Assessment of Mycotoxin Exposure and Associated Risk in Pregnant Dutch Women: The Human Biomonitoring Approach.

Mycotoxins are toxic secondary metabolites produced by various fungi that can contaminate food crops, which, in turn, may lead to human exposure. Chronic exposure to mycotoxins can cause adverse health effects including reproductive and developmental toxicity. Pregnant women and their foetuses present a vulnerable group for exposure to mycotoxins that can cross the placenta. Human biomonitoring of mycotoxins provides a real-life approach to estimate internal exposure. In this pilot study, 24-h urine samples from 36 pregnant Dutch women were analysed for aflatoxin M1 (AFM1), total deoxynivalenol (DON), de-epoxy-deoxynivalenol (DOM-1), total zearalenone (ZEN), total α-zearalenol (α-ZEL), total ß-zearalenol (ß-ZEL) and total zearalanone (ZAN), where 'total' refers to mycotoxins and their conjugated forms. Serum samples from these women were analysed for fumonisin B1 (FB1) and ochratoxin A (OTA). All samples were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The most prevalent mycotoxins were total DON, total ZEN and OTA, with a detection frequency of 100%. DOM-1, total α-ZEL and total ß-ZEL were detected but to a lesser extent, while AFM1, total ZAN and FB1 were undetected. Median concentrations were 4.75 µg total DON/L, 0.0350 µg DOM-1/L, 0.0413 µg total ZEN/L, 0.0379 µg total α-ZEL/L, 0.0189 µg total ß-ZEL/L, and 0.121 µg OTA/L. The calculated median concentration for total ZEN and its metabolites was 0.105 µg/L. Based on two separate risk assessment approaches, total DON exposure in this group was considered to be of low concern. Similarly, exposure to total ZEN and its metabolites in this group was of low concern. For OTA, the risk of non-neoplastic effects was of low concern based on exposure in this group, and the risk of neoplastic effects was of low concern in the majority of participants in this group. The findings of this pilot study confirm the presence of mycotoxins in the urine and serum of pregnant Dutch women, with total DON, total ZEN, and OTA most frequently detected. Exposure to all measured mycotoxins was considered to be of low concern in this group, except for exposure to OTA, which was of low concern for the majority of participants. The study's findings offer valuable insights but should be confirmed using a larger and more diverse sample of the Dutch general population.

Safety assessment of the substance amines, di-C14-C20-alkyl, oxidised, from hydrogenated vegetable oil, for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of amines, di-C14-C18-alkyl, oxidised, renamed by the Panel as amines, di-C14-C20-alkyl, oxidised, from hydrogenated vegetable oil. The substance amines, bis(hydrogenated tallow alkyl) oxidised, consisting of the same components, but originating from tallow, is currently authorised as FCM substance No 768. The vegetable-sourced substance is intended to be used at up to 0.1% w/w as antioxidant and/or stabiliser in the manufacture of polyolefin food contact materials (FCM) and articles intended for contact with dry, aqueous and acidic foods. The substance is a mixture consisting of linear N,N-dialkyl hydroxylamines and their corresponding amine, nitrone and oxime derivatives, as well as further components: tert-N-oxides, secondary amides and carboxylic acids. Specific migration was tested from polyethylene samples in 10% ethanol and 3% acetic acid for 2 h at 100°C followed by 10 days at 60°C. None of the non-authorised components were detected to migrate at detection limits (LoD) in the range 0.003-0.029 mg/kg. The LoD of authorised carboxylic acids was 0.35 mg/kg. The Panel reassessed the genotoxicity studies carried out on FCM No 768 and evaluated two new bacterial reverse mutation tests on the nitrone and oxime derivatives as well as new (qualitative/quantitative) structure-activity relationship (Q)SAR analyses on other components. The Panel concluded that the substance did not raise a concern for genotoxicity. The Panel concluded that the substance is not of safety concern for the consumers if it is used as an additive at 0.1% w/w in the manufacture of polyolefin FCM intended to be in contact with foods simulated by food simulants A, B, C and E, except for infant formula and human milk, for storage above 6 months at room temperature and below, including hot-fill conditions and heating up to 100°C for 2 h.

