Dioxins in the food chain: An endless story?

Transcription

1 Scientific Committee of the Federal Agency for the Safety of the Food Chain Dioxins in the food chain: An endless story? L. Pussemier, V. Vromman and C. Saegerman Workshop on Risk assessment and food safety, Brussels, 20 October 2006

2 Contents Dioxins definitions and main properties PCDD/PCDF/dl-PCB Sources of dioxins and their entry in the food chain PCB and dl-pcb PCDD and PCDF Hazard characterization and exposure of humans through food intake Human and animals studies Determination of a PTWI Intake and trends

3 Contents (2) Example of a recent food incident: «HCl / Animal Fat / Gelatin» Contaminated foodstuffs, origin and patterns Assessment of animal products contamination Assessment of human exposure Via intake of animal products Via intake of gelatin Relative importance of the incident Conclusions & perspectives

4 Dioxins definitions and main properties

5 Dioxins and related chemicals Stuctures PCDDs (dioxins) PCDFs (furans) dl-pcbs (dioxin-like PCBs) Others (brominated compounds, ) Properties Lipophilicity & persistance bioaccumulation Coplanarity ligand to Ah receptor Relevant (toxic) congeners: PCDD (7), PCDF (10), dl- PCB (12) TEQ: Toxic equivalent concentration (sum of congeners; TEF)

6 Cl O Cl PCDD Polychlorinated dibenzodioxins Cl O Cl Cl Cl PCDF Cl Cl Polychlorinated dibenzofurans O Cl dl-pcb Cl Cl Dioxin-like polychlorinated biphenyls Cl

7 Sources and entry in the food chain

8 Sources of dioxins Sources of PCDD/F: Combustion (incinerators & domestic fires) By-products of chemical synthesis (Seveso) Alteration of PCBs (Belgian incident of 1999) Metal industry (smelting, refining, processing) Chlorine bleaching of paper pulp Photochemical processes (atmosphere) Reservoir sources (contamination of clay minerals) Others

9 Sources of dioxins Congener specific formation (e.g. Seveso) vs generic formation (e.g. combustion, alteration of PCB) Recent production (traffic, fires, industry ) vs historic production (chemical industry, metallurgy, waste incineration plants) + geological reservoirs (clays) Diffuse contamination (global environment) vs point contamination (environmental hot spots, fraudulent and/or accidental contamination of food chain)

10 Sources of dl-pcb Sources of dl-pcbs = sources of PCBs: Industrial uses : open (various uses) and confined (capacitors, transformators, etc) Phasing out Environmental reservoir

11 PCDD/F entry in the food chain Main route = through the environment: particulates on plant material (+ soil, sediments) intake by cattle and other animals (hens, fishes) contamination of animal products intake by humans

12 PCDD/F entry in the food chain Secondary routes = food chain contaminations due to lack of control of input materials & processes PCB leakage incidents (cfr PCB pathways) Contamination of additives and technological adjuvants clays citrus pulp, potato peels; HCl fat, gelatin,

13 PCB entry in the food chain Main routes: through the aquatic and terrestrial environment: Air/soil/sediments plant/animals (including fishes) humans Secondary routes: food chain contaminations due to a lack of control of input materials & processes: Japan (1968), rice oil contamination (Yusho) after leakage of heat transfert unit, USA (1979), fat contamination after leakage of transformer in slaughterhouse Belgium (1999): accidental contamination of fat (for feed preparation) due to contamination of recycled oil

14 Hazard characterization and human exposure

15 Hazard characterization TCDD Acute toxicity : oral LD50 from 1 to 5000 mg/kg (guinea pig hamster) Short-term (in animals): metabolic effects and changes in liver, thymus and haematology Genotoxicity : no evidence

16 Human studies (strong evidence) Chloracne: dose-response no clear Cancer: occupational exposure Liver: increase in liver enzymes Reproductive effects: change in sex ratio (Seveso) All other effects are inconsistent or still to be confirmed

