Reference Dose Research Articles

Occurrence of pesticide residues in honey from apiaries with incidents of honeybee poisoning in East China and a corresponding risk assessment for honeybees and Chinese consumers.

We investigated the occurrence of 80 pesticide residues in 96 honey samples from apiaries with honeybee poisoning incidences by liquid chromatography-tandem mass spectrometry and subsequently conducted risk assessments of exposure for in-hive honeybees and Chinese consumers. Six pesticides were detected with residue concentrations ranging from 0.5 to 130.9µg/kg. The mean concentrations of acetamiprid, dinotefuran, hexythiazox, propargite, semiamitraz, and carbendazim in positive samples were 7.9±9.1, 5.9±1.7, 3.0±1.6, 44.2±50.0, 9.0±9.4, and 5.5±4.1µg/kg, respectively. Carbendazim, semiamitraz, and acetamiprid were the major contaminants in honey, with incidences of 99.0%, 93.8%, and 49.0%, respectively. The cooccurrence of pesticides (≥2 pesticides) was detected in 95.9% of the samples, with up to six residual pesticides found in one sample. The HQ (hazard quotient) values of the six pesticides to in-hive honeybees were from 4.7×10-8 to 0.021, less than 1, indicating their acceptable exposure risk to honeybees. In terms of the representative-case and worst-case scenarios, the sum of separate HQs of each pesticide yielding an HI (hazard index) ranged from 0.012 to 0.016 for in-hive worker honeybees and from 0.015 to 0.021 for in-hive larva honeybees, indicating an overall acceptable potential cumulative risk of multiple pesticides to in-hive honeybees. Both the %ARfD (acute reference dose) value (0.0001-0.075) and %ADI (acceptable daily intake) value (0.00002-0.0046) of risky pesticides were much less than 100, revealing acceptable risk exposure to risky pesticides via honey consumption for human health. Thus, our results showed that multipesticide residual honey from apiaries with honeybee poisoning incidents in East China was safe for humans and in-hive honeybees. PRACTICAL APPLICATION: This analytical approach will be used in detecting multiple pesticide residues in honey and risk assessment for dietary exposure to pesticide residues. It can support various surveillance programs about honey safety and in-hive honeybee health evaluation.

Heavy Metal Content of Cadmium (Cd) and Chromium (Cr) in Green Mussels (Perna viridis) and Sediments of Sawojajar Waters, Brebes

Green mussel (Perna viridis) is one of the spesies in Bivalve class which filter the food particles from their surroundings. As filter feeder, it captured anything including plankton, detritus, and even heavy metals. Heavy metals content in green mussels could become dangerous due to the bioaccumulation process. This research aimed to determine the levels of heavy metals Cadmium (Cd) and Chromium (Cr) not only in the tissues of green mussels but also in the sediments of Sawojajar waters, Brebes; current study also determined the feasibility of green mussels for consumption in the perspective of food safety. The method used in this research was a field survey method which conducted in June 2022. The analysis method used AAS refers to the American Public Health Association (APHA) with laboratory tests conducted at the Productivity and Aquatic Environment Laboratory of IPB. The results showed that the content of heavy metal Cd in green mussel samples was at 0.19 mg.kg-1 which was meet the threshold concentration. Whereas, the heavy metal Cr in green mussels’ tissue exceeded the threshold of chromium concentration at 0.21 mg.kg-1. In addition, the heavy metal content of Cd and Cr in sediment were still meet the threshold concentration at 3.2 mg.kg-1 and 0.13 mg.kg-1 respectively. In terms of food safety, the EDI (Estiate Daily Intake) value based on the results of heavy metals Cd and Cr concentrations was 0.11 and 0.13 µg.kg-1.day-1 respectively. The result indicated that these heavy metals concentration had low risk in causing health issue. In the same way, the target hazard value (THQ) of Cd and Cr were not exceeded the RfD (Reference Dose) at 0.109 and 0.036 respectively. These value of THQ for both Cd and Cr indicated low risk in causing cancer and the green mussels are meet the food safety standard

Drinking water as a substantial source of toxic alkali, alkaline and heavy metals: Toxicity and their implications on human health

