Abstract The European Commission asked EFSA to update its 2018 risk assessment on polychlorinated dibenzo‐p‐dioxins and dibenzofurans (PCDD/Fs) and dioxin‐like polychlorinated biphenyls (DL‐PCBs) in feed and food, based on the 2022 WHO Toxic Equivalency Factors (WHO2022‐TEFs). A decrease in sperm concentrations as a consequence of early‐life exposure was still considered the critical effect in rodents and humans. This can only be prevented by ensuring sufficiently low exposure to PCDD/Fs and DL‐PCBs of future mothers. Using the WHO2022‐TEFs, the critical human study in the 2018 Opinion still showed a significant inverse association between PCDD/Fs and sperm concentration, but not when including DL‐PCBs. Therefore, this study was not used to derive a Tolerable Weekly intake (TWI). Instead, a developmental study with TCDD in rats was used to derive a TWI of 0.6 pg. WHO2022‐toxic equivalents (TEQ)/kg bw per week, based on decreased sperm production. Human studies were used as supporting evidence, including an evaluation of necessary uncertainty factors. Dietary exposure assessment based on occurrence data in food from the last decade, showed that using the new TEFs resulted in 27%–35% lower total‐TEQ exposure. Mean exposure (lower to upper bound) to PCDD/Fs and DL‐PCBs for European adult populations varied between 1.87 and 6.10 pg. WHO2022‐TEQ/kg bw per week, and at the P95 between 4.15 and 12.0 pg. WHO2022‐TEQ/kg bw per week. The CONTAM Panel concluded that exposure for European women of childbearing age raises a health concern for their sons at the mean (80%–90% certainty) and P95 (95%–99% certainty) exposure. Including uncertainties regarding the TEFs for DL‐PCBs decreased this certainty. Human milk data confirmed the exceedance of the TWI but to a lesser extent than dietary exposure. The change in TEFs does not affect the transfer rates of individual congeners but it could impact the transfer rates when using Total‐TEQ levels.

Current findings on the relationship between wholegrain intake and breast cancer are inconsistent. We aimed to estimate the association between long-term wholegrain intake and breast cancer risk, specifically investigating: (i) adherence to the updated Nordic Nutrition Recommendations (NNR2023) guidelines on wholegrain intake, and (ii) consumption of specific wholegrain products. Data from food frequency questionnaires were used to assess adherence to NNR2023 guidelines on wholegrain intake and consumption of wholegrain products among 36,479 women (48–83 years) in the Swedish Mammography Cohort at two timepoints. Time-updated Cox proportional hazards regression models were used to estimate multivariable-adjusted hazard ratios (HR) and 95

Abstract The European Commission asked the European Food Safety Authority (EFSA) to assess the risk related to the presence of plant lectins in food. Based on the available evidence, the CONTAM Panel considered only phytohaemagglutinin (PHA), a legume lectin from beans (Phaseolus sp.), for the risk characterisation. Effects of PHA in the small intestine were considered as the critical effect in subacute studies in rats. A lower confidence limit of the benchmark dose (BMDL)10 of 22.9 mg/kg body weight (bw) per day for an increase in small intestine dry weight was selected as the most appropriate reference point for the risk characterisation. The establishment of a health‐based guidance value for PHA was not considered appropriate due to the limitations and uncertainties in the current toxicological evidence, and the margin of exposure (MOE) approach was used for the risk characterisation. The Panel considered that acute exposure resulting in MOEs above 100 is not expected to raise a health concern. As no occurrence data were submitted to EFSA, data for PHA presence in food were identified by a literature search. An arbitrary acute exposure scenario, where only 50% of the lectins are inactivated due to insufficient cooking of food containing lectins (e.g. beans), would result in MOEs below 100. The Panel, accounting for the uncertainties affecting the exposure and hazard assessments, concluded with at least 95% probability that such a dietary exposure would raise health concerns. The Panel also noted that exposure to completely deactivated lectins in food prepared following adequate food processing practices (e.g. soaking and boiling) would not raise health concerns. No risk characterisation could be performed for other lectins due to the lack of relevant toxicological data and/or in some cases lack of occurrence data.

