Risks for animal and human health related to the presence of polychlorinated naphthalenes (PCNs) in feed and food.

EFSA was asked for a scientific opinion on the risks for animal and human health related to the presence of polychlorinated naphthalenes (PCNs) in feed and food. The assessment focused on hexaCNs due to very limited data on other PCN congeners. For hexaCNs in feed, 217 analytical results were used to estimate dietary exposures for food-producing and non-food-producing animals; however, a risk characterisation could not be performed because none of the toxicological studies allowed identification of reference points. The oral repeated dose toxicity studies performed in rats with a hexaCN mixture containing all 10 hexaCNs indicated that the critical target was the haematological system. A BMDL20 of 0.05 mg/kg body weight (bw) per day was identified for a considerable decrease in the platelet count. For hexaCNs in food, 2317 analytical results were used to estimate dietary exposures across dietary surveys and age groups. The highest exposure ranged from 0.91 to 29.8 pg/kg bw per day in general population and from 220 to 559 pg/kg bw per day for breast-fed infants with the highest consumption of breast milk. Applying a margin of exposure (MOE) approach, the estimated MOEs for the high dietary exposures ranged from 1,700,000 to 55,000,000 for the general population and from 90,000 to 230,000 for breast-fed infants with the highest consumption of breast milk. These MOEs are far above the minimum MOE of 2000 that does not raise a health concern. Taking account of the uncertainties affecting the assessment, the Panel concluded with at least 99% certainty that dietary exposure to hexaCNs does not raise a health concern for any of the population groups considered. Due to major limitations in the available data, no assessment was possible for genotoxic effects or for health risks of PCNs other than hexaCNs.

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.

The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE-28, -47, -49, -99, -100, -138, -153, -154, -183 and ­209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE-47, -99, -153, -209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint-specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern.

Guidance for the assessment of detoxification processes in feed.

This statement provides scientific guidance on the information needed to support the risk assessment of the detoxification processes applied to products intended for animal feed in line with the acceptability criteria of the Commission Regulation (EU) 2015/786.

The 2022 world health organization reevaluation of human and mammalian toxic equivalency factors for polychlorinated dioxins, dibenzofurans and biphenyls.

In October 2022, the World Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated. In contrast to earlier panels that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the 2006 REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive "Best-Estimate" TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The "Best-Estimate" TEF derived from the model was used to assign 2022 WHO-TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs.

Constructing a clinical radiographic knee osteoarthritis database using artificial intelligence tools with limited human labor: A proof of principle.

OBJECTIVE: To create a scalable and feasible retrospective consecutive knee osteoarthritis (OA) radiographic database with limited human labor using commercial and custom-built artificial intelligence (AI) tools. METHODS: We applied four AI tools, two commercially available and two custom-built tools, to analyze 6 years of clinical consecutive knee radiographs from patients aged 35-79 at the University of Copenhagen Hospital, Bispebjerg-Frederiksberg Hospital, Denmark. The tools provided Kellgren-Lawrence (KL) grades, joint space widths, patella osteophyte detection, radiographic view detection, knee joint implant detection, and radiographic marker detection. RESULTS: In total, 25,778 knee radiographs from 8575 patients were included in the database after excluding inapplicable radiographs, and 92.5% of the knees had a complete OA dataset. Using the four AI tools, we saved about 800 hours of radiologist reading time and only manually reviewed 16.0% of the images in the database. CONCLUSIONS: This study shows that clinical knee OA databases can be built using AI with limited human reading time for uniform grading and measurements. The concept is scalable temporally and across geographic regions and could help diversify further OA research by efficiently including radiographic knee OA data from different populations globally. We can prevent data dredging and overfitting OA theories on existing trite cohorts by including various gene pools and continuous expansion of new clinical cohorts. Furthermore, the suggested tools and applied approaches provide an ability to retest previous hypotheses and test new hypotheses on real-life clinical data with current disease prevalence and trends.

Decoding the Postulated Entourage Effect of Medicinal Cannabis: What It Is and What It Isn't.

