-F., M.A. Reis-Henriques. The effect of long-term depuration on levels of oxidative stress biomarkers in mullets (Mugil cephalus) chronically exposed to contaminants. Marine Environmental Research, 2007, 64(2): 181-190.
[90]. Maher W. A., Aislabie J.. Polycyclic aromatic hydrocarbons in nearshore marine sediments of Australia[J]. Sci. Total. Environ. , 1992 , 112 :143-164.
[91]. Marthe Monique Gagnon, D.A. Holdway. EROD activity, serum SDH and PAH biliary metabolites in sand flathead(Platycephalus bassensis) collected in Port Phillip Bay,Australia. Marine Pollution Bulletin. 2002(44):230-237.
[92]. Martinsen B., Horsberg T. E., Varma K. J., et al . Single dose pharmacokinetic study of florfenicol in Atlantic salmon (Salmo salar) in seawater at 11 degree C[J] . Aquaculture ,1993 ,112(1) :1-11.
[93]. Mensing T, Marczynski B, Engelhardt B, et al. DNA adduct formation of benzo[a]pyerne in white blood cells of workers exposed to polycyclic aromatic hydrocarbons[J]. International Journal of Hygiene and Environmental Health, 2005,208,173-178.
[94]. Michel C. M. F.. Pharmacokinetics and metabolism of sulfadimethoxine in channel catfish(Ictahurus punctatus)[J].Xenobiolica,1990,51(1):230-238.
[95]. Michel X., Narbonne J. F.. In vivo metabolism of Benzo (a) pyrene in the mussel Mytilus galloprovincialis[J]. Marine environmental research, 1996, 42(1-4):349-351.
[96]. Michèle Roméo and Mauricette Gnassia-Barelli. Effect of Heavy Metals on Lipid Peroxidation in the Mediterranean Clam Ruditapes decussates.Comparative Biochemistry and Physiology C,Pharmacology, Toxicology and Endocrinology, 1997, 118: 33-37.
[97]. Mitchelm C. I., Birmelin C., Livingstone D. R., et al.. Detection of DNA strand breaks in isolated mussel (Mytilus edulis L). Digestive gland cells using the comet assay. Ecotoxicol Environ Safty, 1998,41, 51-58.
[98]. Mitchelmore C. I., Birmelin C., Chipman J. K., et al.. Evidence for cytochrome P450 catalysis and free radical involvement in the production of DNA strand breaks by involvement in the production of DNA stand by benzo [a] pyrene and nitroaromatics in mussel (Mytilus edulis L)digestive gland cells, Aquat Toxicol,1998, 41, 193-212.
[99]. Namdari R., Abedini S., Albright L., et al.. Tissue distribution and elimination of oxytetracycline in sea-pen cultured chinook salmon , Oncorhynchus tshawytscha , and Atlantic salmon , Salmo salar , following medicated - feed treatment [J] . J Appl Aquaculture, 1998, 8 (1) : 39-52.
[100]. Nestorov I. Whole body pharmacokinetic models[J]. Clin Pharmacokinet, 2003, 42(10): 883-906.
[101]. Nichols J. W., Mckim J. M., Lien G. J., Hoffman, A. D., et al.. A Physiologically Based Toxicokinetic Model for Dermal Absorption of Organic Chemicals by Fish. Fundam. Appl. Toxicol, 1996, 31, 229-242.
[102]. Nigro M., Frenzilli G., Scarcelli V., et al.. Induction of DNA strand breakage and apoptosis in the ell Anguilla Anguilla. Mar Environ Res, 2002,54, 517-520.
[103]. Nouws J. F. M., Grondel J. L., Schutte A. R., et al . Pharmacokinetics of ciprofloxacin in carp, Africancatfish and rainbow trout [J] . Vet Quart , 1988(10) :211-216.
[104]. Park E. D., Lightner D. V., Milner N., et al.. Exploratory bioavailabilityand pharmacokinetic studies of sulphadimethoxine and ormetoprim inthe penaeid shrimp , Penaeus vannamei [J] . Aquaculture , 1995 ,130 (2- 3) :113-128.
[105]. Patrizia Mecocci. Age-dependent increases in oxidative damage to DNA, lipids, and protein in human skeletal musecle. Free Radical Biology & Medicine, (1999)26: 303-308.
[106]. Plakas S. M., El-Said K. R., Musser S. M.. Pharmacokinetics, tissue distribution, and metabolismof flumequine in channel catfish ( Ictalurus punctatus) [J]. Aquaculture, 2000, 187 : 1-14.
[107]. Plakas S. M., El-Said K. R., Stehly G. R.. Furazolidone disposition after intravascular and oral dosing in the channel catfish[J] . Xenobiotica , 1994 ,24 (11) :1095-1105.
[108]. Plakas S. M., El-Said KR., Bencsath F A. Pharmacokinetics , tissue distribution and metabolism of acriflavine and proflavine in the channel catfish ( Ictalurus punctatus) [J] . Xenobiotica , 1998 ,28(6) :605-616.
[109]. Plakas S. M., El-Said KR., Stehly GR. Furazolidone disposition after intravascular and oral dosing in the channel catfish[J] . Xenobiotica , 1994 ,24 (11) :1095-1105.