Safety assessment of the substance 'phosphorous acid, triphenyl ester, polymer with 1,4-cyclohexanedimethanol and polypropylene glycol, C10-16 alkyl esters', for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the substance 'phosphorous acid, triphenyl ester, polymer with 1,4-cyclohexanedimethanol and polypropylene glycol, C10-16 alkyl esters', when used as an additive in all types of polyolefins. The substance is a polymer containing ≤ 13% w/w of a low molecular weight fraction (LMWF, < 1000 Da). A polyethylene sample with 0.15% w/w of the substance was used in a comprehensive set of migration tests with food simulants. The specific migration was up to 0.014 and 0.023 mg/kg in 4% acetic acid and 10% ethanol, respectively. Migration into olive oil was estimated by the Panel to be up to 5.3 mg/kg under worst-case conditions of use. The migrating LMWF species were comprehensively identified. Those without phosphorous were either without alerts for genotoxicity or listed in Regulation (EU) 10/2011 with worst-case migrations well below their respective specific migration limits. Toxicological studies were performed using phosphite and phosphate versions of the substance enriched in its LMWF. The substance does not raise a concern for genotoxicity. From a repeated dose 90-day oral toxicity study in rats with a 50:50 phosphite:phosphate blend, the Panel identified a NOAEL of 250 mg/kg bw per day for each component of the blend. No delayed neurotoxicity in hens was observed. The CEP Panel concluded that the substance does not raise a safety concern for the consumer if its LMWF is not higher than 13% w/w, if it is used at up to 0.15% w/w in polyolefin materials and articles intended for contact with all food types, except for infant formula and human milk, for long-term storage at room temperature and below, after hot-fill and/or heating up to 100°C for up to 2 h, and if its migration does not exceed 5 mg/kg food.

Safety assessment of the substance poly(2-hydroxypropanoic acid), n-octyl/n-decyl esters, for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of poly(2-hydroxypropanoic acid), n-octyl/n-decyl esters (OLA8), which is intended to be used as a plasticiser into polylactic acid (PLA) in contact with non-fatty foods. OLA8 is intended to be used at up to 5% and 15% w/w with or without starch, respectively (or with other additives with similar function). The migration for 10 days at 40°C from the film without starch was 0.16 mg/kg in 10% ethanol and 0.01 mg/kg in 3% acetic acid, while from the film with the starch it was well above 0.05 mg/kg food in all simulants. Some of the testing conditions were inconsistently reported. The substance did not induce gene mutations in bacterial cells and did not induce structural chromosomal aberrations or polyploidy in mammalian cells, thus, does not raise concern for genotoxicity. Instead of providing a 90-day oral toxicity study, a hydrolysis study in ■■■■■ was submitted to read-across from the authorised starting substances, ■■■■■ and the ■■■■■. However, the data provided did not allow to perform the read-across, thus no appropriate toxicological data were provided to support migration above 0.05 mg/kg food (including for contact with 10% ethanol and use in combination with starch). The Panel concluded that OLA8 does not raise a safety concern for the consumer if it is used as an additive at up to 15% w/w in the manufacture of PLA articles that do not contain starch (and other additives with similar function), that are intended to be in contact for 10 days at 40°C with foods simulated by 3% acetic acid and from which the migration does not exceed 0.05 mg/kg food.

