Margin Of Exposure Research Articles

Ochratoxin a levels in Turkish coffee: a probabilistic health risk assessment via Monte Carlo simulation.

Throughout history, Turkish coffee has been the most widely consumed type of coffee in Turkey. Therefore, the goal of this study was to determine the amount of ochratoxin A (OTA) present in Turkish coffee and to analyze any potential health hazards. A total of 41 Turkish coffees were collected and analyzed for OTA activity using a competitive enzyme immunoassay (ELISA). Furthermore, dietary exposure and health risk assessments for the Turkish population were calculated based on analytical results and coffee consumption data from the Turkish Nutrition and Health Survey 2019 (TNHS-2019) in three age categories (15-18, 19-64, and 65 + years). Nine of the samples contained more than 2.5μg/kg OTA, with an average of 5.24μg/kg. The OTA concentration in 3 samples exceeded the permissible maximum limit (5μg/kg) established by Turkish legislation, and the mean concentration was 8.41μg/kg. A margin of exposure (MOE) approach was used for risk characterization, considering both non-neoplastic and neoplastic consequences. There were no concerns about health risks because MOEs were more than 10,000 for all categories. Although the levels of OTA analyzed in Turkish coffee did not pose a risk to individuals in the three age categories, emphasis should be placed on minimizing and controlling OTA concentrations in Turkish coffee. Additionally, it is also necessary to consider other food sources that could contribute to OTA exposure.

Premised research on dietary exposure to benzo[a]pyrene, acrylamide, and Nnitrosodimethylamine from common fried and grilled dishes in North Vietnam

Fried and grilled cooking methods and the widespread consumption of certain dishes may expose the population to elevated levels of potentially carcinogenic compounds, such as benzo[a]pyrene (BaP), acrylamide, and N-nitrosodimethylamine (NDMA). This study aims to quickly estimate dietary exposure to these contaminants and assess the associated carcinogenic risk for several common Vietnamese fried and grilled dishes. The concentrations of the target compounds were obtained from the study showed that BaP, NDMA, and acrylamide are the groups of substances of greatest concern. The analytical results of 235 samples of meat and meat products (grilled/fried/smoked), seafood and seafood products (grilled/fried/smoked), processed oils, and potatoes showed that 12 samples detected acrylamide in the range of 5.0 – 162.0 µg/kg found in grilled/fried dishes and 5.0 – 4605 µg/kg for fried potatoes. Additionally, 204 samples detected NDMA in all groups in the range of 0.20 – 15.0 µg/kg, and 27 samples detected BaP in the range of 5.2 – 88 µg/kg in grilled/roasted food. Combined with information on food consumption patterns to estimate dietary exposure, four age groups were divided into under 6 years old, 6 – 18 years old, 18 – 50 years old, and over 50 years old, which showed that the consumption of processed foods by age groups was very different. In particular, the age group from 6 to 50 years old was the group that consumed the most of these foods (14.1 – 140 g/day). Specifically, up to 94.4% of people interviewed ate fried meat, 88.8% ate fried seafood and 85% ate fried potatoes. Risk characterization using the margin of exposure (MOE) and Cancer Slope Factor approaches indicate that certain dishes, such as grilled/smoked meat and fish, and deep-fried foods, may pose a significant cancer risk to Vietnamese consumers.

The Impact of Fat Contents and Different Cooking Processes on the Potential Health Concerns of Polycyclic Aromatic Hydrocarbons in Chicken Doner Kebabs

This study investigated the effects of different fat contents and cooking techniques on the presence of PAHs in chicken doner kebabs, as well as the dietary exposure and potential health risks for the Turkish population. The methodology for the detection and quantification of 16 PAH compounds in chicken doner samples using high-performance liquid chromatography (HPLC-UV) was validated. The limit of detection (LOD), quantification (LOQ), recovery, and relative standard deviation (RSD) were found to be 0.44%–1.14%, 1.45%–3.56%, 63.12%–101.50%, and 0.14%–3.16%, respectively. Our findings revealed that, among the analyzed compounds, BaA was the most dominant PAH compound, and that the charcoal cooking technique resulted in the highest accumulation of both BaP and PAH4 concentrations in chicken doner kebabs. Additionally, a significant increase in PAH levels was observed in relation to higher fat content. Moreover, it was found that the estimated daily intake (EDI) of BaP and PAH4 was higher in charcoal-grilled, well-done, high-fat chicken doner samples. As a result, the fact that the Margin of Exposure (MOE) values calculated for chicken doner samples across the Turkish population are above 10,000 indicates a low level of concern.

