Health-based Guidance Values Research Articles

Adverse outcome pathway exploration of furan-induced liver fibrosis in rats: Genotoxicity pathway or oxidative stress pathway through CYP2E1 activation?

Furan is a widespread endogenous contaminant in heat-processed foods that can accumulate rapidly in the food chain and has been widely detected in foods, such as wheat, bread, coffee, canned meat products, and baby food. Dietary exposure to this chemical may bring health risk. Furan is classified as a possible category 2B human carcinogen by the International Agency for Research on Cancer, with the liver as its primary target organ. Hepatic fibrosis is the most important nontumoral harmful effect of furan and also an important event in the carcinogenesis of furan. Although the specific mechanism of furan-induced liver fibrosis is still unclear, it may involve oxidative stress and genetic toxicity, in which the activation of cytochrome P450 2E1 (CYP2E1) may be the key event. Thus, we conducted a study using an integrating multi-endpoint genotoxicity platform in 120-day in vivo subchronic toxicity test in rats. Results showed that the rats with activated CYP2E1 exhibited DNA double-strand breaks in D4, gene mutations in D60, and increased expression of reactive oxygen species and nuclear factor erythroid 2-related factor 2 in D120. Necrosis, apoptosis, hepatic stellate cell activation, and fibrosis also occurred in the liver, suggesting that furan can independently affect liver fibrosis through oxidative stress and genotoxicity pathways. Point of Departure (PoD) was obtained by benchmark-dose (BMD) method to establish health-based guidance values. The human equivalent dose of PoD derived from BMDL05 was 2.26 μg/kg bw/d. The findings laid a foundation for the safety evaluation and risk assessment of furan and provided data for the further construction and improvement of the adverse outcome pathway network in liver fibrosis.

Re-evaluation of a microbiological acceptable daily intake for tylosin based on its impact on human intestinal microflora

As veterinary drugs available for fish is very restricted, there is growing trials for repurposing livestock drugs as aquatic animal drugs. Tylosin is one of the most effective antibiotics to treat bacterial infections approved for livestock, and would be used in fish. Hence, we investigated the toxicological and microbiological aspects of tylosin to establish health-based guidance value (HBGV) and maximum residue limit (MRL) in fishes, and reevaluated the microbiological acceptable daily intake (mADI) based on updated relevant data and international guildeline. Lastly, exposure assessment was performed to confirm the appropriateness of MRL. By investigating available microbiologcial studies on tylosin, the microbiological point of departure was determined as 0.308 μg/mL, which was mean 50% minimum inhibitory concentration (MIC50), obtained from the Food Safety Committee of Japan (FSCJ) evaluation report. Furthermore, as a factor for the derivation of mADI, the volume of colon content was recently changed to 500 mL in compliance with the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) guidelines. This was previously defined as the mass of colon content (220 g). We applied correction factor 0.224 to the mean MIC50 for tylosin in the equation of mADI, since the drug is transformed to metabolites with reduced activity prior to entering the colon and bound to fecal materials within the colon of human. The mADI was evaluated as 0.01 mg/kg bw/day. Finally, the hazard index, calculated by dividing the estimated chronic dietary exposure by mADI, did not exceed 100%, suggesting that chronic dietary exposure to tylosin residues from veterinary use was unlikely to be a public health concern. Overall, this study contributes significantly in updating HBGV by application of the concept of mADI for the first time in Korea based on the revised microbiological risk assessment guidelines and in providing scientific rationale for the risk management of veterinary drug residues in food.

Exposure Trends to the Non-phthalate Plasticizers DEHTP, DINCH, and DEHA in Children from 2012 to 2017: The Hokkaido Study.

