Research Trends on the Development of Scientific Evidence on the domestic Maximum Residue Limits of Pesticides Mi-Gyung Lee *, Jae-Han Shim 1, Sanghoon Ko 2, Hae-Rang Chung 3 *, 1, 2, 3 Department of Food Science and Biotechnology, Andong National University *, Division of Applied Bioscience and Biotechnolgy, Chonnam National University 1, Department of Food Science and Technology, Sejong University 2, Nutrition for the Future, Inc. 3.. (pesticide residue).. (maximum residue limit, MRL). MRL. MRL (risk assessment),. MRL FAO/WHO (1-3)., MRL. MRL, (field residue data), 1 (acceptable daily intake for human, ADI), (food intake data),. (dietary exposure assessment) (risk characterization). 2000 Corresponding author: Mi-Gyung Lee Department of Food Science and Biotechnology, Andong National University #388 Songcheon-dong, Andong-si, Gyeongbuk 760-749, Korea Tel: +82-54-820-6011 Fax: +82-54-820-6264 email: leemig@andong.ac.kr 41 Food Science and Industry (Vol.43 No.2)
MRL...,. (National Health and Nutrition Survey). 1995 (National Nutrition Survey) (Food Balance Sheet). 1998 24. MRL,,,,.. MRL 1998~1999 2001~2002 (4)... (Lifeline, CARES )...... 55 kg (5) MRL. Codex 55 kg. 60 kg (ADI kg ).,...,,. (general population),, (subpopulation). (vulnerable population) 42
.. 1990 (6). 1996 (Food Quality Protection Act, FQPA). FQPA special provisions for infants and children 10., (single point approach) (deterministic approach) (probabilistic approach). Monte Carlo.. UNEP/FAO/WHO (1). (theoretical maximum daily intake, TMDI), (estimated daily intake, EMDI), (estimated daily intake; EDI), (total diet study, TDS, market basket survey). TMDI MRL. TDS ( ). TMDI, EMDI, TDS. MRL TMDI EMDI. EMDI ( ) EMDI. TDS 1990. TDS,,. TDS TDS. (processing factor).. MRL..,,..... MRL. 43 Food Science and Industry (Vol.43 No.2)
MRL.. (long-term dietary intake) (shortterm dietary intake), (cumulative risk assessment) aggregate risk.. ADI (acute reference dose, ARfD).. (environmental protection agency, EPA). (7-9). LifeLine, CARES, DEEM/Calendex..... MRL. ) -,, -, ) (TMDI, EMDI, EDI, TDI,,, ) ) LifeLine, CARES, ). 2009..,...,,,.. 1995. 1998 1 2001 2, 2005 3, 2007 44
1. 2007 398 39 77 409 29 14 249 25 52 131 99 8 31 3,552 5,113 2007. 2007 5,113.,, < 1>.,,,,. 5,113.. 4 (10). 1 4. 1998 2,163, 2001 2,738, 2005 3,643, 2007 5,113.. 1 2 165 2 3 2,716, 3 4 1,927. 2007 5,. 1998... 2007 3,552. < 1>..... FCID(Food Commodity Intake Database). 45 Food Science and Industry (Vol.43 No.2)
1. FCID EPA OPP(Office of Pesticide Programme) USDA LifeLine TM, CARES, DEEM-Calendex (11). USDA 2 Continuing Survey of Food Intakes by Individuals (CSFII), 1994~1996, 1998 Supplemental Children s Survey. CSFII 19 11,800 21,700. FCID 2. FCID(Food Commodity Intake Database) EPA Sample person data Food code kg (g) 500 EPA CSFII, weighting factors USDA, 100 g (g) 500 < 2>. CARES Lifeline TM FCID. CARES, Lifeline TM User Interface,... VBA(Visual Basic Application) VBA Excel. VBA DB, VBA. 46
3. VBA C# - - - - - Excel Excel - -,, C#. C# C#.. VBA Excel < 3>.. DB C#, Microsoft Access. VBA Microsoft Excel, Access Excel. DB SAS SPSS Access. Access (open database)., 2. 47 Food Science and Industry (Vol.43 No.2)
