Maximum Daily Intake Research Articles

Airborne antibiotics, antimicrobial resistance, and bacterial pathogens in a commercial composting facility: Transmission and exposure risk

Multiple elements associated with antimicrobial resistance in compost may escape into the air during the composting process, including antibiotic resistance genes (ARGs), human pathogenic bacteria (HPBs), and even antibiotics. Although antibiotics play a critical role in the evolution of resistance in HPBs, no information is available on airborne antibiotics in composting facilities. In this study, we systematically quantified airborne antibiotics, ARGs, and HPBs in comparison with those in compost. The burden of antibiotics in the air reached 4.17 ± 2.71 × 102 ng/g, significantly higher than that in compost. The concentration of ARGs (102 copies/g) in air also increased compared with that in compost. Concentrations of target contaminants in air were affected by temperature, organic matter, and heavy metals. Co-occurrence network analysis revealed the connectivity and complexity of antibiotics, ARGs, and HPBs were greater in air than in compost. The maximum daily antibiotic intake dose was up to 1.18 × 10−1ng/d/kg, accompanied by considerable inhalation levels of ARGs and HPBs. Our results reveal the severity of airborne antimicrobial resistance (AMR) elements in composting facilities, highlight the non-negligible amount of antibiotics and their co-existence with ARGs and HPBs, and shed light on the potential role of airborne antibiotics in the evolution of environmental AMR.

Analysis of Total Anthocyanin Levels in Hibiscus (Hibiscus rosa-sinensis L.) Preparations by Differential pH Method Using UV-Vis Spectrophotometry

Red hibiscus is a plant that contains anthocyanins and flavonoids which act as natural dyes and preservatives. Anthocyanins are attractive coloring substances and are not harmful to health, therefore they are widely used in the food and pharmaceutical industries. The maximum allowable daily intake of anthocyanins is 0.25 mg/kg body weight. Excessive intake of anthocyanins can cause poisoning. This study aims to determine the total anthocyanin content in hibiscus extract. The method used to analyze anthocyanin levels is the differential pH method using UV-Vis spectrophotometry. The main advantage of this method is that it provides a simple way to measure very small amounts of substances. The results of the research explained that the qualitative analysis showed that the sample was positive for containing anthocyanins because the acid reagent HCl remained red, this was due to the formation of flavilium. The sample with the base reagent (NaOH) changes color to green due to the formation of a carbinol pseudobase structure. Quantitative analysis of anthocyanins showed that in 10.8876 grams of extract there was an anthocyanin content of 72.4731 mg/L at a dilution of 10 ml. The high level of total anthocyanin in the thick hibiscus extract preparation can be influenced by several things such as the temperature during the drying process, the length of maceration time, the concentration of the solvent used, and the high intensity of light

Antineoplastic drugs in healthcare settings: Occupational exposure and risk graduation

Antineoplastic drugs (ADs) are hazardous medicinal products highlighted in the EU strategic framework on health and safety at work 2021–2027. To minimize workers' chronic exposure in oncologic settings, regular monitoring programs for these drugs are crucial and mandatory in the EU (Directive 2004/37/EC). No surveillance exists in Portugal, thus we intended to assess environmental contamination and to perform occupational exposure and risk graduation in a Portuguese tertiary hospital. Wipe sampling and liquid chromatography–tandem mass spectrometry were employed to analyze thirteen drugs of concern (bicalutamide, capecitabine, cyclophosphamide, cyproterone, doxorubicin, etoposide, flutamide, ifosfamide, imatinib, megestrol, mycophenolate mofetil, paclitaxel, prednisone), eight for the first time worldwide, in 152 surface samples over three sampling campaigns. Surface contamination before general cleaning (worst-case scenario) was higher and more widespread in the pharmacy (84%–98 % positive samples) than in the day-care hospital (40%–72 %). No samples were found above the “action limit” (10000 pg/cm2), but concentrations were frequently above the “safe”/alert level (100 pg/cm2), particularly for cyclophosphamide and ifosfamide (largest campaign's 90th percentiles: 2197 pg/cm2 and 1898 pg/cm2). Despite the approach's nuances, the maximum daily dermal intake calculated (1.6 μg/day, considering a single genotoxic drug) was lower than the acceptable daily intake. This study provided knowledge regarding surface contamination in a European hospital, where occupational exposure to some ADs of concern cannot be ruled out and follow-up monitoring is recommended, even if workers seem unlikely to develop cancer from handling them. Furthermore, this work contributes to the implementation of regular environmental monitoring programs for ADs in Portugal, enhancing compliance with EU recommendations.