AIMS:Little evidence exists on the health implications of adherence to a diet in line with the updated Nordic Nutrition Recommendations (NNR2023). We estimated the association between long-term adherence to NNR2023 and (i) incidence of cardiovascular disease (CVD), and (ii) biomarkers of cardiometabolic health. METHODS:The study population consisted of 76,028 participants from the Swedish Mammography Cohort (SMC) and Cohort of Swedish Men, and 4,267 women in a clinical sub-cohort of SMC. Data from food frequency questionnaires were used to assess NNR2023 adherence at baseline (in 1997) and upon re-investigation in 2009 and 2019. Time-varying multivariable Cox proportional hazards regression models were used to estimate the association between NNR2023 adherence and incidence of major adverse cardiovascular events (MACE) - a composite of acute myocardial infarction, stroke, and CVD mortality - as well as specific CVD events. Quantile regression was used to assess the association between NNR2023 adherence and cardiometabolic biomarkers. RESULTS:During a mean follow-up of 18.7 years (1.48 million person-years), we identified 24,041 cases of MACE. Participants in the highest vs lowest quartile of NNR2023 adherence had 17% (hazard ratio: 0.83; 95% confidence interval: 0.80, 0.86) lower risk of MACE, as well as lower risks of the individual MACE components. Higher NNR2023 adherence was associated with a more favourable blood lipid profile and insulin sensitivity (all p-values < 0.05). CONCLUSION:This study provides evidence for a positive impact of adherence to NNR2023 on cardiovascular health.

Background: Randomized trials have shown that a healthy Nordic diet (HND) improves liver steatosis, but there is limited evidence on the effects of Nordic dietary patterns on the risk of major adverse liver outcomes (MALO). We specified a hypothetical target trial protocol to estimate the effects of adhering to a HND or the Nordic Nutrition Recommendations 2023 (NNR23) on the 24-year risk of MALO in a middle-aged to elderly Swedish population. Methods: Two pooled population-based cohorts including n=64,406 men and women (Cohort of Swedish Men (COSM) and the Swedish Mammography Cohort (SMC)) with repeated measurements on diet and confounders in 1997, 2008/2009 and 2019 were used to emulate population-adapted versions of the diets. Under the assumptions of no unmeasured confounding, selection bias or measurement error, the parametric g-formula was used to estimate 24-year risks of MALO from each hypothetical intervention. Secondary analyses included comparing the HND and NNR23 with a low-adherence group; reducing alcohol as an additional hypothetical intervention; and assessing risk of all-cause mortality. Results: The estimated 24-year risk of MALO in the HND was 0.53% (95% CI: 0.38, 0.73), in the NNR23 diet 0.70% (95% CI: 0.57, 0.90) and in no intervention 0.64% (95% CI: 0.56, 0.77). Estimated risk differences (RDs) of MALO for HND versus no intervention and NNR23 versus no intervention were -0.11% (95% CI: -0.27, 0.07) and 0.06% (95% CI: -0.04, 0.15), respectively. Compared to NNR23, the estimated RD for the HND was -0.17% (95% CI: -0.38, 0.05). Meaningful risk reductions following the HND were estimated when compared to a low-adherence diet group (-1.50% (95% CI: -9.53, -0.05)), when including reducing alcohol, and for all-cause mortality (-2.67% (95% CI: -3.51, -1.85) versus no intervention; -1.68% (95% CI: -2.75, -0.62) versus NNR23)). Conclusion: We estimated no clear risk reductions from a population-adapted HND or a NNR23 diet on the 24-year risk of MALO when compared to each other or no intervention. However, when either compared to a low-adherence group or when including reducing alcohol as a hypothetical intervention or when specifying all-cause mortality as the outcome, we estimated meaningful risk differences following the HND.