The 'entourage effect' term was originally coined in a pre-clinical study observing endogenous bio-inactive metabolites potentiating the activity of a bioactive endocannabinoid. As a hypothetical afterthought, this was proposed to hold general relevance to the usage of products based on Cannabis sativa L. The term was later juxtaposed to polypharmacy pertaining to full-spectrum medicinal Cannabis products exerting an overall higher effect than the single compounds. Since the emergence of the term, a discussion of its pharmacological foundation and relevance has been ongoing. Advocates suggest that the 'entourage effect' is the reason many patients experience an overall better effect from full-spectrum products. Critics state that the term is unfounded and used primarily for marketing purposes in the Cannabis industry. This scoping review aims to segregate the primary research claiming as well as disputing the existence of the 'entourage effect' from a pharmacological perspective. The literature on this topic is in its infancy. Existing pre-clinical and clinical studies are in general based on simplistic methodologies and show contradictory findings, with the clinical data mostly relying on anecdotal and real-world evidence. We propose that the 'entourage effect' is explained by traditional pharmacological terms pertaining to other plant-based medicinal products and polypharmacy in general (e.g., synergistic interactions and bioenhancement).

Should artificial intelligence have lower acceptable error rates than humans?

The first patient was misclassified in the diagnostic conclusion according to a local clinical expert opinion in a new clinical implementation of a knee osteoarthritis artificial intelligence (AI) algorithm at Bispebjerg-Frederiksberg University Hospital, Copenhagen, Denmark. In preparation for the evaluation of the AI algorithm, the implementation team collaborated with internal and external partners to plan workflows, and the algorithm was externally validated. After the misclassification, the team was left wondering: what is an acceptable error rate for a low-risk AI diagnostic algorithm? A survey among employees at the Department of Radiology showed significantly lower acceptable error rates for AI (6.8 %) than humans (11.3 %). A general mistrust of AI could cause the discrepancy in acceptable errors. AI may have the disadvantage of limited social capital and likeability compared to human co-workers, and therefore, less potential for forgiveness. Future AI development and implementation require further investigation of the fear of AI's unknown errors to enhance the trustworthiness of perceiving AI as a co-worker. Benchmark tools, transparency, and explainability are also needed to evaluate AI algorithms in clinical implementations to ensure acceptable performance.

The transfer of environmental contaminants (Brominated and Chlorinated dioxins and biphenyls, PBDEs, HBCDDs, PCNs and PFAS) from recycled materials used for bedding to the eggs and tissues of chickens.

Some types of poultry bedding made from recycled materials have been reported to contain environmental contaminants such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, dioxins), polychlorinated biphenyls (PCBs) brominated flame retardants (BFRs) polychlorinated naphthalenes (PCNs), polybrominated dioxins (PBDD/Fs), perfluoroalkyl substances (PFAS), etc. In one of the first studies of its kind, the uptake of these contaminants by chicken muscle tissue, liver, and eggs from three types of recycled, commercially available bedding material was simultaneously investigated using conventional husbandry to raise day old chickens to maturity. A weight of evidence analysis showed that PCBs, polybrominated diphenylethers (PBDEs), PCDD/Fs, PCNs and PFAS displayed the highest potential for uptake which varied depending on the type of bedding material used. During the first three to four months of laying, an increasing trend was observed in the concentrations of ΣTEQ (summed toxic equivalence of PCDD/Fs, PCBs, PBDD/Fs, PCNs and polybrominated biphenyls), NDL-PCBs and PBDEs in the eggs of chickens raised on shredded cardboard. Further analysis using bio-transfer factors (BTFs) when egg production reached a steady state, revealed that some PCB congeners (PCBs 28, 81, 138, 153 and 180) irrespective of molecular configuration or chlorine number, showed the highest tendency for uptake. Conversely, BTFs for PBDEs showed good correlation with bromine number, increasing to a maximum value for BDE-209. This relationship was reversed for PCDFs (and to some extent for PCDDs) with tetra- and penta- chlorinated congeners showing a greater tendency for selective uptake. The overall patterns were consistent, although some variability in BTF values was observed between tested materials which may relate to differences in bioavailability. The results indicate a potentially overlooked source of food chain contamination as other livestock products (cow's milk, lamb, beef, duck, etc.) could be similarly impacted.