Trace elements accumulation in vegetables and soils of waste dumping sites in southwestern Bangladesh and implication on human health

The untreated municipal solid wastes (MSWs) dumping and improper management causes major concerns of environmental degradation and human health risks. In this study, we collected soil and vegetable from the MSWs dumpsites of Khulna City Corporation (KCC) in southwestern Bangladesh. Trace metals (Pb, Cd, Co, Cr, Cu, Ni, Zn, Fe, Mn) were measured to explore the health risk of cultivated vegetables from dumpsites. Soil contamination was evaluated by geoaccumulation index (Igeo), enrichment factor (EF), contamination factor (CF), and pollution load index (PLI), while health risk was evaluated by transfer factor (TF), estimated daily intake (EDI), target hazard quotient (THQ). Results exhibited that the average trace metals in soil and vegetables followed in the order of Fe > Pb > Mn > Zn > Cu > Cr > Ni > Cd > Co. The Igeo, EF, CF, and PLI values revealed that the soil contamination was dominated by Pd, Cd, Mn, and Zn. The EDI of metals in vegetables were exceed the maximum daily intake only for Fe, Pb, and Cr. The total THQ was > 1, implying potential health hazards for the local people due to the long-term consumption of the cultivated vegetables. The multivariate analysis reveled that the sources of trace metals in the soils and vegetables of dumpsites were natural and anthropogenic. Overall, the findings suggest that growing vegetables in dumpsite is unsafe for long-term consumption by local inhabitants. Immediate action should be taken to protect the environment and human health from trace metal hazards.

Analysis Of Microbial and Chemistry Contamination Thai Tea Drink in Junior High School

Thai Tea drink is the current favorite drink of the current millennial generation. Thai Tea beverage products are usually sold in places that are easily accessible to consumers, such as on the side of the highway. This thing makes Thai Tea beverage products have potential to become a medium for foreign object to enter the body if they are not processed properly. This study aims to determine the safety of Thai Tea beverage products that are sold around junior high schools in Central Bogor District. This study used seven samples taken from 7 junior high schools in seven different sub-districts and used a purposive sampling method. Product analysis was carried out twice, including testing the microbial contamination levels of Total Plate Number, Coliforms, Escherichia coli, heavy metal lead chemical contamination and sucrose content in Thai Tea drinks. Research is also supported by field observations and interviews. The research showed that all samples of Thai Tea drinks contained TPC microbial contamination that exceeded the standard, twelve repetition were contaminated with coliform bacteria and Escherichia coli, all repetition were not detected by heavy metal lead contamination and the sucrose content of all repetition did not exceed the maximum daily sugar intake limit.