BACKGROUND:Dietary nitrate exposure originates from vegetables, drinking water, and is, together with nitrite, used as food additives in animal products. Both compounds can generate N-nitroso compounds, some of which are known animal carcinogens. However, epidemiological evidence regarding nitrate and nitrite intake in relation to colorectal cancer (CRC) risk and its subsites remains limited. METHODS:Nitrate and nitrite intake was assessed by linking a food and drinking water database to food frequency questionnaires completed in 1997 and updated in 2009 and 2019, by 82,009 middle-aged to elderly men and women of two population-based cohorts from the Swedish Infrastructure for Medical Population-based Life-course and Environmental Research. We ascertained incident CRC through the Swedish Cancer Registry from 1998 to 2022. Cox proportional hazards models were fitted to evaluate exposure-outcome associations, presented as hazard ratios (HR) with 95% confidence intervals (CI). RESULTS:We ascertained 3,170 CRC cases. No associations were observed for nitrate intake with CRC. In contrast, when comparing the highest to the lowest quintile, nitrite intake was associated with a dose-dependent higher risk of CRC in men (HR 1.23; 95%CI 1.06-1.43; p-trend<0.05) but not in women. CRC subsite analyses in men indicated the strongest association for distal colon cancer (HR 1.50; 95% CI: 1.13-1.98). CONCLUSION:A higher nitrite intake was associated with a higher CRC risk in men, particularly distal colon cancer. These findings indicate potential sex differences and differential susceptibilities across the colorectum in nitrite-related cancer risk.

Chlorination of drinking water effectively prevents waterborne infections but also results in the formation of potentially carcinogenic disinfection by-products, including trihalomethanes (THMs). Experimental animal studies indicate that the liver and kidney are target organs for THM carcinogenicity, yet epidemiological evidence remains limited for these sites. In this study we assessed the association of long-term exposure to THMs in drinking water with incidence of liver and kidney cancer in two large Swedish population-based cohorts. We included 58,664 adults from the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research (SIMPLER), who were supplied by public drinking water. Individual residential histories were linked to a national database of drinking-water monitoring results to estimate long-term exposure to total THMs. Incident liver and kidney cancer cases were ascertained through linkage to the Swedish National Cancer Register. Multivariable adjusted Cox proportional hazards regression models were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 25 years of follow-up, 183 liver cancer cases and 347 kidney cancer cases were ascertained. Residential drinking water THM exposure was not associated with liver cancer. For kidney cancer, THM was dose-dependently associated with higher risk (p-trend = 0.047) among men with HR 1.54 (95% CI 1.00, 2.38) comparing ≥15 µg THM/L with no drinking water chlorination. No association was observed among women. Although based on a limited number of cases, these findings provide novel prospective cohort evidence on the potential association between long-term THM exposure and kidney cancer at exposure levels below current regulatory limits for drinking water. The observed association warrant confirmation in future independent studies.

This study characterises food and nutrient intake in self-reported diets with varying environmental impacts and evaluates their adherence to dietary guidelines and nutritional adequacy, exploring co-benefits and trade-offs between environmental impact and diet quality. Dietary data were from two population-based cohorts (n = 30 000) of Swedish adults aged 56–70 years. Environmental impact was assessed using an aggregated score based on six environmental indicators. Adherence to dietary guidelines and nutritional adequacy was evaluated against the Nordic Nutrition Recommendations 2023. In line with the dietary guidelines, diets with a lower environmental impact had lower intake of red meat, processed meat, sugar-sweetened beverages, high-fat dairy products, saturated fat, sodium and alcohol, alongside higher intake of whole grains, fibre and polyunsaturated fat. Contrary to the dietary guidelines, lower-impact diets had higher intake of sweets and snacks and lower intake of vegetables, fruits and berries, nuts and seeds, and seafood. While lower-impact diets had a lower intake of protein and most vitamins and minerals, adherence to macronutrient recommendations was generally higher, and micronutrient intake was adequate, except for selenium and vitamin D. This study highlights both co-benefits and trade-offs between environmental and health goals. To prevent negative health effects from diets with lower environmental impact, it is essential to limit foods with low nutritional value (e.g., sweets and snacks) and promote healthy plant-based foods. Potential risks associated with a lower micronutrient intake should be considered, particularly for groups with special requirements, such as children, adolescents, fertile and pregnant women, and the elderly.

