Results of the BfRshort forGerman Federal Institute for Risk Assessment-MEAL study on lead in food recovered food groups substantially contributing to total intake in the German population

The subject of the present opinion is an exposure assessment based on the results of the BfRshort forGerman Federal Institute for Risk Assessment-MEAL study on lead, including a comparison with appropriate reference points from the dose-effect relationship for the health effects associated with chronic lead exposure (Benchmark Dose Lower Confidence Limit, BMDLshort forBenchmark Dose Lower Confidence Limit).

Lead is a metal that occurs ubiquitously. It can enter the environment naturally, but since ancient times release into the environment – and thus the food chain – has occurred primarily through anthropogenic activities. The present opinion deals exclusively with external exposure due to the occurrence of lead in food. Critical consequences of chronic lead exposure include health effects on the central nervous system, the cardiovascular system and the kidneys. As the available study data do not indicate a blood lead concentration at which no health effects are to be expected, lead intake should be minimised as far as possible.

Dietary lead exposure was calculated for children, adolescents and adults in Germany. The most recent representative consumption studies, the "Children's Nutrition Study to Record Food Consumption" (KiESEL study), the nutrition study as a KiGGS module (EsKiMo II) and the National Nutrition Survey II (LODshort forLimit of detection II), were used as the basis for consumption. The occurrence data for lead is based on the National Total Diet Study (BfRshort forGerman Federal Institute for Risk Assessment-MEAL study). The BfRshort forGerman Federal Institute for Risk Assessment-MEAL study is characterised by its coverage of > 90 % of consumption and its consideration of preparation-related changes in levels. 

According to the exposure assessment, "grain and grain products" and "water and water-based beverages" make the highest contribution to average lead intake in all age groups, each accounting for 15 % to 20 %. The main group, "composite dishes", also accounts for a high proportion of average exposure, at 8 % to 11 %. In adults, the group "coffee, cocoa, tea" also contributes substantially to average exposure, at around 16 %. Coffee in particular is a major contributor here.

For lead, the margin of exposure (MOEshort forMargin of Exposure) was calculated based on exposure estimates for different age groups through the consumption of food and using the EFSAshort forEuropean Food Safety Authority reference points for renal toxicity in adults (BMDL10 0.63 µgshort formicrogram/kgshort forkilogram bw/day) or for developmental neurotoxic effects in children (BMDL01 0.5 µgshort formicrogram/kgshort forkilogram bw/day). The MOEshort forMargin of Exposure approach serves to prioritise the urgency of risk management measures. The benchmark dose lower confidence limit (BMDLshort forBenchmark Dose Lower Confidence Limit) values for external exposure were calculated by EFSAshort forEuropean Food Safety Authority (EFSAshort forEuropean Food Safety Authority, 2010) from BMDLshort forBenchmark Dose Lower Confidence Limit values for internal exposure using kinetic models.

According to estimates of external exposure for children, the intake of lead through food consumption is of the same order of magnitude as the BMDL01 of 0.5 µgshort formicrogram/kgshort forkilogram bw/day for developmental neurotoxic effects of lead. For example, the intake for children < 1 year is 0.27 µgshort formicrogram/kgshort forkilogram bw/day (P50, upper bound) or 0.35 µgshort formicrogram/kgshort forkilogram bw/day (P95, upper bound). The lowest MOEshort forMargin of Exposure values are thus calculated for children < 1 year of age at 1.8 (P50, UB¹  ) and 1.4 (P95, UB) and for children aged 1-2 years at 2.3 (P50, UB) and 1.4 (P95, UB). Based on internal exposure data by the German Environmental Survey for Children and Adolescents GerES V (2014-2017) the internal exposure in highly exposed children and adolescents (P95) of all age groups is above the BMDL01 of 12 µgshort formicrogram/L for developmental neurotoxic effects. Even with blood lead levels below the BMDL01, effects on cognitive development parameters in children exposed to lead cannot be ruled out, although EFSAshort forEuropean Food Safety Authority considers the health risk at MOEshort forMargin of Exposure values > 1 as likely to be low.

Exposure is far lower for adolescents and adults than for children (up to four to five times). This results in values between 0.08 and 0.09 µgshort formicrogram/kgshort forkilogram bw/day (P50, upper bound) and 0.14-0.016 µgshort formicrogram/kgshort forkilogram bw/day (P95, upper bound). The MOEshort forMargin of Exposure values resulting from the comparison of exposure and the reference point for renal toxicity (BMDL10 0.63 µgshort formicrogram/kgshort forkilogram bw/day) are between 6.9-7.6 (P50, UB) and 3.8-4.4 (P95, UB) for all age groups between 14 and > 65 years. With regard to the increase in systolic blood pressure and renal toxicity, a level of exposure without effects could not be identified in epidemiological studies. In this respect, exposure cannot be considered harmless, as also pointed out by EFSAshort forEuropean Food Safety Authority, which nevertheless assesses the risk as probably very low at MOEshort forMargin of Exposure values > 1.

The results of the present internal and external exposure assessments show that, despite the substantial decline in internal lead exposure, there is still a need for action to further reduce exposure to the achievable minimum, especially for younger age groups.

