Chemosphere 89 (2012) 1015–1025 Contents lists available at SciVerse ScienceDirect Chemosphere journal homepage: www.elsevier.com/locate/chemosphere Review Review of measured concentrations of triphenyltin compounds in marine ecosystems and meta-analysis of their risks to humans and the environment Andy Xianliang Yi a,b, Kenneth M.Y. Leung a,b,c,d,⇑, Michael H.W. Lam c,d,e, Jae-Seong Lee c,f, John P. Giesy a,b,c,d,e,g,h a The Swire Institute of Marine Science, The University of Hong Kong, Pokfulam, Hong Kong, China School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China Area of Excellence Centre for Marine Environmental Research and Innovative Technology (MERIT), The University of Hong Kong, Pokfulam, Hong Kong, China d State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China e Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China f Department of Chemistry and the National Research Lab of Marine Molecular and Environmental Bioscience, College of Natural Sciences, Hanyang University, Seoul 133-791, South Korea g Department of Veterinary Biomedical Sciences, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, Canada S7N 5B3 h Department of Zoology, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA b c h i g h l i g h t s " We reviewed the fate and toxicities of TPT compounds in marine environments. " Health hazard of TPT to human via consuming contaminated seafood was highlighted. " The current and future ecological risks of TPT to marine ecosystems were analyzed. " Knowledge gaps and future research areas were identified and prioritized. a r t i c l e i n f o Article history: Received 19 March 2012 Received in revised form 10 May 2012 Accepted 17 May 2012 Available online 15 June 2012 Keywords: TPT Antifouling agents Endocrine disruption chemicals Bioaccumulation Organotin Marine pollution a b s t r a c t The state of scientific knowledge regarding analytical methods, environmental fate, ecotoxicity and ecological risk of triphenyltin (TPT) compounds in marine ecosystems as well as their exposure and health hazard to humans was reviewed. Since the 1960s, TPT compounds have been commonly applied as biocides for diverse industrial and agricultural purposes. For instance, they are used as active ingredients in antifouling systems on marine vessels and mariculture facilities, and as fungicides in agriculture. Due to their intensive use, contamination of coastal waters by TPT and its products of transformation has become a worldwide problem. The proportion of quantified TPT to total phenyltin compounds in the marine environment provides evidence that TPT is photodegradable in water and sediment but resistant to biotransformation. Concentrations of TPT in marine biota are consistently greater than concentrations in water and sediment, which implies potential of TPT to bioaccumulate. TPT is toxic to both marine plants and animals. The predicted no effect concentration (PNEC) for TPT, as determined by use of the species sensitivity distribution approach, is 0.64 ng L 1. In some parts of the world, concentrations of TPT in seawater exceed the PNEC, indicating that TPT can pose risks to marine life. Although there is negligible risk of TPT to average human consumers, TPT has been detected in blood of Finnish people and the concentration was greater in fishermen who ate more seafood. It is, therefore, advocated to initiate regular monitoring of TPT in blood and breast milk of populations that consume greater amounts of seafood. Ó 2012 Elsevier Ltd. All rights reserved. Contents 1. 2. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1016 Analytical methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1017 ⇑ Corresponding author at: School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China. Tel.: +852 22990607; fax: +852 25176082. E-mail address: kmyleung@hku.hk (K.M.Y. Leung). 0045-6535/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.chemosphere.2012.05.080 1016 A.X. Yi et al. / Chemosphere 89 (2012) 1015–1025 3. Distribution and bioaccumulation of PTs in the marine ecosystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Distribution of TPT in the marine environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.1. Concentrations of PTs in environmental compartments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.2. Factors affecting distribution of PTs in the environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.3. Temporal variation in concentrations of PTs: implications on effectiveness of restrictions on the use of OTs . . . . . . . . . . . . . 3.2. Proportions of TPT to PTs: relations with degradation and rates of biotransformation of TPT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Bioaccumulation of TPT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.1. Factors affecting bioaccumulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.2. Bioconcentration of TPT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.3. Biomagnification of TPT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4. Summary of environmental fate of TPT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adverse effect of TPT to marine ecosystems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Endocrine disrupting effects on marine organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Species sensitivity distribution for aquatic biota exposed to TPT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.1. Toxicity test of TPT on marine organisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.2. Predicted no effect concentration (PNEC) and evaluation of ecological risks of TPT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Exposures and effects of TPT compounds to humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Appendix A. Supplementary material . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. 5. 6. 