[110]. R. Edenharder J., Frangart M., Hager. Protective Effects of Fruits and Vegetables Against In Vivo Blastogenicity of Byclophosphamide or Benzo [a] pyrene in Mice [J]. Food and Chemical Toxicology. 1998, 36: 637-645.
[111]. Reconatini M, Cavalli A, SAR of 9-amino-1, 2, 3, 4-tetrahydroacridine-based ace-tylcholinesterase inhibitors: sythesis, enzyme in-hibitory activity, QSAR and structure-based comFA of tacrine analogaes [J]. Med Chem, 2000, (43 ): 2007-2018.
[112]. Regoli F., Winston G. W., Gorbi S., et al.. Intergrating enzymatic responses to organic chemical exposure with total oxyradical absorbing capacity and DNA damage in the European eel Anguilla Anguilla. Environ Toxicol Chem, 2003,22, 2120-2129.
[113]. Rouleau C., Gobeil C., Tjaelve H.. Pharmacokinetics and distribution of dietary tributyltin compared to those of methylmercury in the American plaice Hippoglossoides platessoides [J] . Mar Ecol Prog Ser , 1998 ,171 :275-284.
[114]. S. Boleaqub C. Fernandeqb J. Beyer,ac J. V., et al..Accumulation and Effects of Benzo(a)pyrene on Cytochrome P450 1A in Waterborne Exposed and Intraperitoneal Injected Juvenile Turbot (Scophthalmus maximus). Marine Environmenral Research, 1998, 46(l-5): 17-20.
[115]. Sheiner L. B., Donald R, Stanski M. D., et al. Simultaneous modeling of pharmacokinctics and pharmacodynamics: Application to d-tubocurarine[J]. Clin Pharmacol Ther, 1979, 25,358-371.
[116]. Shi J., Benowitz N.L., Denaro C.P., et al.. Pharmacokinetic-pharmacodynamic modeling of Ajmaline: the Efects on Arrhythmia [J]. Clin Pharmacol Ther, 1993, 53(1): 6.
[117]. Skarphéeinsdóttir H, Ericson G, Dalla Zuanna L, Gilek M. Tissue differences, dose-response relationship and persistence of DNA adducts in blue mussels (Mytilus edulis L.) exposed to benzo[a]pyrene[J]. Aquatic Toxicology. 2003(62): 165-177.
[118]. Snieszko S. F., Friddle S. O., Griffin P. J.. Successful treatment of ulcer disease in brook trout ( Salvelinus fontinalis) with Terramycin[J] . Science , 1951 ,113 :717-718.
[119]. Stanley T., Omaye., Peng Z..β-Carotene and protein oxidation : effects of ascorbic acid and a-tocopherol [J] , Toxicology , 2000 , 146 :37-47.
[120]. Tarr B. D., Barron M. G., Hayton WL. Effect of body size on the uptake and bioconcentration of di-2-ethylhexyl phthalate in rainbow trout [J] . Environ Toxicol Chem, 1990, 9, 989-995
[121]. Thibaut R , Debrauwer L , Rao D , et al . Characterization of biliary metabolites of 4-n- nonylphenol in rainbow trout (Oncorhynchus mykiss) [J] . Xenobiotica , 1998 ,28(8) :745-757.
[122]. Touraki M., Niopas I., Kastritsis C.. Bioaccumulation of trimethoprim, sulfamethoxazole and N-acetyl-sulfamethoxazole in Artemia nauplii and residual kinetics in seabass larvae after repeated oral dosing of medicated nauplii [J ] . Aquaculture, 1999, 175 (1) :15-30.
[123]. Tugiyono, Gagnon M. M.. Metabolic disturbances in fish exposed to sodium entachlorophenate(NaPCP) and 3 , 3’, 4 , 4’,5-pentachlorobiphenyl (PCB), individually or combined[J]. Camparative Biochemistry and Physiology Part C,2002, 132, 425-435.
[124]. Ueno R., Okada Y., Tatsuno T.. Pharmacokinetics and metabolism of miloxacin in cultured eel [J] . Aquaculture , 2001 ,193 (1-2) :11-24.
[125]. Uno K., Aoki T., Ueno R.. Pharmacokinetic study of oxytetracycline in cultured rainbow trout , amago salmon , and yellowtail [J] . Nippon Suisan Gakkaishi Bull , 1992 , 58(6) : 1151-1156.
[126]. Varanas U.. Metabolism of Polycyclic Aromatic Hydrocarbons in the Aquatic Environment . Boca Raton, FL, USA: CRC Press Inc, 1989.
[127]. Vick A. M., Hayton W. L.. Methyltestosterone pharmacokinetics and oral bioavailability in rainbow trout ( Oncorhynchus mykiss) [J ] . Aquat Toxicol , 2001 ,52 (3-4) :177-188.
[128]. Wagner J. G., Agahajanian G. K., Bing O. H.. Corrclation of performance test scores with“tissueconcentration”of lyscrgic acid diethylamide in human subjects[J]. Clin Pharmacol Ther 1968, 9, 635-638.