, < 2>... loop... (preor post-regulation). (single chemical) combined exposure(aggregate/cumulative exposure) (long-term exposure) (short-term exposure). (deterministic approach) (probabilistic approach). FAO/WHO,,. FAO/WHO 2002, 2008 6 (12),., FAO/WHO. (12).. o,. o. o,, reference value. o, < 4>. o MRLs JMPR(Joint Meeting on Pesticide Residues) CCPR(Codex Committee on Pesticide Residues)., ( ) ( ). o,,,, LOD/LOQ. o, o 48
4. (FAO/WHO) Pre-regulation Post-regulation - - - maximum levels (MLs) - - - TDSs - - - maximum levels (MLs) - TDSs - GEMS/FOOD - - maximum residue limits (MRLs) -, - Highest residue level from trial(hr) - TDSs - Supervised trial median residue levels(stmrs) - GEMS/Food - - MLs - - TDSs - (, ). o - Supervised trials: worst case.. GAP MRL.,,. - :.. - Targeted data: target.. - post-regulation chronic exposure assessment... - : Standard Mass Balance Assumption. - TDS: TDS. TDS. TDS. TDS 49 Food Science and Industry (Vol.43 No.2)
10~1,000 LODs/LOQs. TDS. Compositing,. TDS. - :. /???,, Good Agriculture Practice(GAP), (, )?? /?? SOPs? -. validation non-detected, non-quantified ( LOD LOQ; Zero ). < 5~6>. - :. ( ). o -,,,,, 5. Systematic error Random error - sampling position - - - ( ) - - 6. Systematic error Random error - - - ( ) - ( ) - - - ground/chopped, - - 50
. - framework (stepwise approach) < 3>., refined exposure assessment. - ( )..., framework.. ( ) < 3>. 3. (FAO/WHO). health-based guidance value(adi, RfD ). JECFA,, JMPR...,. ( ). 90 th percentile. TDS.. Monte-Carlo. JMPR CCPR... Monte Carlo,. Decisioneering Co. Oracle, Crystal Ball Palisades Corp. @ RISK. Monte Carlo Monte Carlo. 51 Food Science and Industry (Vol.43 No.2)
. Combined (Aggregate/Cumulative) (aggregate exposure), (cumulative exposure) < 7>. 4. JMPR Monte Carlo.. ADI PTWI., worst-case.. 1997 FAO/WHO consultation acute reference dose(arfd), ARfD < 4>. EPA OPP(Office of Pesticide Program) (13) Exponent DEEM/Calendex Lifeline group LifelineTM ILSI(International Life Science Institute) CARES (14).,,, < 5>. 5. (15) 7. 52
LifeLine TM Hampshire Research Institute(HRI), EPA, USDA, The LifeLine Group. (aggregate) (Monte Carlo).,,,. Life- Line TM (14). DEEM(Dietary Exposure Evaluation Model) DEEM-FCID/Calendex-FCID Models. (16). DEEM-FCID module: US population( subgroup) FCID. CSFII. Critical Exposure Commodity(CEC) module:. Calendex-FCID module: non-dietary part. CSFII. Monte-Carlo. CARES(Cumulative and Aggregate Risk Evaluation System),. CARES CropLife America(CLA), USEPA USDA, infoscientific.com Novigen Science( Exponent), Sielken & Associates, Summit Research. ILSI Research Foundation CARES (source code) (16,17). CARES,, residential sources(,, ) (aggregate exposure). (cumulative exposure), (,,, ). DEPM(Dietary Exposure Potential Model) Office of Research and Development (ORD) the National Exposure Research Laboratory-Cincinnati (NERL).. ORD., sources (18). DEPM 11 820 (exposure core food, ECF).. 350.. USDA Pesticide Data Program(PDP) Total Diet Study contaminant residue databases. < 8>. DEEM CARES CSFII, LifeLineTM, CSFII. 53 Food Science and Industry (Vol.43 No.2)