¹ Upper Bound

3.1.1 Hazard identification

Lead is a soft and malleable metal (element symbol Pbshort forlead) with a low melting point (327.5 °Cshort fordegrees Celsius) and a high density (11.34 g/cm³short forcubic centimetre), which has a high level of occurrence in the Earth's crust compared to other heavy elements. Since ancient times, it has been released primarily through anthropogenic activities such as mining, smelting and the manufacture of utensils like pots, ointments and paints. More recently, it has been primarily released through the combustion of fossil fuels and the manufacture and use of products which contain lead, such as batteries. There are also natural sources of release, specifically rock erosion and volcanism. Lead in soil comes mainly from atmospheric deposition of, for example, combustion residues. On agricultural land, additional inputs occur mainly through the application of sewage sludge and other organic fertilisers (Nicholson et al.short foret alii (lat. "and others"), 2003). Lead is used in many different areas, such as in the manufacture of batteries and bullet cores, for metal products such as fishing weights, solder and pipes, and for equipment used to shield against X-rays. Due to the health risks, the use of lead in many products has been increasingly restricted worldwide. Leaded petrol has been gradually banned in Germany since the late 1980s, followed by a complete ban throughout the European Union in 2000 (Directive 98/70/EC). Since 2021, the fuel is no longer sold worldwide (UNEP, 2021). The ban on leaded petrol and leaded paint has eliminated the main sources of lead entering the environment (ATSDR, 2020; EFSAshort forEuropean Food Safety Authority, 2010).

Lead does not degrade in the environment and can be found in various chemical forms in all environmental spheres (ATSDR, 2020). The predominant form of lead in the environment is inorganic lead in the oxidation state +2 (e.g. lead phosphate and lead carbonate), with lead usually occurring in compounds with two or more other elements. In industrially synthesised organic lead compounds such as alkyl lead compounds (e.g. tetramethyl lead and tetraethyl lead), lead is almost always present in the oxidation state +4. Both substances are highly volatile, fat-soluble liquids to which humans are mainly exposed in occupational settings (EFSAshort forEuropean Food Safety Authority, 2010). 

The general population's lead exposure occurs through food and water, as well as through the air and, especially in children, through household dust and soil (EFSAshort forEuropean Food Safety Authority, 2010). Outdoor air particles can be another important source. This applies to areas that are exposed to heavy motor vehicle traffic or are located on or near industrial sites. For individuals, ceramic and lead glass containers can be significant sources, as lead from the glazes can migrate into food (the BfRshort forGerman Federal Institute for Risk Assessment, 2020; Heinemeyer & Bösing, 2020). Lead is also a component of tobacco and tobacco smoke.

However, this opinion deals exclusively with external lead exposure due to the occurrence of lead in food. External lead exposure from other sources is not considered in this opinion. 

As lead is ubiquitous in the air, soil and water, it enters the human food chain via plants, fungi and food of animal origin. The occurrence of lead in plants is mainly the result of atmospheric deposition. This means that lead is carried to the surface of fruits and leaves via dust particles and aerosols and is partially absorbed and distributed within the plant. Accordingly, lead concentrations in leaves correlate with atmospheric concentrations (EFSAshort forEuropean Food Safety Authority, 2010). The intake of lead via the roots is rather low, as only a small proportion of the lead in the soil is available to plants. In most plant species, the vast majority of the lead absorbed through the roots remains there, but for some species, translocation of lead from the root system to the above-ground parts of the plant has been demonstrated (ATSDR, 2020). Fungi are more capable of absorbing and accumulating lead from the soil, so that lead concentrations in fungi can exceed those in green crops, fruit and vegetables (Damodaran et al.short foret alii (lat. "and others"), 2013; Orywal et al.short foret alii (lat. "and others"), 2021). Comparatively high lead levels are also frequently detected in marine algae. Various marine algae show a high capacity for passive intake of metals, which can lead to lead intake of up to 270 mgshort formilligram lead/g biomass (Holan & Volesky, 1994). Among edible macroalgae, brown algae have the highest metal binding capacity due to physiological characteristics (Besada et al.short foret alii (lat. "and others"), 2009).

Lead can also enter animal food products via lead-containing plant-based feed, but also via the intake of soil particles, especially by grazing animals (Adamse et al.short foret alii (lat. "and others"), 2017; Laurent et al.short foret alii (lat. "and others"), 2012). Plants and animals can therefore accumulate lead, but there is no enrichment in aquatic or terrestrial food chains. This can be explained in part by the fact that lead is primarily stored in the bones of vertebrates, which limits the probability of it being transferred to other species in the food chain (EFSAshort forEuropean Food Safety Authority, 2010). Lead in drinking water is usually the result of release from lead pipes. Significant levels of lead can also enter the food chain during the production and storage of food and beverages through the use of equipment or containers which contain lead (the BfRshort forGerman Federal Institute for Risk Assessment, 2020; WHO, 2021). Game killed with lead ammunition is also a potential source of exposure for people who regularly consume this meat (the BfRshort forGerman Federal Institute for Risk Assessment, 2010; WHO, 2021). Depending on how the game meat is prepared in the kitchen, e.g. by marinating, the availability of lead from ammunition can be substantially influenced (Schulz et al.short foret alii (lat. "and others"), 2021).

3.1.2 Hazard characterisation

Detailed information on the hazard potential of lead can be found in opinions issued by international committees (e.g. EFSAshort forEuropean Food Safety Authority 2010, EPA 2013, WHO/FAO 2011, ATSDR 2020). Lead has no obvious physiological function in the human body (WHO, 2021).

3.1.2.1 Toxicokinetics

The main routes of lead exposure are oral uptake and inhalation (WHO, 2021). This opinion considers lead exposure through food.

The absorption of lead from the gastrointestinal tract after oral intake is influenced by both physiological factors (e.g. age, nutritional status, pregnancy) and physicochemical properties (e.g. lead species, solubility, size). Gastrointestinal absorption of ingested lead is higher in children than in adults. In adults, the absorption rate of lead is generally 3-10 %, while in infants and young children it can be as high as 50 % (ATSDR, 2020; EFSAshort forEuropean Food Safety Authority, 2010). 

