삭시톡신과 그 유사체: 독성, 분석법, 국내외 오염도 및 관리 동향

국문 초록 (Abstract)

마비성 패독(paralytic shellfish poisoning, PSP)에 의한 중독은 와편모조류(Dinoflagellates)가 생성하는 saxitoxin (STX)이 이매패류 등의 먹이활동에 의해 축적되고 이를 사람이 섭취함으로써 발생한다. 최근 분석기술의 발전으로 와편모조류가 STX외에도 gonyautoxin (GTX) group 및 Nsulfo carbamoyl toxins (C toxin) group 등 다양한 유사체들 을 생성하는 것으로 보고되고 있다. 이에 CODEX, EFSA 에서는 STX외 유사체의 안전관리를 위해 STX 및 유사체를 STX group으로 관리하고자 하는 움직임을 보이고 있다 . 국내의 경우도 STX 유사체를 생성하는 조류의 발생이 이미 보고되고 있으며 실제 홍합에서 유사체의 오염사례도 소수 보고되고 있다. 따라서 국제적인 움직임에 발맞추어 국내에서도 STX 및 유사체의 group 관리를 위한 준비가 필요할 것으로 사료된다. 본 연구에서는 STX 및 유사체의 체계적인 모니터링 및 안전관리의 기반을 마련하고자 STX 및 유사체의 이화학적 특성, 생성조류, 국내외 발생현황, 독성 및 상대독성계수, 분석법, 오염현황 및 관리현황에 대한 폭넓은 검토를 수행하고자 하였다.

다국어 초록 (Multilingual Abstract)

Paralytic shellfish poisoning (PSP) occurs when saxitoxin (STX), which is produced by harmful algae (dinoflagellates) and then accumulated in bivalve shellfish by filter-feeding, is consumed by humans. With recent advances in analysis technology, it has been reported that dinoflagellates also produce a variety of analogues such as the gonyautoxin (GTX) group and the N-sulfo-carbamoyl toxin (C toxin) group, in addition to STX. Accordingly, CODEX and the EFSA are stepping forward to manage STX and analogues as STX groups requiring safety management. In Korea, the occurrence of dinoflagellates producing STX analogues has already been reported, and contamination of analogues (GTX group, C toxin group) in live mussels has also been reported. In this study, in order to provide the basis for systematic monitoring and safety management of STX and analogues, their physicochemical characteristics, occurrence of dinoflagellates, toxicity and toxic equivalency factor, analytical method and occurrence were widely reviewed. This review is expected to contribute to strengthening the safety management of STX and its analogues.

목차 (Table of Contents)

• ABSTRACT
• STX group 독소의 이화학적 특성
• STX group 생성조류의 국내외 발생현황
• STX group 독소의 독성 및 상대독성계수
• STX group 독소의 분석법
• STX group 독소의 국내외 오염현황
• STX group 독소의 국내외 관리현황
• Conclusion and Suggestions
• 국문 요약
• References

참고문헌 (Reference)

1 손명백`, "진해만 해역에서 지중해담치(Mytilus galloprovincialis)의 마비성패독 독화 양상" 한국수산과학회 42 (42): 366-372, 2009

2 Hamasaki, K., "Variability in toxicity of the dinoflagellate Alexandrium tamarense Isolation from Hiroshima Bay, western Japan, as a reflection of changing environmental conditions" 23 : 271-278, 2001

3 Usleber, E., "Two formats of enzyme immunoassay for the detection of saxitoxin and other paralytic shellfish poisoning toxins" 12 (12): 405-413, 1995

4 Poulton, N. J., "Toxin variability in natural populations of Alexandrium fundyense in Casco Bay, Maine—evidence of nitrogen limitation" 52 : 2501-2521, 2005

5 Montoya, N. G., "Toxin variability in cultured and natural populations of Alexandrium tamarense from southern South America-Evidences of diversity and environmental regulation" 56 : 1408-1418, 2010