ObjectivesThe objective of the current study was to optimize a highly sensitive method utilizing microwave digestion and iCAP quadrupole inductively coupled plasma mass spectrometry (Q ICP-MS) for the determination of toxic alkali, alkaline and heavy metals in drinking water, and their implications on human health. MethodsA highly sensitive method based on microwave digestion and iCAP Q ICP-MS have been applied for the determination of potential metals alkali (23Na), alkaline (24 Mg) and heavy metals (75As, 208Pb, 111Cd, 59Co, 66Zn and 63Cu) in drinking water of diverse brand and origin. ResultsThe system has provided excellent quality conditions, such as detection limit (DL, 0.007–0.296 µg/L), quantification limit (QL, 0.023–0.893 µg/L) and coefficient of determination (R2, 0.976–0.998) with recovery >99.95%. Amounts of metals in bottled drinking water (BDW) were ranged from not detected to 74847.15 µg/L, whereas, tap water (TW) constitutes 1.12 to 42776.89 µg/L. Average daily dose (ADD, 0.03–516.715 μg/kg/day), hazard quotient (HQ, 0.001–0.08 μg/kg/day) based on heavy metals oral reference dose, and cancer risk (CR, 0.45–244.67 μg/kg/day) based on heavy metals cancer slope factor were achieved for BDW. Nevertheless, ADD (0.03–1028.19 μg/kg/day), HQ (0.01–0.12 μg/kg/day) and CR (0.42–292.80 μg/kg/day) were obtained for TW. As a result, BDW produced lower toxicity values than TW (high risk). Additionally, BDW was found to be brand specific, particularly for international brands that contained zero or very low levels of metals. ConclusionsCurrent investigations have explored the possible impacts of progressively increasing consumption of drinking water, especially in Saudi Arabia. Up to the present time, the levels of potential heavy metal in such water pose predominantly higher toxicity values in TW. Besides, BDW was found to be the brand specific particularly the international brand which contained either zero or low level of metals. As a result, the results highlight the need for strict policies to address the threat of metals in public water.

Probabilistic methods for non-cancer health effects

Noncancer risk assessment methods and harmonization with cancer assessment methods have advanced from the simple divide a No Observed Adverse Effect Level (NOAEL) by a default safety factor or a linear extrapolation to background of the early 1980's. This advance is due in part due to groups such as the American Industrial Health Council, the National Institute of Environmental Health Sciences, the Society for Risk Analysis, the Society of Toxicology, and the U.S. Environmental Protection Agency, the National Academy of Sciences (NAS), the International Programme on Chemical Safety, and to many independent researchers outside of and within a workshop series sponsored by the Alliance for Risk Assessment prompted by the NAS \\. Several of the case studies from this workshop series, and earlier work such as Bogdanffy et al., demonstrate that the dose response assessment of non-cancer toxicity and the harmonization of cancer and non-cancer methods are more than just a simple reflection of treating all non-cancer toxicity as if it has a threshold, or all cancer toxicity as if it did not. Moreover, one recommendation of NAS \\ was to develop a problem formulation with risk managers prior to conducting any risk assessment. If the development of this problem formulation only necessitates the determination of a safe, or virtually safe dose, then the estimation of a Reference Dose (RfD) or virtually safe dose (VSD) or similar constructs should be encouraged. Not all of our environmental problems need a precise quantitative solution.

Sociodemographic Disparities in Mercury Exposure from United States Coal-Fired Power Plants.

Hazardous air pollutants emitted by United States (U.S) coal-fired power plants have been controlled by the Mercury and Air Toxics Standards (MATS) since 2012. Sociodemographic disparities in traditional air pollutant exposures from U.S. power plants are known to occur but have not been evaluated for mercury (Hg), a neurotoxicant that bioaccumulates in food webs. Atmospheric Hg deposition from domestic power plants decreased by 91% across the contiguous U.S. from 6.4 Mg in 2010 to 0.55 Mg in 2020. Prior to MATS, populations living within 5 km of power plants (n = 507) included greater proportions of frequent fish consumers, individuals with low annual income and less than a high school education, and limited English-proficiency households compared to the US general population. These results reinforce a lack of distributional justice in plant siting found in prior work. Significantly greater proportions of low-income individuals lived within 5 km of active facilities in 2020 (n = 277) compared to plants that retired after 2010, suggesting that socioeconomic status may have played a role in retirement. Despite large deposition declines, an end-member scenario for remaining exposures from the largest active power plants for individuals consuming self-caught fish suggests they could still exceed the U.S. Environmental Protection Agency reference dose for methylmercury.