Dietary exposure of school children to aflatoxin and fumonisin through githeri and effectiveness of nixtamalization in reduction of these toxins in githeri from Turkana County.

Exposure of school children to aflatoxin and fumonisin is mainly through diet. In Kenyan public schools, children are given porridge made from maize flour for breakfast, a mixture of maize and beans, also known as githeri for lunch and ugali for dinner. Nixtamalization has proved to reduce mycotoxins in most cereals and not a mixture of maize and beans. This study, therefore, aimed to assess the exposure of primary school children in Turkana County to aflatoxin and fumonisin through maize-based food under the school meals program and the effectiveness of nixtamalization in the reduction of these mycotoxins. Samples of githeri were randomly collected from all public primary schools (n = 128) under the homegrown school meals program in Turkana County and analyzed for aflatoxin and fumonisin. The data was analyzed using SAS software, version 9.4. The deterministic model was used to calculate the estimated daily intake (EDI) and the margin of exposure (MOE) used to characterize the exposure risk. The contaminated samples were then treated with various concentrations of Ca(OH)2, 0.5-2.5%. The treated samples were cooked for 60 and 75min and soaked for 6 and 8h. Forty percent of the schools contained githeri samples with aflatoxin B1 levels above 5µg/Kg, the maximum limit for Kenya. Exposure to aflatoxin B1 and total aflatoxin was up to 2µg/kg/bw/day. The range for fumonisin exposure was 60-80µg/kg/bw/day. Ca(OH)2 concentration levels of up to 2.5% reduced aflatoxin by 75% and fumonisin by 72%. The findings indicate that githeri is contaminated with aflatoxin and fumonisin which exposes school children to these mycotoxins and nixtamalization can be used to reduce mycotoxin contamination in githeri.

Quantitative risk assessment for aflatoxins in beans from northern Tanzania

Abstract The study focussed on quantitative risk assessment for population exposure to aflatoxins by consuming beans from bean farmers in three villages; Long, Sabilo and Seloto in Babati District, Northern Tanzania. Aflatoxin levels were determined in a total of 144 bean samples; a total of 38 samples were collected from harvesting beans, while 106 samples were collected from stored beans. This kind of assessment allows modelling bean consumption data (kg/kg body weight (bw)/day) using an estimated average weight of an adult of 60 kg with previously collected data for total aflatoxin (AF) contamination (μg/kg) beans samples from the 2013/14 survey. Consumption was estimated by using the minimum annual per capita consumption of beans in Tanzania of 13.02 kg (which is equivalent to 35.67 g/day) and the exposure assessment was performed with the @RISK analysis software. Results from the assessment showed exposure for lower bound (LB) having a mean value of 1.06, 0.79 and 0.95 ng/kg bw/day in Long, Sabilo and Seloto villages, respectively, while for the medium bound (MB) the mean values were 1.33, 1.07 and 1.26 ng/kg bw/day, respectively, and for the upper bound (UB) the values were 1.65, 1.38 and 1.58 ng/kg bw/day, respectively. The margins of exposure (MoE) from this study were below 10,000 for all scenarios and this is of public health concern. Even though all samples had aflatoxin contamination below the maximum tolerable limit (MTL) of 4, 10 and 20 μg/kg for aflatoxins in cereals and pulses in the EU, the East African Community (EAC) and the USA, there is still a serious long-term health implication. Meeting MTL will not by itself guarantee food safety, but using the data collected and available on various health effects from aflatoxin and other mycotoxins, it is important to incorporate them into a risk assessment and show how excessive consumption of foods meets MTLs can still carry significant public health risks.