[129]. Walton D. G., Penrose W. R., Green J.M., The petroleum-indudible mixed function oxidase of cunner Tautogol abrusadspersus (Walbaum): Some characteristics relevant to hydrocarbon monitoring[J]. J Fish Res Board Can,1978,35(12):1547-1552.
[130]. Wang C. G., Zhao Y., Zheng R. H., et al. Effects of tributyltin, benzo[a]pyrene, and their mixture on antioxidant defense systems in Sebastiscus marmoratus Ecotoxicology and Environmental Safety, 2006,65( 3), 381-387.
[131]. Willett K, Steinberg M, et al. Ecposure of killfish to benzo[a]pyrene: comparative metabolism, DNA adduct formation and aryl hydrocarbon (Ah) receptor agonist activities[J].Biochem Physiol, 1995,112(1):93-103
[132]. William R. Gillespie Noncompartmental Versus Compartmental Modelling in Clinical Pharmacokinetics Clin. Pharmacokinet. 1991, 20(4): 253-262.
[133]. Wills E. D.. Evaluation of lipid perocidation in lipids and biological membranes. In: Snell, K., Mullock, B. (Eds.), Biochemical toxicology: a practical approach. IRL Press, Washington, USA,127-152.
[134]. Wintermyer M., Skaidas A., Roy A., et al..The development of a physiologically-based pharmacokinetic model using the distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the tissues of the eastern oyster (Crassostrea virginica)[J]. Marine Environmental Research, 2005, 60, 133-152
[135]. Zeilmaker M. J., Van Eijkeren J. C. H., Olling M.. A PBPK-model for B(a)P in the rat relating dose and liver DNA-adduct level[R]. National institute of public health and the environment bilthoven, the Netherlands, 1999, 1-30
[2]. 2004年青岛市海洋环境质量公报
[3]. 2005年青岛市海洋环境质量公报
[4].白东鲁,陈凯先.药物化学进展[M].北京:化学工业出版社, 2005.
[5].陈大健,王加才,张萍等.氟苯尼考对鲫鱼CYP2E1活性影响的药代动力学评价.中国兽医科学2007, 37(03):269-273
[6].陈海刚,李兆利,徐韵,等.五氯酚钠对鲤鱼肾细胞DNA损伤的体内和体外研究.环境与健康杂志, 2006, 23(6): 515-517.
[7].陈杭,王选,王强力.药动学模型生理化的研究进展.中国药学杂志, 2007, 42(18): 1364-1367.
[8].丛绍强,阴冠程,张永波,董燕霞.PK-PD结合模型在药学研究中的应用.社区医学杂志, 2005, 2(2): 39-40
[9].丁莉.现代药理学研究的新课题――PK-PD结合模型.湖北中医杂志, 2006, 28(7): 51-52.
[10].方展强,杨丽华.重金属在鲫幼鱼组织中的积累与分布[J].水利渔业, 2004, 24(6): 135-138
[11].房文红,邵锦华,施兆鸿,等.斑节对虾血淋巴中诺氟沙星含量测定及药代动力学[J].水生生物学报, 2003, 27(1):13-17.
[12].冯涛,郑微云,洪万树等.苯并(a)芘对大弹涂鱼肝脏芳烃羟化酶活性的影响[J].水产学报,2001,25(2):156-160.
[13].郝琨,柳晓泉,王广基.临床前毒代动力学研究进展[J].中国药科大学学报, 2004,35(3): 195-199.
[14].胡炅,陈汇.药物代谢动力学在药物研究中的应用与进展(上)[J].中国药师, 2007, 10, 654-658.
[15].姬汴生,张银娣.美多洛尔药动学药效学结合模型的研究[J].河南医科大学学报, 1995, 30(1): 34-36.
[16].吉云秀,邵秘华.多环芳烃的污染及其生物修复[J].交通环保,2003, 24(5): 33-37.
[17].贾晓平,林钦.广东沿海养殖牡蛎石油污染研究报告[R].南海水产研究所, 1990.
[18].贾晓平.紫贻贝(Mytilus edulis)软组织中石油烃化合物释放的大力学研究.海洋环境科学, 1989, 8(3): 1-9.
[19].简纪常,吴灶和,陈刚.恩诺沙星在眼斑拟石首鱼体内的药物代谢动力学.找个兽医学报, 2005, 25(2):195-197.
[20].孔繁翔.环境生物学[M].北京:高等教育出版社, 2000,38-56.
[21].郎佩珍,王毅,杨波,王宁,于瑞莲,龙凤山.鲤鱼对硝基苯的生物积累、消除与代谢研究[J].环境科学学报, 1997, 17(2): 213-219.
[22].林建清.生物标志物法研究多环芳烃对海水养殖鱼类的毒性效应(博士学位论文).厦门:厦门大学.2002
[23].林琳.高效液相色谱法分析海水中多环芳烃(PAHs).浙江海洋学院学报(自然科学版), 2002, 21(3): 252-254.
[24].刘国安,金凤玲.单细胞凝胶电泳--一个极有希望应用于临床诊断的技术.国外医学临床生物化学与检验学分册, 2003, 24(2): 117-121.