Phthalates owing to their endocrine-disrupting effects are regulated in certain products, leading to their replacement with substitutions such as di-2-ethylhexyl terephthalate (DEHTP), 1,2-cyclohexane dicarboxylic acid di(isononyl) ester (DINCH), and di(2-ethylhexyl) adipate (DEHA). However, information on human exposure to these substitutes, especially in susceptible subpopulations such as children, is limited. Thus, we examined the levels and exposure trends of DEHTP, DINCH, and DEHA metabolites in 7 year-old Japanese school children. In total, 180 urine samples collected from 2012 to 2017 were used to quantify 10 DEHTP, DINCH, and DEHA metabolites via isotope dilution liquid chromatography with tandem mass spectrometry. DEHTP and DINCH metabolites were detected in 95.6 and 92.2% of the children, respectively, and DEHA was not detected. This study, annually conducted between 2012 and 2017, revealed a significant (p < 0.05) 5-fold increase in DEHTP metabolites and a 2-fold increase in DINCH metabolites. However, the maximum estimated internal exposures were still below the health-based guidance and toxicological reference values. Exposure levels to DEHTP and DINCH have increased considerably in Japanese school children. DEHA is less relevant. Future studies are warranted to closely monitor the increasing trend in different aged and larger populations and identify the potential health effects and sources contributing to increasing exposure and intervene if necessary.

Genotoxicity assessment: opportunities, challenges and perspectives for quantitative evaluations of dose-response data.

Genotoxicity data are mainly interpreted in a qualitative way, which typically results in a binary classification of chemical entities. For more than a decade, there has been a discussion about the need for a paradigm shift in this regard. Here, we review current opportunities, challenges and perspectives for a more quantitative approach to genotoxicity assessment. Currently discussed opportunities mainly include the determination of a reference point (e.g., a benchmark dose) from genetic toxicity dose-response data, followed by calculation of a margin of exposure (MOE) or derivation of a health-based guidance value (HBGV). In addition to new opportunities, major challenges emerge with the quantitative interpretation of genotoxicity data. These are mainly rooted in the limited capability of standard in vivo genotoxicity testing methods to detect different types of genetic damage in multiple target tissues and the unknown quantitative relationships between measurable genotoxic effects and the probability of experiencing an adverse health outcome. In addition, with respect to DNA-reactive mutagens, the question arises whether the widely accepted assumption of a non-threshold dose-response relationship is at all compatible with the derivation of a HBGV. Therefore, at present, any quantitative genotoxicity assessment approach remains to be evaluated case-by-case. The quantitative interpretation of in vivo genotoxicity data for prioritization purposes, e.g., in connection with the MOE approach, could be seen as a promising opportunity for routine application. However, additional research is needed to assess whether it is possible to define a genotoxicity-derived MOE that can be considered indicative of a low level of concern. To further advance quantitative genotoxicity assessment, priority should be given to the development of new experimental methods to provide a deeper mechanistic understanding and a more comprehensive basis for the analysis of dose-response relationships.

Natural Occurrence of Regulated and Emerging Mycotoxins in Wheat Grains and Assessment of the Risks from Dietary Mycotoxins Exposure in China

Wheat grains are susceptible to contamination with various natural mycotoxins including regulated and emerging mycotoxins. This study surveyed the natural presence of regulated mycotoxins, such as deoxynivalenol (DON) and zearalenone (ZEN), and emerging mycotoxins such as beauvericin (BEA), enniatins (ENNs such as ENA, ENA1, ENB, ENB1) and Alternaria mycotoxins (i.e., alternariol monomethyl ether (AME), alternariol (AOH), tenuazonic acid (TeA), tentoxin (TEN), and altenuene (ALT)) in wheat grains randomly collected from eight provinces across China in 2021. The results revealed that each wheat grain sample was detected with at least one type of mycotoxin. The detection rates of these mycotoxins ranged from 7.1% to 100%, with the average occurrence level ranging from 1.11 to 921.8 µg/kg. DON and TeA were the predominant mycotoxins with respect to both prevalence and concentration. Approximately 99.7% of samples were found to contain more than one toxin, and the co-occurrence of ten toxins (DON + ZEN + ENA + ENA1 + ENB + ENB1 + AME + AOH + TeA + TEN) was the most frequently detected combination. The dietary exposure to different mycotoxins among Chinese consumers aged 4–70 years was as follows: 0.592–0.992 µg/kg b.w./day for DON, 0.007–0.012 µg/kg b.w./day for ZEN, 0.0003–0.007 µg/kg b.w./day for BEA and ENNs, 0.223–0.373 µg/kg b.w./day for TeA, and 0.025–0.041 µg/kg b.w./day for TEN, which were lower than the health-based guidance values for each mycotoxin, with the corresponding hazard quotient (HQ) being far lower than 1, implying a tolerable health risk for Chinese consumers. However, the estimated dietary exposure to AME and AOH was in the range of 0.003–0.007 µg/kg b.w./day, exceeding the Threshold of Toxicological Concern (TTC) value of 0.0025 µg/kg b.w./day, demonstrating potential dietary risks for Chinese consumers. Therefore, developing practical control and management strategies is essential for controlling mycotoxins contamination in the agricultural systems, thereby ensuring public health.