Inhibitory Effects of Fruit Powders on the Formation of Polycyclic Aromatic Hydrocarbons in Charcoal-Grilled Pork

Polycyclic aromatic hydrocarbons (PAHs), carcinogenic substances primarily formed through pyrolysis and oxidation of fat at high cooking temperatures, are commonly found at high levels in grilled meats. Reducing PAHs formation by incorporating natural antioxidants, such as through marination, has been demonstrated to be effective. However, the inhibitory effect of fresh phenolic-rich fruit powders on PAHs formation in charcoal-grilled meats remains unknown. To clarify the application of the fruit powders, 15 experimental groups were conducted. All pretreatment techniques (spraying, marinating, and mixing) were applied across all four freeze-dried fruit powders (lemon, guava, papaya, and mango). Each method was systematically tested with each fruit powder to evaluate its effect on inhibiting the formation of the four PAHs (BaA, CHR, BbF, and BaP) in charcoal-grilled pork belly and loin. Firstly, guava powder exhibited the highest phenolic content and antioxidant activity compared to the lemon, papaya, and mango powders (p < 0.05), among which the main phenolic compounds were ellagic acid, quercetin, and epigallocatechin gallate (EGCG). Further, marination of pork belly with guava powder exhibited the highest inhibition rate of PAHs (94.8%), followed by lemon (91.1%), papaya (89.8%), and mango (89.0%), with a statistically significant difference at p < 0.05. The reduction in estimated daily intake (EDI) and the increase in the margin of exposure (MOE) indicate that consuming grilled meat treated with these fruit powders poses no safety concerns and may potentially reduce health risks. Finally, the sensory evaluation showed that marinating with guava powder did not perceptibly affect the sensory attributes of the meat. Overall, this study provides a potent strategy for inhibiting the formation of PAHs in meat during charcoal grilling by incorporating fruit powder while preserving sensory qualities.

Use of physiologically based kinetic modeling to predict neurotoxicity and genotoxicity of methylglyoxal in humans

This study aimed to evaluate human neurotoxicity and genotoxicity risks from dietary and endogenous methylglyoxal (MGO), utilizing physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry as a new approach methodology (NAM) to extrapolate in vitro toxicity data to in vivo dose-response predictions. A human PBK model was defined based on a newly developed and evaluated mouse model enabling the translation of in vitro toxicity data for MGO from human stem cell-derived neurons and WM-266-4 melanoma cells into quantitative human in vivo toxicity data and subsequent risk assessment by the margin of exposure (MOE) approach. The results show that the MOEs resulting from daily dietary intake did not raise a concern for endpoints for neurotoxicity including mitochondrial function, cytotoxicity, and apoptosis, while those for DNA adduct formation could not exclude a concern over genotoxicity. Endogenous MGO formation, especially under diabetic conditions, resulted in MOEs that raised concern not only for genotoxicity but also for some of the neurotoxicity endpoints evaluated. Thus, the results also point to the importance of taking the endogenous levels into account in the risk assessment of MGO.

Update of the risk assessment of brominated phenols and their derivatives in food.

The European Commission asked EFSA to update its 2012 risk assessment on brominated phenols and their derivatives in food, focusing on five bromophenols and one derivative: 2,4,6-tribromophenol (2,4,6-TBP), 2,4-dibromophenol (2,4-DBP), 4-bromophenol (4-BP), 2,6-dibromophenol (2,6-DBP), tetrabrominated bisphenol S (TBBPS), tetrabromobisphenol S bismethyl ether (TBBPS-BME). Based on the overall evidence, the CONTAM Panel considered invivo genotoxicity of 2,4,6-TBP to be unlikely. Effects in liver and kidney were considered as the critical effects of 2,4,6-tribromophenol (2,4,6-TBP) in studies in rats. A BMDL10 of 353 mg/kg body weight (bw) per day for kidney papillary necrosis in male rats was identified and was selected as the reference point for the risk characterisation. The derivation of a health-based guidance value was not considered appropriate due to major limitations in the toxicological database. Instead, the margin of exposure (MOE) approach was applied to assess possible health concerns. Around 78,200 analytical results for 2,4,6-TBP in food were used to estimate dietary exposure for the European population. Considering the resulting MOE values, all far above an MOE of 6000 that does not raise a health concern, and accounting for the uncertainties affecting the exposure and hazard assessments, the CONTAM Panel concluded with at least 95% probability that the current dietary exposure to 2,4,6-TBP does not raise a health concern. Due to lack of occurrence data, no risk assessment could be performed for breastfed or formula-fed infants. No risk characterisation could be performed for any of the other brominated phenols and derivatives included in the assessment, due to lack of data both on the toxicity and occurrence.