Determination of Biogenic Amines in Wine from Chinese Markets Using Ion Chromatography-Tandem Mass Spectrometry.

A method for the determination of nine biogenic amines (BAs) in wine was established using ion chromatography-tandem mass spectrometry (IC-MS/MS) without derivatization. BAs were separated by a cation exchange column (IonPac CG17, 50 mm × 4 mm, 7 µm) with a gradient aqueous formic acid elution. Good linearity was obtained for nine BAs with coefficients of determination (R2) > 0.9972 within the range of 0.01-50 mg/L. The limits of detection and quantification were within the ranges of 0.6-40 µg/L and 2.0-135 µg/L, respectively, with the exception of spermine (SPM). The recoveries were demonstrated within the range of 82.6-103.0%, with relative standard deviations (RSDs) of less than 4.2%. This simple method featuring excellent sensitivity and selectivity was suitable for the quantification of BAs in wines. The occurrence of BAs in 236 wine samples that are commercially available in China was determined. The BA levels in wines of different geographical origins varied significantly. The acute dietary exposure assessment of BAs was carried out by calculating the estimated short-term intake (ESTI) and comparing the acute reference dose (ARfD) specified by the European Food Safety Authority (EFSA). Results showed that the exposure to histamine (HIS) and tyramine (TYR) via the consumption of wines was much lower than the recommended ARfD level for healthy individuals. However, exposure could lead to symptoms in susceptible individuals. These results provided basic data regarding the occurrence and risk of BAs in wines for wine production, health guidance and consumer safety.

Legacy and novel perfluoroalkyl substances in major economic species of invertebrates in South China Sea: Health implication from consumption

Continuously release of perfluoroalkyl substances (PFASs) would pose non-negligible impacts on environment, organisms, and human health. In present study, 18 PFASs in 7 typical economic invertebrates and their habitats were investigated from the South China Sea. The higher concentrations of PFASs in the nearshore water (6.61–15.54 ng/L) and sediment (0.82–8.84 ng/g) obviously due to frequent human activities. Long-chain PFASs have tendency to accumulate in sediment, however, short-chain PFASs dominated in biota. The acute reference dose (%ARfD) and hazard ratios (HR) of major PFASs in biota were all <100 %, and also below 1, respectively, which means that consumption of PFASs from seafood does not pose risk and threat to human health. However, it should be taken into account that the HR of PFHxA in Mimachlamys nobilis reached 0.82. Potential adverse effects toward human health induced by short-chain PFASs (such as <6 C) via invertebrate seafood consumption should be concerned.

Comprehensive assessment of soil and dust heavy metal(loid)s exposure scenarios at residential playgrounds in Beijing, China

Small playgrounds situated within residential communities are popular recreational areas. However, heavy metal(loid)s (HMs) in soil or equipment dust may pose a public health risk. This study provides a comprehensive assessment of the health risk associated with HMs exposure at residential playgrounds in cities, a field that has not been thoroughly investigated previously. 70 soil and 70 equipment dust samples were collected from 30 urban and 40 suburban playgrounds in Beijing. Results indicated significant enrichment of Cu, As, and Ni in the soil with Enrichment Factors (EFs) >5 from both anthropogenic and lithogenic sources. Correlation analyses showed that the levels of Be, Cr, Mn, Co, Ni in soil and Be, Mn, As, Cd in dust were positively correlated with the distance to the nearest highway, with p-values < 0.01. Enrichment and correlation analyses contributed to a better understanding of the sources and transport pathways of HMs in urban environment. Based on a site-specific Conceptual Site Model (CSM), the carcinogenic risks (CRs) and Hazard Quotients (HQs) were quantified for residents as the ratio of HMs exposure to reference doses. Risk assessment indicated the mean predicted CR for children and adults exposed to soil was 3.75 × 10−6 and 5.29 × 10−6, respectively, while that at dust exposure scenarios was lower, at 2.47 × 10−6 and 3.49 × 10−6, respectively, all of which were at the upper end of U.S. EPA's acceptable criteria of 1 × 10−6 to 1 × 10−4. Among the HMs, As and Ni were identified as the priority control contaminants due to significant contribution to CRs. Furthermore, the spatial distribution revealed an increasing trend in health risk from the urban center to the suburbs. This study emphasizes the need for effective measures to mitigate potential health risk and enhance the safety of recreational areas, particularly for susceptible individuals.