17 Animal studies Selection of NOAEL or LOAEL Faqi et al.,1998 (Wistar rats): Decreased sperm production and other alterations in male offspring : LOAEL body burden = 28 ng TCDD/kg bw (maternal body burden) Other studies (decreased sperm count, immune suppression, anogenital distance, ) with comparable LOAEL

18 Extrapolation from rats to humans Estimation of the daily intake in humans that would give the same maternal body burden (BB) as in rats (Faqi et al., 1998): Maternal BB in rats Fetal BB in rats Fetal BB in rats = fetal BB in humans Fetal BB in humans Maternal BB in humans Maternal BB in humans Daily (monthly) intake

19 Uncertainty factors Inter-species extrapolation Inter-individual variability Usually 100 SPECIES DIFFERENCES HUMAN VARIABILITY KINETICS DYNAMICS KINETICS DYNAMICS

20 Extrapolation from rats to humans Uncertainty factors, UF (default): Inter-species variability: Toxicodynamic (2.5) x Toxicokinetic (4.0) Inter-individual variability: Toxicodynamic (3.2) x Toxicokinetic (3.2) UF (default) = 2.5 x 4 x 3.2 x 3.2 = 100 Chemical specific data can be used to replace a default uncertainty factor (UF) by an adjustment factor (AF)

21 Extrapolation from rats to humans Adjustment factors, AF (based on data): Inter-species variability: Toxicodynamic (1.0) x Toxicokinetic (1.0) Inter-individual variability: Toxicodynamic (1.0) x Toxicokinetic (3.2) AF = 1.0 x 1.0 x 1.0 x 3.2 = 3.2

22 Extrapolation from rats to humans Additional uncertainty factor (UF): Additional factor considered: database deficiencies Usually between 3 and 10 Set at 3 UF for TCDD = AF x 3.0 UF for TCDD = 9.6

23 Dietary intake for humans Tolerable intake (EU): SCF (2001): 14 pg/kg/week Tolerable intake (others): WHO: 1-4 pg/kg/day (average corresponds to 14 pg/kg/week JECFA (2002): 70 pg/kg/month to reflect the long half-life of TCDD

24 Dietary intake for humans: conclusions PWTI = 14 pg/kg/week Convergence of different evaluations (EU, WHO) Based on effects on the reproductive system of the male rat after in utero exposure Takes into consideration: The importance of long term exposure Relative exposure of fetus with regard to maternal exposure Potential human variability in kinetics (+ database deficiencies)

25 Intake and trends Mainly through diet (90%) Animal fat (meat, eggs, milk, fish, ) Regional differences in global exposure Finland: 60% from fish and 30% from meat, milk and eggs Germany: 10% from fish and 80% from meat, milk and eggs (EU-SCOOP, 2000)

26 Intake and trends Temporal trend in global exposure Human milk (WHO TEQ in pg/gfat): Nl: ~40 in 1988 ~18 in 2002 Ge: ~34 in 1988 ~12 in 2002 Hu: ~10 in 1988 ~6 in 2002 Dietary intake in Nl (WHO TEQ in pg/kg bw/day) ~9 in 1978 ~4 in 1984 ~2 in 1990 ~1.5 in 1994 ~1 in 1999 (Baars et al.,toxicol. Lett., 2004) (WHO co-ordinated studies)

27 Example of a recent food incident: «HCl / Animal Fat / Gelatin»

28 Origin of the contamination Non filtered HCl batch used for fat extraction and gelatin production (treatment of bones) contained 33 ng TEQ/kg Contamination of porc fat (from 50 pg TEQ/g fat up to 400 pg TEQ/g fat) used for animal feed production and for production of gelatin used for human consumption (up to 2.8 ng TEQ/kg)

29 Dioxin patterns (PB Gelatins incident) Non filtered HCl, porc fat and gelatin showed typical pattern dominated by 1,2,3,7,8 PeCDD and 2,3,7,8 TCDD

