Germany's first Total Diet Study - Occurrence of non-dioxin-like polychlorinated biphenyls and polybrominated diphenyl ethers in foods.

The occurrence of persistent organic pollutants like polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in food represents a public health concern. The BfR MEAL Study was initiated to generate a comprehensive data base of occurrence data for chemicals in the most consumed foods in Germany. Non-dioxin-like PCBs (NDL-PCBs) and PBDEs were analysed in 300 foods, purchased and prepared representatively for the eating behaviour of the population in Germany. Highest levels of NDL-PCBs and PBDEs were detected in spiny dogfish, cod liver, herring, and eel. High NDL-PCB and PBDE levels were observed in other oily fish, wild boar meat, sheep liver, and high-fat dairy products. The comparison of food from conventional and organic production revealed higher NDL-PCB values in the food group 'meat and meat products' if produced organically. Occurrence data of this study will improve future dietary exposure and risk assessments in Germany.

Polychlorinated Biphenyl Concentrations and Estimated Intakes in Fish Oil Supplements on the Japanese Market.

Polychlorinated biphenyls (PCBs) are synthetic organic contaminants that are widespread in the environment. There are 209 PCB congeners. Fish oil produced from marine fish is widely used as a health supplement. PCB contamination of fish oil is of concern. We determined the concentrations of all 209 PCB congeners in commercially available fish oil supplements from Japan and estimated PCB intakes for humans consuming the supplements. We determined the concentrations of non-dioxin-like PCBs separately. The total PCB concentrations in 37 fish oil supplements purchased in Japan were 0.024-19 ng/g whole weight, and the non-dioxin-like PCB concentration range was also 0.024-19 ng/g whole weight. The total PCB intakes calculated for a 50 kg human consuming the supplements were 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)) and the non-dioxin-like PCB intake range was also 0.039-51 ng/day (0.00078-1.0 ng/(kg body weight per day)). The total PCB intakes were much lower than the tolerable daily intake of 20 ng/(kg body weight per day) recommended by the WHO. The results indicated that PCBs in the fish oil supplements pose acceptable risks to humans consuming the fish oil supplements daily.

Predicted versus observed activity of PCB mixtures toward the ryanodine receptor.

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs and similar compounds toward RyR1 activation and related neurotoxicity.

Time series data (2008-2023) of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in bivalves from Shellfish Production Areas of the Basque coast (SE Bay of Biscay).

The accumulation of contaminants in aquatic organisms is of concern to human health due to the potential for exposure through the consumption of seafood. This dataset presents the levels of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and 12 dioxin-like polychlorinated biphenyls (DL-PCBs) (PCB-81, PCB-77, PCB-126, PCB-169, PCB-123, PCB-118, PCB-114, PCB-105, PCB-167, PCB-156, PCB-157 and PCB-189) in bivalves collected annually between 2008 and 2023 from the four Shellfish Production Areas of the Basque coast (southeastern Bay of Biscay). Additionally, data on 6 non-dioxin like polychlorinated biphenyls (NDL-PCBs) (PCB-28, PCB-52, PCB-101, PCB-153, PCB-138 and PCB-180) is provided for the 2012-2023 time period. Depending on the availability of bivalves at each Shellfish Production Area, different species, such as mussels (Mytilus galloprovincialis) and oysters (Magallana gigas and Ostrea edulis) were used for the evaluation. Bivalve samples were analyzed at the accredited Laboratory of Dioxins of the Institute of Environmental Assessment and Water Research - CSIC in Spain, following standardized methodologies according to the specific requirements established at the corresponding EU Regulation. Concentrations and the World Health Organization-Toxic Equivalents (WHO-TEQ) were calculated. Considering the data from the four Shellfish Production Areas and the study period, WHO-TEQ values ranged from 0.12 to 0.64 pg g-1 wet weight for PCDD/Fs and from 0.45 to 2.23 pg g-1 wet weight for DL-PCBs, whereas concentrations ranged from 7.45 to 51.10 ng g-1 wet weight for NDL-PCBs. This database is useful for (i) assessing the spatial and temporal trends of PCDD/Fs and various PCBs in bivalves from the Basque coast, (ii) determining the relative contribution of different congeners, (iii) comparison with levels for human consumption and environmental quality standards, as well as with levels of other biogeographical areas, and (iv) the management of Shellfish Production Areas on the Basque coast.

Predicted Versus Observed Activity of PCB Mixtures Toward the Ryanodine Receptor.

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs, and similar compounds, towards RyR1 activation and related neurotoxicity.

Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180): A postnatal follow-up study in rats.

PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.

Non-dioxin-like polychlorinated biphenyl neurotoxic equivalents found in environmental and human samples.