After absorption, lead is transported via the bloodstream, predominantly bound to red blood cells. The highest concentrations of lead in adults are found in the liver, kidneys and bones. With chronic lead exposure, bones contain > 90 % of the body burden in adults and > 70 % in children. Lead forms stable complexes with phosphate and can replace calcium in hydroxyapatite, a phosphate that forms the main crystalline matrix of bones. Lead is therefore deposited in the bones during growth and remodelling. This means that lead in the bones represents a pool from which small amounts are mobilised over the course of a lifetime and return to the bloodstream. This occurs particularly during phases of physiological or pathological bone demineralisation, such as during pregnancy, breastfeeding or due to osteoporosis in older age. Lead can be transferred from the mother to the foetus and via breast milk to the infant (ATSDR, 2020; EFSAshort forEuropean Food Safety Authority, 2010).

The metabolism of inorganic lead consists of the formation of complexes with a variety of protein and non-protein ligands. Organic lead compounds are actively metabolised in the liver by Pshort forphosphorus-450 enzymes (oxidative dealkylation) (ATSDR, 2020).

Regardless of the route of exposure, lead is mainly excreted through urine and faeces, and to a lesser extent through sweat, saliva, hair, nails, breast milk and seminal fluid. The elimination of lead is multiphase, reflecting the different residence times in different parts of the body. The apparent elimination half-life (t1/2) in blood varies with age and exposure history, ranging from one week to two years. Lead is eliminated from bone with an apparent elimination half-life of one to two decades (ATSDR, 2020).

3.1.2.2 Biomarkers

The biomarkers for exposure used in practice today are measurements of total lead levels in body fluids or tissues such as blood, bone or urine. 

The most commonly used biomarker is the (whole) blood lead level, which is considered the most reliable biomarker for general clinical use and public health surveillance (ATSDR, 2020). This is due to the fact that there is extensive evidence linking blood lead concentrations to clinical effects, and also validated analytical methods as well as reliable blood quality control and reference materials are available (WHO, 2021). Blood lead levels reflect a combination of short-term and long-term exposure, as lead absorbed through the intestine and lead from soft tissue (t1/2 20 to 40 days), lead from the bones also passes into the blood (t1/2) up to 30 years) (EFSAshort forEuropean Food Safety Authority, 2010).

Lead concentrations in plasma and serum are similar, but are very low and close to the limit of quantification (LOQshort forLimit of quantification) of most analytical methods (ATSDR, 2020; EFSAshort forEuropean Food Safety Authority, 2010).

Lead in urine primarily reflects the amount of lead recently ingested. There is a correlation between lead concentrations in urine and blood, but the variations in urine are too large to allow individual blood lead concentrations to be predicted based on lead concentrations in urine (EFSAshort forEuropean Food Safety Authority, 2010). For this reason, and because of the considerable risk of external contamination during sampling, measuring lead in urine is not recommended for routine assessment of lead exposure (EFSAshort forEuropean Food Safety Authority, 2010; Lauwerys & Hoet, 2001).

Unlike lead in blood and urine, lead concentration in bones reflects long-term intake and total body burden, as more than 90 % of the body's lead burden is found in the skeleton. Lead concentration in bone can be determined using non-invasive methods based on X-ray fluorescence. The determination is possible for the tibia, calcaneus and patella. Lead is also incorporated into teeth during tooth formation. Accordingly, lead concentration in bones and teeth is a good measure for epidemiological studies requiring retrospective assessment of exposure (EFSAshort forEuropean Food Safety Authority, 2010).

Hair has been used occasionally for biomonitoring of lead exposure. However, due to the possibility of external contamination, it is not a reliable indicator of lead intake into the body (EFSAshort forEuropean Food Safety Authority, 2010; WHO, 2007).

3.1.2.3 Toxicology

There is a wealth of data on concentration-response relationships in humans for lead. This data comes from studies of occupationally exposed groups, accidents and the general population. Data are available on mutagenicity, carcinogenicity, and neurological, cardiovascular, renal, endocrine, gastrointestinal, immunological and haematological effects, as well as effects on the musculoskeletal system, reproduction and development in humans. Most of these endpoints have also been investigated in animal experiments.

The following is a summary of information on the neurological, renal and cardiovascular effects, reproductive and developmental toxicity, genotoxicity and carcinogenicity of lead.

Acute toxicity

Although the high doses required make it rare, symptoms of acute lead poisoning, especially in cases of occupational exposure or other high lead intake, include abdominal pain (colic), constipation, nausea, vomiting and anorexia. In children, high acute exposure may also lead to toxic encephalopathy.

In general, oral intake of lead as a contaminant from food is not expected to reach levels that lead to acute toxicity. Due to the long elimination half-life of lead from the body, the assessment of health risks due to chronic exposure is therefore the main focus when assessing the health risks of lead in food (EFSAshort forEuropean Food Safety Authority, 2010).

Chronic toxicity

Potential toxicity following chronic lead exposure affects many organ systems and is sometimes observed even at blood lead levels below 50 µgshort formicrogram/L (ATSDR, 2020).

Neurological effects

The developing nervous system has been identified as the most sensitive target organ for the toxic effects of lead in children. The potential neurotoxic effects of lead have been investigated in many studies, meaning that the evidence base is quite solid. There is consistent evidence of inverse relationships between effects on cognitive and neuromotor/neurosensory development parameters and blood lead concentrations in children and adults. In children, these correlations have been observed at blood lead concentrations of 50 μg/L and above, although there is also evidence of neurological effects below 50 μg/L. In adults, neurological impairments have been observed in connection with blood lead levels of 100 μg/L and above, although there is also evidence of effects at blood lead levels of ≤ 50 μg/L.

Overall, based on current knowledge, there is no evidence of lead exposure without adverse effects on the developing nervous system.

Renal effects

The effects of lead on the kidneys have been documented in various studies. The available data show evidence of kidney damage and impaired renal function in connection with blood lead levels in the range of 50–100 μg/L. Similar to the neurological effects, several studies indicate renal effects that have been observed even at blood lead levels below 50 μg/L. Impairments of renal function include proteinuria, impaired transport of organic anions and glucose, and reduced glomerular filtration rate (GFR). At higher blood lead levels (> 300 µgshort formicrogram/L), lead-induced nephrotoxicity is characterized by proximal tubular nephropathy, glomerular sclerosis, interstitial fibrosis and tubular necrosis. Lead-induced impairment of renal function can lead to increased body burden due to reduced lead excretion (ATSDR, 2020).