Abstract The European Commission asked EFSA to update its 2012 risk assessment on Emerging and Novel brominated flame retardants (BFRs) in food. Since the previous Opinion, further information was collected for a total of 27 BFRs. The CONTAM Panel concluded that TDBPP, DBPNG and TBNPA are considered genotoxic and carcinogenic. Based on positive in vitro mutagenicity in mammalian cells, DBE‐DBCH is considered genotoxic. EBTEBPI, DBDPE, PBB‐Acr and TTBP‐TAZ are not genotoxic. Insufficient or absent data precluded the Panel to conclude on the genotoxic potential of the remaining BFRs. Reproductive/developmental toxicity and/or neurotoxicity/neurodevelopmental effects were reported for DBNPG, BEH‐TEBP, EH‐TBB, DBDPE and TDBP‐TAZTO. Reference Points were identified for TDBPP, DBNPG, BEH‐TEBP, EH‐TBB, DBDPE and TDBP‐TAZTO. No health‐based guidance values could be derived for any of the BFRs. Occurrence data were submitted to EFSA for eight BFRs (BEH‐TEBP, EH‐TBB, BTBPE, DBDPE, HBB, PBEB, PBT, TBX). Dietary exposure could be estimated only for BTBPE and HBB, due to the lack of quantitative data for the other BFRs. However, no risk characterisation could be performed for these BFRs due to the lack of a Reference Point. Using the limited available information on dietary exposure estimates reported in the scientific literature, risk characterisation could be performed for BEH‐TEBP, EH‐TBB and DBDPE, and the CONTAM Panel concluded that dietary exposure does not raise a health concern. The Panel considered that the level of certainty was 90% or higher for most of the reported conclusions. Very limited or no information on hazard or exposure were available for HBCYD, TBCO, DBHCTD, HCTBPH, BDBP‐TAZTO, DBP‐TAZTO, OBTMPI, DBS, HEEHP‐TEBP, 4’‐PeBPO‐BDE208 or TTBNPP. Recommendations were formulated to address data gaps, including the need for access to original data, and for the collection of biomonitoring data, occurrence data in food, genotoxicity information and toxicological studies to support the identification of a Reference Point.

BACKGROUND:There is inconclusive evidence of associations between exposure to per- and polyfluoroalkyl substances (PFAS) and diabetes and hypertensive disorders during pregnancy. OBJECTIVES:We conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal drinking water exposure to the sum of four major PFAS (PFAS4; perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA) and perfluorohexanoate (PFHxS)) with gestational diabetes mellitus (GDM), hypertension and preeclampsia. MATERIALS AND METHODS:We included nulliparous women giving birth in Sweden during 2012-2018 in large localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model, we estimated cumulative maternal blood levels of PFAS4 during pregnancy considering residential history, municipal PFAS water concentration and year-specific maternal PFAS background serum levels. The outcomes and individual covariates were ascertained via register linkage. Mean values and 95% Confidence Intervals (CI) of Odds Ratios (OR) were estimated by logistic regression. RESULTS:Among the 109,031 nulliparous women included, with an estimated average 7.8 ng PFAS4/mL serum (standard deviation: 2.0 ng/mL), there were indications of a non-monotonic inverse association for PFAS4 and GDM, corresponding to multivariable-adjusted OR 0.72 (95 % CI: 0.61-0.84) when comparing extreme quartiles. An inverse association were also seen for each PFAS individually. No clear associations were seen for hypertension or preeclampsia, although individual PFAS indicated significant associations, both inverse (PFAS and PFHxS) and direct (PFOS and PFNA) for hypertension. CONCLUSION:In the present study, we observed indications of inverse, non-monotonic associations for PFAS4 and GDM. Some individual PFAS were also associated with hypertension, both direct and inverse. The limitations linked to the exposure assessment still require caution in the interpretation.

