LEAD AND MERCURY Claudia Gundacker
LEAD Ubiquitous environmental pollutant Natural and anthropogenic sources (mining, smelting, soldering, batteries, munitions, water pipelines, paintings, fuel additive) Since 1970ies: regulation, control, restrictions > release into environment is decreasing
Lead uptake via diet, water, air, soil, dust Contaminated food: cereals (not rice) and cereal products potatoes leaf vegetables game meat tap water Dietary weekly intake Women (20 40 yrs): 3 9 µg/kg PTWI (WHO/JECFA): 25 µg/kg EFSA Panel on Contaminants in the Food Chain (CONTAM); Scientific Opinion on Lead in Food. EFSA Journal 2010; 8(4):1570. [147 pp.].
Lead toxicokinetics Inhalation Pb 50 80% Blood Bone Blood 95% (RBC) 5 10% (adults) 30 50% (children) Intestinal absorption 95% 5% (RBC) (Plasma) 5% (Plasma) Renal, fecal excretion Breast milk 95% (lead phosphate) Lead is stored mainly in bones (ionic mimicry: Pb 2+ > Ca 2+ )
Lead toxicokinetics in pregnancy Period of enhanced calcium demands (pregnancy, lactation, menopause, ) > lead is remobilised from bone Pregant women: lead exposure is sum of recent and past exposures Lead passes placenta Lead crosses blood brain barrier
Lead toxicity Blood, cardiovascular system, kidney, endocrine and gastrointestinal system, immune system, reproduction, brain Target organ of prenatal tlexposure > central nervous system > affects cognitive development and behaviour of children
Hu et al. (2006). Fetal Lead Exposure at Each Stage of Pregnancy as a Predictor of Infant Mental Development. Environmental Health Perspectives. Environ Health Perspect, 114 1730 1735 114, 1730 1735. Development, 85(8), 503 510. Jedrychowski et al. (2009). Gender specific differences in neurodevelopmental effects of prenatal exposure to very low lead levels: The prospective cohort study in three year olds. Early Human D l 85(8) 503 510 three most recent longitudinal studies that measured prenatal lead exposure (average blood lead ranging from 1 to 11.5 μg/dl), two found a negative association with subsequent IQ, and one found no effect. In contrast, all five recent longitudinal studies that measured postnatal exposure (average blood lead levels ranging from 6 to 44 μg/dl) found significant associations with cognitive development. Koller et al. 2004, Recent developments in Low Level Lead Exposure and Intellectual Impairment in Children. Environ Health Perspect. 112(9): 987 994.
Results Um MuKi Lead r=0.646, P<0.001
Site specific lead exposure 30 25 CordBl Pb MatBl Pb b (µg/kg) 20 15 Ery P 10 5 0 Bratislava Wien P<0.001
Age of building and residential area P<0.001 P=0.037 N = 10 89 46 52 N = 3 23 73 N = 21 16 60 Lead content in tap water in Vienna and Bratislava below limit value, usually <LOD 13 percent of 288 Viennese households: tap water concentrations >25 μg/l (Haider et al. 2002)
Smoking habits 40 35 30 25 20 15 10 5 0 Bratislava NAB Pb MatBl Pb 40 4% current smokers 35 9% current smokers 30 0 J N=51,51 1 5 J 6 10 J N=17,17 N=14,14 Rauchen (Jahre) 11 23 J N=7,7 Ery Pb (µg/kg) P<0.05 25 20 15 10 5 0 0 J N=45,44 1 5 J N=17,17 Wien 6 10 J N=22,21 Rauchen (Jahre) NAB Pb MatBl Pb 11 23 J N=16,16
Maternal age r=0.091, P>0.05 r=0.276, P=0.006
Summary: Factors of lead exposure tap water (indicated by age of building and residential area) smoking habits maternal age
Risk assessment Lead the provisional tolerable weekly intake (PTWI) of 25 μg/kg b.w. set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and endorsed by the Scientific Committee of Food is no longer appropriate there was no evidence for a threshold for a number of critical endpoints including developmental neurotoxicity EFSA Panel on Contaminants in the Food Chain (CONTAM); Scientific Opinion on Lead in Food. EFSA Journal 2010; 8(4):1570. [147 pp.]. Die kiti kritische Bleiwirkung, i insbesondere auf den sich ihentwickelnden Organismus, betrifft das Nervensystem. Es ist aber nicht möglich, Blutbleikonzentrationen beziehungsweise Schwellen anzugeben, ab denen die kritischen Wirkungen auftreten. Aufgrund der fehlenden Wirkungsschwelle, der Neubewertung des krebserzeugenden Potenzials und neuerer Forschungsergebnisse bewertet die Kommission Human Biomonitoring die Wirkungen von Blei im Blut erneut und setzt als Schlussfolgerung die HBM Werte aus. 2. Addendum zur Stoffmonographie Blei Referenz und Human Biomonitoring Werte der Kommission Human Biomonitoring Bundesgesundheitsbl Gesundheitsforsch h Gesundheitsschutz h h 2009 52:983 986
Risk assessment Lead CDC guideline 100 µg/l ( 0) BMDL 01 EFSA: 12 µg/l ( 29)
Median lead values are low Exposures are decreasing (Vienna: change of leaded water pipes completed in 2007) 80 70 60 CordBl Pb (µg/l) MatBl Pb (µg/l) 50 40 30 20 10 0 Deutschland 1988 (N=17 33) Österreich 1993 (N=51) Polen 1995 (N=15 24) Österreich 2007 (N=31 52) Polen 2006, 2009 (N=240 457) Österreich 2011 (N=100)
Prevention Children: calcium and iron in sufficient amounts (less lead is absorbed and accumulated in bone) Pregnancy: calciumsupplementation during pregnancy reduces lead levels in maternal blood and breast milk > sufficient calciumsupply (particularly when women are Ca deficient) Ettinger et al. 2009. Effect of Calcium Supplementation on Blood Lead Levels in Pregnancy: A Randomized Placebo Controlled Trial. Environ Health Perspect. 117(1): 26 31. Ettinger et al. 2006. Influence of Maternal Bone Lead Burden and Calcium Intake on Levels of Lead in Breast Milk over the Course of Lactation. American Journal of Epidemiology, 163(1), 48 56.