8. Factor LifeLine TM DEEM-Calendex CARES DEPM,, CSFII survey CSFII survey CSFII survey ECF FCID Census FCID database NCHS CARES(Stratified) PDP, TDS ( ) CEC module. CSFII 9,746.,,,. DEEM CARES LifeLine TM. DEEM-FCID LIfeLine TM 95 th,. (16). 8 (19).,, LIMS( ) < 9>. 9. 1999-2007 1,271,292 2002-2007 1,898,836 1,243,000 2002-2007 ( ) 1,200,000 2006-2007 2006-2008 1,000,000 2006-2008 2,000,000 8,613,128 54
. TDS. TDS. TDS. TDS TDS TDS. 1994 (20). 1995 1999,,,. 5 86 1,500 59 15. 1998 (20).. 2000 TDS.,,, TDS. TDS. 2000 2008 8 TDS < 10>.. TDS.. GEMS/Food 1974 FAO/WHO,. 1976 GEMS/Food(Global Environment Monitoring System/Food Contamination Monitoring and Assessment Programme) 10. TDS (2000 ) 2000 5 5~10-21 2001 116-22 2002 79, (196 ) 3 23 2003 108-24 2004 101, (104 ) 2 25 2006 101, - 26 2007 26 (215 ) 11 27 2008 23 (197 ) 38 28 55 Food Science and Industry (Vol.43 No.2)
FAO, UNEP(United Nations Environment Programme) WHO. GEMS/Food.. GEMS/Food,,,., aldrin/dieldrin 13,,,,, polychlorinated biphenyls, dioxin, dibenzofurans. aflatoxin 5. GEMS/Food,,, GEMS/Food.,, TDS. GEMS/Food 1999 2007 4 TDS (29-31).. TDS 1950, 1961 TDS (32). TDS FDA. 200 280 13. FDA (33). TDS(Ref) Food Standard Agency.,, 1966 Food Standard Agency 3., 2 121 24 20. (,,,, ),, (34). TDS. The Food Research Division in the Bureau of Chemical Safety Health Canada. 210 3~4 Kemptville College,.,, PCBs, veterinary drugs, (35). 1969 68 The National Medical Research Council (NHMRC) Market Basket Survey. TDS,,,, (36). 130 20 core food 44 regional food, 66 national food core food 8 4, 44 regional food 2 4, 66 national food 8. 190, 8 (,,,,,,, ),, (37). TDS 4 56
6. TDS 10. 48 composite sample, 4 120 composite sample.,, PCBs,,, (38).. 3 (2005)- (39). 90%. 115 30 85 2 1 14 102 < 6>< 11>.. 11. TDS (85 ),,,,,,,,,,,,, ( ),,,,,,,,,,,, ( ),,,,,,,,,,, /,,,,,,,,,,,,,,,,, (, ),,,,,,, /,,,,,,,,,,,,,,,,,,,,,,,, (2 ), (1 ) (1~2 ) (14 ),,,,,,,,,,,,, 57 Food Science and Industry (Vol.43 No.2)
. 102.. 2009 ( 06~ 08)(21) 98. 3 1 GC-ECD, 2 GC-MSD, 3 LC- MS/MS < 12>... 12. TDS 1 (47 ) Alachlor Bifenthrin Butachlor Chinomethionat Chlorfenapyr Chlorothalonil Chlorpyrifos Chlorpyrifos-methyl Cyflufenamid Cyhalothrin Cypermethrin Diazinon Dichlofluanid Diniconazole α-endosulfan β-endosulfan Endosulfan-Sulfate EPN Ethoprophos Fenarimol Fenbuconazole Fenitrothion Fenpropathrin Fenvalerate Flutolanil Hexaconazole Indoxacarb Iprodion Isoprothioran Methidathion Oxadixyl Paclobutrazol Parathion Pendimethalin Permethrin Phenthoate Pyraclofos Pyrazophos Pyridalyl Quintozen Tebupirimfos Tetraconazole Tetradifon Tolyfluanid Triflumizole Vinclozolin Zoxamide 2 (9 ) Fenthion Fipronil Fludioxonil Procymidon Prothiofos Spirodiclofen Terbufos Tolclofos-methyl Triadimefon 3 (44 ) Acetamiprid Anilofos Azoxystrobin Boscalid Cabofuran Cadusafos Carbendazim Chlorfluazuron Diethofencarb Difenoconazole Dimethomorph Ethaboxam Etoxazole Fenobucarb Fenproximate Flufenoxuron Fluquinconazole Fosthiazate Iprobenfos Kresoxim-methyl Lufenuron Mepaniprim Metabenzthiazuron Metalaxyl Methomyl Methoxyfenozide Napropamide Oxadiazone Penccuron Propamocarb Propiconazole Pyraclostrobin Pyridaben Pyrimethanil Spiromesifen Tebuconazole Tebufenozide Teflubenzuron Thiacloprid Thiamethoxam Thifluzamide Tricyclazole Thiophanate-methyl Trifloxystrobin 58