Health risk assessment of perfluorooctane sulfonate and perfluorooctanoic acid exposure in China based on epidemiological data

BackgroundHealth risk assessment based on epidemiological data for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are evidenced. Whereas information about health-based guidance values (HBGVs) and health risk for Chinese population related to PFOS and PFOA is scarce. ObjectivesTo provide candidate HBGVs for PFOS and PFOA based on Chinese epidemiological data and assess the health risk related to excessive exposure. MethodsWe reviewed scientific literature and collected available original data from epidemiological studies conducted in China. Critical endpoints and data were selected and used in benchmark dose (BMD) analysis to obtain lower confidence limits of BMD (BMDLs) of PFOS and PFOA. Physiologically based pharmacokinetic (PBPK) models were applied to calculate the point of departure (PODs) for PFOS and PFOA, which led to the determination of the HBGVs for the said chemicals. Margin of exposure (MOE) method was used to evaluate the health risk of population based on exposure data among Chinese and HBGVs. ResultsAlanine aminotransferase (ALT), total cholesterol (TC) and birth weight (BW) were selected as critical endpoints. Epidemiological data from 4,224 adults, 2,153 paired mother-newborn, 2,518 newborns, 439 pregnant women and 733 children in China were included in this study. BMDLs and PODs for PFOS are varied while BMDLs for PFOA were similar. PODs for PFOS (1.56 ng/kg/day) and PFOA (1.52 ng/kg/day) based on BW using National Birth Cohort Study were selected as HBGVs. Most MOEs for PFOS and PFOA among Chinese population were larger than 1 and smaller than 100, indicating moderate concern. Around 16% MOEs for PFOS were smaller than 1, implying high concern. ConclusionThe HBGVs for PFOS and PFOA were 1.56 ng/kg/day and 1.52 ng/kg/day, respectively. Health risk of Chinese population related to PFOS and PFOA exposure should be concerned and more studies should be conducted to evaluate the risk of the chemicals.

Pesticide residues in bee bread, propolis, beeswax and royal jelly - A review of the literature and dietary risk assessment.

Due to pollinator decline observed worldwide, many studies have been conducted on the pesticide residue content of apicultural products including bee bread, propolis, beeswax and royal jelly. These products are consumed for their nutraceutical properties, although, little information is available on the human health risk posed by pesticides present in them. In our research, studies dealing with the pesticide contamination of the above-mentioned hive products are reviewed. Dietary exposures were calculated based on the recommended daily intake values and concentration data reported by scientific studies. Potential acute and chronic health risk of consumers were evaluated by comparing the exposure values with health-based guidance values. Available data indicate that a wide range of pesticide residues, especially acaricides may accumulate in bee bread, propolis and beeswax, up to concentration levels of more thousand μg/kg. Based on our observations, tau-fluvalinate, coumaphos, chlorfenvinphos, chlorpyrifos and amitraz are commonly detected pesticide active substances in beehive products. Our estimates suggest that coumaphos and chlorfenvinphos can accumulate in beeswax to an extent that pose a potential health risk to the consumers of comb honey. However, it appears that pesticide residues do not transfer to royal jelly, presumably due to the filtering activity of nurse bees during secretion.

Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept.

Chemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human populations are exposed. This study describes a proof of concept for conducting mixture risk assessment with HBM data, using the population-representative German Environmental Survey (GerES) V as a case study. We first attempted to identify groups of correlated biomarkers (also known as 'communities', reflecting co-occurrence patterns of chemicals) using a network analysis approach (n = 515 individuals) on 51 chemical substances in urine. The underlying question is whether the combined body burden of multiple chemicals is of potential health concern. If so, subsequent questions are which chemicals and which co-occurrence patterns are driving the potential health risks. To address this, a biomonitoring hazard index was developed by summing over hazard quotients, where each biomarker concentration was weighted (divided) by the associated HBM health-based guidance value (HBM-HBGV, HBM value or equivalent). Altogether, for 17 out of the 51 substances, health-based guidance values were available. If the hazard index was higher than 1, then the community was considered of potential health concern and should be evaluated further. Overall, seven communities were identified in the GerES V data. Of the five mixture communities where a hazard index was calculated, the highest hazard community contained N-Acetyl-S-(2-carbamoyl-ethyl)cysteine (AAMA), but this was the only biomarker for which a guidance value was available. Of the other four communities, one included the phthalate metabolites mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) with high hazard quotients, which led to hazard indices that exceed the value of one in 5.8% of the participants included in the GerES V study. This biological index method can put forward communities of co-occurrence patterns of chemicals on a population level that need further assessment in toxicology or health effects studies. Future mixture risk assessment using HBM data will benefit from additional HBM health-based guidance values based on population studies. Additionally, accounting for different biomonitoring matrices would provide a wider range of exposures. Future hazard index analyses could also take a common mode of action approach, rather than the more agnostic and non-specific approach we have taken in this proof of concept.

Methodology for risk-based monitoring of contaminants in food – A case study in cereals and fish

In this study, a methodology was developed that can be used as input for risk-based monitoring plans for chemical contaminants in food products. The novel methodology was applied to a case study in which cereals and fish were evaluated simultaneously for the possible presence of mycotoxins and heavy metals. The methodology was based on hazard quotients that were estimated by dividing the daily intake - using concentrations of the contaminants in the different food products and consumption of the respective products combined per product group - by the health based guidance value (HBGV) or reference points used for assessing potential health concerns (RPHC). The most relevant hazard-product combinations were further ranked based on the volume of import of the ingredients, per import country and a defined contaminant prevalence level per country. For fish, the hazard quotients were around ten times lower compared to the highest hazard quotients in cereals. Consumption of molluscs, mackerel-type fish and herring-type fish contaminated with mercury contributed most to the HBGV or RPHC. The top 25 hazard-product combinations for various age groups included: aflatoxin B1 in combination with wheat, rice (products), maize (products), and pasta, zearalenone in combination with wheat (products), T2/HT2-toxin in combination with rice (products), and DON in combination with wheat (products). The methodology presented showed to be useful in identifying the most relevant hazard-food-age group combinations and the most relevant import countries linked to these that should be included in the monitoring. As such, the method can help risk managers in establishing risk-based monitoring programs.

A time trend of urinary 4-methylbenzylidene camphor metabolites in young adults from Germany

4-methylbenzylidene camphor (4-MBC) is used as a UV-B filter in cosmetics. Two oxidized metabolites of 4-MBC – 3-(4-carboxybenzylidene)camphor (cx-MBC) and 3-(4-carboxybenzylidene)-6-hydroxycamphor (cx-MBC-OH) – were analyzed in 250 24-h urine samples from young adults in Germany. The samples were from the German Environmental Specimen Bank (ESB) and represented exposure in the years 1995, 2005, 2010, 2015 and 2019.A UHPLC-MS/MS method enabled the sensitive determination of both metabolites, with limits of quantification at 0.15 μg L−1 (cx-MBC) and 0.30 μg L−1 (cx-MBC-OH), respectively. A temporal trend of the internal exposure to 4-MBC was clearly noticeable. The metabolite cx-MBC was frequently quantifiable at the beginning of the period: in 70% of the samples in 1995, and 56% in 2005. After 2005, urinary concentrations and detection rates of cx-MBC dropped to reach very low levels. In 2015 and 2019, the detection rate was only 2% and 0%, respectively. A similar trend was observed for cx-MBC-OH, though overall, this metabolite was detected less often and at lower concentration levels than cx-MBC. Nowadays, measurable levels of urinary 4-MBC metabolites are an extremely rare occurrence in Germany. These trends are consistent with the history of 4-MBC use by the cosmetic industry. The highest measured individual concentration of 16.20 μg L−1 (in a sample of the year 2005) was still more than 30 times below the health-based guidance value (HBM-I).An investigation of the ratios between both metabolites uncovered several features of the 4-MBC metabolism which have been essentially overlooked until now. In particular, stereochemical aspects should be explored in future studies.As urine was collected in autumn/winter in Northwestern Germany, the 4-MBC metabolites measured probably do not arise from sunscreen products in a narrow sense. They rather may reveal the use of other skin care products containing 4-MBC for UV protection as an added feature.