Mercury Ubiquitous environmental pollutant Natural and anthropogenic sources (mining, small scale scale gold mining, waste incineration; use of batteries, measuring instruments, lamps, dental amalgam, pesticides, drugs; industry: chlor alkali electrolysis, catalysts) Since decades: regulation, control, restictions > mercury emissions decreasing in northern hemisphere, not on a global scale
Uptake of mercury CH 3 Hg + Methyl Hg: Fish and seafood Hg 0 Hg 0 : Dental amalgam fillings (50% Hg), occupational exposure CH 3 CH 2 Hg + Ethyl Hg: vaccines, drugs JECFA PTWI: 1.6 µg/kg b.w. (MeHg) µg/ g ( g) 5.0 µg/kg b.w. (T Hg)
Mercury toxicokinetics Inhalation 80% (Hg 0 ) Blood CNS MeHg Liver <90% Blood RBC 10% Plasma <10% (I Hg) 95% I Hg (RBC) 95% Kidney (lead 95% (MeHg) Pb 5% 50% (Plasma) RBC phosphate) 50% Plasma Mammary gland Intestinal absorption Excretion via bile Renal excretion Breast milk Berglund et al. (2005). Inter individual variations of human mercury exposure biomarkers: a cross sectional assessment. Environ Health lh4: 20.
Toxicity of mercury Concerns kidney, brain, cardiovascular system, endocrine system, immune system, reproduction Target organ of prenatal MeHg exposure: central nervous system > > impairedneurodevelopment ofchildren (contradicting results in cohort studies) Increasing evidence for low dose effects of MeHg (in vitro) Gundacker, et al. (2011). Proliferation potential of human amniotic fluid stem cells differently responds to mercury and lead exposure. Amino Acids 36(3): 1 13.
Results Um MuKi: Site specific differences 3,5 3,0 CordBl Hg MatBl Hg Ery H Hg (µg/kg) 2,5 2,0 15 1,5 1,0 05 0,5 0,0 Bratislava P=0.019 (CordBl) Wien
Fish consumption CordBl Hg (µg/kg) MatBl Hg (µg/kg) r,551 **,316 Total fish P,000,050 consumption (grams/week) N 38 39 Total fish consumption (grams/week) Marine fish (grams/week) Freshwater fish (grams/week) Marine fish (grams/week) Freshwater fish (grams/week) Hg uptake from fish (µg/week) r,444 **,186,939 ** P,005,256,000 N 38 39 200 r,421 **,371 *,428 **,185 ** P,009,020,000,009 N 38 39 200 200 * * ** ** ** r,368,366,879,818,414 P,023,022,000,000,000 N 38 39 200 200 200
r in Gramm icher Verzeh Wöchentl 500 450 400 350 300 250 200 150 100 50 0 Vienna Bratislava P<0.0505 Vienna: seafood, salmon, fish fingers, plaice/sole, trout, pikeperch Bra slava: sardines/anchovies, canned tuna, tuna steak
Summary: Factors of mercury exposure fish and seafood consumption
Risk assessment Mercury HBM I Wert 5µg/L ( 3)
Mdi Median mercury levels l are low Exposure (in Vienna) remains stable at a low level 7 6 CordBl Hg (µg/l) MatBl Hg (µg/l) 5 4 3 2 1 0 Deutschland 1988 (N=17 33) Spanien 1992 (N=17 27) Österreich 1993 (N=51) Schweden 2002 (N=98 119) Österreich 2007 (N=30 52) Österreich 2011 (N=100)
Hg (µg/kg g) 1200 1000 800 600 400 Prevention Fish consumption: recommended to eat less contaminated species (no tuna, no butterfish, ) but not to refrain from eating fish and seafood (excellent source of n3 PUFAs, vitamin D, selenium, iodine, ) 200 0
Need for action Adequate counselling of pregnant women Reduction of exposures to a minimum