1. Introduction Organotin (OT) molecules are comprised of a tin (Sn) atom which is covalently bound to one or more organic substituents, such as methyl, ethyl, butyl or phenyl groups. Triphenyltin (TPT) compounds are a group of OTs conforming to a general formula (C6H5)3Sn-X, where X is an anion or anionic group, such as chloride, hydroxide and acetate. OTs are hydrophobic due to the presence of hydrocarbon substituents and thus their solubility in water is relatively small (Rüdel, 2003). In the pH range of 6–8, the solubilities of TPT chloride (TPTCl) and TPT oxide (TPTO) in water are approximately 1 mg L 1 at 25 °C (Inaba et al., 1995). TPT compounds such as TPT acetate (TPTA) and TPTCl can be hydrolyzed to TPTOH in the marine environment, and neutral hydroxyl-complexes accounted for more than 93% of TPT compounds in well-buffered seawater (Arnold et al., 1997; Veltman et al., 2006). The log KOW values of TPTs, such as TPTOH and TPTCl are between 3 and 4 (Tsuda et al., 1990a; WHO, 1999), which suggests that these compounds are potentially bioaccumulative. TPTs are major ingredients of antifouling products and fungicides. OT-based antifouling products used on hulls of vessels and submerged mariculture facilities are the main sources of TPT in the marine environment. TPT compounds have also been widely used in agriculture, as fungicides on potatoes, sugar beets, hops and rice against fungal diseases, algae and molluscs (WHO, 1999). For example, in Minnesota, 10.73% of potato crops were treated with TPTOH (Subramanyam, 1993). In Taiwan, 27% of surveyed farmers admitted illegal use of TPTA, even after its complete prohibition in that country (Hu et al., 2009). Thus, agricultural runoff could also contribute to TPT in the marine environment. The amount of total TPT produced annually in China is estimated to be 200 tonnes (Hu et al., 2009), while in Japan, 140–160 tonnes of TPT were produced for export annually during the period 1994–1996 (WHO, 1999). As a result of their common industrial or agricultural applications, TPT compounds have entered various ecosystems, where they interact with organisms. Studies of the distribution and the effects of OTs in the marine environment have been conducted since the late 1980s (Gibbs et al., 1987; Horiguchi et al., 1994; Gomez-Ariza et al., 1998; Leung et al., 2001). OTs, especially trisubstituted molecules, are toxic to aquatic organisms (Fent, 1996a). Due to its effects on marine gastropods and oysters, appli- 1017 1017 1017 1018 1018 1019 1019 1019 1019 1019 1020 1020 1020 1021 1021 1021 1021 1022 1022 1023 1023 cation of OT-based antifoulants on boats of less than 25 m length has been banned since the 1980s in countries including France, the United Kingdom, the USA and Japan (Champ, 2000; Cao et al., 2009). As initiated by the International Maritime Organization (IMO), the Convention on the Control of Harmful Antifouling Systems on Ships (AFS Convention), which was adopted in 2001 and has entered into force since September 2008, bans the use of OTs as biocides in antifouling systems (IMO, 2001; IMO website: http://www.imo.org). In order to facilitate ratification of the AFS Convention by its member states, the European Community (EC) published a specific regulation (EC No 782/2003) to ban the use of harmful OTs in antifouling paints on ships in 2003 (EC, 2003). However, it is likely that OT-based antifouling paints are still being produced and used in some developing countries that are not members of the IMO. Additionally, the continuing agricultural use of TPT compounds as fungicides in Asia will remain a longterm concern. To date, most information on the distribution and toxicity of OTs is about tributyltin (TBT) and its products of transformation, while little information on the occurrence of TPT compounds and their derivatives. Thus, in comparison to TBT, there is a paucity of information on the distribution, toxicity and accumulation of TPT (Fent and Hunn, 1991; Tolosa et al., 1992; Shim et al., 2005a). The only review of TPT, which was published by WHO, described the toxicity of TPT to mammals and their potential toxicity to humans but did not adequately address the fate and ecological effects of TPT in the marine environment (WHO, 1999). This review, which considered information published through September 2011, is the most comprehensive review on the state of scientific knowledge on TPT compounds and is provided as a basis to assess current status and trends and potential risks posed by the chemicals in the marine environment. In particular, the review is focused on measured concentrations of TPT in environmental compartments, such as water, sediment, and biota, their fate in the marine environment, their toxicities and ecological risks towards marine organisms, and their potential hazards to human health via consumption of contaminated seafood. Secondary data on concentrations of TPTs and toxicities, which were reported in the peer-reviewed literature, were used in a metaanalysis to determine current status and potential future trends in exposures and possible effects. Finally, areas or issues which require further research attention are prioritized and highlighted in this review. A.X. Yi et al. / Chemosphere 89 (2012) 1015–1025 2. Analytical methods A variety of methods have been developed for identification and quantification of OTs, and most of these methods share key steps in the analytical procedures for chemical speciation of different compartments of the marine environment including water, sediments and biota. These steps include sample preparation, extraction of OTs, derivatisation, purification and application of appropriate analytical techniques for identification and quantification (de Carvalho Oliveira and Santelli, 2010). The International Organization for Standardization (ISO) has set up the standards for the determination of selected OTs including phenyltins (PTs) in water (ISO 17353, 2004) and soil samples (ISO/SIS 23161-2, 2007). Considering there have been comprehensive reviews of the analytical methods of OTs which summarized the analytical procedures in detail (Abalos et al., 1997; de Carvalho Oliveira and Santelli, 2010), in this section, only a brief introduction on the more widely adopted methods is provided. Collection and preparation of samples are important steps for any chemical analysis. The location and time of sampling are important since there can be spatial and temporal variability in distributions of PTs. For example, the distance to potential sources and seasons of sampling can result in variation in distribution of PTs (see Section 