Transfer of polychlorinated, polybrominated and mixed-halogenated dioxins, furans and biphenyls, polychlorinated naphthalenes and alkanes, polycyclic aromatic hydrocarbons and chlorobenzenes to the milk of dairy cattle from controlled ingestion of industrial and municipal bioresources recycled to agricultural land.

Recycled bioresources (biosolids, compost-like-output, meat and bonemeal ash, poultry litter ash, paper sludge ash) were added to the feed of dairy cattle to simulate incidental ingestion from agricultural utilisation, to investigate the transfer of organic contaminants from the ingested materials to milk. The bioresources were blended with a loamy sand soil at agronomic rates to simulate a single application to land, which was added to the diet at 5 % of the total intake on a dry matter (DM) basis. Biosolids, and control treatments consisting of unamended soil, were also added directly to the feed at 5 % DM. The cattle were fed the bioresource amended diets for a target period of three to four weeks, depending on material, and monitoring continued for four weeks after treatment withdrawal. Milk samples were taken weekly with chemical analysis of selected samples for a range of organic contaminants including: polychlorinated, polybrominated and mixed-halogenated dioxins, furans and biphenyls, polychlorinated naphthalenes and alkanes (often called chlorinated paraffins), polycyclic aromatic hydrocarbons and chlorobenzenes. No statistically significant additional transfer of organic contaminants to the milk was detected due to the relatively low levels of contaminants present when the bioresources were incorporated with soil at agronomic rates. However, direct biosolids ingestion by cattle significantly increased the transfer of contaminants to milk in comparison to control animals. Although present in larger concentrations in biosolids than their chlorinated counterparts, the carry over rates and bioconcentration factors of brominated dioxins and furans were considerably smaller. Direct ingestion of biosolids resulted in most contaminants approaching, but not always completely reaching, steady state concentrations within the treatment feeding period, however, concentrations generally declined to control values within four-weeks after withdrawing the biosolids-amended diet.

Decontamination process for dioxins and dioxin-like PCBs from fish oil and vegetable oils and fats by a physical process with activated carbon.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) assessed a decontamination process of fish oils and vegetable oils and fats to reduce the concentrations of dioxins (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans, abbreviated together as PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) by adsorption to activated carbon. All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. Data provided by the feed food business operator (FBO) were assessed for the efficacy of the process and to demonstrate that the process did not adversely affect the characteristics and properties of the product. The limited information provided, in particular on the analysis of the samples before and after decontamination, did not allow the CONTAM Panel to conclude whether or not the proposed decontamination process is effective in reducing PCDD/Fs and DL-PCBs in the fish- and vegetable oils and fats. Although there is no evidence from the data provided that the decontamination process leads to detrimental changes in the nutritional composition of the fish- and vegetable oils, it is possible that the process could deplete some beneficial constituents (e.g. vitamins). Taken together, it was not possible for the CONTAM Panel to conclude that the decontamination process as proposed by the FBO is compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.

Heart Failure Population with Therapeutic Response to Sacubitril/Valsartan, Spironolactone and Candesartan: FDA Perspective.

Sacubitril/valsartan was approved by the Food and Drug Administration in 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure (HHF) in patients with chronic heart failure with reduced ejection fraction defined as left ventricular ejection fraction (LVEF) ≤ 40%. This approval was based on PARADIGM-HF trial. Subsequently, PARAGON-HF was conducted to support a claim for sacubitril/valsartan in patients with heart failure with preserved ejection fraction (HFpEF), defined as LVEF ≥ 45%. PARAGON-HF failed to meet the pre-defined threshold for statistical significance for the primary composite endpoint. However, analysis of the primary endpoint by LVEF as a continuous variable demonstrated that sacubitril/valsartan was efficacious in patients with mildly abnormal LVEF similar to patients with LVEF ≤ 40% evaluated in PARADIGM-HF. This led to a broader indication for sacubitril/valsartan-"to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. LVEF is a variable measure, so use clinical judgment in deciding whom to treat." This article describes the rationale for a revised indication for sacubitril/valsartan, emphasizes the need to go beyond a dichotomous classification of HF based on a traditional LVEF cut-off and clarifies that the product label for sacubitril/valsartan does not refer to HFpEF.