Assessment of internal radiation exposure caused by radon in commercially bottled spring waters consumed in Turkey

ABSTRACT The variation of dissolved radon levels in water supplies remains of interest since radon ingested through drinking water can give considerable radiation to the lining of the stomach. This study aims to determine the radon concentration levels in bottled spring drinking water (BSW) brands commercially sold in Turkey using a radon gas monitor and to assess the internal radiation exposure caused by the ingestion and inhalation of radon. The activity concentrations of radon analyzed in 77 BSW brands varied from 7.1±0.8 to 28.7±2.7 mBq/L with an average of 15.7±5.1 mBq/L. The total annual effective dose was estimated to assess the radiological risk for three age groups in four different scenarios based on annual drinking water intake. All estimated dose values are well below the recommended reference dose of 100 µSv for drinking water. Therefore, radon gas in the investigated BSW samples poses no significant radiological risk to the public.

Status, sources, and human health risk assessment of DDT pesticide residues in river sediments in a highly developed agricultural region in the upper Yangtze River in China.

The concentrations of DDT and its metabolites in 19 sediment samples from a highly developed agricultural region in the upper reaches of the Yangtze River were measured. Non-carcinogenic hazard quotient for different age groups was evaluated using reference doses provided by the USEPA, and the excess lifetime cancer risk due to eating fish was assessed based on the local eating habits. The results showed that this region had a high level of residual DDT (12.84 ± 8.97 ng/g), which mainly came from the historically used technical DDT in agriculture. The non-carcinogenic risk was just acceptable in the region, but 11 of the 19 sites showed an unacceptable carcinogenic risk. Although DDT has been banned for decades, there were still notable health risks, especially for children. Special attention should be given to the potential health risks in historically developed agricultural regions.

Benchmark dose calculations for PFAS exposure based on two data sets on immunotoxic effects

BackgroundExposure to perfluorinated alkylate substances (PFAS) is associated with harmful effects on human health, including developmental immunotoxicity. This outcome was chosen as the critical effect by the European Food Safety Authority (EFSA), which calculated a new joint reference dose for four PFAS using a Benchmark Dose (BMD) analysis of a study of 1-year old children. However, the U.S. Environmental Protection Agency (EPA) recently proposed much lower exposure limits.MethodsWe explored the BMD methodology for summary and individual data and compared the results with and without grouping for two data sets available. We compared the performance of different dose-response models including a hockey-stick model and a piecewise linear model. We considered different ways of testing the assumption of equal weight-based toxicity of the four PFAS and evaluated more flexible models with exposure indices allowing for differences in toxicity.ResultsResults relying on full and decile-based data were in good accordance. However, BMD results for the larger study were lower than observed by EFSA for the smaller study. EFSA derived a lower confidence limit for the BMD of 17.5 ng/mL for the sum of serum-PFAS concentration, while similar calculations in the larger cohort yielded values of about 1.5 ng/mL. As the assumption of equal weight-based toxicity of the four PFAS seems questionable, we confirmed dose-dependencies that allowed potency differences between PFAS. We also found that models linear in the parameters for the BMD analysis showed superior coverage probabilities. In particular, we found the piecewise linear model to be useful for Benchmark analysis.ConclusionsBoth data sets considered could be analyzed on a decile basis without important bias or loss of power. The larger study showed substantially lower BMD results, both for individual PFAS and for joint exposures. Overall, EFSA’s proposed tolerable exposure limit appears too high, while the EPA proposal is in better accordance with the results.