6 Krock, B., "Toxin profile of Alexandrium catenella from the Chilean coast as determined by liquid chromatography with fluorescence detection and liquid chromatography coupled with tandem mass spectrometry" 6 : 734-744, 2007

7 Wiberg, G. S., "Toxicologic studies on paralytic shellfish poison" 2 : 607-615, 1960

8 Cho, E. S., "Thecal plates, toxin content and growth of five clones of Alexandrium tamarense (Dinophyceae) isolated from Jinhae Bay, Korea" 40 (40): 435-439, 2001

9 MacKenzie, L., "The dinoflagellate genus Alexandrium (Halim) in New Zealand coastal waters: comparative morphology, toxicity and molecular genetics" 3 : 71-92, 2004

10 Finch, S. C., "The acute toxicity of tetrodotoxin and tetrodotoxin-saxitoxin mixtures to mice by various routes of administration" 10 : 423-, 2018

11 Food and Agriculture Organization, "Technical paper on toxicity equivalency factors for marine biotoxin associated with bivalve molluscs" 1-108, 2016

12 Codex Alimentarius, "Standard for live and raw bivalve molluscs CXS292"

13 Turner, A. D., "Single-laboratory validation of a multitoxin ultra-performance LC-hydrophilic interaction LC-MS/MS method for quantitation of paralytic shellfish toxins in bivalve shellfish" 98 : 3-, 2015

14 Gomaa, M. N., "Simultaneous occurrence of saxitoxins and biogenic amines in mackerel fish" 5 (5): 5178-5187, 2011

15 Zhang, F., "Shellfish toxins targeting voltage-gated sodium channels" 11 : 4698-4723, 2013

16 Food and Drug Administration, "Sec. 540.250 Compliance policy guide. Compliance program 7303.842"

17 Qiu, J., "Screening of cyclic imine and paralytic shellfish toxins in isolates of the genus Alexandrium (Dinophyceae) from Atlantic Canada" 77 : 108-118, 2018

18 Roggatz, C. C., "Saxitoxin and tetrodotoxin bioavailability increases in future oceans" 9 : 840-844, 2019

19 Minister of Health Labour and Welfare, "Regarding the establishment of Guidelines for risk management of shellfish poisoning in bivalves"

20 Borkman, D. G., "Recurrent vernal presence of the toxic Alexandrium tamarense/Alexandrium fundyense (Dinoflagellata) species complex in Narragansett Bay, USA" 32 : 73-80, 2014

21 Lawrence, J. F., "Quantitative determination of paralytic shellfish poisoning toxins in shellfish Comparison of AOAC 2005.06 LC method with other methodologies 1269 using prechromatographic oxidation and liquid chromatography with fluorescence detection: collaborative study" 88 (88): 1714-1732, 2005

22 Llewellyn, L. E., "Postmortem analysis of samples from a human victim of a fatal poisoning caused by the xanthid crab, Zosimus aeneus" 40 : 1463-1469, 2002

23 Oshima, Y., "Postcolumn derivatization liquid chromatographic method for paralytic shellfish toxins" 78 : 528-532, 1995

24 José J. Bustillos-Guzmán, "Paralytic toxin profile of the marine dinoflagellate Gymnodinium catenatum Graham from the Mexican Pacific as revealed by LC-MS/MS" Informa UK Limited 1-14, 2015

25 Lee, J. S., "Paralytic shellfish toxins in the mussel Mytilus edulis and Dinoflagellate Alexandrium tamarense from Jinhae bay, Korea" 25 (25): 144-150, 1992

26 Maria João Botelho, "Paralytic shellfish toxin profiles in mussel, cockle and razor shell under post-bloom natural conditions: Evidence of higher biotransformation in razor shells and cockles" Elsevier BV 154 : 104839-, 2020

27 Botelho, M. J., "Paralytic shellfish toxin profiles in mussel, cockle and razor shell under post-bloom natural conditions: Evidence of higher biotransformation in razor shells and cockles" 154 : 104839-, 2020