Flavouring Group Evaluation 80, Revision 2 (FGE.80Rev2): Consideration of alicyclic, alicyclic-fused and aromatic-fused ring lactones evaluated by the JECFA (61st and 82nd meetings) structurally related to an aromatic lactone evaluated in FGE.27.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 14 flavouring substances assigned to the Flavouring Group Evaluation 80 (FGE.80), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Thirteen substances have already been considered in FGE.80 and its revision and in FGE.96 [FL-no: 10.005, 10.024, 10.025, 10.050, 10.061, 10.069, 10.070, 10.072, 10.169, 13.009, 13.012, 13.161 and 16.055]. The remaining flavouring substance 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one [FL-no: 10.057] has been cleared with respect to genotoxicity in FGE.217Rev3 and it is considered in this revision 2 of FGE.80. The substance [FL-no: 10.057] was evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, threshold of toxicological concern (TTC) and available data on metabolism and toxicity. The Panel concluded that [FL-no: 10.057] does not give rise to safety concerns at its levels of dietary intake, when estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substance, the specifications for the material of commerce have also been considered and the information provided was complete for [FL-no: 10.057]. However, for the flavouring substance [FL-no: 10.057] in the present revision and for eight substances evaluated in previous revisions, the 'modified Theoretical Added Maximum Daily Intakes' (mTAMDIs) values are above the TTC for their structural class (III). For four substances previously evaluated in FGE.80Rev1 and in FGE.96, use levels are still needed to calculate the mTAMDI estimates. Therefore, in total for 13 flavouring substances, data on uses and use levels should be provided to finalise their safety evaluations. For [FL-no: 10.050, 10.069 and 13.161], information on the composition of stereoisomeric mixtures is needed.

Heavy metal contamination (Cu, Pb, and Cd) of washed and unwashed roadside blackberries (Rubus fruticose L.).

Foraging provides a multitude of individual, social, and environmental benefits. With green spaces decreasing in the United Kingdom, there is an opportunity for roadside verges to become valuable foraging resources; however, there is public concern over the safety of roadside forage. Human ingestion of heavy metal contaminants, such as copper (Cu), lead (Pb), and cadmium (Cd), originating from traffic activity, induces toxic effects in the body. Therefore, maximum Cu, Pb, and Cd guideline limits for human consumption in small fruits were established. However, studies of heavy metal concentrations in roadside forage and the effects of surface washing on concentrations are limited. This study examined Cu, Pb, and Cd in washed and unwashed wild blackberries (Rubus fruticose L.) along a main road in Kent, UK, and compares the values with maximum guideline limits. In all 44 samples, Cu, Pb and Cd concentrations were well below the maximum guideline limit or daily reference intake (RI) value. Cu and Pb concentrations were below the maximum daily intake in every sample if foragers eat one portion (80 g) of berries a day, but consuming a larger quantity of berries per day (e.g., 1 kg) could lead to an intake above the guideline limit for Cu (1 mg) and Pb (0.1 mg), but not Cd (0.03 mg). Washing did not significantly reduce the concentrations of Cu (p = 0.174) or Cd (p = 0.752) in blackberries, but did significantly reduce the Pb concentration (p < 0.001). However, Pb concentration was below maximum guideline limits for every sample regardless of washing treatment. Thus, wild blackberries collected from the roadside were suitable for human consumption, although the findings are not representative of all foraged berries or road networks. Integr Environ Assess Manag 2024;20:2107-2115. © 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Toxicological assessment of cadmium exposure through Hyphantria cunea larvae on the predation fitness of Arma chinensis

Heavy metals are defined as an abiotic factor that affects the efficiency of biological pest control. This study constructed a cadmium (Cd)-polluted artificial diets–Hyphantria cunea–Arma chinensis food chain to analyze the effects of Cd exposure on the ability of A. chinensis to control H. cunea. The results revealed that Cd was transferred through the artificial diet to H. cunea larvae and A. chinensis nymphs via a biological amplification effect. After feeding on Cd-accumulated H. cunea larvae, the body weight of A. chinensis nymphs reduced, mortality increased, developmental duration prolonged, and the expression of growth regulatory genes (EX, cycE, and MER) decreased. Cd activated the antioxidant defense system of the nymphs, accompanied by a significant enhancement in the contents of H2O2 and MDA, marked damage to the midgut sub-microstructure, and a remarkable induction in the expression of genes crucial for the mitochondrial pathway/ER stress–apoptosis pathway. Cd significantly diminished the contents of total amino acids, glucose, free fatty acids, and expression of the genes (HK2, PFK, IDH1, and IDH2) essential for the TCA cycle and glycolysis in the nymphs. The preference of the A. chinensis nymphs to Cd-treated H. cunea larvae was evidently reduced. Cd diminished the search-ability, food intake, instantaneous attack rate, and maximum theoretical daily food intake but prolonged the feeding time of the nymphs. Taken together, Cd exposure reduces the ability of A. chinensis nymphs to control H. cunea and provides a new challenge for the efficiency of insect pest control using natural enemies. These findings have important reference value for optimizing pest control strategies in heavy metal polluted areas.