A dosing strategy model of deep deterministic policy gradient algorithm for sepsis patients

BackgroundA growing body of research suggests that the use of computerized decision support systems can better guide disease treatment and reduce the use of social and medical resources. Artificial intelligence (AI) technology is increasingly being used in medical decision-making systems to obtain optimal dosing combinations and improve the survival rate of sepsis patients. To meet the real-world requirements of medical applications and make the training model more robust, we replaced the core algorithm applied in an AI-based medical decision support system developed by research teams at the Massachusetts Institute of Technology (MIT) and IMPERIAL College London (ICL) with the deep deterministic policy gradient (DDPG) algorithm. The main objective of this study was to develop an AI-based medical decision-making system that makes decisions closer to those of professional human clinicians and effectively reduces the mortality rate of sepsis patients.MethodsWe used the same public intensive care unit (ICU) dataset applied by the research teams at MIT and ICL, i.e., the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) dataset, which contains information on the hospitalizations of 38,600 adult sepsis patients over the age of 15. We applied the DDPG algorithm as a strategy-based reinforcement learning approach to construct an AI-based medical decision-making system and analyzed the model results within a two-dimensional space to obtain the optimal dosing combination decision for sepsis patients.ResultsThe results show that when the clinician administered the exact same dose as that recommended by the AI model, the mortality of the patients reached the lowest rate at 11.59%. At the same time, according to the database, the baseline mortality rate of the patients was calculated as 15.7%. This indicates that the patient mortality rate when difference between the doses administered by clinicians and those determined by the AI model was zero was approximately 4.2% lower than the baseline patient mortality rate found in the dataset. The results also illustrate that when a clinician administered a different dose than that recommended by the AI model, the patient mortality rate increased, and the greater the difference in dose, the higher the patient mortality rate. Furthermore, compared with the medical decision-making system based on the Deep-Q Learning Network (DQN) algorithm developed by the research teams at MIT and ICL, the optimal dosing combination recommended by our model is closer to that given by professional clinicians. Specifically, the number of patient samples administered by clinicians with the exact same dose recommended by our AI model increased by 142.3% compared with the model based on the DQN algorithm, with a reduction in the patient mortality rate of 2.58%.ConclusionsThe treatment plan generated by our medical decision-making system based on the DDPG algorithm is closer to that of a professional human clinician with a lower mortality rate in hospitalized sepsis patients, which can better help human clinicians deal with complex conditional changes in sepsis patients in an ICU. Our proposed AI-based medical decision-making system has the potential to provide the best reference dosing combinations for additional drugs.

Locomotion and brain gene expression exhibit sex-specific non-monotonic dose-response to HFPO-DA during Drosophila melanogaster lifespan

BackgroundLegacy per- and polyfluoroalkyl substances (PFAS), known for their environmental persistence and bio-accumulative properties, have been phased out in the U.S. due to public health concerns. A newer polymerization aid used in the manufacture of some fluoropolymers, hexafluoropropylene oxide-dimer acid (HFPO-DA), has lower reported bioaccumulation and toxicity, but is a potential neurotoxicant implicated in dopaminergic neurodegeneration. ObjectiveWe investigated HFPO-DA’s bio-accumulative potential and sex-specific effects on lifespan, locomotion, and brain gene expression in fruit flies. MethodsWe quantified bioaccumulation of HFPO-DA in fruit flies exposed to 8.7 × 104 µg/L of HFPO-DA in the fly media for 14 days via UHPLC-MS. Long-term effect on lifespan was determined by exposing both sexes to 8.7 × 102 – 8.7 × 105 µg/L of HFPO-DA in media. Locomotion was measured following 3, 7, and 14 days of exposures at 8.7 × 101 – 8.7 × 105 µg/L of HFPO-DA in media, and high-throughput 3′-end RNA-sequencing was used to quantify gene expression in fly brains across the same time points. ResultsBioaccumulation of HFPO-DA in fruit flies was not detected. HFPO-DA-induced effects on lifespan, locomotion, and brain gene expression, and lowest adverse effect level (LOAEL) showed sexually dimorphic patterns. Locomotion scores significantly decreased in at least one dose at all time points for females and only at 3-day exposure for males, while brain gene expression exhibited non-monotonic dose-response. Differentially expressed genes correlated to locomotion scores revealed sex-specific numbers of positively and negatively correlated genes per functional category. ConclusionAlthough HFPO-DA effects on locomotion and survival were significant at doses higher than the US EPA reference dose, the brain transcriptomic profiling reveals sex-specific changes and neurological molecular targets; gene enrichments highlight disproportionately affected categories, including immune response: female-specific co-upregulation suggests potential neuroinflammation. Consistent sex-specific exposure effects necessitate blocking for sex in experimental design during HFPO-DA risk assessment.