3.1.2). After collection, to guarantee stability of PTs before chemical analysis, samples should be stored in the dark at 20 °C (Abalos et al., 1997). For both biotic and abiotic matrices, the use of organic solvents of lesser to moderate polarity in combination with hydrochloric acid or acetic acid accounts for more than 50% of the extraction procedures (Abalos et al., 1997). Extraction with tetramethylammonium hydroxide (Guðmundsdóttir et al., 2011) or potassium hydroxide (Nagase et al., 1995), have also been applied to decompose the biological matrices as an alternative to acid leaching. However, there is no agreement on the most appropriate solvent to use for extraction. Extraction methods have been developed to isolate and concentrate analytes from both biotic and abiotic matrix including solid phase extraction (SPE), supercritical fluid extraction (SFE) and solid-phase microextraction (SPME). After extraction, derivatisation is used to produce volatile OTs that can be separated by use of gas chromatography (GC). Derivatisation methods are based on alkylation or hydridization. Sodium tetraethylborate (NaBEt4) is widely applied for ethylation (Ashby and Craig, 1991), and sodium borohydride (NaBH4) is adopted for hydridization (Abd-Allah, 1995). A clean-up step is crucial for removal of matrix components, such as lipids, proteins, sulfur and high boiling point compounds that might interfere with the recovery, identification or quantification of OTs (de Carvalho Oliveira and Santelli, 2010). This step is usually conducted after derivatisation (Stewart and Thompson, 1994), and most commonly used adsorbents are silica, alumina, and florisil. For identification and quantification of PTs, the most commonly used technique is gas chromatography (GC) because this method of separation can be coupled with an element-specific detection method, such as mass spectrometry (GC/MS) (Ishizaka et al., 1989; Ashby and Craig, 1991; Arnold et al., 1998), atomic absorption spectrometry (GC/AAS) (Tas et al., 1991; Ceulemans et al., 1998), flame photometric detection (GC/FPD) (Carlier-Pinasseau et al., 1997), microwave-induced or inductively-coupled plasma atomic emission spectrometry (GC/MIP-AES or GC/ICP-AES) (Tutschku et al., 1994; Becker et al., 1997). Separation by liquid chromatography (LC) has also been employed as the separation step in analyses of OTs. Derivatisation is not required when LC is used, which minimizes both time and cost. Compared to GC, nevertheless, LC is less sensitive because of its poorer power to separate chemicals (Rosenberg et al., 2000), thus limited numbers of chemical can be identified in a single analysis (Garcia-Alonso et al., 1993). Because it is more sensitive than other commonly used 1017 techniques, ICP-MS is being used more as the detector for identification and quantification of PTs (Bianchi et al., 2006). Apparently, more concerted efforts are needed to harmonize and standardize the analytical methods for quantifying various PTs in environmental samples. To advance this process, more inter-laboratory calibration studies (e.g., the European QUASIMEME laboratory performance studies; http://www.quasimeme.org/) should be fostered and conducted in different geographical regions. 3. Distribution and bioaccumulation of PTs in the marine ecosystem There is little information on concentrations of PTs in marine ecosystems. Concentrations of PTs in marine waters, sediments, and biota have been assembled in the Supplementary materials (i.e., Appendix A: Tables S1–S5). Whenever concentrations were less than the limit of detection (DL), a surrogate value of half of the DL was reported (USEPA, 1998; Helsel, 2006). Concentrations were then compared among regions and locations by use of standard statistical software, PASW 18 (SPSS Inc., Chicago, IL). To facilitate comparisons among reported concentrations all values were expressed dry weight (dw). Concentrations expressed wet weight (ww) were converted to dw by use of the following dw/ ww proportions: 15% for invertebrate (Phillips, 1985), 20% for fish (CRESP, 2006) and 33.3% for livers in bird/mammal (Scanlon, 1982; Yang and Miyazaki, 2003). Concentrations of TPTs and their chemodynamics are discussed simultaneously. 3.1. Distribution of TPT in the marine environment 3.1.1. Concentrations of PTs in environmental compartments Mean concentrations of PTs in various environmental compartments at different locations are illustrated (Fig. 1). Concentrations of PTs in seawater are often near to, or less than the DL of currently available instrumental analytical methods (Table S1). PTs can only be detected at more contaminated locations, such as harbors or marinas (Nemanič et al., 2002). Concentrations of TPT in sediments are greater than in seawater, with the greatest concentration of 40 ng Sn g 1 dw occurring in Japan (Harino et al., 1998). TPT, which has a relatively great sediment–water partition coefficient, with reported values ranging from 2.1 104 to 1.1 105 L kg 1 (Fent, 1996a), has a relatively strong affinity for sediments and suspended particulates. Therefore, TPTs become deposited into benthic sediments, which are the primary sink for TPT in the marine environment. PTs have been detected in invertebrates, fishes, birds and mammals from various locations (Tables S2–S4). The greatest concentration of TPT, 5.9 lg g 1 dw, was measured in the blue mussel (Mytilus edulis) (Higashiyama et al., 1991). Concentrations of TPT generally increase in the order: water < sediment < invertebrate and fish (in Japan and south China), whereas in Japan and Western Europe concentrations of TPT in birds and mammals were less than those in fishes or invertebrates (Fig. 1). This might be due to variable patterns of bioaccumulation of TPT (Section 3.3) among organisms in marine food webs. Concentrations of TPT were compared among invertebrates, fishes, birds and mammals, by use of the non-parametric Kruskal–Wallis test. However, no significant differences among these three groups was observed (v2 = 2.314, p > 0.05). This is due to the relatively large variance within groups due to the wide range of locations and times included in the analysis. Thus, it is difficult to stratify and/or aggregate the available data in a way to make meaningful comparisons among these groups. 