.,,.. (concentration factor), (reduction factor). (processing factor). (mg/kg) (mg/kg)... TMDI ADI.,,. post-regulation. EMDI. 13. Codex MRL Code No. Carbaryl Chlorpyrifos- Diquat Fenitrothion Parathion Pirimiphos methyl -methyl -methyl <Rice products, > GC 0649 Rice 5 PoP 10 Po 10-3 - CM 0649 Rice, husked 5 Po - 1-1 2 CM 1205 Polished rice - - 0.2 1-1 CM 1206 Rice bran, unprocessed - - - 20 PoP - 20 Rice straw & fodder, AS 0649 - - - - 10 - dry <Wheat products, > GC 0654 Wheat 5 Po 10 Po 2-5 - CM 0654 Wheat bran, unprocessed 20 PoP 20 PoP 5 20 10 20 PoP CF 0654 Wheat bran, processed - - - 2 - - CF 1211 Wheat flour 0.2 PoP 2 Po 0.5 2-2 PoP CF 1212 Wheat wholemeal 2 PoP - 2 5-5 PoP CF 1210 Wheat germ - - - - - - CP 1211 White bread - 0.5 PoP - 0.2-0.5 PoP CP 1212 Wholemeal bread - 2 PoP - - - 1 PoP AS 0654 Wheat straw & fodder - - - - - - Po : Post-harvest treatment of the commodity PoP: Post-harvest treatment of the primary food commodity 59 Food Science and Industry (Vol.43 No.2)
14. Codex MRL Code No. Clethodim Dimethipin Haloxyfop Permethrin Phorate Paraquat <Vegetable oils, > SO 0495 Rapeseed 0.5-2 0.05(*) 0.1 - OC 0495 Rapeseed oil, crude 0.5(*) - 5 - - - OR 0495 Rapeseed oil, edible 0.5(*) - 5 - - - VD 0541 Soybean, dry 10 - - 0.05(*) 0.05 - OC 0541 Soybean oil, crude 1-0.2 0.1 - - OR 0541 Soybean oil, edible 0.5(*) - 0.2 - - - SO 0691 Cottonseed 0.5 0.5 0.2 0.5-0.2 OC 0691 Cottonseed oil, crude 0.5(*) 0.1 0.5 - - - OR 0691 Cottonseed oil, edible 0.5(*) 0.02(*) - 0.1-0.05(*) SO 0697 Peanut - - - - 0.1 - OC 0697 Peanut oil, crude - - - - 0.05(*) - OR 0697 Peanut oil, edible - - - - 0.05(*) - SO 0702 Sunflower seed 0.5 0.5-1 - 2 OC 0702 Sunflowerseed oil, crude 0.1 0.1-1 - 0.05 OR 0702 Sunflowerseed oil, edible 0.05 0.02(*) - 1-0.05 (*) following MRL: at or above the limit of quantitation < 13~14>(41)., ( ),,,,.,,,,, ( ),,. (),,..,, /, (42). 0% 97% < 15>.,. 45%. 10%.. ( ) 43~100% 91% < 16>.. (postharvest pesticides). 60
15. (%) (%) * (%) (%) * 45~94 66 5/6 55~98 81 5/6 0 0 1/1 33 33 1/1 24~77 43 7/8 38~94 54 7/8 11~85 41 11/16 26~96 58 11/14 44~70 57 2/2 51 51 1/1 43~78 60 3/3 69~81 74 3/3 23~90 55 4/6 20~93 52 3/6 20~83 51 3/3 61~94 82 3/3 46 46 1/1 64 64 1/1 (+ ) 6~36 21 2/2 70 70 1/1 0~68 38 5/5 33~75 53 5/5 - - - 13 13 1/1 2~87 52 4/5 3~94 64 4/5 43~97 75 5/6 76~94 87 3/3 51~80 63 4/4 - - - 0~93 34 3/3 24~95 60 2/2 22~40 30 5/6 25~75 49 6/7 6~95 71 3/4 29~83 56 2/2 0~97 45 13~98 56 * / 16. (%) (%) * 95~98 97 4/4 100 100 1/1 43~100 92 7/7 73 73 1/1 90~100 98 4/4 64~100 94 6/7 71~100 82 3/3 43~100 91 * /. 5~97% 51% < 17>.,,... 76%,,, 60% 90% < 18>. 61 Food Science and Industry (Vol.43 No.2)
17. / (%) (%) * 10 10 1/1 15~87 41 7/7 5~97 62 11/13 16 16 1/1 71 71 1/1 72~89 81 2/2 39~96 69 5/5 60~62 61 2/2 5~97 51 * /,,. (whole grain),,. (processing study). FAO Manual (2)., LOQ (significant residues). 0.1 mg/kg. 0.1 mg/kg RfD ADI. 0.01 mg/kg 5 mg/kg.., 18. (%) (%) * <> 59~87 71 4/4 87~100 95 4/4 80~90 84 4/6 67 67 1/1 50~80 65 2/2 50~100 76 <> 39~100 65 4/4 15~86 59 4/5 42~81 50 3/5 20~99 66 10/6 15~100 60 + 90 * / 62