30 Dioxins pattern comparison Pig fat Gelatin HCl OCDD 2,3,4,6,7,8-HxCDF 1,2,3,7,8,9-HxCDF 1,2,3,4,6,7,8-HpCDF 1,2,3,4,7,8,9-HpCDF OCDF 2,3,7,8-TCDD 1,2,3,7,8-PeCDD 1,2,3,4,7,8-HxCDD 1,2,3,6,7,8-HxCDD 1,2,3,7,8,9-HxCDD 1,2,3,4,6,7,8-HpCDD 1,2,3,4,7,8-HxCDF 1,2,3,6,7,8-HxCDF 2,3,7,8-TCDF 1,2,3,7,8-PeCDF 2,3,4,7,8-PeCDF % of total TEQ

31 Dioxin patterns (other incidents) PCB contamination of fat (Belgian outbreak 1999) : PCDF! Eggs contamination of free range hens (Sci Com 2002/35): OCDD! Dioxin contamination of feed (potato peels with contaminated clay, The Netherlands, 2004) : OCDD (+ HpCDD)!

32 OCDD OCDD Pattern in pig fat (in relative TEQ) 1,2,3,6,7,8-HxCDF 2,3,4,6,7,8-HxCDF 1,2,3,7,8,9-HxCDF 1,2,3,4,6,7,8-HpCDF 1,2,3,4,7,8,9-HpCDF OCDF 2,3,7,8-TCDD 1,2,3,7,8-PeCDD 1,2,3,4,7,8-HxCDD 1,2,3,6,7,8-HxCDD 1,2,3,7,8,9-HxCDD 1,2,3,4,6,7,8-HpCDD 1,2,3,4,6,7,8-HpCDD Pattern in pig fat (in relative cc) 1,2,3,6,7,8-HxCDF 2,3,4,6,7,8-HxCDF 1,2,3,7,8,9-HxCDF 1,2,3,4,6,7,8-HpCDF 1,2,3,4,7,8,9-HpCDF OCDF 2,3,7,8-TCDD 1,2,3,7,8-PeCDD 1,2,3,4,7,8-HxCDD 1,2,3,6,7,8-HxCDD 1,2,3,7,8,9-HxCDD 1,2,3,4,7,8-HxCDF 2,3,4,7,8-PeCDF 1,2,3,4,7,8-HxCDF 2,3,4,7,8-PeCDF 2,3,7,8-TCDF 1,2,3,7,8-PeCDF ,3,7,8-TCDF 1,2,3,7,8-PeCDF

33 OCDD OCDD HxCDD HpCDD HpCDD HxCDD HxCDD HxCDD Patterns in Mahlton Clays (in relative TEQ) Mahlton Clay A01 Mahlton Clay FT Tocar HXCDF HxCDF HxCDF HpCDF HpCDF OCDF 2378-TCDD PeCDD HxCDD Patterns in Mahlton Clays (in relative cc) HX CDF HxCDF HxCDF HpCDF 789-HpCDF OCDF 2378-TCDD PeCDD HxCDD HxCDF HxCDF PeCDF PeCDF 2378-TCDF PeCDF 2378-TCDF PeCDF Mahlton Clay 01 Mahlton Clay FT Tocar 87

34 100,0 90,0 80,0 70,0 60,0 50,0 40,0 30,0 20,0 10,0 0,0 Patterns during the 1999 outbreak (in relative TEQ) Egg Chicken meat Feed Yusho rice oil PeCDF PeCDF HxCDF HXCDF HxCDF HxCDF HpCDF HpCDF OCDF 2378-TCDD PeCDD HxCDD HxCDD HxCDD HpCDD OCDD Patterns during the 1999 outbreak (in relative cc) PeCDF HxCDF HXCDF HxCDF HxCDF HpCDF HpCDF OCDF 2378-TCDD PeCDD HxCDD HxCDD HxCDD HpCDD OCDD 2378-TCDF 100,0 90,0 80,0 70,0 60,0 50,0 40,0 30,0 20,0 10,0 0,0 Egg Chicken meat Feed Yusho rice oil 2378-TCDF PeCDF