Clinical Research Evidence Supporting Administration and Dosing Recommendations of Medicinal Cannabis as Analgesic in Cancer Patients.

The analgesic potential of Cannabis sativa L.-based medicinal cannabis products for treatment of cancer associated chronic pains has gained increased interest in recent years. To ensure a controlled distribution of these products and investigate their therapeutic potential, several countries have established so-called pilot trials. Many doctors, however, are hesitant to prescribe medicinal cannabis primarily due to lack of research evidence regarding the products' efficacy, safety and thus questionable dosing guidelines. This review aims to elucidate clinical research supporting administration of medicinal cannabis in cancer patients for analgesic purposes. The cannabinoids' effects on the endocannabinoid system (ECS) and its implication in pain regulation is included to illustrate the complexity related to this research field. Published clinical studies on medicinal cannabis primarily consist of observational studies and only one pilot randomized controlled trial (RCT), where more RCTs exist on the cannabis-based product, Sativex® (GW Pharma Ltd., Cambridge, UK). The studies indicate analgesic potential, however non-significantly, for most patients and with acceptable safety profile. Summarizing, high-quality RCTs are scarce in this research field, and the limitations of the observational studies complicates interpretation of clinical outcomes. Despite discrepancy among the studies, they do show indications for administration and dosing regimens providing analgesic effects for some cancer patients.

Update of the risk assessment of hexabromocyclododecanes (HBCDDs) in food.

The European Commission asked EFSA to update its 2011 risk assessment on hexabromocyclododecanes (HBCDDs) in food. HBCDDs, predominantly mixtures of the stereoisomers α-, ß- and γ-HBCDD, were widely used additive flame retardants. Concern has been raised because of the occurrence of HBCDDs in the environment, food and in humans. Main targets for toxicity are neurodevelopment, the liver, thyroid hormone homeostasis and the reproductive and immune systems. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour in mice can be considered the critical effects. Based on effects on spontaneous behaviour in mice, the Panel identified a lowest observed adverse effect level (LOAEL) of 0.9 mg/kg body weight (bw) as the Reference Point, corresponding to a body burden of 0.75 mg/kg bw. The chronic intake that would lead to the same body burden in humans was calculated to be 2.35 µg/kg bw per day. The derivation of a health-based guidance value (HBGV) was not considered appropriate. Instead, the margin of exposure (MOE) approach was applied to assess possible health concerns. Over 6,000 analytical results for HBCDDs in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary LB exposure to HBCDDs were fish meat, eggs, livestock meat and poultry. The CONTAM Panel concluded that the resulting MOE values support the conclusion that current dietary exposure to HBCDDs across European countries does not raise a health concern. An exception is breastfed infants with high milk consumption, for which the lowest MOE values may raise a health concern.

Assessment of an application on a detoxification process of groundnut press cake for aflatoxins by ammoniation.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on an application for a detoxification process of groundnut press cake for aflatoxins by ammoniation. Specifically, it is required that the feed decontamination process is compliant with the acceptability criteria specified in the Commission Regulation (EU) 2015/786 of 19 May 2015. The CONTAM Panel assessed the data provided by the feed business operator with respect to the efficacy of the process to remove the contaminant from groundnut press cake batches and on information demonstrating that the process does not adversely affect the characteristics and the nature of the product. Although according to the literature the process may be able to reduce aflatoxin levels below the legal limits, the Panel concluded that the proposed decontamination process, on the basis of the experimental data submitted by the feed business operator, cannot be confirmed for compliance with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015. The Panel recommended sufficient sample testing before and after the process, under the selected conditions, to ensure that the process is reproducible and reliable and to demonstrate that the detoxification is not reversible. In addition, genotoxicity testing of extracts of the treated feedingstuff and of the identified degradation products would be necessary. Finally, information on the transfer rate of AFB1 to AFM1 excretion in milk for animals fed the ammoniated product, in comparison to the starting material and on the ammoniation process changes of the nutritional values of the feed material should be provided.