Non-dioxin like polychlorinated biphenyls (NDL PCB) are recognized neurotoxicants with implications on altered neurodevelopment and neurodegeneration in exposed organisms. NDL PCB neurotoxic relative potency schemes have been developed for a single mechanism, namely activity toward the ryanodine receptor (RyR), or combined mechanisms including, but not limited to, alterations of RyR and dopaminergic pathways. We compared the applicability of the two neurotoxic equivalency (NEQ) schemes and applied each scheme to PCB mixtures found in environmental and human serum samples. A multiple mechanistic NEQ predicts higher neurotoxic exposure concentrations as compared to a scheme based on the RyR alone. Predictions based on PCB ortho categorization, versus homologue categorization, lead to a higher prediction of neurotoxic exposure concentrations, especially for the mMOA. The application of the NEQ schemes to PCB concentration data suggests that PCBs found in fish from US lakes represent a considerable NEQ exposure to fish consuming individuals, that indoor air of schools contained high NEQ concentrations representing an exposure concern when inhaled by children, and that levels already detected in the serum of adults and children may contribute to neurotoxicity. With further validation and in vivo exposure data the NEQ scheme would help provide a more inclusive measure of risk presented by PCB mixtures.

Dietary exposure to non-dioxin-like PCBs of the Hong Kong adult population from a total diet study.

Dietary exposure of Hong Kong adults to the sum of the six indicator PCBs (Σ6 PCBs; PCB 28, 52, 101, 138, 153, and 180) was estimated in this study using the Total Diet Study (TDS) approach. Seventy one commonly-consumed food items of animal origin were sampled in four seasons and prepared as consumed in 2010-2011. The results showed that the main dietary source of Σ6 PCBs to the adult population was 'fish, seafood and their products' which accounted for 84.3% of the total exposure. About 50% of the total exposure was contributed by four fish species: salmon (cooked salmon and salmon sashimi, 19.9%), mandarin fish (14.7%), pomfret fish (8.5%) and yellow croaker (7.5%). Salmon was found to contain the highest mean level of Σ6 PCBs of 5.7 ng g-1 fresh weight at upper bound estimation, ranging from 4.4 to 6.3 ng g-1. The lower bound and upper bound exposure estimates of Æ©6 PCBs to the average consumer of the population were found to be 0.68 and 1.38 ng kg-1 body weight day-1 respectively while for high consumers, the lower bound and upper bound exposure estimates were 3.08 and 3.84 ng kg-1 body weight day-1 respectively. In addition, the dietary exposures to individual indicator PCB congeners were also estimated.

Scientific assistance to assess the detoxification process for dioxins and PCBs in sunflower cake by hexane extraction.

EFSA was requested to provide scientific assistance to the European Commission on a detoxification process for dioxins and polychlorinated biphenyls (PCBs) from sunflower cake by hexane extraction in an emergency situation, as specified in Article 7 of Commission Regulation (EU) 2015/786. The process entails hexane extraction of sunflower oil from the cake to remove dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) as well as dioxin-like (DL-) and non-dioxin-like (NDL-) PCBs. The data provided by the applicant were assessed with respect to the efficacy of the process, absence of solvent residues and on information demonstrating that the process does not adversely affect the nature and characteristics of the product. According to data provided, the process was effective in producing a sunflower meal that contained concentrations of PCDD/Fs and DL-PCBs, and NDL-PCBs (6 indicator PCBs) about 90% lower than in the sunflower cake. The data showed that it is possible to meet the current EU maximum levels with respect to these contaminants using this process. It is unlikely that hazardous substances (i.e. hexane) remain in the final product. The extraction of the oil from the sunflower cake produces sunflower meal, which has a different nutrient content and nutritional value than the original sunflower cake, but is suitable to be used in animal nutrition with no specific legal limitations in the use or the inclusion levels in the diets. The applicant indicated that the crude oil, as well as the co-products resulting of the processing of this oil, could only be used for technical purposes. No information was provided regarding the disposal or reuse of the hexane. EFSA concluded that the proposed detoxification process to remove PCDD/Fs and PCBs from sunflower cake by means of solvent extraction to produce sunflower meal, met the acceptability criteria provided in Commission Regulation (EU) 2015/786.