[25].刘凌云,郑光美.普通动物学[M],北京:高等教育出版社, 1997, 198-219
[26].刘彦,李健,王群,刘淇.鳗弧菌感染牙鲆药物代谢动力学模型的初步建立[J].海洋水产研究, 2007, 28(2): 76-83.
[27].罗松柏,何绍雄.生理要带动力学模型的进展与应用.药学学报, 1997, 32(2): 151-160.
[28].骆苑蓉,胡忠,郑天凌,黄栩.红树林沉积物中的微生物对苯并[a]芘的降解研究[J].厦门大学学报(自然科学版),2005,44:75-79.
[29].丘耀文,周俊良, Maskaoui K.,等.大亚湾海域水体和沉积物中多环芳烃分布及其生态危害评价.热带海洋学报, 2007,4, 72-80.
[30].田蕴,郑天凌,王新红,骆苑蓉.厦门马銮湾养殖海区多环芳烃的污染特征.海洋环境科学, 2003, 22(1): 29-33.
[31].王广基,刘晓东,柳晓泉等.药物代谢动力学[M].化学工业出版社, 2005.
[32].王佳山,仲兆庆,王福寿.PAH的危害及产生的途径[J].山东环境,2001,2:41-43.
[33].王群,李健,孙修涛.呋喃唑酮在黑鲷体内的代谢动力学和残留研究[J].青岛海洋大学学报, 2002 ,32(增) :45-49.
[34].王群,孙修涛,刘德月.土霉素在黑鲷体内的药物代谢动力学研究.海洋水产研究, 2001, 22(1): 42-47.
[35].徐凤山.中国海双壳类软体动物[M].北京:科学出版社,1997 (3):68-70.
[36].徐楠,王春霞,呼世斌等.五种多环芳烃化合物对鲤鱼肝微粒体芳烃羟化酶的诱导[J].中国环境监测,2000,16(6):9-12
[37].徐维海,林黎明,朱校斌,王新亭.四环素类抗菌药物在吉富罗非鱼体内的代谢动力学研究.水产科学, 2004, 23(3): 1-3.
[38].薛良义,李卢,周济胜.硝基苯和氯苯对鲫鱼血细胞DNA损伤的研究.水利渔业, 2005, 25(3): 8-9.
[39].薛焰,郭立玮,袁红宇,等.药理效应法测定超细粉马钱子和普通粉马钱子的药动学参数[J].南京中医药大学学报, 2002, 18(2):94-95.
[40].杨红梅,王浩,刘艳琴,殷晓燕.高效液相色谱法测定肉类食品中苯并芘残留的研究[J].食品研究与开发, 2006, 27(10): 124-126.
[41].杨先乐,湛嘉,胡鲲.氯霉素在尼罗罗非鱼血浆中的药代动力学研究.水产学报, 2005, 29(1):60-65.
[42].杨永亮,麦碧娴,潘静.胶州湾表层沉积物中多环芳烃的分布及来源.海洋环境科学. 2003, 22(4): 38-43.
[43].袁彦华,孙连军,郭秀兰等.多环芳烃化合物环境污染研究.环境与健康杂志, 2002(10): 72-73.
[44].郑丙辉,孟伟.环境污染物对水生生物产生氧化压力的分子生物标志物[J].生态学报, 2007, 27(1): 180-188.
[45].中国食品工业标准汇编(肉、禽、蛋及其制品卷,第二版)[M].北京:中国标准出版社, 2003. 476.
[46].朱必凤,邓少平,林志红.芳烃羟化酶与鲫鱼组织富集多环芳烃和代谢释放的关系.中国环境科学. 1996, 16(1): 38-41.
[47].朱靳良,邓丽霞,李芳红等.用单细胞凝胶电泳检测砷、汞、铅致DNA损伤的研究[J].卫生毒理学杂志. 1998, 12(3): 141-145.
[48]. Abbas R., Hayton W. L.. A Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Paraoxon in Rainbow Trout[J]. Toxicology and applied pharmacology, 1997, 145(1) : 192-201.
[49]. Abbas R., Hayton W.. Gas chromatographic determination of parathion and paraoxon in fish plasma and tissues[J] . J Anal Toxicol , 1996 ,20 (3) :151-154.
[50]. Abedini S., Namdari R., Law F. C. P.. Comparative pharmacokinetics and bioavailability of oxytetracycline in rainbow trout and Chinook salmon[J]. Aquaculture, 1998, 162 (1) : 23-32.
[51]. Avci A.,Kacmaz M., Durak I.. Peroxidation in muscle and liver tissues from fish in a contaminated river due to a petroleum refinery industry.Ecotoxicology and Environmental Safety, 2005,60:101-105.
[52]. Barron M. G., Schultz M. A., Hayton W. L.. Presystemic branchial metabolism limits di-2-ethylhexyl phthalate accumulation in fish [J] . Toxicol Appl Pharmacol , 1989, 98 :49 - 57.
[53]. Barron M. G., Tarr B. D., Hayton W. L.. Temperature dependence of di-2-ethylhexyl phthalate pharmacokinetics in rainbow trout [J] .Toxicol Appl Pharmacol , 1987 ,88, 305-312.