Human health risk from co-occurring mycotoxins in dairy: A feed-to-fork approach

The presence of multiple mycotoxins in bovine dairy products can lead to potentially harmful health effects. This study examined the risk to human health from multiple mycotoxins in bovine dairy products using a feed-to-fork approach. It conducted a component-based risk assessment, using the toxicity of the most potent mycotoxin as a reference for others. The model also accounted for the influence of varying feed composition on mycotoxin contamination, considering monthly feeding pattern changes in Ireland. The probabilistic risk assessment uses Monte Carlo simulation to capture uncertainty and variability present in the model. The risk characterisation was undertaken using the Margin Of Exposure (MOE) method, where if the MOE was below 10,000, then the population's health was considered at risk. This study investigated the risk to human health from single mycotoxins and a combination of mycotoxins. The results showed that all mycotoxins were of low risk. However, the risk increased when aflatoxin was included in the co-occurring groups. Since 5% of the MOE was less than 10,000, the Irish population (male and female) was at relatively low risk of consuming aflatoxin or other co-occurring mycotoxin-contaminated milk. In comparison, the age group 8-12 years were at a relatively higher risk, with 10% of the MOE less than 10,000. The carry-over rates, the concentration of mycotoxin in feed components and the feeding composition were the most sensitive parameters. An increase in aflatoxin production in feed components can occur under climate scenarios and thus needs to be monitored, preventing any risks from aflatoxin or a combination of co-occurring mycotoxins. This study underscores the need for continuous monitoring and preventive measures, especially in feed components that are sensitive to aflatoxin-producing fungi that may contaminate bovine feed.

Re-evaluation of silicon dioxide (E 551) as a food additive in foods for infants below 16 weeks of age and follow-up of its re-evaluation as a food additive for uses in foods for all population groups.

The present opinion is the follow-up of the conclusions and recommendations of the Scientific Opinion on the re-evaluation of silicon dioxide (E 551) as a food additive relevant to the safety assessment for all age groups. In addition, the risk assessment of silicon dioxide (E 551) for its use in food for infants below 16 weeks of age is performed. Based on the newly available information on the characterisation of the SAS used as E 551 and following the principles of the 2021 EFSA Guidance on Particle-TR, the conventional safety assessment has been complemented with nano-specific considerations. Given the uncertainties resulting from the limitations of the database and in the absence of genotoxicity concern, the Panel considered that it is not appropriate to derive an acceptable daily intake (ADI) but applied the margin of exposure (MOE) approach for the risk assessment. The Panel concluded that the MOE should be at least 36 for not raising a safety concern. The calculated MOEs considering the dietary exposure estimates for all population groups using the refined non-brand loyal scenario, estimated at the time of the 2018 re-evaluation, were all above 36. The Panel concluded that E 551 does not raise a safety concern in all population groups at the reported uses and use levels. The use of E 551 in food for infants below 16 weeks of age in FC 13.1.1 and FC 13.1.5.1 does not raise a safety concern at the current exposure levels. The Panel also concluded that the technical data provided support an amendment of the specifications for E 551 laid down in Commission Regulation (EU) No 231/2012. The paucity of toxicological studies with proper dispersion protocol (with the exception of the genotoxicity studies) creates uncertainty in the present assessment of the potential toxicological effects related to the exposure to E 551 nanosize aggregates.

Simultaneous detection of multiple mycotoxins in Radix Dipsaci and estimation of exposure risk for consumers