Concentrations of organic contaminants in industrial and municipal bioresources recycled in agriculture in the UK.

Many types of bioresource materials are beneficially recycled in agriculture for soil improvement and as alternative bedding materials for livestock, but they also potentially transfer contaminants into plant and animal foods. Representative types of industrial and municipal bioresources were selected to assess the extent of organic chemical contamination, including: (i) land applied materials: treated sewage sludge (biosolids), meat and bone meal ash (MBMA), poultry litter ash (PLA), paper sludge ash (PSA) and compost-like-output (CLO), and (ii) bedding materials: recycled waste wood (RWW), dried paper sludge (DPS), paper sludge ash (PSA) and shredded cardboard. The materials generally contained lower concentrations of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (PCBs) relative to earlier reports, indicating the decline in environmental emissions of these established contaminants. However, concentrations of polycyclic aromatic hydrocarbons (PAHs) remain elevated in biosolids samples from urban catchments. Polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs) were present in larger amounts in biosolids and CLO compared to their chlorinated counterparts and hence are of potentially greater significance in contemporary materials. The presence of non-ortho-polychlorinated biphenyls (PCBs) in DPS was probably due to non-legacy sources of PCBs in paper production. Flame retardent chemicals were one of the most significant and extensive groups of contaminants found in the bioresource materials. Decabromodiphenylether (deca-BDE) was the most abundant polybrominated diphenyl ether (PBDE) and may explain the formation and high concentrations of PBDD/Fs detected. Emerging flame retardant compounds, including: decabromodiphenylethane (DBDPE) and organophosphate flame retardants (OPFRs), were also detected in several of the materials. The profile of perfluoroalkyl substances (PFAS) depended on the type of waste category; perfluoroundecanoic acid (PFUnDA) was the most significant PFAS for DPS, whereas perfluorooctane sulfonate (PFOS) was dominant in biosolids and CLO. The concentrations of polychlorinated alkanes (PCAs) and di-2-ethylhexyl phthalate (DEHP) were generally much larger than the other contaminants measured, indicating that there are major anthropogenic sources of these potentially hazardous chemicals entering the environment. The study results suggest that continued vigilance is required to control emissions and sources of these contaminants to support the beneficial use of secondary bioresource materials.

Risk to human health related to the presence of perfluoroalkyl substances in food.

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances (PFASs) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS. These made up half of the lower bound (LB) exposure to those PFASs with available occurrence data, the remaining contribution being primarily from PFASs with short half-lives. Equal potencies were assumed for the four PFASs included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and 'other children' showed a twofold higher exposure. Upper bound exposure was 4- to 49-fold higher than LB levels, but the latter were considered more reliable. 'Fish meat', 'Fruit and fruit products' and 'Eggs and egg products' contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/mL for the sum of the four PFASs in serum was identified for 1-year-old children. Using PBPK modelling, this serum level of 17.5 ng/mL in children was estimated to correspond to long-term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake (TWI) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI, which is of concern.

Risk assessment of chlorinated paraffins in feed and food.