Assessment of a decontamination process for dioxins and PCBs from fish meal by hexane extraction and replacement of fish oil.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of a decontamination process for fish meal. This process entails solvent (hexane) extraction of fish oil from fish meal to remove dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) as well as dioxin-like (DL-) and non-dioxin-like (NDL-) polychlorinated biphenyls (PCBs) followed by replacement with decontaminated fish oil. All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. The data provided by the feed business operator were assessed with respect to the efficacy of the process, absence of solvent residues, and on information demonstrating that the process does not adversely affect the nature and characteristics of the product. According to data provided, the process was effective in removing PCDD/Fs and DL-PCBs by approximately 70% and NDL-PCBs by about 60%. The data showed that it is possible to meet the current EU requirements with respect to these contaminants, provided that the level of contamination of untreated fish meal is within the range of the tested batches. It is unlikely that hazardous substances (i.e. hexane) remain in the final product. The Panel considered that there is no evidence that fish oil extraction followed by replacement with decontaminated fish oil leads to detrimental changes in the nutritional composition of the fish meal, although some beneficial constituents (e.g. lipophilic vitamins) might be depleted. The feed business operator submitted information to demonstrate safe disposal of the waste material. The CONTAM Panel concluded that the proposed decontamination process to remove dioxins (PCDD/Fs) and PCBs from fish meal by means of solvent extraction and fish oil replacement was assessed to be compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.

Ryanodine receptor and FK506 binding protein 1 in the Atlantic killifish (Fundulus heteroclitus): A phylogenetic and population-based comparison.

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine receptors (RyR), microsomal Ca2+ channels of broad significance. Teleost fish may be important models for NDL PCB neurotoxicity, and we used sequencing databases to characterize teleost RyR and FK506 binding protein 12 or 12.6kDa (genes FKBP1A; FKBP1B), which promote NDL PCB-triggered Ca2+ dysregulation. Particular focus was placed on describing genes in the Atlantic killifish (Fundulus heteroclitus) genome and searching available RNA-sequencing datasets for single nucleotide variants (SNV) between PCB tolerant killifish from New Bedford Harbor (NBH) versus sensitive killifish from Scorton Creek (SC), MA. Consistent with the teleost whole genome duplication (tWGD), killifish have six RyR genes, corresponding to a and b paralogs of mammalian RyR1, 2 and 3. The presence of six RyR genes was consistent in all teleosts investigated including zebrafish. Killifish have four FKBP1; one FKBP1b and three FKBP1a named FKBP1aa, FKBP1ab, likely from the tWGD and a single gene duplicate FKBP1a3 suggested to have arisen in Atherinomorphae. The RyR and FKBP1 genes displayed tissue and developmental stage-specific mRNA expression, and the previously uncharacterized RyR3, herein named RyR3b, and all FKBP1 genes were prominent in brain. We identified a SNV in RyR3b encoding missense mutation E1458D. In NBH killifish, 57% were heterozygous and 28% were homozygous for this SNV, whereas almost all SC killifish (94%) lacked the variant (n≥39 per population). The outlined sequence differences between mammalian and teleost RyR and FKBP1 together with outlined population differences in SNV frequency may contribute to our understanding of NDL PCB neurotoxicity.

Non-dioxin-like PCBs: a survey on fishery and aquaculture from the Mediterranean area.

A sampling campaign from 21 sites in Italy was conducted: 15 species from fishery and three species from aquaculture, for a total of 40 determinations, were considered. A careful sample preparation preceded the instrumental analysis that was carried out by means of GC-ECD and GC-MS. Good laboratory practice was achieved by the participation in proficiency tests, by the use of certified reference materials and by applying other directives recommended by international organisations. Concentrations measured in this work were compared with a TDI proposed by some international bodies: for a person weighing 70 kg one-third of the samples from fishery, when consumed, lead to exceed this TDI if the average fish daily consumption per capita is considered. Based on the data obtained here some hypotheses on environmental spreading and influence of PCBs on human health are made. Some suggestions about the preparation of fish for consumption are also given.

Non-dioxin-like polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) induce chondrocyte cell death through multiple pathways.

Environmental pollutants are known to have adverse effects on human health. However, the link between chemical exposure and osteoarthritis remains little investigated. This study sought to assess in vitro the effect of several non-dioxin-like polychlorinated biphenyls (NDL-PCBs) on chondrocytes viability and apoptosis induction. Murine chondrogenic ATDC-5 cell line and human T/C-28a2 immortalized chondrocytes were exposed to NDL-PCBs 101, 153 and 180. Cell viability was examined using MTT assay. Necrosis was evaluated by LDH assay. Expression of apoptotic related proteins, such as caspase-3, Bcl-2 and Bax was assessed by Western blot analysis. Finally, oxidative stress was evaluated by malondialdehyde (MDA) assay and the Oxidative Stress Index. In vitro exposure to NDL-PCBs caused strong reduction of cell viability in a concentration-dependent manner. Data from LDH assay showed cellular necrosis induction. Caspase-3 activation, as well as, altered Bcl2/Bax ratio and p38 MAP-kinase phosphorylation also suggested apoptosis induction. Finally, MDA levels and Oxidative Stress Index revealed that PCBs drive chondrocyte death via increase of oxidative stress. The viability of murine and human chondrocytes was reduced in presence of PCBs. The activity of PCBs on cell viability is likely to be mediated by complex alterations involving regulation mechanisms of apoptosis, necrosis and oxidative stress.