Like many traditional Chinese herbal medicines, preparations from Radix Dipsaci are at risk of contamination by harmful mycotoxins; however, there have been no reports of actual contamination. In this study, we developed an analytical method to simultaneously detect eight mycotoxins in Radix Dipsaci and estimate the exposure risk for consumers. We have developed an analytical method utilizing ultra-high performance liquid chromatography and tandem mass spectrometry to accurately determine the levels of AFB1, AFB2, AFG1, AFG2, OTA, ZEN, T-2 and ST mycotoxins in 45 batches of Radix Dipsaci sourced from major medicinal herb markets across five regions in China. We also analyzed migration of mycotoxins from the raw herbs into water decoction. Based on these results and data on human consumption of the herbal medicine, we estimated risk of exposure and acceptable exposure limits to mycotoxins in the Radix Dipsaci using the “margin of exposure (MOE)” method. Of the 45 batches of Radix Dipsaci, 48.89% contained at least one of the eight mycotoxins, 24.44% contained one, 17.78% contained two and 6.67% contained three. The most frequent mycotoxins were aflatoxin B1, present in 35.56% of batches (at 0.25–34.84 μg/kg); aflatoxin G1, 15.56% (1.99–44.05 μg/kg); and ochratoxin A, 22.22% (16.11–143.38 μg/kg). These three mycotoxins transferred from the raw herb into water decoction at respective rates of 20.20%, 29.14%, and 24.80%. The 95th percentile values of the MOE risk factors for health effects of AFB1 were below 10,000 at high doses but above 10,000 at low doses of Radix Dipsaci long-term treatment. With the reduction in duration of exposure years, the MOE values of AFB1 and AFG1 gradually reverted to within the acceptable range. The mean, 50th, and 95th percentile values of the MOE risk factors for health effects of OTA exceeded 10,000 regardless of whether consumers received a low or high dose of Radix Dipsaci treatment for durations ranging from 1 to lifetime. Based on this exposure and a typical human diet, we have estimated the respective 20-year exposure limits for Radix Dipsaci to be 5.821 μg/kg, 4.035 μg/kg, and 56.073 μg/kg for the three mycotoxins under consideration. Contamination with multiple mycotoxins is frequently observed in Radix Dipsaci, and the three most prevalent contaminants have been found to leach into water decoctions, thereby posing a potential health hazard for individuals consuming this herbal preparation. This work highlights the need to monitor herbal medicines for mycotoxin contamination in order to protect consumers.

Exposure to Aflatoxins and Ochratoxin A From the Consumption of Selected Staples and Fresh Cow Milk in the Wet and Dry Seasons in Ghana.

Across sub-Saharan Africa, the heavy reliance on mycotoxin-susceptible staple foods means that populations in the region are particularly vulnerable to chronic mycotoxin exposure. This study assessed the exposure risk to ochratoxin A (OTA) and aflatoxins (AFs) from 18 samples of selected staple foods (maize, millet, groundnut) and 56 fresh cow milk samples collected from across Ghana. The foods were sampled simultaneously to maximise comparability, and at two timepoints in March/April (during the dry season) and July/August (during the rainy season) to assess the effects of duration of storage and seasonal conditions on the mycotoxin levels as measured by high-performance liquid chromatography. The margin of exposure (MOE) approach was used to assess the exposure risk from consumption of the sampled foods. Each of the sampled staples was contaminated with OTA (0.19-3.11 ng/g) and at least one AF (0.75-13.05 ng/g B1, ND-12.12 ng/g B2, 0.1-9.95 ng/g G1, ND-16.78 ng/g G2). Up to 67% had contamination above European Food Safety Authority (EFSA) maximum limits, and 50% were above Ghana Standards Authority (GSA) limits. The fresh cow milk samples were contaminated with AFM1 in the range of 0.05-1.49 ng/g, with 95% above EFSA limits and 36% above GSA limits. Aflatoxin contamination in the staples was high, particularly in July/August when the wet conditions may have adversely impacted the handling and storage of farm produce. Variation in AFM1 between the two sampling periods mirrored total aflatoxin in the staples, suggesting that even if dairy cattle were grazing in open pasture and not being rationed on stored feed, then there was a high environmental presence of aflatoxigenic fungi. The MOE estimates were ≤ 533.09, far below the safe cut-off of 10,000 for suspected carcinogenic compounds. The high mycotoxin levels indicate a priority risk to child nutrition which relies heavily on cereal mixes based on one or all the three sampled staples. The data from this study underscore the urgent need for interventions to better appreciate and address mycotoxin exposure for enhanced food security and public health in Ghana and across sub-Saharan Africa.