Risk assessment of dietary exposure to trace elements that are reproductive toxicants: Lead, molybdenum and nickel. The case study of Armenia

The research aimed to assess dietary exposure to developmental toxicants (Mo, Ni, Pb) among the Armenian adult female population of reproductive age (18–49 years). Commonly consumed foods with a daily intake of more than 1 g in Armenia have been selected to assess the occurrence of Mo, Ni, and Pb. Food consumption data among the adult population in Armenia were collected in the frame of the national survey via 24-h recall method. Estimated daily intakes (EDI) and associated potential health risks for both mean and high (95 percentile) consumers were assessed based on the health-based guidance values (HBGVs). None of the EDI values for the developmental toxicants via individual food consumption exceeded the HBGVs, however, the EDI of Pb in the case of aggregate consumption of all food products exceeded HBGV of 0.5 μg/kg b.w./day, indicating possible concerns for the neurodevelopmental effects. Noticeably, the intake of Pb through some individual food items (cheese curd, beef and veal, pelmeni and khinkali, black coffee, tap water) and the aggregate consumption of all the studied foods led to a Margin of Exposure lower than 10 compared to HBGV.This study is the first one carried out on dietary exposure to developmental toxicants among women of fertile age in a Caucasus country. The outcomes prompt the need to investigate sources of Pb pollution in foods consumed in Armenia (natural or human-derived environmental pollution, as well as food contact materials, etc.) and may pave the way for similar studies in the Caucasus region.

The 2021 European Union report on pesticide residues in food.

Under European Union legislation (Article 32, Regulation (EC) No 396/2005), EFSA is to provide an annual report assessing the pesticide residue levels in foods on the European market. In 2021, 96.1% of the overall 87,863 samples analysed fell below the maximum residue level (MRL), 3.9% exceeded this level, of which 2.5% were non-compliant, i.e. samples exceeding the MRL after accounting for the measurement uncertainty. For the EU-coordinated multiannual control programme subset, 13,845 samples were analysed of which 2.1% exceeded the MRL and 1.3% were non-compliant. To assess acute and chronic risk to consumer health, dietary exposure to pesticide residues was estimated and compared with available health-based guidance values (HBGVs). A new pilot methodology based on probabilistic assessment was introduced to provide the probability of subjects being expose to an exceedance of the HBGV. Recommendations to risk manager are given to increase the effectiveness of European control systems and to ensure a high level of consumer protection throughout the EU.

Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014-2021).

As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA+PFNA+PFHxS+PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.

Does Cannabidiol (CBD) in Food Supplements Pose a Serious Health Risk? Consequences of the European Food Safety Authority (EFSA) Clock Stop Regarding Novel Food Authorisation

In the European Union (EU), cannabidiol (CBD) products extracted from Cannabis sativa L. require pre-marketing authorisation under the novel food regulation. Currently, 19 CBD applications are being assessed by the European Food Safety Authority (EFSA). During the initial assessment of the dossiers, the EFSA Panel on Nutrition, Novel Foods, and Food Allergens (NDA) identified several knowledge gaps that need to be addressed before the evaluation of CBD can be finalised. The effects of CBD on the liver, gastrointestinal tract, endocrine system, nervous system, psychological function, and reproductive system need to be clarified. The contribution of this research is to provide an evidence-based assessment of the potential risks associated with CBD products, and to provide recommendations for risk management in the European Union while awaiting the finalisation of novel food applications. The available literature allows for a benchmark dose (BMD)–response modelling of several bioassays, resulting in a BMD lower confidence limit (BMDL) of 20 mg/kg bw/day for liver toxicity in rats. Human data in healthy volunteers showed increases in the liver enzymes alanine aminotransferase and aspartate aminotransferase in one study at 4.3 mg/kg bw/day, which was defined by the EFSA NDA panel as the lowest observed adverse effect level (LOAEL). The EFSA NDA panel recently concluded that the safety of CBD as a novel food cannot be assessed, resulting in a so-called clock stop for the applications until the applicants provide the required data. The authors suggest that certain CBD products still available on the EU market as food supplements despite the lack of authorisation should be considered “unsafe”. Products exceeding a health-based guidance value (HBGV) of 10 mg/day should be considered “unfit for consumption” (Article 14(1) and (2)(b) of Regulation No. 178/2002), while those exceeding the human LOAEL should be considered “injurious to health” (Article 14(1) and (2)(a) of Regulation No 178/2002).