Safety assessment of 'waxes, paraffinic, refined, derived from petroleum-based or synthetic hydrocarbon feedstock, low viscosity' for use in food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) assessed the safety of the 'waxes, paraffinic, refined, derived from petroleum-based or synthetic hydrocarbon feedstock, low viscosity' (FCM No. 93), for which the uses were requested to be extended for articles in contact with fatty foods. Migration from low-density polyethylene samples containing 1% w/w of a representative wax was tested in food simulants. In fatty food simulants, the migration of mineral oil saturated hydrocarbons (MOSH) ≤ C35 was 142 mg/kg food, exceeding the overall migration limit for plastic FCM. Mineral oil aromatic hydrocarbons (MOAH) with at least two rings are largely removed during the manufacturing process. Based on various lines of evidence, the Panel concluded that any concern for the potential presence of MOAH with two or more conjugated aromatic rings can be ruled out. Based on the genotoxicity studies and on the content of polycyclic aromatic hydrocarbons (PAHs), the substance does not raise a concern for genotoxicity. Available toxicokinetic data showed a limited accumulation of MOSH. No adverse effects were observed up to the highest tested dose of 9 g/kg body weight per day in a 90-day repeated oral toxicity study in Sprague-Dawley rats. The available results showed that FCM No. 93 is devoid of endocrine activity. The provided information on chronic toxicity and carcinogenicity was limited and inadequate to reach conclusions on these endpoints. Therefore, the CEP Panel concluded that under the intended and tested conditions of uses, the substance does not raise safety concern for the consumer if used to a level ensuring that its migration into food is no more than 5 mg/kg.

Current Advances, Research Needs and Gaps in Mycotoxins Biomonitoring under the HBM4EU-Lessons Learned and Future Trends.

Mycotoxins are natural metabolites produced by fungi that contaminate food and feed worldwide. They can pose a threat to human and animal health, mainly causing chronic effects, e.g., immunotoxic and carcinogenic. Due to climate change, an increase in European population exposure to mycotoxins is expected to occur, raising public health concerns. This urges us to assess the current human exposure to mycotoxins in Europe to allow monitoring exposure and prevent future health impacts. The mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1) were considered as priority substances to be studied within the European Human Biomonitoring Initiative (HBM4EU) to generate knowledge on internal exposure and their potential health impacts. Several policy questions were addressed concerning hazard characterization, exposure and risk assessment. The present article presents the current advances attained under the HBM4EU, research needs and gaps. Overall, the knowledge on the European population risk from exposure to DON was improved by using new harmonised data and a newly derived reference value. In addition, mechanistic information on FB1 was, for the first time, organized into an adverse outcome pathway for a congenital anomaly. It is expected that this knowledge will support policy making and contribute to driving new Human Biomonitoring (HBM) studies on mycotoxin exposure in Europe.

Safety assessment of the process Loop Polymers, used to recycle polyethylene and polypropylene printed offcuts and scrap for use as food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Loop Polymers (EU register number RECYC252). The input consists of polyethylene (PE) and polypropylene (PP) offcuts and scrap from the production of food contact packaging that has not been in contact with food, but carry coatings, ink systems and adhesives. Decontaminated material is intended to be used to produce new articles for their original application. The Panel considered critical the management system put in place to provide full traceability from input to the final product, the material review before processing, as well as the removal of coatings, ink systems and adhesives during recycling. The CEP Panel considered that the applicant did not demonstrate that coatings, ink systems and adhesives were adequately removed during the process. Consequently, it concluded that the applicant has not demonstrated that the recycling process is able to reduce the contamination of the PE or PP recyclate to a concentration that does not pose a risk to human health.

Safety assessment of the process LOGIFRUIT, used to recycle high-density polyethylene and polypropylene crates for use as food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process LOGIFRUIT (EU register number RECYC260). The input consists of pre-washed high-density polyethylene (HDPE) or polypropylene (PP) crates from closed and controlled food distribution loops. The process separates crates by material type. Crates are ground to flakes, possibly extruded to pellets and used by companies approved to be in the loop to manufacture new crates. The Panel considered that the quality management system (QAS) put in place to ensure compliance of the origin of the input with Commission Regulation (EC) No 282/2008 and to provide full traceability is critical. The Panel concluded that, when run under the conditions described, the input of the process LOGIFRUIT exclusively originates from product loops which are in closed and controlled chains. The process is designed to ensure that only crates intended for food contact are used and that contamination other than by food can be ruled out. Therefore, the recycling process LOGIFRUIT to produce HDPE and PP crates to be used in contact with fruits and vegetables, and packed meat and fish, dairy, bakery and pastry products is not of safety concern.