Stochastic health risk assessment of aflatoxin M1 in cow's milk among Lebanese population

This study quantitatively assessed AFM1 exposure through consumption of cows' milk in Lebanese adolescents and adults. Lebanon-specific, non-aggregated data on (i) milk intake and body weight – from an existing survey for adults and from a new survey for adolescents, and (ii) AFM1 occurrence in milk, were fitted to distributions and incorporated into a probabilistic model. Risk of hepatocellular carcinoma (HCC) for milk consumers was estimated considering the incidence of hepatitis B virus in Lebanon and characterized using the margin of exposure (MOE). All subgroups’ mean risk estimates, expressed as additional HCC cases per 100 000 population per year, were significantly different (p < 0.05), and ranged from 2.2x10−4 for adult males to 4.9x10−4 for adolescent males. This variation is attributed to significant differences in body weight and milk intake. MOE identified adolescent males and females as at-risk populations (mean 9628 and 8108, respectively). For adults, levels of concern were only reached with extreme consumption and/or contamination events. Considering that exposure from other sources (e.g., dairy) is cumulative, control of AFM1 in milk in Lebanon should be a risk management priority to ensure protection of younger populations.

Impact of formulation and home storage conditions on the content of furan and derivatives in powdered infant formula

While autoxidation of Polyunsaturated Fatty Acids (PUFAs) is a potential source of furan and its derivatives, the regulatory obligation to enrich powdered infant formulae (PIF) with some of these compounds might raise safety issues. The aim of this study was to investigate the impact of formulation and home storage conditions on the generation of furan and its derivatives in PIF. Furan, 2-methylfuran (2-MF) and 3-methylfuran (3-MF) were monitored by a validated SHS-GC-Q Exactive-Orbitrap MS method in six PIF formulated with high or low concentrations of different PUFAs (ALA, ARA, DHA), pro-oxidants (iron) and anti-oxidants (vitamins) and stored for 21 days under more or less oxidizing home storage conditions, including temperature (19 °C or 40 °C) and oxygen exposure (protected or not from ambient air). For the three compounds, the quality of the measurements in PIF was first confirmed with suitable linearity, limits of quantification, precision and recoveries. In a second step, the impact of the formulation was evaluated on six PIF commercial samples differing significantly in their composition in ALA, ARA, DHA, iron and/or vitamin E and C. While furan was quantifiable (2.8 µg/kg) in only one PIF with high content of DHA and iron and low level of vitamins, 2-MF was only quantifiable in two other PIF which were distinguished by a 15 to 20 % higher ALA content and 3-MF was not detected in any of the six PIF studied.. In a third step, the effect of storage conditions was studied on the six PIFs and the increase in storage temperature to 40 °C led to an increase of up to 33 % in the 2-MF concentration in the two PIF formulations where it was quantifiable. Nevertheless, the estimation of the Margin of Exposure (MOE) showed that the risk related to furan and its derivatives could be ruled out regardless of the formulation or storage conditions. Finally, in order to explore other derivatives and to investigate the mechanisms involved in the generation of furan compounds in PIF, a suspect screening approach was implemented on the SHS-GC-Q Exactive Orbitrap MS data. It made it possible on the one hand to point out two additional furan derivatives in PIF, 2-ethylfuran and 2-pentylfuran. On the other hand, it enabled to discuss the oxidation pathways involved in the generation of furan compounds in PIF from profiling of known PUFA oxidation markers also detected in the samples.

Estimation of the Dietary Acrylamide Exposure of the Turkish Population: An Emerging Threat for Human Health.

Acrylamide is a contaminant formed during heat treatment that poses potential health risks and occurs naturally in foods. Therefore, it is crucial to evaluate exposure from the consumption of foods containing acrylamide since dietary exposure continues throughout life. In this study, the acrylamide exposure level of people living in Türkiye is estimated. Consumption of a total of 28 foods in 9 different food groups was calculated using a deterministic model under two different scenarios. The exposure levels were evaluated in terms of carcinogenic, non-carcinogenic and neurotoxic health risks. The daily total acrylamide exposure levels of individuals aged 15 and older were determined as 58 µg/day (0.85 µg/kg bw/day) and 196 µg/day (2.80 µg/kg bw/day) for the good and bad scenarios, respectively. The highest daily acrylamide exposure in the good scenario came from brewed black tea (29%), whereas French fries (50%) were the source of highest daily acrylamide exposure in the bad scenario. According to the hazard index (HI) and margin of exposure (MOE) data, the good scenario (all food) is considered safe, while the bad scenario (all food) has potential and serious health risks. According to the carcinogenic risk (CR) data, both scenarios carry significant health risks. It is therefore important that consumers, producers and official institutions collaborate and take measures to reduce acrylamide exposure.