Dissipation kinetics and the evaluation of dietary risks associated with deltamethrin, ethion, fenazaquin, and fenpropathrin on bell pepper (Solanum annuum L.).

Bell peppers, a globally significant crop, face infestations from various pests. In a study, bell peppers were treated with deltamethrin, ethion, fenazaquin, and fenpropathrin at recommended and double the doses, repeated twice with a 10-day interval. The QuEChERS method underwent validation for linearity, matrix match, accuracy, and precision in bell pepper matrices for residue analysis. The limit of detection for the tested pesticides on bell peppers was 0.01mg/L, with a quantification limit of 0.05mg/L. Recovery studies showed a range of 94.80% to 102.80%. Initial deposits of deltamethrin, ethion, fenazaquin, and fenpropathrin on bell peppers at recommended doses were 0.371, 1.237, 0.617, and 0.640mg/L, respectively, and at double doses were 0.712, 1.945, 1.221, and 1.189mg/L, respectively. Safe waiting periods of 10, 11, 10, and 8days were suggested for deltamethrin, ethion, fenazaquin, and fenpropathrin, respectively. The corresponding half-lives for the pesticides were 1.96, 1.79, 2.06, and 1.69days, all following first-order dissipation kinetics. Dietary risk assessment indicated Hazard Quotients (HQ) below 1 and Theoretical Maximum Daily Intake (TMDI) below Acceptable Daily Intake (ADI) and Maximum Permissible Intake (MPI) levels. Therefore, at their recommended doses, the pesticides were deemed safe for bell pepper cultivation.

Highly sensitive two-dimensional ion chromatography mass spectrometry method for nitrite determination in hydroxypropyl methylcellulose

Due to their potential adverse health effects, some N-nitrosamines in drug products are strictly regulated with very low maximum daily intake limits. Nitrosamines can be formed from the reaction of nitrite and secondary or tertiary amines when both species co-exist in the drug synthesis or formulation process. One key strategy to mitigate nitrosamine risk in drugs is to select low-nitrite containing pharma excipients for formulation. It is necessary to develop a sensitive method for trace nitrite determination in pharma excipients as it enables drug producers to study nitrosamine formation kinetics and select excipient suppliers. This study details the development and validation of a two-dimensional ion chromatography mass spectrometry (2D-IC/MS) method for trace nitrite determination in hydroxypropyl methylcellulose (HPMC), one of the most important pharmaceutical excipients used in many drug formulations. The 2D-IC system was operated in heart-cutting mode with a concentrator column coupling the two dimensions. A standard bore anion-exchange column was used in the first dimension (1D) to enable a large volume injection for increased sensitivity and provide improved resolution between nitrite and the interfering chloride peak. A high efficiency microbore anion-exchange column with different selectivity was used in the second dimension (2D) to resolve nitrite from other interfering species. The use of 2D-IC resulted in significantly improved resolution, solving the sensitivity loss issue due to ion suppression from an otherwise 1D separation. MS detection with selective ion monitoring and isotope labeled nitrite internal standard further improve the method specificity, accuracy, and ruggedness, as compared with conductivity detection. For trace determination, it is also extremely important to have a clean blank. For this purpose, a novel cleaning procedure using a strong anion wash was developed to remove nitrite contamination from labware. The optimized method was validated with linearity of nitrite in the concentration range of 18.5–5005.8 ng/g having a regression coefficient of >0.9999, precision with RSD at 3.5–10.1 % and recovery of 90.5–102.4 %. The limit of detection and limit of quantitation were 8.9 and 29.6 ng/g relative to the HPMC sample, or equivalent to 89 and 296 pg/g in the sample solution, respectively.