Cardiovascular effects

Epidemiological studies in adults suggest the possibility of cardiovascular effects at blood lead levels in the range of 50–500 μg/L. Some studies suggest that the occurrence of cardiovascular effects may also occur at blood lead levels below 50 µgshort formicrogram/L. The most frequently studied effects are those on blood pressure, with studies showing an increase in systolic and diastolic blood pressure. Other cardiovascular effects of lead include an increased risk of heart disease, arteriosclerosis, altered cardiac conduction, and increased mortality due to cardiovascular disease (ATSDR, 2020).

Effects on reproduction and development (other than neurological development)

Lead also has effects on the reproductive system and is classified as a category 1A reprotoxic substance (“May damage fertility. May damage the unborn child.” – Repr. 1A) and as "Lact." ("May cause harm to breastfed children.") in accordance with the Regulation on Classification, Labelling and Packaging (CLP Regulation) of chemicals in the EU (Regulation (EC) No 1272/2008)."). The observed effects impact both the male and female reproductive systems. For example, human observational studies indicate that lead can, for example, cause changes in serum levels of reproductive hormones or damage sperm.

Genotoxicity

Numerous in vivo and in vitro studies have been conducted to investigate the genotoxicity of lead. The data on genotoxicity indicate that lead is not directly genotoxic. Numerous studies on workers report a positive association between blood lead concentration and the occurrence of clastogenic effects such as an increased number of cells with micronuclei, an increased number of mutated T-cell receptors or a higher rate of DNA damage observed in the comet assay. Whether lead in the blood is actually the cause of the observed effects could not be conclusively proven. A weak indirect genotoxic effect is suspected due to the formation of reactive oxygen species and a reduction in DNA repair activity (EFSAshort forEuropean Food Safety Authority, 2010).

Carcinogenicity

In rodents, high lead exposure compounds has been associated with the development of tumours in a variety of organs – particularly the kidneys, lungs, prostate and adrenal glands. It has also been found to promote the formation of kidney tumours (EFSAshort forEuropean Food Safety Authority, 2010). This is consistent with the assessment by other committees, which classify lead and lead compounds as potentially carcinogenic to humans at high concentrations (NTP, 2021).

3.1.2.4 Concentration-response relationships and reference points for risk characterisation

Modelling of the concentration-response relationships of lead for the health risk assessment of chronic effects in humans is based on epidemiological studies (ATSDR, 2020; EFSAshort forEuropean Food Safety Authority, 2010; EPA, 2013; FAO/WHO, 2011). Various committees have identified developmental neurotoxicity in children up to at least seven years of age, as well as cardiovascular effects and nephrotoxicity in adults, as critical effects of (inorganic) lead that should be used for risk characterisation (EFSAshort forEuropean Food Safety Authority, 2010).

The most sensitive and relevant endpoint for children is intellectual deficits, which can be measured as a reduction in IQ (full scale IQ). As a reference point for risk characterisation, EFSAshort forEuropean Food Safety Authority (2010) determined a BMDL01 of 12 μg/L lead in blood (lower limit of the 95 % confidence interval of the benchmark dose (BMD01) , which is associated with a calculated decrease in IQ of 1 %, corresponding to a decrease of one point on the IQ scale). The BMDLshort forBenchmark Dose Lower Confidence Limit represents the dose associated with the lower limit of the 95 % confidence interval belonging to the so-called "benchmark dose" (BMDshort forBenchmark Dose)², in this case the BMD01. The data basis for this modelling was an evaluation of the relationships between blood lead levels and full-scale IQ scores in 1,333 children aged 5 to 7 or 10 years who had participated in seven international population-based longitudinal cohort studies (Lanphear et al.short foret alii (lat. "and others"), 2005). The relationship between dietary lead intake and blood lead levels in children up to the age of seven was estimated using the Integrated Exposure Uptake Biokinetic (IEUBK) model³ . Using the IEUBK model, a BMDL01value of 0.50 μg/kgshort forkilogram body weight (BW) per day was calculated for dietary lead intake (Table 1) (EFSAshort forEuropean Food Safety Authority, 2010).

The sensitivity of the foetus to the effects of lead on neurological development is unknown. EFSAshort forEuropean Food Safety Authority assumes that the developing foetus is at least as sensitive to this lead exposure as a young child (EFSAshort forEuropean Food Safety Authority 2010). Since the ratio between foetal and maternal blood lead concentrations in the umbilical cord is approximately 0.9, EFSAshort forEuropean Food Safety Authority calculates a maternal blood lead level of 13 μg/L, which corresponds to the BMDL01 for effects on neurodevelopment (12 μg/L). This corresponds to a dietary exposure of 0.54 μg/kgshort forkilogram bw/day.

For the EFSAshort forEuropean Food Safety Authority (2010) concentration-effect analysis with regard to cardiovascular effects in adults, blood pressure was found to be the most sensitive endpoint. A 1 % increase in systolic blood pressure (SBP) per year or on average in the general population was considered critical for public health, as this would lead to increased risks of cardiovascular mortality due to coronary heart disease (CHD) at the population level. Based on SBP in four epidemiological studies (longitudinal and cross-sectional studies), a mean BMDL01 value of 36 μg/L lead in blood was calculated (EFSAshort forEuropean Food Safety Authority, 2010; Glenn et al.short foret alii (lat. "and others"), 2003; Glenn et al.short foret alii (lat. "and others"), 2006; Nash et al.short foret alii (lat. "and others"), 2003; Vupputuri et al.short foret alii (lat. "and others"), 2003). The relationship between dietary lead intake and blood lead levels in adults was estimated using the model developed by Carlisle and Wade (1992) (Carlisle & Wade, 1992). Using this model, a BMDLshort forBenchmark Dose Lower Confidence Limit value for dietary lead intake in adults of 1.50 μg/kgshort forkilogram bw/day was calculated for lead-related effects on the cardiovascular system (Table 1) (EFSAshort forEuropean Food Safety Authority, 2010).