While family history of cardiovascular disease (CVD) is a well-established non-modifiable risk factor of CVD, it remains unclear which modifiable CVD risk factors may further increase risk in subjects with a family history. Recent research suggests that cardiometabolic risk markers may be particularly relevant. To assess interactions between a family history of CVD and established as well as less established cardiometabolic risk factors in relation to risk of CVD in a cohort of 60-year-old men and women. The cardiometabolic factors considered were hypercholesterolemia, LDL- and HDL cholesterol, ApoB, ApoA1, ApoB/ApoA1 ratio, Lp(a), uric acid, PCSK9, BMI, waist circumference, hypertension, and diabetes. Family history of CVD was defined as having at least one first-degree relative affected by coronary heart disease or stroke before the age of 70 (mother) or 65 (father/sibling). After excluding prevalent CVD, 3875 participants remained for analysis. The participants were followed from baseline, 1997-1998, for incident fatal or non-fatal CVD events until they reached approximately 75 years of age and 85 years of age, respectively. Using Cox proportional hazards model, we calculated hazard ratios (HR) and 95% confidence intervals (CI) for: 1) each of the cardiometabolic factors in absence of family history of CVD; 2) family history of CVD in absence of the exposure to each of the cardiometabolic factors, and 3) the combination of a family history of CVD and the respective cardiometabolic factor. Interactions were assessed by modelling cross-product terms (p multiplicative) and calculating relative excess risk due to interaction (RERI). All models were adjusted for classical CVD risk factors. The prevalence of a family history of CVD was 27.4%. Results based on the shorter follow-up revealed a statistically significant interaction (p multiplicative 0.023) for the co-presence of elevated serum levels of PCSK9 (>75th percentile) and family history. The HR (95% CI) for the combination of elevated PCSK9 and family history was 1.43 (1.34-2.24) whereas for increased PCSK9 alone it was 1.21 (0.99-1.47) and for a family history alone it was 1.20 (1.00-1.73). The corresponding results based on the longer follow-up were less pronounced (p multiplicative 0.056). The RERI was not statistically significant. For the other cardiometabolic factors we observed no significant interaction with a family history, regardless of length of follow-up. Of the cardiometabolic factors under study, we found that elevated PCSK9 was a significantly stronger risk factor for suffering a CVD event before the age of 75 in individuals with a family history of CVD compared to individuals without such a family history. This finding supports CVD preventive guidelines highlighting the need to closely monitor subjects with a family history of CVD for cholesterol-related risk markers.

Chronic exposure to the metal(loid)s arsenic, cadmium, lead, and mercury via contaminated food or drinking water may induce kidney toxicity, but there is little consensus on the biological processes involved. Health risk assessment of these substances is further complicated by coexposures and the sometimes unclear causal interpretation of population studies. To address these issues, we developed a common adverse outcome pathway (AOP) describing how these metal(loid)s can induce kidney toxicity. Upon identification of renal dysfunction resulting from proximal tubular damage as a common adverse outcome, we developed the AOP by collecting evidence from relevant (experimental) studies. Evaluation of the weight of evidence revealed a moderate to high confidence in this AOP. It enhances our mechanistic understanding of metal(loid)-induced kidney toxicity and provides scientific evidence for a causal relationship between the adverse effect and effect biomarkers. As such, this is an example of how AOPs can facilitate next-generation risk assessment of combined exposure to different contaminants.

AIMS:The association between alcohol consumption and risk of peripheral artery disease (PAD) is inconclusive. We conducted this study to examine the association between alcohol consumption and PAD risk in two de novo cohort studies and a meta-analysis of observational studies. METHODS AND RESULTS:A systematic review was conducted to identify studies on alcohol consumption in relation to PAD risk. We further used data from two cohorts of 70 116 Swedish and 405 406 British adults and performed a meta-analysis of results from previously published studies and current cohort studies. There was a U-shaped association between alcohol consumption and incident PAD risk in the Swedish and British cohorts. The meta-analysis of results of these two cohorts and previously published studies found that compared with non- or never-drinkers, the relative risk of PAD was 0.83 [95% confidence interval (CI) 0.77-0.89], 0.81 (95% CI 0.74-0.90), and 0.94 (95% CI 0.83-1.07) for light, moderate, and high-to-heavy alcohol drinkers, respectively. The nonlinear meta-analysis revealed a possibly U-shaped association between alcohol consumption and PAD risk (P nonlinearity <0.001). The risk of PAD was observed to be the lowest for 2 drinks/week and to be pronounced for ≥10 drinks/week. All these associations persisted in a sensitivity meta-analysis including cohort and other types of observational studies. CONCLUSION:Alcohol intake ≤2 drinks/week was associated with a reduced risk of PAD, and the risk of PAD became pronounced with intake ≥10 drinkers/week.