28 Han, M., "Paralytic shellfish toxin production by the dinoflagellate Alexandrium pacificum (Chinhae Bay, Korea) in axenic, nutrient-limited chemostat cultures and nutrient-enriched batch cultures" 104 : 34-43, 2016

29 Mons, M.N., "Paralytic shellfish poisoning: A review" National Institute of Public Health and Environment (RIVM) 1998

30 Kim, C. J., "Paralytic shellfish poisoning toxin analysis of the genus Alexandrium (Dinophyceae) occurring in Korean coastal waters" 71 : 1-11, 2005

31 Garcı a, C., "Paralytic shellfish poisoning : post-mortem analysis of tissue and body fluid samples from human victims in the Patagonia fjords" 43 : 149-158, 2004

32 Schantz, E. J., "Paralytic shellfish poison VI. A procedure for the isolation and purification of the poison from toxic clams and mussel tissues" 79 : 5230-5235, 1957

33 Mariana I. C. Raposo, "Paralytic Shellfish Toxins (PST)-Transforming Enzymes: A Review" MDPI AG 12 (12): 344-, 2020

34 Ramos, P. B., "Oxidative stress in rats induced by consumption of saxitoxin contaminated drink water" 37 : 68-74, 2014

35 Mattarozzi, M., "Optimization of a rapid QuEChERS sample treatment method for HILIC-MS2 analysis of paralytic shellfish poisoning (PSP) toxins in mussels" 60 : 138-145, 2016

36 European Food safety Authority, "Marine biotoxins in shellfish – Saxitoxin group" 1019 : 1-76, 2009

37 O’Neill, K., "Low dose extended exposure to saxitoxin and its potential neurodevelopmental effects : A review" 48 : 7-16, 2016

38 Ministry of Food and Drug safety, "Korean Food Standard. Chapter 2"

39 Perreault, F., "Investigation of animal and algal bioassays for reliable saxitoxin ecotoxicity and cytotoxicity risk evaluation" 74 : 1021-1026, 2011

40 Laabir, M., "Influence of environmental factors on the paralytic shellfish toxin content and profile of alexandrium catenella(dinophyceae)isolated from the mediterranean sea" 11 : 1583-1601, 2013

41 Fast, M. D., "In vitro transformation of paralytic shellfish toxins in the clams Mya arenaria and Protothaca staminea" 5 : 79-90, 2006

42 Gessner, B. D., "Hypertension and identification of toxin in human urine and serum following a cluster of mussel-associated paralytic shellfish poisoning outbreaks" 35 : 711-722, 1997

43 Dell'Aversano, C., "Hydrophilic interaction liquid chromatography--mass spectrometry for the analysis of paralytic shellfish poisoning (PSP) toxins" 1081 (1081): 190-201, 2005

44 Buszewski, B., "Hydrophilic interaction liquid chromatography (HILIC)—a powerful separation technique" 402 : 231-247, 2012

45 Health Canada, "Health canada's maximum levels for chemical contaminants in foods"

46 Food and Drug Administration, "Fish and Fishery Products Hazards and Controls Guidance Fourth Edition - Appendix 5: FDA and EPA Safety levels in Regulations and Guidance"

47 Robertson, A., "First report of saxitoxin in octopi" 44 : 765-771, 2004

48 Shin, C., "Exposure assessment to paralytic shellfish toxins through the shellfish consumption in Korea" 108 : 274-279, 2018

49 Melegari, S. P., "Evaluation of cytotoxicity and cell death induced in vitro by saxitoxin in mammalian cells" 78 : 1189-1200, 2015

50 Sullivan, J. J., "Enzymatic transformation of PSP toxins in the littleneck clam (Protothaca staminea)" 114 : 465-472, 1983

51 EURLMB, "EURLMB SOP for analysis of Paralytic shellfish toxins (PST) by precolumn HPLC-FLD according to OMA AOAC 2005.06, Version 1"