Evaluation of irrigation, drinking, and risk indices for water quality parameters of alpine lakes.

Alpine lakes are aquatic ecosystems that maintain and regulate water supply for the downstream streams, rivers, and other reservoirs. This study examined the water characteristics of various alpine lakes in Gilgit-Baltistan, Northern Pakistan. For this purpose, water was sampled and investigated for basic parameters, anions, and cations using the multi-parameter analyzers and atomic absorption spectrophotometer. Physicochemical parameters of alpine lakes were noted under the World Health Organization water guidelines, except for fluoride (F-) and turbidity in 4.3% and 36% of samples, respectively. Water quality index (WQI) classified samples (93%) as excellent and good quality (7%). Results showed maximum chronic daily intake values (0.14 ± 0.01mg/kg-day) for nitrate (NO3-) and hazard quotient (0.80 ± 0.24) for F- in children via water intake from Upper Kachura and Shausar Lakes, respectively. Statistical analyses of Piper and Gibbs's plots revealed that the water quality is mainly characterized by bedrock geology.

Dietary Exposure of Filipinos to Pesticide Residues in Rice (Oryza sativa) Using National Theoretical Maximum Daily Intake (NTMDI) Approach

Exposure to pesticides, at levels above the regulatory limits, is detrimental to health. Rice, being a staple food of Filipinos, is a significant vector of pesticide residues in the diet. The current study aimed to determine the exposure of Filipinos to different pesticide residues in well-milled rice using the National Theoretical Maximum Daily Intake (NTMDI) approach. The NTMDI of 71 permitted pesticide active ingredients (PAIs) was estimated using the 2013 national food consumption data, established maximum residue limits (MRL), and the estimated average weight of the population groups. Estimates were then compared with the acceptable daily intake (ADI) for each PAI. The top six PAIs were then subjected to probabilistic analysis of exceeding the ADI. Results showed that all Filipino population groups were at risk of exposure to thiram, isoprocarb, and carbofuran with a 100% probability of exceeding the ADI. Exposures of Filipinos to these PAIs across all population groups were up to 870, 435, and 348% ADI, respectively. Infants and children were the most at-risk populations due to their low body weight. The NTMDI estimates, therefore, recognize the need to conduct a more refined dietary exposure assessment on the identified PAIs.

Arsenic (As) accumulation in different genotypes of indica rice (Oryza sativa L.) and health risk assessment based on inorganic As.

To reveal differences in arsenic (As) accumulation among indica rice cultivars and assess the human health risks arising from inorganic arsenic (iAs) intake via rice consumption, a total of 320 field indica rice samples and corresponding soil samples were collected from Fujian Province in China. The results showed that available soil As (0.03 to 3.83mg/kg) showed a statistically significant positive correlation with total soil As (0.10 to 19.45mg/kg). The inorganic As content in brown rice was between 0.001 and 0.316mg/kg. Among the cultivars, ten brown rice samples (3.13%) exceeded the maximum contaminant level (MCL) of iAs in food of 0.2mg/kg in China. The estimated daily intake (EDI) and calculated individual incremental lifetime cancer risk (ILCR) ranged from 0.337µg/day to 106.60µg/day and from 8.18 × 10-6 to 2.59 × 10-3, respectively. Surprisingly, the average EDI and the EDIs of 258 (80.63%) brown rice samples were higher than the maximum daily intake (MDI) of 10µg/day in drinking water as set by the National Research Council. The mean ILCR associated with iAs was 54.3 per 100,000, which exceeds the acceptable upper limit (AUL) of 10 per 100,000 set by the USEPA. Notably, the cultivars Y-Liang-You 1 and Shi-Ji 137 exhibited significantly higher mean ILCRs compared to the AUL and other cultivars, indicating that they pose more serious cancer risks to the local population. Finally, this study demonstrated that the cultivars Yi-Xiang 2292 and Quan-Zhen 10 were the optimal cultivars to mitigate risks associated with iAs to human health from rice consumption.