Abstract The European Commission asked EFSA to update its 2014 risk assessment on perchlorate in food. Perchlorate is a contaminant of both natural and anthropogenic sources present in food and drinking water. It is a substrate for the sodium iodide symporter (NIS) and competitively inhibits the uptake of iodide into the thyroid. Experimental animal studies show that perchlorate exposure during pregnancy can result in neurodevelopmental toxicity. The CONTAM Panel established a tolerable daily intake of 1.4 μg/kg body weight per day, based on the inhibition of thyroid iodine uptake in healthy adults. The tolerable daily intake (TDI) takes into account the sensitivity of the fetus to maternal thyroid hormone disturbance and uncertainty around the impact of iodine deficiency on the effects of perchlorate during fetal development. This TDI is applicable for both a short‐term (approximately 2‐week period) and chronic exposures based on the mode of action of perchlorate, its toxicokinetic properties and the key study used to derive the TDI. An acute reference dose (ARfD) was not deemed necessary. EFSA received a total of 40,356 analytical results, between 2016 and 2022, which were considered for the dietary exposure assessments. A chronic dietary exposure assessment for all age groups and a short‐term dietary exposure assessment for pregnant women were calculated. The CONTAM Panel concluded that chronic and short‐term dietary exposure estimates to perchlorate were below the TDI for all age groups including pregnant women, with the exception at the upper bound of the P95 for infants, breastfed infants and formula‐fed infants. Even if the limitations in analytical methods, leading to a large difference between lower bound (LB) and upper bound (UB) dietary exposure, reduces the certainty in this conclusion for infants, breastfed infants and formula‐fed infants, the uncertainty analysis indicates a higher (above 50%) likelihood of ‘no concern’ for all scenarios.

Atrial fibrillation (AF) is a common cardiac arrhythmia with strong genetic components, yet its underlying molecular mechanisms and potential therapeutic targets remain incompletely understood. We conducted a cross-population genome-wide meta-analysis of 168,007 AF cases and identified 525 loci that met genome-wide significance. Two loci of PITX2 and ZFHX3 genes were identified as shared across populations of different ancestries. Comprehensive gene prioritization approaches reinforced the role of muscle development and heart contraction while also uncovering additional pathways, including cellular response to transforming growth factor-beta. Population-specific genetic correlations uncovered common and unique circulatory comorbidities between Europeans and Africans. Mendelian randomization identified modifiable risk factors and circulating proteins, informing disease prevention and drug development. Integrating genomic data from this cross-population genome-wide meta-analysis with proteomic profiling significantly enhanced AF risk prediction. This study advances our understanding of the genetic etiology of AF while also enhancing risk prediction, prevention strategies, and therapeutic development.