[54]. Barron M. G.., Plakas S. M., Wilga P. C.. Chlorpyrifos pharmacokinetics and metabolism following intravascular and dietary administration in channel catfish[J] . Toxicol Appl Pharmacol , 1991 ,108 (3) : 474-482.
[55]. Baumann P. C., W. D. Smith and M. Ribick. Hepatic tumorrares and polynuclear aromatic hydrocarbon levels in two populatins of brown bull-head (Ictalurus nebulosus). In M. Cooke, A .J. Dennis and G. L .F ischer, eds., Polynuclear Aromat ic Hydrocarbons: Physical Biological Chemisry [M ]. Battelle Press, Columbus, OH, 1981.93-102.
[56]. Boehm P. D., Quinn J.G... The persistence of chronically accumulated hydrocarbons in the hardshell clam Mercenaria mercenaria[J]. MarineBiology,1977,44:227-233
[57]. Bogaards J. J. P., Freidig A. P., van Bladeren P. J.. Prediction of isoprene diepoxide levels in vivo in mouse, rat and man using enzyme kinetic data in vitro and physiologically-based pharmacokinetic modeling Chemico-Biological Interactions. 2001, 138, 247-265.
[58]. Bolger M., Carrington C.. Hazard and risk assessment of crud oil in subsistence seafood samples from Prince William Sound: lessens learned from the ExxonValdez[A]. In L. Jay Fielde al. (eds.). Evaluating and communicating Subsistence Seafoo Safetyina Cross-Cultural Contex: Lessons Learned from the Exxon Valdez Oil Spill. Pensacola: Society of Enviromental Toxicology and Chemistry,1999: 195-204.
[59]. Bradford M. M.. Arapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding[J]. Anal Biochem, 1976,72:248-254
[60]. Bucheli T D, Font K. Induction of cytochrome P450 as a biomarker for environmental contamination in aquatic ecosystems [J]. Grit Rev Enviro Sci Techn.1995, 25(3):201-268.
[61]. Bungay P. M., Dedrick R. L., Guarino A. M.. Pharmacokinetic modeling of the dogfish shark ( Squalus acanthias ) : distribution and urinary and biliary excretion of phenol red and its glucuronide[J] . J Pharmcok Biopharm, 1976, 4 :377-388.
[62]. C.Cossu, A.Doyotte, M.C.Jacquin, et al. Glutathione reductase, selenium-deoendent glutathione peroxidase glutathione levels, and lipid peroxidation in freshwater bivalves, Unio tomidus, as biomarkers of aquactic contamination in field studies. Ecotoxicology and Environmental Safety.1997(38):122-131.
[63]. Cavalieri E L, Rogan E G. Central role of radical cations in metabolic activation of polycyclicaromatic hydrocarbons. Xenobiotica, 1995, 25 (7), 677-688.
[64]. Cederberg J., Basu S., Eriksson U. J.. Increased rate of lipid peroxidation and protein carbonylation in experimental diabetic pregnancy[J] . Diabetologia , 2001 , 44 (6) :766-774.
[65]. Chou B. Y. H., Liao C, M., Lin M, C., Cheng H. H.. Toxicokinetics/toxicodynamics of arsenic for farmed juvenile milkfish Chanos chanos and human consumption risk in BFD-endemic area of Taiwan. Environment International, 2006,32,545-553.
[66]. Clark K. J. . Temperature and species comparisons of benzocaine pharmacokinetics , metabolism and physiologically based pharmacokinetic model within Channel catfish , Ictalurus punctatus, and YellowPerch , Perca flavescens [J] . Dissertation Abstracts International Part B : Science and Engineering. 2000, 60(8): 3880.
[67]. Company R., Serafim A., Cosson C., et al. Effect of cadmium, copper and mercury on antioxidant enzyme activities and lipid peroxidation in the gills of the hydrothermal vent mussel Bathymodiolus azoricus.Marine Environmental Research, 2004, 58:377-381.
[68]. Della-Rocca G., Zaghini A., Magni A.. Pharmacokinetics of amoxicillin in sea bream ( Sparus aurata) after oral and intravenous administrations. 1 : comparation of serum concentrations evaluated with two different analytical methods [J] . Boll Soc Ital Patol Ittica, 1998 ,10 (24) :45-50.
[69]. Driscoll S. B. K., Schaffner L. C., Dickhut R. M.. Toxicokinetics of Fluoranthene to the Amphipod, Leptocheirus pkumufosus, in Water-only and Sediment Exposures. Marine Environmental Research, 1998, 45(3): 269-284.
[70]. F.Gagné, C. B., J.Hellou (). Endocrine disruption and health effects of caged mussels,Elliptio complanata, placed downstream from a primary-treated municipal effluent plume for 1 year. Comparative Biochemistry and Physiology, 2004, C , 138: 33-44.
[71]. Galcazzi R., Benet L., Sheiner L. B., Rclationship between the pharmacokinetics and pharmacodynamics of procainamide[J]. Clin Pharmacol Ther, 1976, 20, 278-289.
[72]. GB5009.27- 2003.食品中苯并(a)芘的测定[S].北京:中国标准出版社, 2004.
[73]. GB5009.27- 2003.食品中苯并(a)芘的测定[S].北京:中国标准出版社, 2004.