Delineation of trace metal level in fish feed and farmed fish, Tilapia (Oreochromis mossumbicus) and their consequences on human health

The purpose of this research was to determine the possible health risks by identifying the trace metal content of feed and cultured tilapia fish in the Noakhali fish farms and Laxmipur/Central Coast district of Bangladesh. Commercial fish feed samples were collected from twelve randomly selected aquaculture farms on the central coast of Bangladesh. Trace metals, lead (Pb), manganese (Mn), zinc (Zn), copper (Cu), nickel (Ni), and chromium (Cr) concentrations in the edible muscle of tilapia fish and feeds were monitored by Energy Dispersive X-ray Fluorescence (EDXRF). Lead (9.37 ± 3.54 mg/kg) and Mn (7.94 ± 4.15 mg/kg) concentrations in tilapia were four and eight times higher than the WHO maximum levels. In feed samples, Sujola (SF) had the highest metal pollution index (MPI) value, and Rupshi Quality (RF) had the lowest. However, Tang Way and popular Surma fishes were similar in metal pollution index in fish feed. Trace metal daily intake values were lower than the maximum acceptable daily intakes, demonstrating low risk in this study. The carcinogenic and non-carcinogenic health risks of consuming farm-cultured fish due to trace metals were relatively low and have less potential hazards to human health. This study will provide a baseline for monitoring trace metals in different edible aquatic organisms and recommends further investigation in different natural ecosystems and policy making.

The first report on the assessment of maximum acceptable daily intake (MADI) of pesticides for humans using intelligent consensus predictions.

Direct or indirect consumption of pesticides and their related products by humans and other living organisms without safe dosing may pose a health risk. The risk may arise after a short/long time which depends on the nature and amount of chemicals consumed. Therefore, the maximum acceptable daily intake of chemicals must be calculated to prevent these risks. In the present work, regression-based quantitative structure-activity relationship (QSAR) models were developed using 39 pesticides with maximum acceptable daily intake (MADI) for humans as the endpoint. From the statistical results (R2 = 0.674-0.712, QLOO2 = 0.553-0.580, Q(F1)2 = 0.544-0.611, and Q(F2)2 = 0.531-0.599), it can be inferred that the developed models were robust, reliable, reproducible, accurate, and predictive. Intelligent Consensus Prediction (ICP) was employed to improve the external predictivity (Q(F1)2 =0.579-0.657 and Q(F2)2 = 0.563-0.647) of the models. Some of the chemical markers responsible for toxicity enhancement are the presence of unsaturated bonds, lipophilicity, presence of C< (double bond-single bond-single bonded carbon), and the presence of sulphur and phosphate bonds at the topological distances 1 and 6, while the presence of hydrophilic groups and short chain fragments reduces the toxicity. The Pesticide Properties Database (PPDB) (1694 pesticides) was also screened with the developed models. Hence, this research work will be helpful for the toxicity assessment of pesticides before their synthesis, the development of eco-friendly and safer pesticides, and data-gap filling reducing the time, cost, and animal experimentation. Thus, this study might hold promise for future potential MADI assessment of pesticides and provide a meaningful contribution to the field of risk assessment.

Biological significance of long-term bisphenol A release in the saliva of patients wearing orthodontic appliances: A systematic review and meta-analysis.