BACKGROUND:This study aimed to investigate the association between alcohol consumption and squamous cell cancers of the upper aerodigestive tract (UADT), using data from 28 cohorts within the Pooling Project of Prospective Studies of Diet and Cancer (DCPP). METHODS:Individual-level data from 2 365 437 participants were pooled. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models to quantify the association between alcohol consumption (g/day) and UADT cancer risk, adjusting for potential confounders. Analyses were conducted by sex, smoking status, geographic region, and alcoholic beverages. RESULTS:Over a median follow-up of 15.5 years, 6903 UADT cancer cases were identified. Alcohol consumption was positively associated with UADT cancer risk overall. Even at intakes as low as 5-<15 g/day, the HR estimate was 1.12 (95% CI = 1.03 to 1.21) compared with the reference group (0.1-<5 g/day). The HR10 g/day (95% CI) was 1.16 (1.14 to 1.18) for women and 1.12 (1.11 to 1.13) for men (Pheterogeneity < .0001). HR10 g/day estimates were 1.14 (1.13 to 1.15) in current, 1.10 (1.09 to 1.12) in former, and 1.15 (1.12 to 1.18) in never smokers. Consistent UADT HR10 g/day estimates were observed across all beverage types. HR10 g/day estimates varied across geographic regions, with HR10 g/day (95% CI) equal to 1.15 (1.14 to 1.17) in Europe-Australia, 1.13 (1.11 to 1.15) in Asia, and 1.11 (1.09 to 1.12) in North America (Pheterogeneity < .0001). CONCLUSION:Alcohol consumption was associated with UADT cancer risk, irrespective of smoking status or beverage type. However, due to differential baseline risks, alcohol is expected to impact the UADT cancer burden more in smokers than never smokers. These findings support public health strategies to reduce alcohol consumption.

Abstract The European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the derivation of a health‐based guidance value (HBGV) for Δ8‐tetrahydrocannabinol (Δ8‐THC) in food with an assessment of the occurrence of Δ8‐THC and the co‐occurrence with Δ9‐THC in hemp and hemp‐derived products. Data from a clinical study were used to inform on the relative potency between Δ9‐THC and Δ8‐THC. The point estimate of the relative potency (ratio Δ9‐THC/Δ8‐THC) was in the range between 1 and 1.4, with 95% confidence between 0.97 and 1.63. Based on this range, the CONTAM Panel, using a conservative approach, set a relative potency factor of one for Δ8‐THC. The CONTAM Panel had previously set an acute reference dose (ARfD) of 1 μg/kg body weight for Δ9‐THC derived from adverse effects on human central nervous system (CNS). Given the similarity in the effects and the mode of action between Δ8‐THC and Δ9‐THC, the Panel considered that the established ARfD can be considered as a group ARfD for the sum of Δ8‐ and Δ9 THC. Regarding the occurrence of Δ8‐THC, the majority of samples were left censored, in particular for hemp infusion leaves, hemp seed oil and hemp seeds (96%–99%). Highest detection rates and levels were found in the categories ‘Sugar and similar, confectionery and water‐based sweet desserts’ and ‘Products for non‐standard diets, food imitates and food supplements’. Of 1145 samples, both substances were detected together in only 96 samples. If the two substances are produced naturally, a Δ8‐THC to Δ9‐THC ratio below 1 is expected; however, many of the samples, positive for Δ8‐THC, were above this ratio indicating either addition of semi‐synthetic Δ8‐THC, formation during processing or enrichment of the natural Δ8‐THC.

BACKGROUND:Teratogenic properties of perfluoroalkyl substances (PFAS) have been assessed in a few studies, however, epidemiological evidence for an association is inconclusive. OBJECTIVES:We conducted a Swedish nation-wide register-based cohort study to assess the associations of estimated fetal exposure to the sum of drinking water perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with major congenital malformations. METHODS:We included all births in Sweden during 2012-2018 of mothers residing ≥four years prior to partus in localities served by municipal drinking water where PFAS concentrations have been measured in drinking water. We estimated the fetal PFAS4 exposure by using a one-compartment toxicokinetic model - including maternal residential history, municipal PFAS water concentration and year-specific PFAS maternal background concentrations as input data - and accounting thereafter PFAS-specific transplacental transfer factors to estimate the fetal PFAS4 exposure. By register linkage we obtained birth outcomes and covariates. Odd ratios (OR) and 95 % confidence intervals (CI) of the associations between estimated PFAS in foetuses and major congenital malformations were estimated by logistic regressions and, complementary, by quantile g-computation regression for mixture effects. RESULTS:Analyses of 256,659 newborns of which 5,357 were diagnosed with major congenital malformations, revealed associations between fetal PFAS4 exposure and malformations on the nervous system OR, 2.84 (95 % CI: 1.38-5.84, p-trend: 0.008) and chromosomal anomalies OR, 1.50 (95 % CI: 1.07-2.10, p-trend: 0.009) comparing extreme quartiles. For the individual PFAS and in the quantile g-computation model, there were indications of an association between PFAS and urinary defects, OR 1.96 (95 % CI: 1.59-2.43, p-trend mixed effect: <0.001), primarily driven by PFOA and PFHxS. DISCUSSION:Modelled fetal sum of PFAS4 was associated with malformations of the nervous system and chromosomal anomalies, while the mixture assessment revealed associations with defects on urinary system. As the underlying toxicological mechanisms remains unclear, further investigation is warranted.