Defined daily dose definition in medication adherence assessment in asthma

ABSTRACT Adherence to inhaled corticosteroids (ICS) has been described as poor. In adherence studies, if the actual prescribed dosing is not available, generic defined daily doses (DDD) are applied instead when assessing adherence. We evaluated asthma patients’ adherence in a large prospective follow-up survey. We also analysed whether World Health Organization (WHO) and Global Initiative for Asthma (GINA) reference doses give different results. The current study was cross-sectional and included respondents attending to HeSSup follow-up questionnaire in 2012. Altogether 1,141 of 12,854 adult participants answered positively to the question about having asthma. According to the Finnish Social Insurance Institutions’ medication register, 686 of them had purchased ICS medication during 2011. DDDs for ICS by WHO as well as medium doses from GINA report were used as reference doses to evaluate adherence. To estimate adherence to ICS, the proportion of days covered (PDC) over one year was calculated for every patient. If the lower limit of GINA medium ICS dose was used as a reference, 65% of the patients were adherent (PDC ≥ 80%). Use of WHO’s DDD as reference halved the proportion of adherent patients. Adherence was higher among those using a combination inhaler of corticosteroid and long-acting β2-agonist compared to those using steroid only inhalers. Use of WHO’s daily defined doses as reference values may lead to underestimation of adherence to inhaled corticosteroids. Thus, attention should be paid when choosing the reference doses for the evaluation of adherence to inhaled corticosteroids in asthma.

Determination of methylmercury and inorganic mercury in human hair samples of individuals from Colombian gold mining regions by double spiking isotope dilution and GC-ICP-MS

With the aim to distinguish between routes of exposition to mercury (Hg) in artisanal and small-scale gold mining (ASGM) communities and to distinguish between Hg contamination sources, Hg species composition should be performed in human biomarkers. In this work, Hg species-specific determination were determined in human hair samples (N = 96), mostly non-directly occupied in ASGM tasks, from the six most relevant gold mining Colombian regions. Therefore, MeHg, Hg(II) and THg concentrations were simultaneously determined by double spiking species-specific isotope dilution mass spectrometry (IDMS) and GC-ICP-MS. Only 16.67% of participants were involved at some point in AGSM works and fish consumption ranged from 3 to 7 times/week, which is between medium and high intake levels. The median concentration of THg obtained from all samples is higher than the reference dose weekly acceptable of MeHg intake established by the EPA (1 ppm), whereas a 25% were more than 4 times higher than the WHO level (2.2 μg Hg g−1). Median THg value of individuals consuming fish 5–7 times per week was significantly higher (p < 0.05) than those of the other consuming groups (12.5 μg Hg g−1). Most of the samples presented a % of MeHg relative to THg higher than 80%. The average % of Hg(II)/THg was 11% and only 10 individuals presented a Hg(II) content over 30%. No significant differences (p > 0.05) were found when the amount of Hg(II) was compared between people involved in AGSM task and people not involved. Interestingly, significant differences among the evaluated groups where found when the percentage of the Hg(II)/THg ratio of these groups were compared. In fact, people involved in AGSM tasks showed 1.7 times higher Hg(II)/THg vs. inhabitants uninvolved. This suggest that Hg(II) determination by IDMS-GC-ICP-MS could be a good proxy for evaluating Hg(II) adsorption by direct exposure to mercury vapors onto hair.

Phthalates and phthalate metabolites in urine from Tianjin and implications for platelet mitochondrial DNA methylation.