19. ( ) ( ) 90 20 100 60,, 120 20.....,. (,, ).... < 19>.,,,. < 7>(43)...,,,,,,.., ADI. (RAC, raw agricultural commodity) (field-treated commodity).. (spiked sample) 7. 63 Food Science and Industry (Vol.43 No.2)
. (aging of the residue)..,.,.,,,. (, ). 2..,.,, (package storage) (bulk storage)........ U.S. EPA Residue Chemistry Test Guidelines, OPPTS 860.1520 Processed food/feed, 1996, FAO Submission and Evaluation of Pesticide Residues Data for the Estimation of Maximum Residue Levels in Food and Food, 2002, EU Guidelines for the Generation of Data Concerning Residues as Provided in Annex Part A, Section 6 and Annex, Part A, Section 8 of Directive 91/414/EEC Concerning the Placing of Plant Protection Products on the Market, 1997....,,. 1995 1 1 (World Trade Organization, WTO) SPS (Agreement on application of sanitary and phytosanitary measures) 15. WTO/SPS. SPS 3,. Codex Alimentarius Commission 64
,, ( ),,. Codex (44). WTO/SPS 3 -... MRL. OECD. OECD 2014,,. OECD... 1. WHO. Guidelines for Predicting Dietary Intake of Pesticide Residues (revised). GEMS/Food in collaboration with Codex Committee on Pesticide Residues (WHO/FSF/FOS/97.7) WHO, Geneva (1997) 2. FAO. Manual on the Submission and Evaluation of Pesticide Residue Data for the Estimation of Maximum Residue Levels in Food and Feed. UN FAO, Rome. 192 pp. (2002) 3. WHO. Project to update the principles and methods for the assessment of chemicals in food. WHO, Geneva. Available from URL: http://wwww.who.int. Accessed Jun. 10 (2010) 4..., 6.,. pp. 93-106 (2008) 5.. 32(4): 65-66 (1999) 6. National Research Council. Pesticides in the Diets of Infants and Children. National Academy Press, Washington, D.C. USA (1993) 7. Lee M.-G. Estimation of cumulative dietary risk of pesticides sharing acetylcholinesterase inhibitory effects. Food Sci. Biotechnol. 12(1): 43-50 (2003) 8. Lee, M.-G. Relative potency factors derived from NOAELs for assessing cumulative risk of pesticides. Food Sci. Biotechnol. 11(6):690-693 (2002) 9. Lee H., Han, J., Yoon, E., Kim, H., Hwang, I.G., Choi, D.M., Lee, K.B., Won, K.P., Song, I.S., Park, S.E., Shin, D.C. Cumulative risk assessment of organophosphorus pesticides in the diet. J. Food Hyg. Safety 16(1): 21-26 (2001) 10.,. 4 1 (2007). http://knhanes.cdc.go.kr/. 2009 3 19 11. United States Department of Agriculture, Agricultural Research Service. Food Commodity Intake Database. Available From http://www.ars.usda.gov/. Accessed Jun. 15 (2010) 12. FAO/WHO. Principles and methods for the risk assessment of chemicals in food. Draft May. Available from http://www.who.int/. Accessed Jun. 15 (2010) 13. U.S. EPA. Guidance on cumulative risk assessment of pesticide chemicals that have a common mechanism of toxicity 2002a. U.S. Environmental Protection Agency, Washington, D.C. USA (2002) 14. The LifeLine Group Inc. LifeLine Version 4.4, Software for Modeling Aggregate and Cumulative Exposures to Pesticides and Chemical. The LifeLine Group Inc., Annandale, VA, USA (2007) 15. FIFRA Scientific Advisory Panel. Cumulative and aggregate risk evaluation system (CARES) Model Review. FIFRA Scientific Advisory Panel Meeting, April 30 - May 1. Available from www.epa.gov/. Accessed Jun. 15 (2010) 65 Food Science and Industry (Vol.43 No.2)