For nephrotoxicity, the prevalence of chronic kidney disease (CKD) in adults was analysed based on the NHANES study (1999-2006, cross-sectional data) (EFSAshort forEuropean Food Safety Authority, 2010; Navas-Acien et al.short foret alii (lat. "and others"), 2009). The BMDL10 value of 15 µgshort formicrogram/L lead in blood calculated by EFSAshort forEuropean Food Safety Authority is based on a 10 % change, defined as a reduction in GFR to values below 60 mL/1.73 m² body surface area per minute. For dietary lead intake, using the above-mentioned model (Carlisle & Wade, 1992), a BMDL10 value of 0.63 μg/kgshort forkilogram bw per day is calculated for adults as a reference point for the risk characterisation of lead-related effects on the kidneys (Table 1) (EFSAshort forEuropean Food Safety Authority, 2010).
 
² Benchmark dose (BMDshort forBenchmark Dose): dose determined using mathematical dose-response modelling, which is           associated with a specific effect strength in the studies underlying the modelling (in the case of BMDshort forBenchmark Dose 1, for example, an increase in the effect of 1%).
³Available at: External Link:https://www.epa.gov/superfund/lead-superfund-sites-software-and-users-manuals
 

International committees point out that for various critical endpoints, including developmental neurotoxicity, blood lead concentrations at which no health effects are to be expected could not be identified in epidemiological studies (ATSDR, 2020; EFSAshort forEuropean Food Safety Authority, 2010; FAO/WHO, 2011). It is therefore not possible to derive a health-based guidance value (HBGVshort forHealth-Based Guidance Value). Furthermore, opinions point out that in epidemiological studies, blood lead levels below 10 µgshort formicrogram/L may also be associated with observations such as intellectual deficits in children. 

The provisional tolerable weekly intake (PTWI) of 25 µgshort formicrogram/kgshort forkilogram bw derived by JECFA (FAO/WHO, 1993) is no longer considered suitable for risk characterisation of dietary lead intake by international committees, including JECFA itself (FAO/WHO, 2011).

EFSAshort forEuropean Food Safety Authority (2010) recommends calculating the margins of exposure (MOEs⁴ ) to support risk characterisation. Regarding the interpretation of MOEshort forMargin of Exposure values, EFSAshort forEuropean Food Safety Authority (2010) concludes that for adults, with respect to the increase of SBP or the reduction of GFR, and for children, with respect to effects on IQ, an MOEshort forMargin of Exposure of 10 or greater would be sufficient to ensure that there is no appreciable risk of a clinically significant effect. Even at MOEs > 1, EFSAshort forEuropean Food Safety Authority estimates the risk of lead-related blood pressure increase or reduction of GFR to be very low and of effects on IQ likely to be low, but not such that it could be dismissed as of no potential concern.

Until updated models of reference points for dietary lead intake are available, the BfRshort forGerman Federal Institute for Risk Assessment considers the reference points published by EFSAshort forEuropean Food Safety Authority (2010) to be a suitable basis for an initial risk characterisation. The BfRshort forGerman Federal Institute for Risk Assessment points out that these reference points correspond to the state of scientific knowledge in 2010. As described in EFSAshort forEuropean Food Safety Authority (2010), exposure is compared with the reference points and MOEshort forMargin of Exposure values are calculated.

⁴ A margin of exposure (MOEshort forMargin of Exposure) refers to the quotient of a suitable reference point from the dose-effect relationship and the estimated human exposure to the substance. A benchmark dose lower confidence limit (BMDLshort forBenchmark Dose Lower Confidence Limit) is often used as a reference point, i.e. a dose that is associated with a specific increase in the effect of a substance. An MOEshort forMargin of Exposure value is not a health-based guidance value (HBGVshort forHealth-Based Guidance Value). Rather, it serves to prioritise the urgency of risk management measures for substances for which, based on current knowledge, no safe intake level can be derived.

3.2.1 External exposure via food

3.2.1.1 Data basis for consumption

The data basis for consumption by infants, toddlers and children between 0.5 and < 6 years of age was provided by the "Children's Nutrition Study to Record Food Consumption" (KiESEL study). A total of 1,104 children aged between six months and five years participated in KiESEL. The survey was conducted between 2014 and 2017. Based on an interview, the parents or legal guardians completed a questionnaire on general nutrition, nutrition in the first year of life, and a Food Propensity Questionnaire on rarely consumed food. Of these, 1,008 children and their parents also participated in the nutrition survey using a weighing/estimation protocol. The children's food consumption was documented in a weighing protocol for three consecutive days and in a 1-day weighing protocol on an independent day. In addition, out-of-home consumption (e.g. in childcare facilities) was recorded using a reduced estimation protocol (Nowak et al.short foret alii (lat. "and others"), 2022a; Nowak et al.short foret alii (lat. "and others"), 2022b) . The results from the weighing protocols were used for the evaluation, and only non-breastfed individuals were taken into account (N = 952).

The KiGGS module (EsKiMo II) (Mensink et al.short foret alii (lat. "and others"), 2021) served as the data basis for consumption among children between the ages of 6 and < 12. As part of EsKiMo II, 2,644 children and adolescents aged 6 to < 18 years were surveyed about their food consumption and eating habits between 2015 and 2017. These children and adolescents had previously participated in the second wave of the Robert Koch Institute's "Study on the Health of Children and Adolescents in Germany" (KiGGS) Wave 2. The four-day weighing protocols of 1,190 children between the ages of 6 and < 12 were used for the exposure assessment. Consumption from the age of 14 onwards is covered by NVS II.