Safety evaluation of the food enzyme chymosin from the genetically modified Kluyveromyces lactis strain CIN.

The food enzyme chymosin (EC 3.4.23.4) is produced with the genetically modified Kluyveromyces lactis strain CIN by DSM Food Specialties B.V. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its recombinant DNA. It is intended to be used in milk processing for cheese production and for the production of fermented milk products. Dietary exposure was estimated to be up to 0.73 mg total organic solids (TOS)/kg body weight (bw) per day in European populations. Genotoxicity tests did not raise a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1,000 mg TOS/kg bw per day, the highest dose tested, which when compared with the estimated dietary exposure, results in a margin of exposure of at least 1,300. Similarity of the amino acid sequence of the food enzyme to those of known allergens was searched for and four matches were found. The Panel considered that under the intended conditions of use the risk of allergic sensitisation and elicitation reactions by dietary exposure, although unlikely, cannot be excluded, particularly for individuals sensitised to cedar pollen allergens. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Safety assessment of the process Cajas y Palets en una Economia Circular (CAPEC), used to recycle high-density polyethylene and polypropylene crates for use as food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Cajas y Palets en una Economia Circular (CAPEC) (EU register number RECYC242). The input consists of crates made of high-density polyethylene (HDPE) or polypropylene (PP) originating from closed and controlled product loops for the packaging of whole fruits and vegetables. Flakes or pellets are produced that will be used by manufacturers of new crates for food contact. The Panel considered that the management system put in place to ensure compliance of the origin of the input with Commission Regulation (EC) No 282/2008 and to provide full traceability from input to final product is the critical process step. It concluded that the input of the process CAPEC originates from product loops which are in closed and controlled chains designed to ensure that only materials and articles that have been intended for food contact are used and that contamination can be ruled out when run under the conditions described by the applicant. The recycling process CAPEC is therefore suitable to produce recycled HDPE and PP crates intended to be used in contact with fruits and vegetables.

Identification and prioritisation for risk assessment of phthalates, structurally similar substances and replacement substances potentially used as plasticisers in materials and articles intended to come into contact with food.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids was requested by the European Commission to re-evaluate the risks to public health related to the presence of plasticisers such as phthalates, structurally similar substances and replacement substances, as a consequence of migration from food contact materials (FCMs). As the first part of the two-part mandate, EFSA was tasked with identifying and prioritising those plasticisers used in FCMs that may warrant further data collection and eventual risk assessment. Close collaboration with the European Chemicals Agency (ECHA) was requested in the mandate. Substances potentially used as plasticisers were identified using Annex II of the mandate, ECHA's PLASI inventory, the Plastics Regulation and the Regenerated Cellulose Film Directive, the ECHA database, the ECHA grouping approach, and consultation with the Member States. Only substances authorised for FCMs at EU or at national level were prioritised. Five substances classified either as carcinogenic, mutagenic, toxic to reproduction Cat. 1 (under CLP) or as endocrine disruptors, persistent, bioaccumulative and toxic, very persistent/very bioaccumulative (under REACH) were placed into an 'exclusion group'. Prioritisation was based on the date of the most recent risk assessment in the context of FCM, with substances assessed before 2001 being placed in the high-priority group, substances assessed between 2001 and 2011 in the medium-priority group and substances assessed after 2011 in the low-priority group. For the EU stream, the 76 substances were split into 59 high-, 14 medium- and 3 low-priority substances. For the nationally authorised stream, the split of the 72 substances is 66, 3 and 3, respectively. The outcome of follow-up calls for data in support of the exposure assessment will be used for a final ranking.