1018 A.X. Yi et al. / Chemosphere 89 (2012) 1015–1025 Fig. 1. Distribution of TPT in compartments of the marine environment. To allow for better visualization of a range of concentrations, mean TPT concentrations in each area are expressed as Log10[mean conc.] + 2. 3.1.2. Factors affecting distribution of PTs in the environment Distributions of OTs such as BTs and PTs in marine environments depend on several factors, among which distance from potential sources is of the primary importance (Minchin et al., 1995; Leung et al., 2006; Guðmundsdóttir et al., 2011). Shipping activities are the most intense in coastal areas such as harbors, estuaries or marinas, thus these areas have been regarded as the most problematic among sources of OTs. There is a general trend of decreasing concentrations of OTs in organisms with distance from sources (Evans, 1999), and their concentrations in pelagic species are greater than those of demersal species (Rumengan et al., 2008). Concentrations of OTs in deep-sea areas were poorly studied because it had been deemed unlikely for these pollutants to be transported to such depths. However, Borghi and Porte (2002) conducted a survey around the northwest Mediterranean Sea and for the first time, reported the maximum concentration of TPT, as great as 1.4 lg Sn g 1 ww, in deep-sea fish. This observation of TPT in deep-sea fish indicates that TPT persists in the marine environment and can be transported to greater depths in the water column. Concentrations of PTs in the marine environment can vary among seasons (Lee et al., 2006). In contrast to TBT, concentrations of which were reported to be greater in winter and lesser in summer (Rivaro et al., 1997), concentrations of TPT in organisms have been found to be greater in summer (Hung et al., 1998, 2001; Lee et al., 2005). Because antifouling paints are not the only source of PTs, this seasonal trend of PTs might be due to their use in aquaculture nets and application of PT-containing biocides in both mariculture and agriculture during the summer (Hung et al., 1998; Meng et al., 2009). PTs are accumulated differentially among tissues and organs of marine organisms. In fish, liver is prone to accumulate greater concentrations of TPT than are other organs such as gills or digestive glands (Morcillo et al., 1997; Harino et al., 2000). A similar trend has been observed in marine mammals, where the greatest con- centration of total OTs was found in liver (Berge et al., 2004). Because of the greater affinities of OTs to sulfhydryl groups such as glutathione, the pattern of distribution among tissues or organs is dependent on contents of protein, rather than lipids (Iwata et al., 1997; Strand and Jacobsen, 2005; Hu et al., 2009). In addition to the factors mentioned above, species-specific characters might also influence the distribution of the PTs and thus contribute to more variation among species, even at the same trophic level. For instance, concentrations of PTs and BTs are lesser in marine mammals that are covered with fur, because OTs tend to be bound to sulfhydryl groups in hair, which in turn can be shed (Tanabe, 1999; Berge et al., 2004). Maternal transfer of PTs is another possible mechanism to reduce the tissue burden of PTs in the mother, which might also contribute to different patterns of distributions among tissues. This phenomenon has been reported to occur in Dall’s porpoises (Phocoenoides dalli) (Yang et al., 2007), the Japanese medaka (Oryzias lapipes) (Zhang et al., 2008) and Chinese sturgeons (Acipenser sinensis) (Hu et al., 2009). 3.1.3. Temporal variation in concentrations of PTs: implications on effectiveness of restrictions on the use of OTs In order to evaluate the effectiveness of restrictions of use, a long-term monitoring of OTs concentrations was conducted in various developed countries. As expected, after the restriction of their use in antifouling products, concentrations of OTs have been decreasing in estuarine areas of Japan (Port of Osaka) (Harino et al., 1999), the United Kingdom (Irish Sea) (Oliveira et al., 2009), South Korea (East Sea and Yellow Sea) (Choi et al., 2009), Iceland (Guðmundsdóttir et al., 2011), Northern Europe (North Sea and Baltic Sea) (Rüdel et al., 2003) and Southern Europe (Sousa et al., 2007). Thus, restrictions in use have been at least partially success in reducing concentrations of OTs the coastal marine environment. Nonetheless, exceptions to this general decrease in concentrations of OTs have been reported for other locations. For example, concentrations of OTs, in particular PTs have not been A.X. Yi et al. / Chemosphere 89 (2012) 1015–1025 1019 et al., 2009). Based on the available results, it can be concluded that the rate of biotransformation of TPT is relatively slow. 3.3. Bioaccumulation of TPT Fig. 2. Ratios of triphenyltin (TPT) to total phenyltins (PT) (%) in compartments of the marine environment. DPT: diphenyltin. MPT: monophenyltin. decreasing in Hong Kong (Nakayama et al., 2009; Kevin Ho, unpublished data). These exceptions seem to occur in busy shipping areas with fresh inputs of OTs, probably from the continued illegal uses of OTs, and from uses of OT-based antifouling systems on ships and mariculture facilities in countries which did not impose the IMO’s regulation on their uses. 3.2. Proportions of TPT to PTs: relations with degradation and rates of biotransformation of TPT The ratio between concentrations of TPT and total PT can be used as an approximate measure of transformation of TPT by chemical or biological means. A greater proportion of TPT relative to that of total PTs indicates a lesser rate of transformation of TPT in the environment or a lesser rate of biotransformation of TPT. Thus, ratios of concentrations of TPT, Di-PT (DPT) and Mono-PT (MPT) to concentrations of total PTs were calculated for different compartments among various marine environments (Fig. 2). TPT constitutes only 15.7% of total PTs in seawater, while percentages of DPT and MPT are 31.4% and 52.9%, respectively. These ratios are consistent with measured rates of photolysis of TPT, whereby DPT and MPT and some water-soluble, non-extractable OT polymers are formed (Soderquist and Crosby, 1980). Similar distributions were observed in sediments, in which proportions of TPT, DPT and MPT were 12.5%, 28.1% and 59.4%, respectively. Degradation of TPT occurs relatively slowly in sediments, and photodegradation, rather than microbial degradation, is the primary pathway of degradation of TPT in sediments (Fent et al., 1991a,b; Kannan and Lee, 1996). The smaller proportion of TPT, relative to that of total PTs in sediments might also be attributable to a decreasing input of TPT in areas that were studied (Midorikawa et al., 2004). Unlike abiotic compartments, TPT is consistently the dominant compound in marine invertebrates and fish, with TPT contributing 63.4% and 65.8% of total PTs in invertebrates and fishes, respectively (Fig. 2). This is consistent with TPT being poorly biotransformed. For instance, during a 96 h exposure of larvae of the minnow Phoxinus phoxinus biotransformation of TPT was not observed (Fent et al., 1991a,b). Only 2.5% of TPT was biotransformed during 14 d in the goldfish Carassius auratus (Tsuda et al., 1988). The half-life of TPT in the guppy Poecilia reticulata was at least 48 d (Tas et al., 1991). The rate of biotransformation of TPT is less than that of TBT in some organisms, such as the mussels M. edulis and M. coruscus and oyster Crassostrea gigas (Higashiyama et al., 1991; Shim et al., 2005b). TPT is also the predominant PT in birds and marine mammals, with a slightly lesser ratio of 49.0%. Although there are no reports on the rate of in vivo biotransformation of TPT in marine birds or mammals, a recent study that used hepatic microsomes from Dall’s porpoises found that little (<3%) TPT was biotransformed (Yang 3.3.1. Factors affecting bioaccumulation Bioaccumulation and biomagnification of persistent organic pollutants (POPs), including organochlorine pesticides, such as DDT and its transformation products, methylmercury and polychlorinated biphenyls (PCBs) and OTs, can affect the resultant toxic effects of these chemicals to aquatic organisms (van der Oost et al., 2003). In general, xenobiotics that can be biomagnified have the following properties: (1) a large octanol–water partition coefficient (KOW); (2) persistence and (3) a slow rate of elimination (Clarkson, 1995). Among these properties, the log KOW is of primary importance in determining the bioaccumulation of a chemical where a greater log KOW value generally indicates a greater accumulative potential. The log KOW values vary among different TPTs because of various anions/ anionic groups that are combined with the Sn atom. Generally speaking, the log KOW values of TPTs range from 3.0 to 5.0, and TPTOH, which is the most abundant PT species in marine environment, has a log KOW value of 3.5 (Arnold et al., 1997). Bioaccumulation of chemicals depends not only on hydrophobicity, but also physicochemical parameters, such as salinity, presence of humic acid and pH that can alter speciation, thereby affecting bioavailability of chemicals. For instance, bioconcentration factors (BCFs) of both TBT and TPT for the freshwater guppy (Lebistes reticulatus) are approximately twice as great as those for marine fishes (Tsuda et al., 1990a), which is indicative of a negative effect of salinity on accumulation of TBT and TPT. Bioaccumulation of TBT by marine mussels is inversely proportional to the concentration of humic materials in the water (Laughlin et al., 1986). In contrast, accumulation of OTs by aquatic organisms is directly proportional to pH. Bioaccumulation of both TBT and TPT was greater for both invertebrates and fishes at pH 7.8 than at pH 6.8 or 6.0 (Tsuda et al., 1990b). Apart from these abiotic factors, biotic factors, such as life stage of the organism and species-specific characteristics, can potentially affect the bioaccumulation of TPTs (Fent, 1996a). 3.3.2. Bioconcentration of TPT Accumulation of TPT from water/sediments has been studied in algae, invertebrates and fishes. A BCF of 1.1 105 was reported for the alga Scenedesmus obliquus after 96 h exposure to TPT (Huang et al., 1993). Marine invertebrates can accumulate OTs quickly and the BCFs for accumulation of TPT by marine mussels Mytilus graynus and M. edulis were 4.3 104 and 3.6 104, respectively (Suzuki et al., 1998). Bioconcentration of TPT has been determined for several fishes, including the guppy (Poecilia reticulate), rainbow trout (Salmo gairdneri), common carp (Cyprinus carpio), red sea bream (Pagrus major), mullet (Mugil cephalus), filefish (Rudarius ercodes) and minnow (Phoxinus phoxinu); among which the greatest BCF was 4.1 103, which was observed for R. ercodes (Fent et al., 1991a,b; Tsuda et al., 1987; Tas et al., 1989; Yamada and Takayanagi, 1992). 3.3.3. Biomagnification of TPT Little is known about biomagnification of TPT. Studies of trophic transfer of TPT have rarely been conducted under controlled laboratory conditions. Most studies of trophic transfer of TPT have been conducted in the field and because it is impossible to know the exact nature of exposure or trophic relationships, only apparent biomagnification factors (BMFs) can be estimated. There has been only one documented study of biomagnification conducted in a controlled laboratory exposure of marine organisms to TPT. The BMF of TPT was estimated to be 0.57, which is approximately twice as great as that of TBT (Yamada et al., 1994). Since the BMF of TPT is less than 1020 A.X. Yi et al. / Chemosphere 89 (2012) 1015–1025 Fig. 3. Environmental fate of triphenyltin (TPT) in the marine ecosystem. DPT: diphenyltin. MPT: monophenyltin. 1.0, it is assumed that TPT would not be biomagnified. Based on the available information collected during field investigations, however, it appears that TPT is biomagnified in marine food webs (Stäb et al., 1996; Kono et al., 2008). The BMF for TPT was estimated to be 3.7 in Bohai Bay, China (Hu et al., 2006) and from 2.2 to 5.4 in coastal areas of Japan (Murai et al., 2008), while BMF values of TBT in both regions were less than 1.0. Neither of these studies determined concentrations of TPT in organisms at the highest trophic level such as marine mammals or fish-eating birds. There is only one study of accumulation of TPT along a more comprehensive food web. In that study conducted in Denmark, species from seaweed to marine mammals were investigated. Concentrations of TPT in fish-eating birds and marine mammals were less than in the fishes consumed by these predators. The authors of that report suggested that the fish-eating birds and marine mammals could likely biotransform and excrete TPT. Thus, TPT is unlikely to be accumulated to these higher trophic levels (Strand and Jacobsen, 2005). 