A new approach for risk assessment of pulmonary toxicants: a preliminary study using didecyldimethylammonium chloride.

Current human risk assessments often rely on animal toxicity data to establish point of departure (POD) values, followed by the application of uncertainty factors. Consequently, there is growing interest in alternative toxicity testing methods that reduce reliance on animal models. In this study, we propose a novel approach for inhalation toxicity risk assessment that integrates in silico and in vitro methods. Human primary alveolar epithelial cells were exposed to aerosolized didecyldimethylammonium chloride (DDAC) to assess cytotoxicity. This was followed by transcriptome analysis and biological pathway investigation, utilizing adverse outcome pathway (AOP), to calculate the POD. Additionally, human DDAC exposure was simulated using a multiple-path particle dosimetry (MPPD) model to predict exposure levels in the human alveolar region via inhalation. The results from in silico and in vitro studies were then compared, and a comprehensive risk assessment was performed. The POD for AOP 452 key events-oxidative stress, inflammation, epithelial-mesenchymal transition (EMT), apoptosis, and autophagy-was found to range between 19.0 and 23.89ng/cm2, according to benchmark dose calculation tools. The estimated human exposure to DDAC in the alveolar region under actual exposure conditions was 0.164ng/cm2/day, resulting in a margin of exposure (MOE) ranging from 121 to 145, suggesting caution regarding DDAC inhalation exposure. This study presents a novel risk assessment method that compares estimated human inhalation exposure values to in vitro results, applying the human equivalent concentration concept. Our findings demonstrate the potential for conducting human risk assessments using both in silico and in vitro methods as alternatives to traditional in vivo studies.

Mock Assessment: Acute prospective cumulative risk assessment

Abstract This Mock assessment is a part of the Framework Partnership Agreement between ANSES and EFSA with the help of RIVM to investigate the feasibility of a tiered approach proposed by EFSA for prospective acute cumulative risk assessment (CRA). Three tiers address successively a need for prospective CRA (Tier 0), the safety of the MRL (Tier I) and the safety of the intended GAP (Tier II). ANSES tested this approach with an application for change of MRL for the active substance tefluthrin (with acute effects on functional alterations of the motor division) on carrot based on a new intended use. For each tier, the Margin of Exposure (MOE) was calculated for 9 populations with MCRA software using input data provided by EFSA. At P99.9 of exposure, all the adjusted MOET at Tier I and Tier II of all populations were below the threshold of 100. Different settings were tested (IESTI equation, consumption data, adjustment for uncertainties, cycle of monitoring data…). With respect to Tier I, the trigger value of 1000 for the MOETier 0 is pragmatic. In the vast majority of cases, when the MOETier 0 is above 1000, the MOETTier I would be above 100. With respect to Tier II, a MOETier 0 higher than 1000 ensures a MOETTier II above 100. Tier I could be considered a good first estimate for a prospective CRA with conservative parameters for the foreground. Two routes were tested to account for uncertainties. One was not possible. The second resulted in a new median multiplicative factor (MF)exposure*toxicology of 2.82 that differs significantly from the value of 5.13 found in the retrospective assessment. Despite the simplifications envisaged, the uncertainty analysis seems difficult to be implemented on a routine basis and it might be useful to define criteria to identify cases where an uncertainty analysis is really needed.