Phthalates (PAEs) are important synthetic substances in plastics, attracting much attention due to their potential effects on the cardiovascular system. In this study, urine and blood samples from 39 individuals were collected in Tianjin, China. Phthalates and phthalate metabolites (mPAEs) were analyzed using gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. The polymerase chain reaction (PCR) products from bisulfite-treated mitochondrial DNA (mtDNA) samples were analyzed using pyrosequencing technology. The detection frequencies for 9 PAEs varied from 2.56 to 92.31%, and those for 10 mPAEs varied from 30.77 to 100%. The estimated daily intakes (EDIs) and cumulative risk of PAEs were calculated based on the experimental statistics of urinary PAEs and mPAEs. For PAEs, the HIRfD (hazard index corresponding to reference doses) values of 10.26% of participants and the HITDI (hazard index corresponding to tolerable daily intake) values of 30.77% of participants were estimated to exceed 1, suggesting a relatively high exposure risk. The mtDNA methylation levels in the MT-ATP8 and MT-ND5 were observed to be lower than in the MT-ATP6. Mono-ethyl phthalate (MEP) and MT-ATP8 were positively correlated with triglyceride levels (p < 0.05). Based on the association of PAEs, mtDNA methylation, and triglycerides, the mediating role of mtDNA methylation between PAEs and cardiovascular diseases (CVDs) was analyzed in this study, but no mediated effect was observed. The effects of PAE exposure on cardiovascular diseases (CVDs) should be investigated further.

Derivation of subacute guidance values for chemical contaminants of drinking water quality standard in Japan

The concentration of chemicals in drinking water may transiently and accidently exceed the Drinking Water Quality Standard (DWQS). If the level of a contaminant is not expected to cause adverse effects for a limited period of exposure, immediate suspension of the water supply may not be necessary. Assessments should be conducted using subacute guidance values (SGVs). In this study, we assessed 26 chemicals for the DWQS to establish the SGVs. Principally, a key study was selected from subacute studies to derive a Subacute Reference Dose (saRfD). The SGV was calculated from the saRfD for adults (drinking water intakes: 40 mL/kg/day) and children (drinking water intakes: 150 mL/kg/day). No allocation factor was applied to derive the SGV. We established the SGV for 20 chemicals, which were 2–38 times higher than the corresponding DWQS. However, SGVs for six chemicals were the same as the corresponding DWQS. Therefore, immediate action will be required for these six accidental contaminants. Our established SGVs are useful for assessing accidental contamination.

Design and characterization of an aperture system and spot configuration for ocular treatments with a gantry-based spot scanning proton beam.

Proton therapy is a key modality used in the treatment of ocular melanoma. Traditionally ocular sites are treated using a dedicated eyeline with a passively scattered proton beam and a brass aperture. This work aims to design and characterize a beam-collimating aperture to treat ocular targets with a gantry-based spot scanning proton beam. A plastic aperture system that slides into the gantry nozzle of a spot scanning proton beam was designed and constructed. It consists of an intermediate scraper layer to attenuate stray protons and a 3D-printed patient-specific aperture positioned 5.7cm from the surface of the eye. The aperture system was modeled in TOPAS and Monte Carlo simulations were validated with film measurements. Two different spot configurations were investigated for treatment planning and characterized based on lateral penumbra, central axis (CAX) dose and relative efficiency. Alignment and leakage were investigated through experimental film measurements. Range was verified using a multi-layer ionization chamber. Reference dose measurements were made with a PinPoint 3D ion chamber. Neutron dose was evaluated through Monte Carlo simulations. Aperture alignment with radiation isocenter was determined to be within 0.31mm at a gantry angle of 0°. A single-spot configuration with a 10mm diameter aperture yielded film-measured lateral penumbras of 1mm to 1.25mm, depending on depth in the spread-out Bragg peak. TOPAS simulations found that a single spot configuration results in a flat dose distribution for a 10mm diameter aperture and provides a CAX dose of less than 106% for apertures less than 14mm in diameter. For larger targets, adding four corner spots to fill in the dose distribution is beneficial. Trade-offs between lateral penumbra, CAX dose and relative efficiency were characterized for different spot configurations and can be used for future clinical decision-making. The aperture was experimentally determined to not affect proton beam range, and no concerning leakage radiation or neutron dose was identified. Reference dose measurements with a PinPoint ion chamber were within 2.1% of Monte Carlo calculated doses. The aperture system developed in this work provides a method of treating ocular sites on a gantry-based spot scanning proton system. Additional work to develop compatible gaze tracking and gating infrastructure is ongoing.