3.4. Summary of environmental fate of TPT Primary sources of TPT in the marine environment are releases from antifouling products used in boats or mariculture facilities, and agricultural runoff, although other potential sources include treated or untreated sewage effluent discharges, and surface runoff via storm drainage discharges (Fig. 3; Fent, 1996b; Arnold et al., 1998). TPT can be enriched in sediments while it is photolized in both surface seawater and sediments in shallow water. Marine organisms can accumulate TPT directly from seawater or sediments, as well as through their diet. It has been confirmed that TPT can be biomagnified from phytoplankton and zooplankton to fish. But more information will be needed to confirm the details of biomagnification to higher trophic levels, such as marine mammals and fish-eating birds. 4. Adverse effect of TPT to marine ecosystems 4.1. Endocrine disrupting effects on marine organisms OTs have been implicated as endocrine disruptors primarily through studies of aquatic organisms, among which imposex of marine gastropods is the most well-defined endocrinal effect caused by OTs. Therefore, monitoring for incidence of imposex in neogastropod species has become a common method to monitor for effects of OTs in coastal marine environment worldwide. Imposex is the development of vas deferens and penis in females (Gibbs et al., 1997), which can lead to reproductive failure, and subsequent decreases in populations where imposex occurs (Gibbs et al., 1987, 1988). Imposex was first associated with TBT in the early 1980s, and since then it has been reported to occur in at least 195 species of gastropods (Lima et al., 2011), such as Nucella lapillus, Nassarius reticulates, Thais bronni and Thais clavigera (Gibbs and Bryan, 1986; Bryan et al., 1988; Horiguchi et al., 1995; Barreiro et al., 2001). Although TPT occurred with TBT in coastal areas and TBT was known to cause imposex, it was not until the mid1990 when Japanese scientists confirmed that TPT could also cause imposex in T. clavigera (Horiguchi et al., 1994, 1996). More recently the occurrence of imposex in marine gastropods collected from coastal areas of different countries has been associated with TPT (Japan: Horiguchi et al., 1994; Spain: Solé et al., 1998; Korea: Shim et al., 2000). Positive relationships between concentrations of TPT and rates of imposex have been reported since the mid-1990. Results of a study conducted in the laboratory where TPT was injected into T. clavigera demonstrated that TPT does cause imposex (Horiguchi et al., 1996). A similar result was subsequently observed for Bolinus brandaris (Santos et al., 2006). However, due to species-specific properties, this phenomenon is not necessarily observed in all gastropods. For example, when TPT was injected into N. lapillus, it did not cause imposex, even at concentrations as great as 1 lg TPTCl g 1 body weight (Bryan et al., 1988). Similarly, TBT was also reported to not cause imposex in the dove snail, Columbella rustica (Gibbs et al., 1997). Possible mechanisms by which OTs cause imposex in gastropods have been described by Horiguchi (2009). There are four previously proposed pathways, including: (1) increasing androgen content through inhibition of cytochrome P450-dependent aromatase (Bettin et al., 1996); (2) inhibition of testosterone excretion (Ronis and Mason, 1996); (3) interference with the neuroendocrine system (Féral and LeGall, 1983), and (4) abnormal release of the neuropeptide, APGWamide (Oberdörster and McClellan-Green, 2000). However, none of these hypotheses adequately explains A.X. Yi et al. / Chemosphere 89 (2012) 1015–1025 onset of imposex, and thus the mechanism of OT-induced imposex is still not completely elucidated (Horiguchi, 2009). Recently, a hypothesis regarding the mechanisms by which OT induces imposex has been proposed by Nishikawa et al. (2004). Those authors demonstrated that OT could directly bind to a retinoid X receptor (RXR) and act as agonists, thereby inducing imposex in gastropods. RXR has been shown to be involved in induction of male-type genitalia in female gastropods (Horiguchi et al., 2007; Horiguchi, 2009). TPT-induced effects on the endocrine system have also been reported in fish. For instance, TPT can affect reproduction by suppressing spawning frequency and reducing the number of eggs produced by female medaka, Oryzias latipes (Zhang et al., 2008), or by inhibiting testicular development in male rockfish Sebastiscus marmoratus (Sun et al., 2011); TPT’s binding to RXR can also cause deformities of the eye in the Chinese sturgeon Acipenser sinenses (Hu et al., 2009). In general, effects of OTs on the endocrine system of fish are initiated by inhibition of enzymes like cytochrome P450 and production of the egg yolk phospholipoprotein vitellogenin (Hinfray et al., 2006; Miller et al., 2007). Apart from gastropods and fish, TPT have been reported to induce malformation in embryos of amphibians such as the African clawed frog (Xenopus tropicalis) (Yuan et al., 2011). Crustaceans form a ubiquitous group of invertebrates, and many of them have been chosen as model species in aquatic toxicity tests, including the water flea (Daphnia magna), the mysid Siriella armata, and the copepod Tigriopus japonicus. TPT and other OT compounds can have adverse effects on molting, growth and reproduction of crustaceans (Rodríguez et al., 2007). Effects of OTs on sexual differentiation process of crustaceans have been neglected, which may deserve further research to fill the knowledge gaps. 4.2. Species sensitivity distribution for aquatic biota exposed to TPT 4.2.1. Toxicity test of TPT on marine organisms OTs, in particular the tri-substituted compounds are more toxic to aquatic organisms than are inorganic Sn compounds (Fent, 1996a; Hoch, 