52 Touzet, N., "Dynamics of co-occurring Alexandrium minutum (Global Clade) and A. tamarense (West European) (Dinophyceae) during a summer bloom in Cork Harbour, Ireland (2006)" 57 : 268-278, 2010

53 Durán-Riveroll, L. M., "Docking simulation of the binding interactions of saxitoxin analogs produced by the marine dinoflagellate gymnodinium catenatum to the voltage-gated sodium channel Nav1.4" 8 : 129-, 2016

54 Han, M. S., "Distribution and toxin profiles of Alexanfrium tamarense (Lebour) balech (Dinoflagellate)in the Southeastern coastal waters, Korea" 8 (8): 7-13, 1993

55 Ministry of Food and Drug Safety, "Development of analytical method and monitoring of paralytic shellfish poisoning toxins in aquatic products"

56 Buzy, A., "Development of a capillary electrophoresis Method for the Characterization of Enzymatic Products Arising from the carbamoylase digestion of paralytic shellfish poisoning toxins" 688 : 301-316, 1994

57 Perez, S., "Determination of toxicity equivalent factors for paralytic shellfish toxins by electrophysiological measurements in cultured neurons" 24 (24): 1153-1157, 2011

58 Wu, Y., "Determination of paralytic shellfish toxins in dinoflagellate Alexandrium tamarense by using isotachophoresis/capillary electrophoresis" 29 : 399-404, 2006

59 Jellett, J. F., "Detection of paralytic shellfish poisoning (PSP) toxins in shellfish tissue using MIST Alert, a new rapid test, in parallel with the regulatory AOAC mouse bioassay" 40 (40): 1407-1425, 2002

60 Loftin, K. A., "Cyanotoxins in inland lakes of the United States : Occurrence and potential recreational health risks in the EPA National Lakes Assessment 2007" 56 : 77-90, 2016

61 김희연, "Comparison of Paralytic Shellfish Toxin Profiles of Alexandrium tamarense and Blue Mussel (Mytilus edulis) in Korea" 한국식품과학회 24 (24): 751-756, 2015

62 European Commission, "Commission regulation (EC) No 2074/2005. Official Journal of the European Union"

63 Zepeda, R. J., "Chronic toxicity study of neosaxitoxin in rats" 12 : 5055-5071, 2014

64 Zepeda, R. J., "Chronic toxicity study of neosaxitoxin in rats" 12 : 5055-5071, 2014

65 Beak, S. H., "Change in Paralytic Shellfish Toxins in the Mussel Mytilus galloprovincialis Depending on Dynamics of Harmful Alexandrium catenella (Group I) in the Geoje Coast (South Korea) during Bloom Season" 12 : 442-, 2020

66 Canadian Food Inspection Agency, "Canadian Shellfish Sanitation Program manual, Section B - Shellfish harvest areas"

67 Diehl, F., "Behavioral alterations induced by repeated saxitoxin exposure in drinking water" 22 : 18-, 2016

68 Food Standards Australia and New Zealand, "Australia New Zealand Food Standards Code -Schedule 19 - Maximum levels of contaminants and natural toxicants"

69 Selwood, A. I., "Acute toxicities of the saxitoxin congeners gonyautoxin 5, gonyautoxin 6, decarbamoyl gonyautoxin 2&3, decarbamoyl neosaxitoxin, C-1&2 and C-3&4 to mice by various routes of administration" 9 : 73-, 2017

70 Munday, R., "Acute toxicities of saxitoxin, neosaxitoxin, dicarbamoyl saxitoxin and gonyautoxins 1&4 and 2&3 to mice by various routes of administration" 76 : 77-83, 2013

71 Association of Official Analytical Chemists, "AOAC official methods of analysis" 59-61, 2000

72 Botana, L. M., "A toxicological perspective to climate change : aquatic toxins" 29 : 619-625, 2016