16. FIFRA Scientific Advisory Panel. A Model Comparison: Dietary (Food and Water) Exposure in DEEM/Calendex, CARES, and LifeLine. FIFRA Scientific Advisory Panel Meeting, Arlington, VA, April 28-29. U.S. Environmental Protection Agency, Washington, D.C., USA (2004) 17. CARES Version 2.0. Cumulative and Aggregate Risk Evaluation System, CARES Help document, Nov. 7 (2003) 18. U.S. EPA. Dietary Exposure Potential Model, A Model Using Extant Food Databases to Estimate Dietary Exposure to Chemical Residues. Latest Version 5.0 Released April. Available from http://www.epa.gov/. Accessed Jun. 15 (2010) 19...., (2007) 20...., (2009) 21...., (2000) 22...., (2001) 23..., (2002) 24...,, (2003) 25...., (2004) 26...., (2006) 27...., (2008) 28...,, (2008) 29. WHO. GEMS/Food Total Diet Studies. Report of the 2nd International Workshop on Total Diet Studies, 4-15 February, Brisbane, Australia. World Health Organization (2002) 30. WHO. Dietary Exposure Assessment of Chemicals in Food. Report of a Joint FAO/WHO Consultation Annapolis 2-6 May, Maryland, USA. World Health Organization (2005) 31. WHO. Report of the Regional Workshop on Total Diet Studies 5-7 December, Jakarta, Indonesia. World Health Organization (2007) 32. Jean A. T. Pennington. Total diet studies-experiences in the United States. J. Food Composition and Analysis 13: 539-544 (2000) 33. FDA. Total diet study. Food and Drug Administration. Available from: http://www.fda.gov/. Accessed Jun. 15 (2010) 34. Food Standards Agency. UK - 1997 Total diet study-fluorine, bromine and iodine (Number 05/00). Food Standards Agencey. Available from: http://www.food.gov.uk/. Accessed Jun. 15 (2010) 35. Health Canada. Canadian total diet study. Health Canada. Available from: http://www.hc-sc.gc.ca/. Accessed Jun. 15 (2010). 36. Food Standards Australia New Zealand. The Australian total diet study survey. Food Standards Australia New Zealand. Available from: http://www.foodstandards.gov.au/. Accessed Jun. 15 (2010) 37. Sue-Sun Wong. Conducting total diet study for pesticide exposure. 3rd International Workshop on Crop Protection Chemistry in Lain America: Environment, Safety and Regulation 9-12 Nov. (2009) 38. Chen Junshi, Junquan Gao. The Chinese total diet study in 1990. Part. Chemical contaminants. J. AOAC Int. 76(6): 1193-1205 (1993) 39.. 2005 ()., (2005) 40.. 2010. Available from: http://www.kfda.go.kr/. Accessed Jun. 15 (2010) 41. Joint FAO/WHO Food Standards Programme. Report of the 32nd Session of the Codex Committee on Pesticide Residues. Codex Alimentarious Commission, FAO/WHO, Rome, Italy (1998) 42... 131 (1996) 43. APVMA. Residue Guideline No. 7-Processing Studies. Australian Pesticides and Veterinary Medicines Authority. Available from: http://www.apvma.gov.au. Accessed Jun. 15 (2010) 44.. SPS TBT. 30(4) 56-63 (1997) 66