2001). The toxic effects of OTs, primarily TBTs, have been of concern and have been widely studied during the past few decades. Nevertheless, much of the information is for TBTs (Hall and Pinkney, 1985). Information on toxicity of TPTs is available for only a few species of marine algae, invertebrate and fishes (Table S5). For algae, inhibition of growth has been the most studied measurement endpoint. Median effect concentrations, EC50 values, for algae growth test ranged between 0.59 and 51.5 lg L 1 (Table S5). Besides inhibition of growth, other indices including chlorophyll or phycocyanin content, photosynthesis inhibition and nitrate reductase have also been applied to study the toxic effect of TPT on algal species (Mooney and Patching, 1995; Huang et al., 1996). Among these indices, nitrate reductase was the most sensitive to the effects of TPT (Huang et al., 2002). Sensitivity of invertebrates to TPT varied among species’ median lethal concentrations (LC50) or EC50, ranging from 0.8 to more than 560 000 lg L 1. Among species of invertebrates tested, the copepod Acanthocyclops venustus was the most sensitive to TPT while the bivalve Mercenaria mercenaria was the most tolerant (Table S5). Most data on the toxicity of TPT to fishes have been obtained for larvae or juveniles (Fent and Meier, 1992, 1994). LC50 values for fishes ranges from 7.1 to 62 lg L 1. In addition, TPT compounds can affect feeding and swimming behavior of tadpoles of the European frog, (Rana esculenta; synonym of Pelophylax kl. esculentus) (Semlitsch et al., 1995). To determine the risks of chemicals it is useful to determine the mechanism of action prior to conducting testing whole individuals (Fent, 1996a). Uptake of OTs by microorganisms is primarily through adsorption of organic moieties of OTs onto the cell surface 1021 (Avery et al., 1993). Triorganotin compounds such as TBT and TPT exert their toxicities through interaction with membrane lipids (Mooney and Patching, 1995), thereby disrupting respiration and photosynthesis of algae. Toxicity of OTs is related to total surface area of microorganisms such as unicellular algae, and the lipid solubility of OT chemicals (Cooney and Wuertz, 1989). Toxicity of TPT in vitro has been determined. Toxicity of TPT to PLHC-1 fish hepatoma cells was correlated with in vivo toxicity of mortality in fish (Brüschweiler et al., 1995). TPTs can interact with different intracellular enzymes. For example, cytochrome P450 and glutathione-S-transferase are both involved in biotransformation of xenobiotics, but TPTs can inhibit their expression, thus leading to dysfunction of the detoxicification system (George and Buchanan, 1990; Fent and Bucheli, 1994). Also, TPT compounds increase intracellular calcium storage by slowing mobilization of Ca2+, which in turn causes hyperpolarization of cell membranes (Miura and Matsui, 1991). TBT and TPT are equally potencies to most species that have been tested. Relatively few toxicological studies, especially full life-cycle chronic toxicity tests have been conducted for TPT and little is known about the mechanism of action. Toxicities of OTs are thought to be additive (WHO, 1999), but there is virtually no relevant, specifically designed study to investigate and elucidate the interactions among different OT compounds. 4.2.2. Predicted no effect concentration (PNEC) and evaluation of ecological risks of TPT Acute toxicity of TPT to 15 marine species of different trophic levels (six algal species, two arthropod species, four mollusc species and three fish species) were obtained from peer-reviewed literature or the ECOTOX database (USEPA, 2011a), with species geometric means calculated if multiple studies had been conducted for the same species. The average toxicity values for the 15 species were ranked and used to construct a species sensitivity distribution (SSD) according to the method described in Wheeler et al. (2002). From the SSD analysis (Fig. 4) which was performed on log-transformed data by use of an SSD generator (downloaded from USEPA; USEPA, 2011b), an HC5 (hazardous concentration to 5% of species or protective of 95% of species) value for TPT was determined to be 0.117 lg Sn L 1 (95% CI: 0.064–0.216 lg Sn L 1). By applying an acute to chronic ratio of 10 and an assessment factor of 10 to the lower 95% CI of HC5, which is 0.064 lg Sn L 1 (Chapman et al., 1998), a chronic predicted no effect concentration (PNEC) was estimated to be 0.64 ng Sn L 1. Larvae of the oyster (Crassostrea virginica) were the most sensitive to TPTOH with an LC50 value of 0.32 lg L 1 (or 0.10 lg Sn L 1). The Hazard Quotient (HQ) approach was applied to estimate the ecological risks posed by TPT. Based on values of HQs, which are defined as the quotient of a measured concentration in the environment (MEC) divided by the PNEC, TPT might pose risks to marine organisms in coastal environments of Japan, Korea, and the Mediterranean Sea (Table 1). Nevertheless, it is worth noting that most of these data are not recent, thus it is not reliable to predict the current ecological risks caused by TPT using these data. Therefore, more current information for TPT distributions is needed to evaluate its current environmental risks. 5. Exposures and effects of TPT compounds to humans Humans are exposed to multiple chemicals in the environment and their diet, including OTs and thus the potential health risks of OTs to humans should be considered (Golub and Doherty, 2004). These sources of OTs are various and widespread. For instance, food containers made of PVC polymers (Kannan et al., 1992), seafood from markets (Guérin et al., 2007) and even tap water that 1022 A.X. Yi et al. / Chemosphere 89 (2012) 1015–1025 Proportion of species affected 1.0 Central tendency 95% CI 0.8 R2 = 0.962 0.6 0.4 Crassostrea virginica 0.2 0.0 0.01 HC5 = 0.117 µg L-1 (95% CI: 0.064 – 0.216 µg L-1) 0.1 1 10 100 TPT conc. (µg/L as Sn) Fig. 4. Species sensitivity distribution (SSD) of TPT to marine species. Table 1 Hazard quotient (HQ) in different countries or areas. MEC: measured environmental concentration. Area Year MEC (ng Sn L Japan 1996 5.25 Korea 1997– 1998 2006 1.2 1988 19.5 China France and Spain (Mediterranean Sea) 0.09 Reference 1 HQ ) Harino et