The National Consumption Survey II (NVS II) conducted by the Max Rubner Institute (MRIshort forMax Rubner Institute) served as the data basis for consumption among adolescents and adults between the ages of 14 and 80. The NVS II is the current representative study on consumption among the German population. The study, in which around 20,000 people aged between 14 and 80 were surveyed about their eating habits using three different methods (dietary history, 24-hour recall and weighing protocol), took place throughout Germany between 2005 and 2006 (Krems et al.short foret alii (lat. "and others"), 2006; MRIshort forMax Rubner Institute, 2008). The consumption evaluations are based on data from the two independent 24-hour recalls of the NVS II, which were collected in a computer-assisted interview using "EPIC-SOFT". Data from 13,926 people for whom both interviews were available were evaluated.

These consumption studies are suitable for estimating long-term consumption levels. The intake estimates were evaluated according to the age groups listed in Table 2.
 

3.2.1.2 Data basis for concentrations in food

Lead was examined in the core module of the BfRshort forGerman Federal Institute for Risk Assessment-MEAL study in all 356 foods on the MEAL food list . Based on the 24-hour recalls from NVS II for adolescents and adults and the VELS data for children (Banasiak et al.short foret alii (lat. "and others"), 2005), the MEAL food list covers at least 90 % of the average food intake of different age groups in the German population for each main food group and also takes into account rarely consumed foods with known high concentrations of undesirable substances. The MEAL food was purchased between December 2016 and May 2019 in four different regions across Germany, with the product selection taking into account the different shopping habits of the German population as well as regional and seasonal characteristics. The information underlying the representative composition of the samples was collected through consumer studies and generated from market data. The food was prepared in the MEAL study kitchen, replicating typical consumer behaviour. The food and dishes were then pooled and homogenised (Sarvan et al.short foret alii (lat. "and others"), 2017). Specific details on data collection and the presentation and discussion of lead concentrations have already been published (Fechner et al.short foret alii (lat. "and others"), 2022). The highest concentrations were found in the main food group "coffee, cocoa, tea", which is mainly due to the high concentrations in cocoa powder, which was measured without preparation and is therefore undiluted. High concentrations are also found in the main groups "pulses, nuts, oilseeds and spices" and "vegetables and vegetable products". In addition to cocoa powder, the highest lead concentrations were measured in the following food: spices, porcini mushrooms, mussels, liver, herbs and algae.

3.2.1.3 Estimation of long-term exposure across all food

Methodology

For each participant in the aforementioned consumption studies, the average long-term consumption per MEAL food was determined in relation to individual body weight and linked to the respective measured lead concentration. Levels below the limit of detection or quantification (LOQshort forLimit of quantification) were treated according to the modified lower bound (mLB) and upper bound (UB) approach. In the mLB approach, results below the limit of quantification (LOQshort forLimit of quantification) (< LOQshort forLimit of quantification) were assigned the value of the limit of detection (LODshort forLimit of detection) and results below the limit of detection (< LODshort forLimit of detection) were assigned the value zero. In the UB approach, results below the limit of quantification (< LOQshort forLimit of quantification) were assigned the value of the respective limit of quantification (LOQshort forLimit of quantification) and results below the limit of detection were assigned the value of the respective limit of detection (LODshort forLimit of detection).

The exposure assessment was differentiated to the characteristics of organic or conventional production. This means that if MEAL foods were sampled separately according to their production type, they were not averaged but assigned to two separate evaluations. All food that was not differentiated according to production type (seasonal, regional or unspecified  ) was included in the scenario of consumption of primarily conventionally produced food together with conventionally produced food, and all exclusively organically produced food was included in the scenario of consumption of primarily organically produced food. A total of 105 of the 356 MEAL food samples examined were differentiated by production type. In both exposure scenarios, it was assumed that all individuals consumed either exclusively organically produced or conventionally produced products, provided that a differentiation was made in the food list. Differences in exposure are based solely on differences in occurrence data, as no differentiation was made in the consumption data.

Total dietary exposure was determined on the basis of all respondents who participated in the dietary survey. The medianClose dialogmedianMedianTo glossary (P50) and the 95th percentile (P95) of the resulting exposure distribution are shown. Exposure is given in µgshort formicrogram/kgshort forkilogram bw per day.

Long-term lead exposure across all foods

Table 3 shows lead intake for primarily conventional product selection. Depending on age groups and percentiles, exposure in the UB approach is between 13 % and 60 % higher than when using the mLB approach. As it represents the more conservative scenario, the following comments refer only to the results using the UB approach. The figures using the mLB approach are also listed in the tables. 

On average, children under one year of age show the highest exposure at 0.27 µgshort formicrogram/kgshort forkilogram BW per day. In the case of the 95th percentile, children aged 1 to < 3 years show an exposure of 0.36 µgshort formicrogram/kgshort forkilogram BW per day. Across all age groups considered by KiESEL, the median calculated exposure is between 0.17 and 0.27 µgshort formicrogram/kgshort forkilogram BW per day. Lead exposure decreases with increasing age. For children aged 6–11 years with median exposure, lead intake is between 0.11 and 0.14 µgshort formicrogram/kgshort forkilogram BW per day. Lead intake in P95 for this age group is between 0.18 and 0.23 µgshort formicrogram/kgshort forkilogram BW per day. 

Lower lead intake relative to body weight is found for median exposed adolescents and adults over the age of 14, in the range of 0.08 to 0.09 µgshort formicrogram/kgshort forkilogram BW/day, and for the P95 of this age group, in the range of 0.14 to 0.16 µgshort formicrogram/kgshort forkilogram BW/day. 