Dietary exposure to non-dioxin-like PCBs of different population groups in Austria.

The dietary exposure to the sum of the six indicator PCBs (Σ6 PCBs; PCB 28, 52, 101, 138, 153, and 180) across different Austrian population groups was assessed in this study by combining data on occurrence from food of the Austrian market (n=157) analysed during 2006-2011 with national food consumption data. The most contaminated food group was meat, poultry, game and offal with average levels of ndl-PCBs of 5.20 ng g(-1) fat. In fish and fish products and eggs, mean concentrations of 3.89 ng g(-1) fresh weight (fw) and 4.00 ng g(-1) fat, respectively, were found. In milk and dairy products average concentrations ranged from 3.07 to 4.44 ng g(-1) fat. The mean dietary intake of Σ6 PCBs was estimated to be 3.37 ng kg(-1) bw d(-1) for children (6-15 years old), 3.19 ng kg(-1) bw d(-1) for women (19-65 years) and 2.64 ng kg(-1) bw d(-1) for men (19-65 years). In all three population groups, milk and dairy products was the major contributing food group to the total dietary intake (50-55%) followed by fish and fish products (23-27%). The exposure of all Austrian population groups is well below the tolerable daily intake (TDI) of 10 ng kg(-1) bw d(-1) proposed by WHO, accounting for 34% in children, 32% in women and 26% in men.

Expression and function of ryanodine receptor related pathways in PCB tolerant Atlantic killifish (Fundulus heteroclitus) from New Bedford Harbor, MA, USA.

Atlantic killifish (Fundulus heteroclitus) thrive in New Bedford Harbor (NBH), MA, highly contaminated with polychlorinated biphenyls (PCBs). Resident killifish have evolved tolerance to dioxin-like (DL) PCBs, whose toxic effects through the aryl hydrocarbon receptor (AhR) are well studied. In NBH, non-dioxin like PCBs (NDL PCBs), which lack activity toward the AhR, vastly exceed levels of DL congeners yet how killifish counter NDL toxic effects has not been explored. In mammals and fish, NDL PCBs are potent activators of ryanodine receptors (RyR), Ca(2+) release channels necessary for a vast array of physiological processes. In the current study we compared the expression and function of RyR related pathways in NBH killifish with killifish from the reference site at Scorton Creek (SC, MA). Relative to the SC fish, adults from NBH displayed increased levels of skeletal muscle RyR1 protein, and increased levels of FK506-binding protein 12 kDa (FKBP12) an accessory protein essential for NDL PCB-triggered changes in RyR channel function. In accordance with increased RyR1 levels, NBH killifish displayed increased maximal ligand binding, increased maximal response to Ca(2+) activation and increased maximal response to activation by the NDL PCB congener PCB 95. Compared to SC, NBH embryos and larvae had increased levels of mtor and ryr2 transcripts at multiple stages of development, and generations, while levels of serca2 were decreased at 9 days post-fertilization in the F1 and F2 generations. These findings suggest that there are compensatory and heritable changes in RyR mediated Ca(2+) signaling proteins or potential signaling partners in NBH killifish.

Dietary exposure of the Belgian adult population to non-dioxin-like PCBs.

Non-dioxin-like polychlorinated biphenyls (ndl-PCBs), and some of their metabolites, might initiate neurological, neuroendocrinological, immunological and carcinogenic effects. Dietary exposure of the Belgian adult population to ndl-PCBs was investigated in this study. Foods from five food groups, collected in Belgium in 2008, were analyzed by GC-MS/MS for the six indicator PCBs (PCB 28, 52, 101, 138, 153 and 180). Results were expressed as the sum of the six congeners. A dietary exposure assessment was performed, combining ndl-PCBs levels found in food with data from the national food consumption survey of 2004. Fish and fish products were the dominating food group in terms of contamination level, with the highest levels measured in the composite sample «other fishes¼ (18.58 ng/g FW). The dietary exposure of the Belgian population (n=3083) to ndl-PCBs ranged from 5.33 ng/kg b.w./day on average to 16.10 ng/kg b.w./day at the 99th percentile, using the lower bound concentration. The mean dietary exposure mainly originates from Fish and fish products (54.3%), followed by dairy products (28.5%). As neither EFSA nor JECFA have set a Tolerable Daily Intake for ndl PCBs, uncertainty remains about how to interpret the exposure data in terms of public health.