al. (1998) Shim et al. (2005a,b) Wang et al. (2008) Alzieu et al. (1991) 8.2 1.9 0.14 30.5 passes through PVC pipes (Sadiki et al., 1996) are sources of OTs. Food, especially seafood and fishery products are considered the primary sources of OTs (Guérin et al., 2007) to humans. In addition to oral uptake from contaminated foodstuffs, cutaneous absorption via the respiratory tract is likely to happen and should not be neglected (Colosio et al., 1991). There have been two reports related to the adverse effects of TPTs on humans (Manzo et al., 1981; Colosio et al., 1991) via accidental exposure to TPT-based pesticides by farmers. These patients exhibited similar symptoms of TPT poisoning, including dizziness and nausea. TPT may also lead to possible impairment of the central nervous system and liver damage. Since no quantitative toxicological data on humans is available, potential toxic effects on humans can only be extrapolated from results of tests on other mammals like rats, rabbits or pigs and the estimated human intake of these chemicals. A diet of 50 mg TPTOH kg 1 of diet did not have adverse effect on rats even after 276 d of the continuous dietary exposure (Kimbrough, 1976). The guineapig has been reported to be the most sensitive species and its growth inhibition was observed at concentration as little as 1 mg TPTA kg 1 of diet (Stoner, 1966). TPTs are slowly eliminated from rats and guinea pigs (Stoner, 1966; Verschuuren et al., 1966). Similar as in marine organisms, aromatase may be a toxicological target of TPT in mammals as well. For example, in rats, TPT exposure can affect brain and gonadal aromatase activity in a sex-dependent fashion (Hobler et al., 2010). Immunotoxicity is considered to be the most sensitive, or critical endpoint for exposure of mammals to TPT (Boyer, 1989). Based on immunological responses of experimental animals, the acceptable daily intake (ADI) of TPT compounds for humans has been set at 0.5 lg kg 1 bw d 1 (Lu, 1994; WHO, 1999). Considering that TBT, dibutyltin (DBT), dioctyltin (DOT) and TPT have similar modes of immunotoxic effects to organisms, it is more reasonable to derive an ADI for this whole group of chemicals (Guérin et al., 2007). Based on an assumption that toxic effects of these compounds are additive, the European Food Safety Authority (EFSA) established the tolerable daily intake (TDI) value of this group of OTs to be 0.25 lg kg 1 bw d 1 (EFSA, 2004). There have been reports on concentrations of OTs in food and its implications for public health risks. The results of these risk assessments published before 2000 have been summarized (Belfroid et al., 1999). Over the last decade, studies of concentrations of TPT in seafood have been conducted in China (Cao et al., 2009), Finland (Rantakokko et al., 2006), France (Guérin et al., 2007), Japan (Ueno et al., 1999) and Portugal (Santos et al., 2009), respectively. In some of these recent studies, TPTs were detected in seafood at considerable concentrations (Ueno et al., 1999; Guérin et al., 2007). Most of these surveys on OTs in foodstuffs found that the daily uptake from food were less than the ADI or TDI values, and therefore suggested negligible risks to average consumers. However, there were limitations of these surveys. For example, OTs can also originate from other market products other than seafood, such as potatoes, fruits and vegetables (Rantakokko et al., 2006). Furthermore, dietary intakes of OTs among children of less than average bodyweights have not been estimated. Daily intake can also be significantly greater for those who consume large amounts of contaminated food. OTs have been detected in human blood and liver. Butyltins (BTs) were first found in human blood in late 1990s (Kannan et al., 1999) and their residues in human livers were detected in samples collected from the Japanese and Polish people (Kannan and Falandysz, 1997; Takahashi et al., 1999). Average concentrations of BTs in livers of Polish people (2.4–11 ng g 1 wet wt) were less than those in Japanese (59–96 ng g 1 wet wt). TPT has been detected in blood of Finnish people. Concentrations of TPT in blood of humans were greater in people who consumed greater amounts of seafood (Rantakokko et al., 2008). Therefore, from the viewpoint of public health, it is rational to devote effort to further reducing the OTs in the environment. It is also advocated to initiate monitoring of TPT and its degradants in human blood and breast milk samples, especially in the population with greater seafood consumption such as fishermen and people living nearby the coast. Such monitoring schemes can be easily integrated with the existing programmes for monitoring POPs. 6. Summary Due to wide-spread application in antifouling products and agriculture, TPT compounds can be detected in various compartments of the marine environment. TPT can undergo photolysis in water and sediment but is not easily biotransformed by marine organisms. TPT can be bioaccumulated and potentially biomagnified through the marine food web of lower trophic levels, such as from phytoplankton and zooplankton to fishes. TPT is toxic to marine organisms, with the predicted no effect concentration (PNEC) for chronic, continuous exposure of 0.64 ng Sn L 1. The PNEC was derived by use of the species sensitivity distribution approach. Based on this PNEC and concentrations measured in the marine environment, TPT was determined to pose risks to marine organisms in some regions. Current concentrations of TPT pose a di minimus risk to humans, but there are significant uncertainties in the assessment of risks to humans due to limitations in both estimates of exposure and predicted thresholds for effects this assessment. Acknowledgements This study was substantially supported by the Area of Excellence Scheme under the University Grants Committee of Hong A.X. Yi et al. / Chemosphere 89 (2012) 1015–1025 Kong SAR China (Project No. AoE/P-04/2004) and by the Research Grants Council through a General Research Fund (Project No. HKU 7034/07P). The research was also supported, in part, by a Discovery Grant from the Natural Science and Engineering Research Council of Canada (Project # 326415-07). 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