BACKGROUND:Chlorination is a widespread method for drinking water disinfection that has the drawback of introducing potentially carcinogenic chemical by-products to drinking water. OBJECTIVE:We systematically evaluated the epidemiologic evidence of exposure to trihalomethane (THM) disinfection by-products and risk of cancer. METHODS:We conducted a systematic review and meta-analysis of epidemiologic studies that assessed the association of exposure to residential concentrations of THMs with risk of cancer in adults. A protocol was preregistered in PROSPERO (CRD42023435491). PubMed, Embase, Web of Science, and Cochrane were searched for publications up to April 2024. Study selection and risk of bias appraisal using the National Toxicology Program Office of Health Assessment and Translation (NTP OHAT) tool was done in duplicate. Summary risk estimates were assessed using random effects meta-analysis and one-stage dose-response meta-analysis. RESULTS:The literature search resulted in 2,022 records, of which 29 publications assessing 14 different cancers were eligible for inclusion. Summary relative risks (RRs) were estimated for bladder cancer and colorectal cancer based on 5,860 and 9,262 cases and 84,371 and 90,272 participants, respectively. The summary RR of bladder cancer for the highest exposed compared with the lowest was 1.33 (95% CI: 1.04, 1.71), and in the dose-response analysis, RRs were statistically significant above THM concentrations of 41μg/L. For colorectal cancer, the summary RR was 1.15 (95% CI: 1.07, 1.24). CONCLUSION:According to the World Cancer Research Fund criteria, we found limited-suggestive evidence that THM in drinking water increases the risk of bladder and colorectal cancer at levels below current regulatory limits in the US and EU, indicating that these fail to protect against cancer in the general population. https://doi.org/10.1289/EHP14505.

INTRODUCTION:Ambient air pollution and road traffic noise are stroke risk factors, but evidence on their potential joint effects remains limited. This study investigated the independent and joint associations of air pollution and road traffic noise on stroke incidence using both multiplicative and additive scales. METHODS:We followed stroke incidence in ten cohorts in Sweden, Denmark, and Finland. We modelled annual average levels of outdoor particulate matter < 2.5 µm (PM2.5), nitrogen dioxide (NO2) and road traffic noise at residential addresses. We applied Cox proportional hazards regression to evaluate their single association. We assessed multiplicative interaction with interaction terms in Cox models and additive interaction using the Relative Excess Risk due to Interaction method. RESULTS:We followed 136,897 adults for 20 years, and 8.0 % experienced stroke incidence. PM2.5, NO2 and road traffic noise were associated with higher stroke risk in single-exposure models. Multiplicative models showed higher HRs between PM2.5 and stroke at higher levels of noise and vice versa: HRs per 5 μg/m3 of PM2.5 were 1.06 (95 % CI:0.94-1.21) at 40 dB and 1.11 (95 % CI:0.85-1.44) at 80 dB of road traffic noise; HRs per 12 dB of road traffic noise were 1.06 (95 % CI:1.01-1.11) at 4 μg/m3 and 1.17 (95 % CI:0.82-1.68) at 48 μg/m3 of PM2.5. Additive models showed that the combined association of PM2.5 and road traffic noise was 4 % (RERI = 0.04 (95 % CI:-0.05;1.12)) higher than the sum of their individual association. CONCLUSION:PM2.5 and road traffic noise showed a non-significant synergistic association on stroke incidence.