Levels of mercury in hair among pregnant women in Iceland

To limit exposure to methylmercury several countries have implimented specific advice on fish intake to pregnant women as well a measuring compliance through regular human biomonitoring. Despite fish intake being relatively high in Iceland, human biomonitoring data on mercury is scarce. We measured mercury in hair from 120 pregnant women recruited in 2021 from the the Reykjavik Capital area. At recruitment, information on fish intake during the past four months was recorded. Hair mercury concentrations were compared to existing health based guidance values and associatons with fish intake was explored. Mean (standard deviation) mercury concentration in hair was 0.48 μg/g (0.33). All participants had concentrations in hair below 1.8 μg/g, which corresponds to the hair value that the tolerable daily intake set by the European Food Safety Authority is derived from, while 5% had concentrations above 1.1 μg/g, which corresponds to the hair value that the US-EPA reference dose is derived from. Mean mercury concentrations in hair increased in a dose dependent manner (p for trend p<0.001) from 0.25 μg/g among women who consumed fish ≤ 3/month (n=24) and up to 0.80 mg/g among those consuming fish 3-4/ week (n=16). The few (n=3) women who reported to have eaten shark (p<1/month) were all at the higher end of the exposure distribution. Our results suggest that exposure is generally below the tolerable daily intake set by EFSA but may in some women exceed the reference dose established by the US-EPA.

Peat and disinfectant powder used in swine husbandry systems – quantification of oral intake using toxic metals as potential markers

ABSTRACT The use of enrichment and bedding materials in pig husbandry intends to comply with the animals’ behavioural needs to perform natural exploratory behaviour, which is strongly connected to foraging behaviour. It can thus be assumed that pigs will ingest a certain material quantity possibly posing a risk to animal health and food safety as previous studies identified contaminants in enrichment and bedding materials. However, risk assessment requires knowledge about the effective amount of ingested material. Voluntary material intake of pigs with free access to peat and disinfectant powder was estimated by measuring the tissue levels of toxic metals originating from the respective materials in 28 pigs (seven groups, n = 4) via inductively coupled plasma mass spectrometry and comparing the results to tissue levels of pigs fed with known amounts of metals. Additionally, as markers of consumption, n-alkanes and acid insoluble ash naturally occurring in the materials and titanium dioxide, added as an external marker to disinfectant powder, were analysed in pigs’ faeces. Tissue levels of toxic metals as well as marker analyses in pigs’ faeces could prove material consumption. Results revealed mean voluntary intake levels of peat and disinfectant powder by pigs up to 7% and 2% of the daily ration. Hence, a transfer of contained toxic metals into the food chain might occur. Although current maximum levels for toxic elements in animal tissues were not exceeded due to dietary inclusion of peat or disinfectant powder, dietary exposure through food of animal origin should be reduced to a possible minimum. This applies specifically for elements, where no health-based guidance values for humans could have been derived (e.g. arsenic). Thus, labelling guidelines for enrichment and bedding materials can be a perspective to limit the entry of toxic metals and trace elements into the environment.

Evaluation of the genotoxic potential of acrylamide: Arguments for the derivation of a tolerable daily intake (TDI value).

This opinion of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) presents arguments for an updated risk assessment of diet-related exposure to acrylamide (AA), based on a critical review of scientific evidence relevant to low dose exposure. The SKLM arrives at the conclusion that as long as an appropriate exposure limit for AA is not exceeded, genotoxic effects resulting in carcinogenicity are unlikely to occur. Based on the totality of the evidence, the SKLM considers it scientifically justified to derive a tolerable daily intake (TDI) as a health-based guidance value.