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of chlorinated paraffins in feed and food. The data for experimental animals were reviewed and the CONTAM Panel identified the liver, kidney and thyroid as the target organs for the SCCP and MCCP mixtures tested in repeated dose toxicity studies. Decreased pup survival and subcutaneous haematoma/haemorrhage were also identified as critical effects for an MCCP mixture. For the LCCP mixtures tested, the liver was identified as the target organ. The Panel selected as reference points a BMDL 10 of 2.3 mg/kg bw per day for increased incidence of nephritis in male rats, and of 36 mg/kg bw per day for increased relative kidney weights in male and female rats for SCCPs and MCCPs, respectively. For LCCPs, a reference point relevant for humans could not be identified. Due to the limitations in the toxicokinetic and toxicological database, the Panel concluded that derivation of a health-based guidance value was not appropriate. Only limited data on the occurrence of SCCPs and MCCPs in some fish species were submitted to EFSA. No data were submitted for LCCPs. Thus, a robust exposure assessment and consequently a complete risk characterisation could not be performed. A preliminary risk characterisation based only on the consumption of fish was performed, and the calculated margins of exposure suggested no health concern for this limited scenario. The Panel noted that dietary exposure will be higher due to the contribution of CPs from other foods. The Panel was not able to identify reference points for farm animals, horses and companion animals. No occurrence data for feed were submitted to EFSA. Therefore, no risk characterisation could be performed for any of these animal species.

Congener patterns of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls as a useful aid to source identification during a contamination incident in the food chain.

Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) are still considered among the most important groups of contaminants in the food chain. Self-control by food producers and official control by authorities are important activities that allow contaminant sources to be traced and promote further reduction in food and feed levels. Strict but feasible maximum levels were set by the EU Commission for food and feed to support this strategy, as well as action levels and thresholds. When products exceed these levels, it is important to trace the source of contamination and take measures to remove it. Congener patterns of PCDD/Fs and PCBs differ between sources and are important tools for source identification. Therefore, patterns associated with different sources and incidents relating to various feed matrices and certain agricultural chemicals were collated from published scientific papers, with additional ones available from some laboratories. The collection was evaluated for completeness by presentations at workshops and conferences. Primary sources appear to derive from 5 categories, i) by-products from production of organochlorine chemicals (e.g. PCBs, chlorophenols, chlorinated pesticides, polyvinyl chloride (PVC)), ii) the result of combustion of certain materials and accidental fires, iii) the use of inorganic chlorine, iv) recycling/production of certain minerals, and v) certain naturally occurring clays (ball clay, kaolinite). A decision tree was developed to assist in the identification of the source.

Association of endocrine active environmental compounds with body mass index and weight loss following bariatric surgery.

INTRODUCTION: The objective of this study was to study associations of a wide range of halogenated biphenyls, dibenzo-p-dioxins, dibenzofurans and diphenylethers with body mass index (BMI) and evaluate changes in their concentration following bariatric surgery. METHODS: Subcutaneous fat, visceral fat and liver tissue samples were collected from 106 patients undergoing Roux-en-Y gastric bypass surgery for weight loss or patients who were undergoing abdominal surgery for nonbariatric reasons. We measured concentrations of an extensive panel of chlorinated and brominated biphenyls, dioxins, and furans, and brominated diphenylethers in the samples. We conducted linear regression to examine associations with BMI, adjusting for age and gender. Changes in concentration for indicator chemicals were evaluated in samples collected following bariatric surgery in a small subpopulation. RESULTS: After adjustments for age and gender and correction for multiple testing, seven ortho-chlorinated biphenyls, one nonortho-chlorinated biphenyl, four PCDD/Fs and one ortho-brominated biphenyl were associated with BMI. The strongest associations between BMI and lipid-adjusted concentrations were seen with PCB-105 in subcutaneous fat (beta = 16.838 P-val = 1.45E-06) PCB-126 in visceral fat (beta = 15.067 P-val = 7.72E-06) and PCB-118 (beta = 14.101 P-val = 2.66E-05) in liver. The concentrations of sum PCBs, chlorinated toxic equivalent quantity (TEQ's) and brominated compounds increased significantly with weight loss in subcutaneous fat in a group of ten individuals resampled up to five years after bariatric surgery and substantial weight loss. CONCLUSION: We show that selected polychlorinated biphenyls PCBs and structurally related polychlorinated dibenzo-p-dioxins dibenzofurans (PCDD/Fs) were associated with BMI. Concentrations of these lipophilic compounds in subcutaneous fat increased following bariatric surgery.