Orthodontic appliances contain Bisphenol A and are controversial due to its potential risks for human health. Thus, the aim of the present research was to identify the presence of Bisphenol A in the saliva of patients wearing orthodontic appliances. A systematic search of the literature was conducted in four electronic databases (PubMed, Embase, Scopus, and Web of Science) and a manual search of grey literature. Research was done up to March 2023, without language restrictions. Based on inclusion/exclusion criteria, data were extracted by two independent reviewers. A total of 2293 potentially eligible articles were identified, of which 8 were finally included. The studies included a total of 238 patients and showed a moderate quality in the PEDro scale. All the devices studied released Bisphenol A into the saliva, with the polycarbonate brackets being the ones that released it for a longer time. The most significant increase occurred in the first 30 minutes after bonding with composites, reaching 697 µg/g. with polycarbonate brackets. Although a statistically significant increase of Bisphenol A levels in the saliva of orthodontic patients were found, this increase does not exceed the maximum allowable daily intake. Thus, the use of these materials can be considered safe for human health. Key words:BPA, Bisphenol-A, cytotoxicity, Orthodontic materials, Composite resins.

Increasing exposure to the UV filters octocrylene and 2-ethylhexyl salicylate in Germany from 1996 to 2020: Human biomonitoring in 24-h urine samples of the German Environmental Specimen Bank (ESB)

The UV filters octocrylene (OC) and 2-ethylhexyl salicylate (EHS) are commonly used in sunscreens and frequently detected in environmental media. However, knowledge on human exposures is scarce.In this human biomonitoring (HBM) study, we analyzed concentrations of exposure biomarkers specific to OC (CPAA, DOCCA, 5OH-OC) and EHS (5OH-EHS, 5oxo-EHS, 5cx-EPS) in 24-h urine samples (n = 420) from the German Environmental Specimen Bank (ESB). These samples were collected from German students (20–29 years; 30 males/30 females per year) between 1996 and 2020 (4-year intervals; collection in winter).We found continuously increasing OC and EHS exposures (Jonckheere-Terpstra; p < 0.001) documented by very few to no samples with concentrations of the most sensitive biomarkers CPAA and 5cx-EPS above the limit of quantification (LOQ) in 1996 (5 % and 0 %, respectively) and reaching 100 % and 93 % above the LOQ in 2016, with median concentrations of 4.79 and 0.071 µg/L, respectively. In 2020, biomarker concentrations slightly decreased to 3.12 µg/L CPAA (97 %>LOQ) and 0.060 µg/L 5cx-EPS (88 %>LOQ). This general trend was confirmed by the other biomarkers, however at lower detection rates. Based on metabolite excretion in the 24-h urine samples and human toxicokinetic data, we calculated maximum daily intakes (DI) of 17 µg/(kg bw * d) OC and 59 µg/(kg bw * d) EHS. Based on a derived no-effect level (DNEL) of 0.8 mg/(kg bw * d), the OC exposures of individuals in our study did not indicate any health risk. Similarly, for EHS all biomarker concentrations were well below the HBM-I values of 12 µg/L 5OH-EHS and 11 µg/L 5cx-EPS.Our data proves the general applicability of specific OC and EHS metabolites for HBM in the general population and shows clearly increasing exposures. Higher (co-)exposures must be expected in populations with increased sunscreen use such as (summer) vacationers, children and outdoor workers.

Immunotoxicity of cynobacterial toxin Microcystin-LR is mitigated by Quercitin and himalaya tonic Liv52