Safety assessment of bleached cellulose pulp for use in plastic food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids assessed the safety of the substance bleached cellulose pulp, consisting of cellulose fibres (70-92%) and hemicellulose (8-30%) obtained from pine and spruce wood. The substance is intended to be used ■■■■■ in polyethylene and polypropylene food contact materials. The final articles are intended to be used for all food types and for long-term storage at room temperature, with or without a short time at higher temperature, including hot-fill. Low-density polyethylene samples containing ■■■■■ of the substance were subjected to a broad set of migration tests with food simulants and extraction tests with dichloromethane. The limits of detection ranged from ■■■■■ (when specified). The Panel noted that they do not ensure the detection of genotoxic substances at a concentration leading to a human exposure above the Threshold of Toxicological Concern. Moreover, not all possibly migrating substances were identified or amenable to the analytical methods applied. No toxicological data were provided for the substance itself, as its migration into food is not expected. The safety of the potentially migrating substances of low molecular mass detected was addressed individually and was considered adequate. However, the Panel considered this approach insufficient owing to a substantial fraction of unidentified components. The Panel concluded that the information provided by the applicant does not allow the safety assessment of the substances below 1,000 Da from bleached cellulose pulp from pine and spruce wood used in plastic food contact materials potentially migrating into food. Therefore, the Panel could not conclude on the safety of the use of bleached cellulose pulp from pine and spruce wood as a plastic additive.

Safety assessment of the process Srichakra Polyplast, based on the Starlinger iV+ technology, used to recycle post-consumer PET into food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process Srichakra Polyplast (EU register number RECYC229), which uses the Starlinger iV+ technology. The input is hot caustic washed and dried poly(ethylene terephthalate) (PET) flakes mainly originating from collected post-consumer PET containers, with no more than 5% PET from non-food consumer applications. The flakes are dried and crystallised in a first reactor, then extruded into pellets. These pellets are crystallised, preheated and treated in a solid-state polycondensation (SSP) reactor. Having examined the challenge test provided, the Panel concluded that the drying and crystallisation (step 2), extrusion and crystallisation (step 3) and SSP (step 4) are critical in determining the decontamination efficiency of the process. The operating parameters to control the performance of these critical steps are temperature, air flow and residence time for the drying and crystallisation step, and temperature, pressure and residence time for the extrusion and crystallisation step as well as the SSP step. It was demonstrated that this recycling process is able to ensure that the level of migration of potential unknown contaminants into food is below the conservatively modelled migration of 0.1 µg/kg food. Therefore, the Panel concluded that the recycled PET obtained from this process is not of safety concern when used at up to 100% for the manufacture of materials and articles for contact with all types of foodstuffs for long-term storage at room temperature, with or without hotfill. The final articles made of this recycled PET are not intended to be used in microwave and conventional ovens and such uses are not covered by this evaluation.

Safety assessment of the process deSter, used to recycle plastic catering tableware for use as food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process deSter (EU register number RECYC196). The input consists of catering tableware food contact articles from airline on-board services, made of polypropylene (PP), polyethylene terephthalate (PET), styrene acrylonitrile resin (SAN) or acrylonitrile butadiene styrene (ABS). The recyclate produced by deSter will be used to manufacture articles for the same on-board services. The Panel considered that the management system put in place to ensure compliance of the origin of the input with Commission Regulation (EC) No 282/2008 and to provide full traceability from input to final product is the critical process step. The process deSter uses only materials and articles intended for food contact and ensures that any contamination can be ruled out, since the input originates from this product loop managed in a closed and controlled chain. Therefore, the Panel concluded that the recycled materials obtained from this process and used within this loop are not of safety concern, when used at up to 100% for the manufacture of plastic tableware for contact with all types of foodstuffs under the conditions of use of the articles before recycling.

Biomarkers of effect as determined in human biomonitoring studies on hexavalent chromium and cadmium in the period 2008-2020.