"Grain and grain products" and "water and water-based beverages" make the highest contribution to average lead intake in all age groups, accounting for 15 % to 20 % respectively. Among these, wheat products such as white bread/rolls, puff pastry snacks, wholemeal and brown bread, and drinking water or mineral water are the main contributors. However, cow's milk, butter and apples are also among the ten food items with the highest contribution to lead exposure in all consumption studies considered. The main group, "composite dishes", also accounts for a high proportion of average exposure, at 8 % to 11 %. In adults, the group "coffee, cocoa, tea" also contributes substantially to average exposure, at around 16 %. Coffee in particular is a major contributor here.

Depending on their age group, consumers who primarily chose organic foods consumed 3–8 % more lead than consumers who primarily chose conventional products. This was solely due to differences in occurrence data, as the same consumption data was used. It should be noted that no fundamentally higher tendency was observed across all organic food. Rather, differences were noticeable in individual foods (e.g. olives or culinary herbs), and no tendency was observed within the individual main groups (Fechner et al.short foret alii (lat. "and others"), 2022). 

Intake estimates for the organic scenario are presented in the appendix (Table 7).
 

Comparison of exposure assessments from the European region

In a European comparison (Table 4), lead exposure in infants, toddlers and children is of the same order of magnitude as the intake levels reported in the French TDS. Children and adolescents aged 3 to 17 years consumed an average of 0.27 µgshort formicrogram/kgshort forkilogram bw daily (Arnich et al.short foret alii (lat. "and others"), 2012). In the Spanish TDS, the mean daily intake for children and adolescents aged 6 to 15 years was in the range of 0.06 µgshort formicrogram/kgshort forkilogram bw/day (LB) to 0.12 µgshort formicrogram/kgshort forkilogram bw/day (UB), which is also similar to the exposure assessment for children and adolescents based on the EsKiMO II study (Marín et al.short foret alii (lat. "and others"), 2017). By contrast, the results from the EFSAshort forEuropean Food Safety Authority exposure assessment show substantially higher lead intake levels. Depending on the age group and analytical limit considered, this ranged between 0.73 and 1.54 µgshort formicrogram/kgshort forkilogram bw/day. The data used for this assessment does not come from a TDS but instead from various monitoring programmes of the Member States (EFSAshort forEuropean Food Safety Authority, 2012), which, due to the selection of food, the date of collection of the occurrence data and the analytical methods used, and the sampling of predominantly unprocessed food, lead to differing results, as was to be expected (Kolbaum, 2022).

A similar picture emerges from a comparison of adolescents and adults. The values from the Spanish TDS (0.03 (LB)–0.06 (UB) µgshort formicrogram/kgshort forkilogram bw per day) are of the same order of magnitude as the exposures estimated here (Marín et al.short foret alii (lat. "and others"), 2017), while the exposure assessments from the French TDS (0.2 µgshort formicrogram/kgshort forkilogram bw/day (MB)) are above the values from Germany and Spain (Arnich et al.short foret alii (lat. "and others"), 2012). Once again, the results from the EFSAshort forEuropean Food Safety Authority opinion are higher than those from the various TDS. Here, average exposures in the range of 0.42–0.63 µgshort formicrogram/kgshort forkilogram bw/day were determined.

3.2.1.4 Uncertainties

The concept of a TDS involves drafting a food list (TDS food list) comprising foods that represent at least 90 % of the consumption in the target population. This means a reduction in uncertainties regarding the occurrence data of a TDS compared to other data collections, such as food monitoring. From a methodological point of view, another advantage is that in a TDS, ingredient level determinations are made on the basis of prepared and ready-to-eat foods, thus taking into account any changes in levels that may occur during the preparation of meals. A TDS provides a representative data set with regard to the average consumption levels of a wide range of foods and thus provides a very good basis for determining long-term exposure (Kolbaum, 2022).

It should be noted that none of the pooled samples analysed in the BfRshort forGerman Federal Institute for Risk Assessment-MEAL study exceeded the legally specified maximum levels. However, based on the analysis of pooled samples it is not possible to estimate the proportion of individual food samples that would exceed a specified maximum value. This means that the occurrence data collected in the course of a TDS are not suitable for monitoring maximum levels, and it cannot be ruled out that individual samples within the pool samples may have exceeded the maximum level.

For an exposure assessment, occurrence data must be combined with consumption data. The data for children (KiESEL, EsKiMo II) was collected as part of the KiGGS wave 2 between 2014 and 2017. The consumption data for adolescents and adults (NVS II) was collected in 2005/2006. It cannot be ruled out that consumption habits in the German population have changed since then.

Due to the consideration of > 90 % (but < 100%) of consumption within a TDS, the lead exposure determined here may underestimate the actual exposure across all food consumed. However, as food that is consumed in large quantities and food with known high lead content were included in the estimate, the possible underestimation is considered to be low.

The intake estimate used the average consumption over the protocol days. This may lead to an overestimation of exposure at the margins of the distribution, as intra-individual variability was not sufficiently reflected. However, compared to the EFSAshort forEuropean Food Safety Authority recommendation to use at least two protocol days, KiESEL and EsKiMO II already provide improved coverage of intra-individual variability.

3.2.2 Internal exposure (human biomonitoring)

The focus of the German Environmental Survey GerES V (2014-2017) was human biomonitoring of a representative sample of children and adolescents in Germany aged 3 to 17 years (UBAshort forGerman Environment Agency, 2023). Among other things, lead concentrations in the blood of 720 children and adolescents were examined (Vogel et al.short foret alii (lat. "and others"), 2021). In all individuals examined, blood lead concentrations were above the limit of quantification (LOQshort forLimit of quantification). Children aged 14 to 17 had slightly lower median and P95 blood lead concentrations than younger children, but not in terms of maximum concentrations. The highest internal exposure was found in children in the youngest age group examined, aged 3 to 5 years. Lower concentrations were observed in girls than in boys (data not shown). A comparison with earlier studies showed a downward trend in blood lead concentrations. The concentrations in the blood of children and adolescents were 38 % lower than in GerES IV in the period 2003–2006. The statistical indicators of the results for lead concentrations in blood from the GerES V study are shown in Table 5.
 