Concentrations of Tetrabromobisphenol-A and hexabromocyclododecane in Thai child daycare centre dust and the exposure risk for young children

Children spend one-third of their day in child daycare centres, where they may be exposed to toxic chemicals, such as tetrabromobisphenol-A (TBBPA) and hexabromocyclododecane (HBCDD), from indoor dust. However, studies on the exposure of TBBPA and HBCDD in schools remain scarce, especially in Thailand, where no such study has yet been reported. Therefore, in this study, we collected dust samples from 20 child daycare centres in Thailand and analysed them for flame retardants, TBBPA and HBCDD. TBBPA was detected in all samples with a median concentration of 35 ng g−1 (range, 14–5017.7 ng g−1). The median level of HBCDD was lower than the quantitation limit (LOQ) with <LOQ to 86.6 ng g−1 of dust sample. The electronic density score was calculated from the number of electronic appliances divided by each sampled surface floor area that revealed an abundance of TBBPA in the dust in rooms with many electronic items. The use of electronic devices, especially printers, that were found to be related to the high TBBPA concentration in the room, should be minimised in child daycare centres. The children's exposure to these chemicals from dust was estimated for dust ingestion and dermal absorption. The combined exposure was lower than the established reference dose value, and the hazard quotient for children via these two pathways were ranged 0.7 × 10−6 – 2.7 × 10−4 for TBBPA and 1.8 × 10−5 – 4.9 × 10−5 for HBCDD, which did not exceed 1.0. Although there is uncertainty regarding the potential health effects of long-term exposure to these substances, it is undeniable that child daycare centres represent a source of exposure to these substances for children. Further investigation of other intake routes of several flame retardants in child daycare centres and identification of the sources of these substances is warranted to decrease children's health risks from exposure to these harmful substances in child daycare centres.

RENEB Inter-Laboratory Comparison 2021: The Cytokinesis-Block Micronucleus Assay.

The goal of the RENEB inter-laboratory comparison 2021 exercise was to simulate a large-scale radiation accident involving a network of biodosimetry labs. Labs were required to perform their analyses using different biodosimetric assays in triage mode scoring and to rapidly report estimated radiation doses to the organizing institution. This article reports the results obtained with the cytokinesis-block micronucleus assay. Three test samples were exposed to blinded doses of 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 13 mA, ∼75 keV, 1 Gy/min). These doses belong to 3 triage categories of clinical relevance: a low dose category, for no exposure or exposures inferior to 1 Gy, requiring no direct treatment of subjects; a medium dose category, with doses ranging from 1 to 2 Gy, and a high dose category, after exposure to doses higher than 2 Gy, with the two latter requiring increasing medical attention. After irradiation the test samples (no. 1, no. 2 and no. 3) were sent by the organizing laboratory to 14 centers participating in the micronucleus assay exercise. Laboratories were asked to setup micronucleus cultures and to perform the micronucleus assay in triage mode, scoring 500 binucleated cells manually, or 1,000 binucleated cells in automated/semi-automated mode. One laboratory received no blood samples, but scored pictures from another lab. Based on their calibration curves, laboratories had to provide estimates of the administered doses. The accuracy of the reported dose estimates was further analyzed by the micronucleus assay lead. The micronucleus assay allowed classification of samples in the corresponding clinical triage categories (low, medium, high dose category) in 88% of cases (manual scoring, 88%; semi-automated scoring, 100%; automated scoring, 73%). Agreement between scoring laboratories, assessed by calculating the Fleiss' kappa, was excellent (100%) for semi-automated scoring, good (83%) for manual scoring and poor (53%) for fully automated scoring. Correct classification into triage scoring dose intervals (reference dose ±0.5 Gy for doses ≤2.5 Gy, or reference dose ±1 Gy for doses >2.5 Gy), recommended for triage biodosimetry, was obtained in 79% of cases (manual scoring, 73%; semi-automated scoring, 100%; automated scoring, 67%). The percentage of dose estimates whose 95% confidence intervals included the reference dose was 58% (manual scoring, 48%; semiautomated scoring, 72%; automated scoring, 60%). For the irradiated samples no. 2 and no. 3, a systematic shift towards higher dose estimations was observed. This was also noticed with the other cytogenetic assays in this intercomparison exercise. Accuracy of the rapid triage modality could be maintained when the number of manually scored cells was scaled down to 200 binucleated cells. In conclusion, the micronucleus assay, preferably performed in a semi-automated or manual scoring mode, is a reliable technique to perform rapid biodosimetry analysis in large-scale radiation emergencies.