A number of human biomonitoring (HBM) studies have presented data on exposure to hexavalent chromium [Cr(VI)] and cadmium (Cd), but comparatively few include results on effect biomarkers. The latter are needed to identify associations between exposure and adverse outcomes (AOs) in order to assess public health implications. To support improved derivation of EU regulation and policy making, it is of great importance to identify the most reliable effect biomarkers for these heavy metals that can be used in HBM studies. In the framework of the Human Biomonitoring for Europe (HBM4EU) initiative, our study aim was to identify effect biomarkers linking Cr(VI) and Cd exposure to selected AOs including cancer, immunotoxicity, oxidative stress, and omics/epigenetics. A comprehensive PubMed search identified recent HBM studies, in which effect biomarkers were examined. Validity and applicability of the markers in HBM studies are discussed. The most frequently analysed effect biomarkers regarding Cr(VI) exposure and its association with cancer were those indicating oxidative stress (e.g., 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), glutathione (GSH)) and DNA or chromosomal damage (comet and micronucleus assays). With respect to Cd and to some extent Cr, ß-2-microglobulin (B2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) are well-established, sensitive, and the most common effect biomarkers to relate Cd or Cr exposure to renal tubular dysfunction. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM)-1 could serve as sensitive biomarkers of acute kidney injury in response to both metals, but need further investigation in HBM studies. Omics-based biomarkers, i.e., changes in the (epi-)genome, transcriptome, proteome, and metabolome associated with Cr and/or Cd exposure, are promising effect biomarkers, but more HBM data are needed to confirm their significance. The combination of established effect markers and omics biomarkers may represent the strongest approach, especially if based on knowledge of mechanistic principles. To this aim, also mechanistic data were collected to provide guidance on the use of more sensitive and specific effect biomarkers. This also led to the identification of knowledge gaps relevant to the direction of future research.

Assessment of the impact of the IARC Monograph Vol. 121 on the safety of the substance styrene (FCM No 193) for its use in plastic food contact materials.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) was requested by the European Commission to re-evaluate the safety of styrene (FCM No 193) for use in plastic food contact materials (FCM) following the classification by the International Agency for Research on Cancer (IARC) as 'probably carcinogenic to humans'. The IARC Monograph pertains to hazard identification, based on studies on high-dose occupational exposures by inhalation and animal studies, also mainly by inhalation. The Panel considered that the IARC conclusions cannot be directly applied to the evaluation of risks for consumers from the oral exposure to styrene, but also concluded that, based on the data provided in the IARC Monograph and by the industry, a concern for genotoxicity associated with oral exposure to styrene cannot be excluded. The migration of styrene into foods packed in styrenic plastics is below 10 µg/kg for the majority of the foods, but up to 230 µg/kg was reported. Migration tends to be high for contact with fatty foods, and/or with high surface to volume ratios of the FCM. Dietary exposure of the consumers to styrene migrating from styrenic plastics was estimated in the order of 0.1 µg/kg body weight (bw) per day. It is in the same range as exposure from styrene present in foods as such. The dietary exposure (food component plus migration from styrenic plastics) is similar or lower than that by inhalation in the general population. Taking the human exposure data into account, the Panel concluded that a systematic review of genotoxicity and mechanistic data, comparative toxicokinetics and analysis of species differences is required for assessing the safety of styrene for its use in FCM.

Review and priority setting for substances that are listed without a specific migration limit in Table 1 of Annex 1 of Regulation 10/2011 on plastic materials and articles intended to come into contact with food.

The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) was requested by the European Commission to review the substances for which a Specific Migration Limit (SML) is not assigned in Regulation (EU) No 10/2011. These substances had been covered by the Generic SML of 60 mg/kg food, but with Regulation (EU) 2016/1416 it was removed, necessitating their re-examination. EFSA was requested to identify those substances requiring an SML to ensure the authorisation is sufficiently protective to health, grouping them in high, medium and low priority to serve as the basis for future re-evaluations of individual substances. The CEP Panel established a stepwise procedure. This took into account existing hazard assessments for each substance on carcinogenicity/mutagenicity/reprotoxicity (CMR), bioaccumulation and endocrine disruptor (ED) properties along with the use of in silico generated predictions on genotoxicity. Molecular weights and boiling points were considered with regard to their effect on potential consumer exposure. This prioritisation procedure was applied to a total of 451 substances, from which 78 substances were eliminated at the outset, as they had previously been evaluated by EFSA as food contact substances. For 89 substances, the Panel concluded that a migration limit should not be needed. These are in the lists 0 and 1 of the Scientific Committee for Food (SCF), defined as substances for which an Acceptable Daily Intake (ADI) does not need to be established, along with substances that are controlled by existing restrictions and/or generic limits. Of the remaining 284 substances, 179 were placed into the low priority group, 102 were placed into the medium priority group and 3 were placed into the high priority group, i.e. salicylic acid (FCM No 121), styrene (FCM No 193) and lauric acid, vinyl ester (FCM No 436).