[74]. GB5009.27- 2003.食品中苯并(a)芘的测定[S].北京:中国标准出版社, 2004.
[75]. Géret F., Jouan A., Bebianno M. J., et al. Influence of metal exposure on metallothionein synthesis and lipid peroxidation in two bivalve mollusks: the oyster (Crassostrea gigas) and the mussel (Mytilus edulis).Aquatic Living Resources, 2002, 15(1): 61-66.
[76]. Goldberg E D. The surveillance of coastal marine waters with bivalves: The mussel watch. In:Analytical Techiques in Environmental Chemistry: Proceedings of the International Congress, Barcelona, Spain, November 1978 (J. Albaigés, Ed.), 373-386.
[77]. H. Skarphéeinsdóttir, G. Ericson, L. Dalla Zuanna, M. Gilek.. Tissue differences, dose-/response relationship and persistence of DNA adducts in blue mussels (Mytilus edulis L.) exposed to benzo[a]pyrene. Aquatic Toxicology 2003, 62, 165-177
[78]. Hattum B. V., Montanes J. F. C.. Toxicokinetics and Bioconcentration of Polycyclic Aromatic Hydrocarbons in Freshwater Isopods. Environ. Sci. Technol. 1999,33,2409-2417.
[79]. Ishizaki T., Hirayama I., Tawara K., et al.. Pharmacokinctics and pharmacodynamics in young normal and elderly hypcrtensive subjects: A study using sotalol as a model drug[J]. J Pharm Exp Ther, 1980, 212, 173-181.
[80]. Jacob J., Karcher W.. Polycyclic aromatic hydrocarbon of environmental and occupational importance[J] . Fresenius Z. Anal. Chem. , 1986 , 323 : 1-10.
[81]. James M. O., Barron M G. Disposition of sulfadimethoxine in the lobster( Homarus americanus) [J] . Vet Hum Toxicol , 1988 , 30 (1 suppl . ) :36-40.
[82]. Kitzman J. V., Holley J. H., Huber W. G.., et al . Pharmacokinetics and metabolism of fenbendazole in channel catfish[J] . Vet Res Commun , 1990 ,14 (3) :217-226.
[83]. Kristine L. Willett, Cody Wilson,Jane Thomsen,et al. Evidence for and against the presence of polynuclear aromatic hydrocarbon and 2,3,7,8-tetrachloro-p-dioxin binding proteins in the marine nussels,Bathymodiolus and Modiolus modiolus. Aquatic Toxicology.1999(48):51-64.
[84]. Labieniec M.. Response of DNA, proteins and membrane bilayer in the digestive gland cells of freshwater mussel Unio tumidus to tannins exposure. Toxicology in Vitro, 2004, 18, 773-781.
[85]. Law R.J., Hellou J. Contamination of fish and shellfish following oil spill incidents[J]. Environmental Geoscience, 1999, 6: 90-98
[86]. Liao C. M., Liang H. M., Chen B. C. et al.. Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan[J]. Environmental Pollution, 2005,135,221–233.
[87]. Liao C. M., Liang H. M., Chen B. C., et al.. Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan. Environmental Pollution, 2005,135,221-233.
[88]. Livingstone D. R., Nasci C, Sole M., et al.. Apparent induction of a cytochrome P450 with immunochemical similarities to CYPIA in digestive gland of the mussel (Mytilus galloprovincialis L) with exposure to 2,2,’3,4,4,’5’-hexachlorobiphenyl and A rochlor 1254, Aquat Toxicol, 1997,38, 205-224.
[89]. M. Ferreira , P. M.-F., M.A. Reis-Henriques. The effect of long-term depuration on levels of oxidative stress biomarkers in mullets (Mugil cephalus) chronically exposed to contaminants. Marine Environmental Research, 2007, 64(2): 181-190.
[90]. Maher W. A., Aislabie J.. Polycyclic aromatic hydrocarbons in nearshore marine sediments of Australia[J]. Sci. Total. Environ. , 1992 , 112 :143-164.
[91]. Marthe Monique Gagnon, D.A. Holdway. EROD activity, serum SDH and PAH biliary metabolites in sand flathead(Platycephalus bassensis) collected in Port Phillip Bay,Australia. Marine Pollution Bulletin. 2002(44):230-237.
[92]. Martinsen B., Horsberg T. E., Varma K. J., et al . Single dose pharmacokinetic study of florfenicol in Atlantic salmon (Salmo salar) in seawater at 11 degree C[J] . Aquaculture ,1993 ,112(1) :1-11.
[93]. Mensing T, Marczynski B, Engelhardt B, et al. DNA adduct formation of benzo[a]pyerne in white blood cells of workers exposed to polycyclic aromatic hydrocarbons[J]. International Journal of Hygiene and Environmental Health, 2005,208,173-178.
[94]. Michel C. M. F.. Pharmacokinetics and metabolism of sulfadimethoxine in channel catfish(Ictahurus punctatus)[J].Xenobiolica,1990,51(1):230-238.
[95]. Michel X., Narbonne J. F.. In vivo metabolism of Benzo (a) pyrene in the mussel Mytilus galloprovincialis[J]. Marine environmental research, 1996, 42(1-4):349-351.