Risk assessment of low-dose ethanol in food.

A high variety of food contains low doses of ethanol which are sometimes difficult to identify by consumers (adults or children). However, even low doses of ethanol intake raises several toxicological concerns. In the present study, an enzymatic assay and an HS-GC/MS procedure were applied to determine the ethanol levels of 1260 samples from different food categories covering "nonalcoholic" beer, fruit juices/drinks, baked goods, bananas and baby foods. Based on these results, ethanol levels resulting from acute or chronic ethanol intake was calculated using consumption data from the EFSA Comprehensive European Food Consumption Database. Thus, health-based guidance values (HBGV) for ethanol intake were derived for acute or chronic exposure based on the available literature. For acute exposure, very few samples resulted in concerning ethanol uptake levels but following chronic exposure the here derived HBGV level was exceeded in several cases. This is mainly due to the following reasons: (1) certain amounts of ethanol are still tolerated in "nonalcoholic" beer and (2) presence of endogenous produced ethanol in bananas or baked goods via fermentation. Most analysed food samples, however, do not result in elevated ethanol doses linked with a potentially high risk following acute and chronic consumption by adults and children.

Human biomonitoring guidance values (HBM-GVs) for priority substances under the HBM4EU initiative - New values derivation for deltamethrin and cyfluthrin and overall results.

The European Initiative HBM4EU aimed to further establish human biomonitoring across Europe as an important tool for determining population exposure to chemicals and as part of health-related risk assessments, thus making it applicable for policy advice. Not only should analytical methods and survey design be harmonized and quality assured, but also the evaluation of human biomonitoring data. For the health-related interpretation of the data within HBM4EU, a strategy for deriving health-based human biomonitoring guidance values (HBM-GVs) for both the general population and workers was agreed on. On this basis, HBM-GVs for exposure biomarkers of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), phthalates (diethyl hexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), butyl benzyl phthalate (BBzP), and bis-(2-propylheptyl) phthalate (DPHP)), bisphenols A and S, pyrethroids (deltamethrin and cyfluthrin), solvents (1-methyl-2-pyrrolidone (NMP), 1-ethylpyrrolidin-2-one (NEP), N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC)), the heavy metal cadmium and the mycotoxin deoxynivalenol (DON) were developed and assigned a level of confidence. The approach to HBM-GV derivations, results, and limitations in data interpretation with special focus on the pyrethroids are presented in this paper.

HBM4EU results support the Chemicals' Strategy for Sustainability and the Zero-Pollution Action Plan.

One of the major goals of the European Human Biomonitoring Initiative (HBM4EU) was to bridge the gap between science and policy by consulting both policy makers and national scientists and generating evidence of the actual exposure of residents to chemicals and whether that exposure would be suggest a potential health risk. Residents' perspectives on chemical exposure and risk were also investigated. HBM4EU's research was designed to answer specific short-term and long-term policy questions at national and European levels, and for its results to directly support regulatory action on chemicals. A strategy was established to prioritise chemicals for analysis in human matrices, with a total of 18 substances/substance groups chosen to be investigated throughout the five-and a -half-year project. HBM4EU produced new evidence of human exposure levels, developed reference values for exposure, investigated determinants of exposure and derived health-based guidance values for those substances. In addition, HBM4EU promoted the use of human biomonitoring data in chemical risk assessment and developed innovative tools and methods linking chemicals to possible health impacts, such as effect biomarkers. Furthermore, HBM4EU advanced understand of effects from combined exposures and methods to identify emerging chemicals. With the aim of supporting policy implementation, science-to-policy workshops were organised, providing opportunities for joint reflection and dialogue on research results. I, and indicators were developed to assess temporal and spatial patterns in the exposure of European population. A sustainable human biomonitoring monitoring framework, producing comparable quality assured data would allow: the evaluation of time trends; the exploration of spatial trends: the evaluation of the influence of socio-economic conditions on chemical exposure. Therefore, such a framework should be included in the European Chemicals' Strategy for Sustainability and the data would support the Zero Pollution Action Plan.