Microcystin-LR (MC-LR) has received worldwide concern for its hepatotoxicity with maximum acceptable daily intake of 0.0015 mg/L (1.5 μg/L) [Federal-Provinicial-Territorial-Committee-on-drinking-water-2002]. Comprehensive immunotoxicity data is still deficient with MC-LR. To curb the menace of MC-LR, Quercitin (QE), himalaya made hepatotonic Liv52 were studied. To investigate the immunotoxic properties of MC-LR, QE and Liv52, primary splenocyte cells prepared, cultured, and immunoproliferation assay with mitogens lipopolysaccharide (LPS) or concanavalin A, (Con A) was done for, immunophenotyping, cell cycle and apoptotic studies. In current study, we have divided the splenocytes into 4 groups, i.e., Group I: Normal saline, Group II: MC-LR (0.1 μM), Group III: MC-LR (0.1 μM) + QE (20 μM), and Group IV: MC-LR (0.1 μM) + Liv52 (25 μg/ml) and treated with maximum < CC50 concentration. MC-LR enhanced proliferation of Con A and LPS stirred splenocytes at 24 h, whereas QE and Liv52 both act as antimitogenic. With combined mixture of MC-LR + QE, a significant increase in proliferation compared to mitogen or MC-LR was observed. MC-LR down-regulated expression of CD19+, CD3e+, CD4+, CD8+, (1.05%), (18.9%), (8.9%), and (7.8%) respectively in comparison to Group I. Down-regulation of 10% and 28% is observed in CD19+ and CD4+ populations with MC-LR and QE. The Liv52 addition concealed MC-LR adverse properties in most effective way. MC-LR induced G1-phase significant declined cell cycle arrest at S phase (9.26%) and G2/M phase (26.31%) was observed. QE and Liv52 mask the activity of MC-LR. Further apoptotic study revealed that MC-LR treatment decreases late apoptotic cells compared to control with no significant change in live and early apoptotic cells. Although QE increased live cells and Liv52 significantly increased late apoptotic cells, these results suggest that a <CC50 concentration (0.1 μM) of MC-LR may have immunosuppressive activity. Liv52 is found to be a more potent drug to counteract this cyanotoxin.

Safety of 3'-sialyllactose (3'-SL) sodium salt produced by a derivative strain (Escherichia coliNEO3) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3'-sialyllactose (3'-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3'-SL (sodium salt), but it also contains sialic acid, d-glucose, d-lactose, 3'-sialyllactulose and 6'-sialyllactose sodium salts and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli NEO3) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The applicant applies for the same uses and use levels as already assessed for 3'-SL sodium salt produced by a genetically modified strain of E. coli K-12 DH1, with the exception for the use in FS, which is proposed to be higher (from 0.5 to 1.0 g/day) in individuals from 3 years of age. Since the NF as a food ingredient would be consumed at the same extent as the already assessed 3'-SL sodium salt, no new estimates of theintakes have been carried out. The Panel notes that the maximum daily intake of 3'-SL from the proposed use of the NF in FS for individuals from 3 years of age (1.0 g/day) is lower than the estimated highest mean daily intake of 3'-SL in breastfed infants. FS are not intended to be used if other sources of 3'-SL are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

Learning and memory deficits produced by aspartame are heritable via the paternal lineage

Environmental exposures produce heritable traits that can linger in the population for one or two generations. Millions of individuals consume substances such as artificial sweeteners daily that are declared safe by regulatory agencies without evaluation of their potential heritable effects. We show that consumption of aspartame, an FDA-approved artificial sweetener, daily for up to 16-weeks at doses equivalent to only 7–15% of the FDA recommended maximum daily intake value (equivalent to 2–4 small, 8 oz diet soda drinks per day) produces significant spatial learning and memory deficits in mice. Moreover, the cognitive deficits are transmitted to male and female descendants along the paternal lineage suggesting that aspartame’s adverse cognitive effects are heritable, and that they are more pervasive than current estimates, which consider effects in the directly exposed individuals only. Traditionally, deleterious environmental exposures of pregnant and nursing women are viewed as risk factors for the health of future generations. Environmental exposures of men are not considered to pose similar risks. Our findings suggest that environmental exposures of men can produce adverse impact on cognitive function in future generations and demonstrate the need for considering heritable effects via the paternal lineage as part of the regulatory evaluations of artificial sweeteners.