[96]. Michèle Roméo and Mauricette Gnassia-Barelli. Effect of Heavy Metals on Lipid Peroxidation in the Mediterranean Clam Ruditapes decussates.Comparative Biochemistry and Physiology C,Pharmacology, Toxicology and Endocrinology, 1997, 118: 33-37.
[97]. Mitchelm C. I., Birmelin C., Livingstone D. R., et al.. Detection of DNA strand breaks in isolated mussel (Mytilus edulis L). Digestive gland cells using the comet assay. Ecotoxicol Environ Safty, 1998,41, 51-58.
[98]. Mitchelmore C. I., Birmelin C., Chipman J. K., et al.. Evidence for cytochrome P450 catalysis and free radical involvement in the production of DNA strand breaks by involvement in the production of DNA stand by benzo [a] pyrene and nitroaromatics in mussel (Mytilus edulis L)digestive gland cells, Aquat Toxicol,1998, 41, 193-212.
[99]. Namdari R., Abedini S., Albright L., et al.. Tissue distribution and elimination of oxytetracycline in sea-pen cultured chinook salmon , Oncorhynchus tshawytscha , and Atlantic salmon , Salmo salar , following medicated - feed treatment [J] . J Appl Aquaculture, 1998, 8 (1) : 39-52.
[100]. Nestorov I. Whole body pharmacokinetic models[J]. Clin Pharmacokinet, 2003, 42(10): 883-906.
[101]. Nichols J. W., Mckim J. M., Lien G. J., Hoffman, A. D., et al.. A Physiologically Based Toxicokinetic Model for Dermal Absorption of Organic Chemicals by Fish. Fundam. Appl. Toxicol, 1996, 31, 229-242.
[102]. Nigro M., Frenzilli G., Scarcelli V., et al.. Induction of DNA strand breakage and apoptosis in the ell Anguilla Anguilla. Mar Environ Res, 2002,54, 517-520.
[103]. Nouws J. F. M., Grondel J. L., Schutte A. R., et al . Pharmacokinetics of ciprofloxacin in carp, Africancatfish and rainbow trout [J] . Vet Quart , 1988(10) :211-216.
[104]. Park E. D., Lightner D. V., Milner N., et al.. Exploratory bioavailabilityand pharmacokinetic studies of sulphadimethoxine and ormetoprim inthe penaeid shrimp , Penaeus vannamei [J] . Aquaculture , 1995 ,130 (2- 3) :113-128.
[105]. Patrizia Mecocci. Age-dependent increases in oxidative damage to DNA, lipids, and protein in human skeletal musecle. Free Radical Biology & Medicine, (1999)26: 303-308.
[106]. Plakas S. M., El-Said K. R., Musser S. M.. Pharmacokinetics, tissue distribution, and metabolismof flumequine in channel catfish ( Ictalurus punctatus) [J]. Aquaculture, 2000, 187 : 1-14.
[107]. Plakas S. M., El-Said K. R., Stehly G. R.. Furazolidone disposition after intravascular and oral dosing in the channel catfish[J] . Xenobiotica , 1994 ,24 (11) :1095-1105.
[108]. Plakas S. M., El-Said KR., Bencsath F A. Pharmacokinetics , tissue distribution and metabolism of acriflavine and proflavine in the channel catfish ( Ictalurus punctatus) [J] . Xenobiotica , 1998 ,28(6) :605-616.
[109]. Plakas S. M., El-Said KR., Stehly GR. Furazolidone disposition after intravascular and oral dosing in the channel catfish[J] . Xenobiotica , 1994 ,24 (11) :1095-1105.
[110]. R. Edenharder J., Frangart M., Hager. Protective Effects of Fruits and Vegetables Against In Vivo Blastogenicity of Byclophosphamide or Benzo [a] pyrene in Mice [J]. Food and Chemical Toxicology. 1998, 36: 637-645.
[111]. Reconatini M, Cavalli A, SAR of 9-amino-1, 2, 3, 4-tetrahydroacridine-based ace-tylcholinesterase inhibitors: sythesis, enzyme in-hibitory activity, QSAR and structure-based comFA of tacrine analogaes [J]. Med Chem, 2000, (43 ): 2007-2018.
[112]. Regoli F., Winston G. W., Gorbi S., et al.. Intergrating enzymatic responses to organic chemical exposure with total oxyradical absorbing capacity and DNA damage in the European eel Anguilla Anguilla. Environ Toxicol Chem, 2003,22, 2120-2129.
[113]. Rouleau C., Gobeil C., Tjaelve H.. Pharmacokinetics and distribution of dietary tributyltin compared to those of methylmercury in the American plaice Hippoglossoides platessoides [J] . Mar Ecol Prog Ser , 1998 ,171 :275-284.
[114]. S. Boleaqub C. Fernandeqb J. Beyer,ac J. V., et al..Accumulation and Effects of Benzo(a)pyrene on Cytochrome P450 1A in Waterborne Exposed and Intraperitoneal Injected Juvenile Turbot (Scophthalmus maximus). Marine Environmenral Research, 1998, 46(l-5): 17-20.