The Human Biomonitoring (HBM) Commission of the German Federal Environment Agency has derived reference values for lead in the blood of children from the GerES V study (2014-2017). These values are 15 µgshort formicrogram/L (girls aged 3 to 17, boys aged 11 to 17) and 20 µgshort formicrogram/L (boys aged 3 to 10). In its latest update of the reference values for adults, the Commission derived preliminary reference values of 30 µgshort formicrogram/L for women and 40 µgshort formicrogram/L for men from data from the Environmental Specimen Bank 2010-2015 (UBAshort forGerman Environment Agency, 2019). Reference values are determined statistically and describe the average exposure of the population or a specific population group at a given point in time. This does not imply any health risk assessment. The HBM Commission reevaluated the effects of lead in blood and suspended the HBM values for lead for the toxicological assessment of internal lead exposure in whole blood due to the lack of a threshold effect, the reassessment of carcinogenic potential and recent research findings (UBAshort forGerman Environment Agency, 2009).

3.3 Risk characterisation

Based on exposure assessments for different age groups to lead through food consumption, the respective MOEshort forMargin of Exposure values were calculated using the reference points for renal toxicity in adults (BMDL10 0.63 µgshort formicrogram/kgshort forkilogram bw per day) and for developmental neurotoxic effects in children (BMDL01 0.5 µgshort formicrogram/kgshort forkilogram bw per day) (Table 6). For risk characterisation, the exposure assessment was based on the assumption that mainly conventionally produced food was consumed. The resulting MOEshort forMargin of Exposure values based on the exposure assessment on the consumption of mainly organically produced food are presented in the appendix (Table 8).
 
 

Children

According to estimates of external exposure for children, lead intake through food consumption is of the same order of magnitude as the BMDL01 of 0.5 µgshort formicrogram/kgshort forkilogram bw/day. The lowest MOEshort forMargin of Exposure values are calculated for children < 1 year of age with 1.8 (P50, UB) and 1.4 (P95, UB) and for children aged 1–2 years with 2.3 (P50, UB) and 1.4 (P95, UB), meaning that for the youngest age group, the MOEshort forMargin of Exposure is a maximum of 2. A small proportion of the youngest age groups exceeds the benchmark dose lower confidence limit BMDL01 (1 to 2 % of children < 1 to 2 years of age, data not shown). 

For the toxicological assessment of internal lead exposure in children, the blood lead levels of the relevant age groups can be compared with the BMDL01 of 12 µgshort formicrogram lead/L blood as a reference point for the developmental neurotoxic effects of lead in children (Chapter 3.2.2 ). EFSAshort forEuropean Food Safety Authority (2010) uses the corresponding BMDL01 for the assessment of external exposure only for children up to 7 years of age. According to the results from GerES V, the high internal exposure (P95) of children up to 7 years of age exceeds the blood level of 12 µgshort formicrogram lead/L (Table 5). The high internal exposure of older children is also above the blood level of 12 µgshort formicrogram/L. The reference values for lead in the blood of children derived by the HBM Commission on the basis of GerES V data of 15 µgshort formicrogram/L (girls aged 3 to 17, boys aged 11 to 17) and 20 µgshort formicrogram/L (boys aged 3 to 10) therefore also exceed the benchmark dose lower confidence limit BMDL01 of 12 µgshort formicrogram lead/L blood. In children with blood lead levels in the range of the median, internal exposure is close to the BMDL01, especially in the younger age groups (3 to 10 years), but does not exceed it.

Overall, the data show that external lead exposure in children, especially in the younger age groups, through food consumption is in the order of magnitude of the BMDL01 for developmental neurotoxic effects of lead, and that internal exposure in highly exposed children (P95) of all age groups exceeds this value. The latter reflects not only dietary lead exposure, but exposure from all sources. Even with blood lead levels below the BMDL01, effects on cognitive development parameters in children exposed to lead cannot be ruled out, although EFSAshort forEuropean Food Safety Authority considers the health risk at MOEshort forMargin of Exposure values > 1 likely to be low.

Adolescents and adults

Lead intake by adolescents and adults through food consumption is below the BMDL10 of 0.63 µgshort formicrogram/kgshort forkilogram bw/day and hardly differs between the age groups considered (14 - > 65 years). The MOEshort forMargin of Exposure values resulting from the comparison of exposure and the reference point for renal toxicity (BMDL10 0.63 µgshort formicrogram/kgshort forkilogram bw/day) are between 6.9 and 7.6 (P50, UB) and 3.8 and 4.4 (P95, UB) for all age groups between 14 and > 65 years.

Based on the assumption that the developing foetus is at least as sensitive to the effects of lead as a small child, EFSAshort forEuropean Food Safety Authority (2010) used a lower BMDL01 of 0.54 µgshort formicrogram/kgshort forkilogram bw/day for developmental neurotoxicity of lead in pregnant women compared to the endpoint of renal toxicity. A comparison of this BMDL01 with the dietary lead intake of pregnant women cannot be made in the context of this opinion, as no consumption data for pregnant women are available. When considering the exposure of adults aged 18 to 35 years as representative of pregnant women in relation to the BMDL01 of 0.54 µgshort formicrogram/kgshort forkilogram bw/day (Table 3), MOEshort forMargin of Exposure values would be in a similar range to those for (non-pregnant) adolescents and adults (data not shown).

Recommendation for action

The results of the present internal and external exposure assessments show that, despite the substantial decline in internal lead exposure, there is still a need to minimise lead intake, especially for younger age groups.
 

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