35 OCDD OCDD 1,2,3,4,6,7,8 HpCDD 1,2,3,4,6,7,8 HpCDD 1,2,3,7,8, 9 HxCDD 1,2,3,7,8, 9 HxCDD 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Patterns in eggs (in relative TEQ) 1,2,3,6,7,8 HxCDF 1,2,3,7,8,9 HxCDF 2,3,4,6,7,8 HxCDF 1,2,3,4,6,7,8 HpCDF 1,2,3,4,7,8,9 HpCDF OCDF 2,3,7,8 TCDD 1,2,3,7,8 PeCDD 1,2,3,4,7,8 HxCDD 1,2,3,6,7,8 HxCDD Patterns in eggs (in relative cc) 1,2,3,6,7,8 HxCDF 1,2,3,7,8,9 HxCDF 2,3,4,6,7,8 HxCDF 1,2,3,4,6,7,8 HpCDF 1,2,3,4,7,8,9 HpCDF OCDF 2,3,7,8 TCDD 1,2,3,7,8 PeCDD 1,2,3,4,7,8 HxCDD 1,2,3,6,7,8 HxCDD 1,2,3,4,7,8 HxCDF 1,2,3,4,7,8 HxCDF 2,3,4,7,8 PeCDF 2,3,4,7,8 PeCDF 2,3,7,8 TCDF 1,2,3,7,8 PeCDF 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2,3,7,8 TCDF 1,2,3,7,8 PeCDF

36 Dioxin transfer from feed to animal products COR (Carry Over Rate) = (flux in matrix)/(flux in source) N.B. Applicable when «flux in matrix» is mesurable (e.g. levels in daily production of milk or eggs) BCF (BioConcentration Factor) = (concentration in matrix)/(concentration in source) N.B. Need to rely on well documented studies carried out in experimental conditions close to the «real» conditions (animal species, feed, exposure time, etc)

37 BCF determination BCF derive from a study by Hoogenboom et al., 2004 Experimental conditions: Pigs (3 month old) and broilers (3 weeks old) Feed Fat content: 2% (pigs) et 5% (broilers) ad libitum Exposure time: 7 days; no clearance period

38 BCF determination Pig Poultry Total dioxin intake (ng TEQ) Duration of the intake (days) 7 7 Amount of feed per day (kg) 1,2 0,09 Total dioxin intake per day (ngteq/day) 54 3,71 Dioxin concentration in feed (ng TEQ/kg) 45 42,69 Fat content of feed (%) 2 5,00 Dioxin concentration in ingested fat (ng TEQ/kg fat) Concentration in animal fat ( 7d + 0d) (ng TEQ/kg fat) BCF 0,0116 0,119

39 Estimation of the dioxin ccns in animal products COMMODITY Concentration in feed fat (pg TEQ/g fat) Bioconcentration factor (BCF) Concentration in animal fat (pg TEQ/g fat) Pig 50 0,0116 0,580 Chicken 50 0,119 5,973 Pig 220 0,0116 2,552 Chicken 220 0,119 26,281 Pig 400 0,0116 4,640 Chicken 400 0,119 47,783

40 Risk assessment for consumers of porc and poultry Consumption data (porc and poultry fat): Results of survey carried out by the Institute of Public Health (2004) 3 concentration levels corresponding to 50, 220 and 400 pg TEQ/g fat in feed

41 Risk assessment for consumers of gelatin Consumption data: Results of survey carried out by the Institute of Public Health (2004) 1 concentration level (worst case): 2.8 pg TEQ/g product

42 Risk assessment: summary Foodstuff Consump tion (IPH) Weekly intake %TWI Intake after 3 month % Increase of BB Units g/person/ day pg TEQ/kg bw/week pg TEQ/kg bw/ 3 month Poultry fat 1,303 0,91 6,49 10,90 0,22 Porc fat 7,42 0,50 3,58 6,02 0,12 Gelatin 1,68 1,68 12,02 20,19 0,41 Poultry fat 1,303 4,00 28,54 47,94 0,97 Porc fat 7,42 2,21 15,77 26,50 0,54 Gelatin 1,68 1,68 12,02 20,19 0,41 Poultry fat 1,303 7,26 51,88 87,17 1,76 Porc fat 7,42 4,02 28,68 48,18 0,97 Gelatin 1,68 1,68 12,02 20,19 0,41