[115]. Sheiner L. B., Donald R, Stanski M. D., et al. Simultaneous modeling of pharmacokinctics and pharmacodynamics: Application to d-tubocurarine[J]. Clin Pharmacol Ther, 1979, 25,358-371.
[116]. Shi J., Benowitz N.L., Denaro C.P., et al.. Pharmacokinetic-pharmacodynamic modeling of Ajmaline: the Efects on Arrhythmia [J]. Clin Pharmacol Ther, 1993, 53(1): 6.
[117]. Skarphéeinsdóttir H, Ericson G, Dalla Zuanna L, Gilek M. Tissue differences, dose-response relationship and persistence of DNA adducts in blue mussels (Mytilus edulis L.) exposed to benzo[a]pyrene[J]. Aquatic Toxicology. 2003(62): 165-177.
[118]. Snieszko S. F., Friddle S. O., Griffin P. J.. Successful treatment of ulcer disease in brook trout ( Salvelinus fontinalis) with Terramycin[J] . Science , 1951 ,113 :717-718.
[119]. Stanley T., Omaye., Peng Z..β-Carotene and protein oxidation : effects of ascorbic acid and a-tocopherol [J] , Toxicology , 2000 , 146 :37-47.
[120]. Tarr B. D., Barron M. G., Hayton WL. Effect of body size on the uptake and bioconcentration of di-2-ethylhexyl phthalate in rainbow trout [J] . Environ Toxicol Chem, 1990, 9, 989-995
[121]. Thibaut R , Debrauwer L , Rao D , et al . Characterization of biliary metabolites of 4-n- nonylphenol in rainbow trout (Oncorhynchus mykiss) [J] . Xenobiotica , 1998 ,28(8) :745-757.
[122]. Touraki M., Niopas I., Kastritsis C.. Bioaccumulation of trimethoprim, sulfamethoxazole and N-acetyl-sulfamethoxazole in Artemia nauplii and residual kinetics in seabass larvae after repeated oral dosing of medicated nauplii [J ] . Aquaculture, 1999, 175 (1) :15-30.
[123]. Tugiyono, Gagnon M. M.. Metabolic disturbances in fish exposed to sodium entachlorophenate(NaPCP) and 3 , 3’, 4 , 4’,5-pentachlorobiphenyl (PCB), individually or combined[J]. Camparative Biochemistry and Physiology Part C,2002, 132, 425-435.
[124]. Ueno R., Okada Y., Tatsuno T.. Pharmacokinetics and metabolism of miloxacin in cultured eel [J] . Aquaculture , 2001 ,193 (1-2) :11-24.
[125]. Uno K., Aoki T., Ueno R.. Pharmacokinetic study of oxytetracycline in cultured rainbow trout , amago salmon , and yellowtail [J] . Nippon Suisan Gakkaishi Bull , 1992 , 58(6) : 1151-1156.
[126]. Varanas U.. Metabolism of Polycyclic Aromatic Hydrocarbons in the Aquatic Environment . Boca Raton, FL, USA: CRC Press Inc, 1989.
[127]. Vick A. M., Hayton W. L.. Methyltestosterone pharmacokinetics and oral bioavailability in rainbow trout ( Oncorhynchus mykiss) [J ] . Aquat Toxicol , 2001 ,52 (3-4) :177-188.
[128]. Wagner J. G., Agahajanian G. K., Bing O. H.. Corrclation of performance test scores with“tissueconcentration”of lyscrgic acid diethylamide in human subjects[J]. Clin Pharmacol Ther 1968, 9, 635-638.
[129]. Walton D. G., Penrose W. R., Green J.M., The petroleum-indudible mixed function oxidase of cunner Tautogol abrusadspersus (Walbaum): Some characteristics relevant to hydrocarbon monitoring[J]. J Fish Res Board Can,1978,35(12):1547-1552.
[130]. Wang C. G., Zhao Y., Zheng R. H., et al. Effects of tributyltin, benzo[a]pyrene, and their mixture on antioxidant defense systems in Sebastiscus marmoratus Ecotoxicology and Environmental Safety, 2006,65( 3), 381-387.
[131]. Willett K, Steinberg M, et al. Ecposure of killfish to benzo[a]pyrene: comparative metabolism, DNA adduct formation and aryl hydrocarbon (Ah) receptor agonist activities[J].Biochem Physiol, 1995,112(1):93-103
[132]. William R. Gillespie Noncompartmental Versus Compartmental Modelling in Clinical Pharmacokinetics Clin. Pharmacokinet. 1991, 20(4): 253-262.
[133]. Wills E. D.. Evaluation of lipid perocidation in lipids and biological membranes. In: Snell, K., Mullock, B. (Eds.), Biochemical toxicology: a practical approach. IRL Press, Washington, USA,127-152.
[134]. Wintermyer M., Skaidas A., Roy A., et al..The development of a physiologically-based pharmacokinetic model using the distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the tissues of the eastern oyster (Crassostrea virginica)[J]. Marine Environmental Research, 2005, 60, 133-152
[135]. Zeilmaker M. J., Van Eijkeren J. C. H., Olling M.. A PBPK-model for B(a)P in the rat relating dose and liver DNA-adduct level[R]. National institute of public health and the environment bilthoven, the Netherlands, 1999, 1-30