Concentrations of dimethylaniline and other metabolites in milk and tissues of dairy cows treated with lidocaine.

Lidocaine is a topical anaesthetic drug used in dairy cows for laparotomy (caesarean section, abomasal displacement). Because there are no registered drugs for this indication, it can be applied under the so-called Cascade rules (off-label use), with the restriction that the off-label withdrawal periods of 7 days for milk and 28 days for meat are taken into account. In animals, lidocaine is rapidly metabolised into various metabolites, one being 2,6-dimethylaniline (DMA) which is reported to possess carcinogenic and mutagenic properties and detected also in milk. To investigate whether the off-label withdrawal periods are long enough to exclude the presence of lidocaine and DMA, and potential other metabolites, in edible products, a study was performed with eight dairy cows treated with lidocaine by injection in the abdominal muscles. At various time points blood samples, milk and urine were collected. Four animals were slaughtered 3.5 h after treatment, the other four after 48.5 h. The injection site, meat, liver and kidney were analysed for levels of lidocaine, DMA, monoethylglycinexylidide (MEGX) and 3-OH-lidocaine. It was shown that DMA is an important metabolite in dairy cows and can be detected in both meat and milk. In addition, also MEGX, 3-OH-lidocaine and three other metabolites were identified and to some extent quantified. These metabolites were 4-OH-lidocaine, lidocaine-N-oxide and 4-hydroxy-DMA. The latter compound was the most important metabolite in urine. However, levels in milk and meat decreased rapidly after the application. Overall, it can be concluded that the off-label withdrawal times of 7 and 28 days for milk and meat, respectively, guarantee the absence of detectable levels of lidocaine and metabolites.

World Health Organization estimates of the global and regional disease burden of four foodborne chemical toxins, 2010: a data synthesis.

Background Chemical exposures have been associated with a variety of health effects; however, little is known about the global disease burden from foodborne chemicals. Food can be a major pathway for the general population's exposure to chemicals, and for some chemicals, it accounts for almost 100% of exposure.  Methods and Findings Groups of foodborne chemicals, both natural and anthropogenic, were evaluated for their ability to contribute to the burden of disease.  The results of the analyses on four chemicals are presented here - cyanide in cassava, peanut allergen, aflatoxin, and dioxin.  Systematic reviews of the literature were conducted to develop age- and sex-specific disease incidence and mortality estimates due to these chemicals.  From these estimates, the numbers of cases, deaths and disability adjusted life years (DALYs) were calculated.  For these four chemicals combined, the total number of illnesses, deaths, and DALYs in 2010 is estimated to be 339,000 (95% uncertainty interval [UI]: 186,000-1,239,000); 20,000 (95% UI: 8,000-52,000); and 1,012,000 (95% UI: 562,000-2,822,000), respectively.  Both cyanide in cassava and aflatoxin are associated with diseases with high case-fatality ratios.  Virtually all human exposure to these four chemicals is through the food supply.  Conclusion Chemicals in the food supply, as evidenced by the results for only four chemicals, can have a significant impact on the global burden of disease. The case-fatality rates for these four chemicals range from low (e.g., peanut allergen) to extremely high (aflatoxin and liver cancer).  The effects associated with these four chemicals are neurologic (cyanide in cassava), cancer (aflatoxin), allergic response (peanut allergen), endocrine (dioxin), and reproductive (dioxin).