43 A posteriori validation Dioxin cc (predicted using BCF) Determined cc (mean) Determined cc (maximum) Cc in pig fat (pg TEQ/g fat) (n=55) 13.9 (n=55) Cc in poultry fat (pg TEQ/g fat) (n=13) 16 (n=13)

44 Relative importance of the PB Gelatins incident in 2005 Estimated duration of HCl contamination period = 37 d (28/09/2005 till 5/11/2005) Free fatty acid fat production (FFA): 600 kg/d Total amount of FFA fat produced: kg (= 0.02% of total annual production in Be) Total amount of dioxins produced during the incident: 22 mg TEQ Total amount of dioxins entering the food chain: 13 mg TEQ (Data kindly provided by D.G.Politique de contrôle (FASFC))

45 Impact of the 2005 incident: comparison with the 1999 incident Amount of dioxins in food chain in 2005 due to the 2005 incident: 13 mg TEQ (total) (DG Politique de contrôle) Amount of dioxins in the food chain in 1999 due to the Verkest incident: 1000 mg TEQ (PCDD/F) and 2000 mg TEQ (total) (Bernard & Fierens, 2002)

46 Impact of the 2005 incident: comparison with global exposure of the Belgian population Intake is about 2 pg TEQ (total)/kg bw day (CSH/HGR estimation, Report 7300/1, 2001) = 120 pg TEQ (total) / person / day = 1.2 mg TEQ/day for the entire Belgian population ( people) = 1.2 * 365 = 438 mg TEQ (total) / year Before 1980, intake was probably 5 to 10 times higher (Baars et al., Toxicol. Lett., 2004) = ca to mg TEQ (total) / year

47 Impact of the 2005 incident: summary Background (80 ) Background (2000) Incident (1999) Incident (2005) Imissions into the food chain?? 2 g TEQ g TEQ Intake by Belgian population 2-4 g TEQ/year 0.4 g TEQ/year??

48 How to further reduce exposure to dioxins? Avoid any new incident. Surveillance Programme: Focus on critical materials and foodstuffs Take appropriate risk management measures: ban on Baltic herring and salmon (BELSPO Project CP/56) Communicate with public: problem of wrong risk perception for homeproduced food (free range hens, for example)

49 Conclusions (1/4) Dioxins are associated to several health problems (multiple targets): Reproduction Cancer Immunosuppression, Toxic at very low concentrations for some animal species Many chemicals are involved (Ah ligands), xenobiotics or natural; complex mixtures; analytical problems. Lot of variability (inter and intra species) Long term effects (body burden rather than short term intake)

50 Conclusions (2/4) Several pathways for the entry in the food chain: environment, technological chemicals (HCl, floating clays), additives (ball clays), leakage from heat transfer units, capacitors, fraudulent recycling Intake above guidance value by a significant portion of the population

51 Conclusions (3/4) Significant decline in emissions and in intake during the last decades; halving of BB since 80. Food incidents considered separately have negligible health consequences in the short term, but there is a need to lower the body burden (significant parts of population have intake above PTWI)

52 Conclusions (4/4) New (unknown) sources (and chemicals) still appearing or detected (eggs from private owners, HCl, new Ah ligands) Need to continue monitoring (surveillance programme) with special focus on: Critical materials entering the food chain including technological adjuvants and additives All dioxin-like compounds (CALUX?) Special dietary habits (farmed salmon, wild eel, home-produced food, ) Need to continue efforts for better a communication with the consumers

53 Acknowledgements Thanks to all the members of the SCI COM working groups on dioxins: SCI COM 2002/35 & 2005/28 (free range hens) SCI COM 2004/25 & 2005/40 (contaminants in fish) SCI COM 2006/06 (Gelatin & Fat from Porc and poultry)