Mock assessment: Chronic prospective cumulative risk assessment

Abstract This Mock assessment is a part of the Framework Partnership Agreement between ANSES and EFSA with the help of RIVM to investigate the feasibility of a tiered approach proposed by EFSA for prospective chronic cumulative risk assessment (CRA). Three tiers address successively (i) a need for prospective CRA (Tier 0) using a deterministic approach to estimate the foreground exposure based on IEDI equation, (ii) a first estimation of prospective CRA (Tier I) using a probabilistic approach to estimate the background exposure at P99.9 and a deterministic approach to estimate the foreground exposure at mean or P97.5 consumption and (iii) a second estimation of prospective CRA (Tier II) using a probabilistic approach to estimate the background and foreground exposure at P99.9. ANSES tested this approach with an MRL application for the active substance fenamidone (with chronic effects on the thyroid) on lettuce, based on a new intended use currently under assessment at national level. For each Tier, the Margin of Exposure (MOE) was calculated for 9 populations with MCRA software using input data provided by EFSA and settings according to EFSA protocol. Different combinations of settings were tested as part of sensitivity analyses (consumption data, adjustment for additional uncertainties, cycle of monitoring data, etc.) and were used as the basis for discussion of different open points (trigger value in Tier 0, use frequency for the focal combination in tier II, ad hoc uncertainty analysis to account for additional uncertainties, etc.) to be addressed before prospective CRA could be implemented as a routine exercise. Finally, based on these discussions, recommendations were made to consolidate the approach for chronic prospective CRA.

Safety evaluation of curdlan as a food additive.

The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of curdlan as a new food additive used as firming and gelling agent, stabiliser, thickener. Curdlan is a high molecular weight polysaccharide consisting of β-1,3-linked glucose units, produced by fermentation from Rhizobium radiobacter biovar 1 strain NTK-u. The toxicological dataset consisted of sub-chronic, chronic and carcinogenicity, reproductive and developmental toxicity studies as well as genotoxicity. Invivo data showed that curdlan is not absorbed as such but is extensively metabolised by the gut microbiota into CO2 and other innocuous compounds. Curdlan was not genotoxic and was well-tolerated with no overt organ-specific toxicity. Effects observed at very high doses of curdlan, such as decreased growth and increased cecum weight, are common for indigestible bulking compounds and therefore considered physiological responses. In a combined three-generation reproductive and developmental toxicity study, decreased pup weight was observed during lactation at 7500 mg curdlan/kg body weight (bw) per day, the highest dose tested. The Panel considered the observed effects as treatment-related and adverse, although likely secondary to nutritional imbalance and identified a conservative no observed adverse effect level (NOAEL) of 2500 mg/kg bw per day. Despite the limitations noted in the dataset, the Panel was able to conclude applying the margin of exposure (MOE) approach. Given that curdlan and its break-down products are not absorbed and that the identified adverse effect is neither systemic nor local, no adjustment factor was deemed necessary. Thus, an MOE of at least 1 was considered sufficient. The highest exposure estimate was 1441 mg/kg bw per day in toddlers at the 95th percentile of the proposed maximum use level exposure assessment scenario. The Panel concluded that there is no safety concern for the use of curdlan as a food additive at the proposed uses and use levels.

Baby Foods: 9 Out of 62 Exceed the Reference Limits for Acrylamide.

Acrylamide (AA) is a contaminant resulting from the Maillard reaction and classified by the International Agency for Research on Cancer (IARC) as a probable carcinogen in Group 2A, with proven neurotoxic effects on humans. European Union (EU) Regulation No. 2017/2158 is currently in force, which establishes measures meant to reduce AA levels in food and sets reference values, but not legal limits, equal to 40 and 150 μg/kg AA in processed cereal-based foods intended for infants and young children and in biscuits and rusks, respectively. For this reason, sixty-two baby foods were analyzed using ultra-high performance liquid chromatography with diode array detector and quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q-TOF/MS) to check whether industries were complying with these values, even though AA control is not legally mandatory. In total, 14.5% of the samples exceeded the reference values; these were homogenized chicken products (211.84 ± 16.53, 154.32 ± 12.71, 194.88 ± 7.40 μg/kg), three biscuits (276.36 ± 0.03, 242.06 ± 0.78, 234.78 ± 4.53 μg/kg), a wheat semolina (46.07 ± 0.23 μg/kg), a homogenized product with plaice and potatoes (45.52 ± 0.28 μg/kg), and a children's snack with milk and cocoa (40.95 ± 0.32 μg/kg). Subsequently, the daily intake of AA was estimated, considering the worst-case scenario, as provided by the consumption of homogenized chicken products and biscuits. The results are associated with margins of exposure (MOEs) that are not concerning for neurotoxic effects but are alarming for the probable carcinogenic effects of AA.