Quantitative risk ranking of mycotoxins in milk under climate change scenarios.

Mycotoxins are toxic fungal metabolites that may occur in crops. Mycotoxins may carry-over into bovine milk if bovines ingest mycotoxin-contaminated feed. Due to climate change, there may be a potential increase in the prevalence and concentration of mycotoxins in crops. However, the toxicity to humans and the carry-over rate of mycotoxins from feed to milk from bovines varies considerably. This research aimed to rank emerging and existing mycotoxins under different climate change scenarios based on their occurrence in milk and their toxicity to humans. The quantitative risk ranking took a probabilistic approach, using Monte-Carlo simulation to take account of input uncertainties and variabilities. Mycotoxins were ranked based on their hazard quotient, calculated using estimated daily intake and tolerable daily intake values. Four climate change scenarios were assessed, including an Irish baseline model in addition to best-case, worst-case, and most likely scenarios, corresponding to equivalent Intergovernmental Panel on Climate Change (IPCC) scenarios. This research prioritised aflatoxin B1, zearalenone, and T-2 and HT-2 toxin as potential human health hazards for adults and children compared to other mycotoxins under all scenarios. Relatively lower risks were found to be associated with mycophenolic acid, enniatins, and deoxynivalenol. Overall, the carry-over rate of mycotoxins, the milk consumption, and the concentration of mycotoxins in silage, maize, and wheat were found to be the most sensitive parameters (positively correlated) of this probabilistic model. Though climate change may impact mycotoxin prevalence and concentration in crops, the carry-over rate notably affects the final concentration of mycotoxin in milk to a greater extent. The results obtained in this study facilitate the identification of risk reduction measures to limit mycotoxin contamination of dairy products, considering potential climate change influences.

Human health risk assessment of bisphenol A (BPA) through meat products.

Meat and meat products are often consumed in our daily diet, providing essential nutrients. Contamination by chemical hazards, including bisphenol A (BPA) in meat products, is a concern and is continuously monitored. BPA is well-known for its endocrine-disrupting properties, which may cause potential toxicological effects on reproductive, nervous, and immune systems. Dietary consumption is the main route of BPA exposure, and meat products are a major contributor. BPA exposure from meat consumption is the focus of this review. This review found that BPA has been widely detected in canned and non-canned meat products. BPA in canned meat is assumed to be predominantly from migration from can coatings. Relatively low levels are observed in non-canned products, and the source of contamination in these products has yet to be definitively identified. A recent European Food Safety Authority (EFSA) draft opinion has proposed to lower the tolerable daily intake of BPA from 4 µg kg body weight (bw)-1 day-1 to 0.04 ng kg body weight (bw)-1 day-1, therefore potential health risks need to be addressed. This review has investigated potential contamination at the farm, industrial processes, and retail levels. Data gaps in the literature are also identified to improve future food safety in the meat industry. Also, a unified risk assessment strategy has been proposed. Further understanding of BPA migration in meat products is needed as a part of the exposure assessment to reduce potential risk, and more data on the dose-response relationship will help comprehend potential adverse health effects of BPA on humans. This research will inform the public, meat producers and processing industry, and policymakers on potential exposure to BPA and risk reduction measures, thus, ensuring food safety.

Analysis of the levels of metal(loid)s in environmental compartments in Ireland towards a screening measure for potential relative risk using open-source datasets.

Several metals and metalloids (metal(loid)s) have been identified as potential pollutants. Naturally occurring background levels and anthropogenic sources (direct or indirect) contribute to the baseline concentration of metal(loid)s in the environment. Recorded metal(loid)s in various environmental media (soil, water, sediment) were evaluated from existing databases. The first database is the national soil database or Soil Geochemical Atlas of Ireland (SGAI). The second one is a higher resolution Tellus project database created by the Geological Survey Ireland. This study focussed on 16 metal(loid)s: As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sb, Sn, U, V, and Zn. A Risk Quotient (RQ) and Integrated Risk Quotient (IRQ) were used to analyse individual and combined effects of selected metal(loid)s due to the potential ingestion by humans through the food chain. The results revealed that in a few locations of Ireland, the predicted environmental concentration (PEC) of As, Cd, Pb and Zn in the soil was higher than the threshold values resulting in an RQ exceedance of 1. The RQ values of metal(loid)s corresponding to the water, and sediment samples suggest minimal exceedance of threshold values. The exceedance of the IRQ values (>2) for the soil, water, and sediment samples is 32.3 %, 14.8 %, and 1.3 %, respectively. Regions along the East coast of Ireland may pose a higher potential relative risk compared to other parts of Ireland. This research suggests the need for in-depth risk assessment studies on Cd, As and Pb, which showed elevated levels. Furthermore, it is essential to understand the fate of metal(loid)s and their risk assessment to inform regulations around metal(loid)s where intervention may be required.

Quantitative microbial human exposure model for faecal indicator bacteria and risk assessment of pathogenic Escherichia coli in surface runoff following application of dairy cattle slurry and co-digestate to grassland.

Animal waste contains high numbers of microorganisms and therefore can present a potential biological threat to human health. During episodic rainfall events resulting in runoff, microorganisms in the waste and soil may migrate into surface runoff, contaminating surface water resources. A probabilistic human exposure (HE) model was created to determine exposure to faecal indicator bacteria (FIB): total coliforms (TC), E. coli and enterococci following application of bio-based fertiliser (dairy cattle slurry, digestate) to grassland; using a combination of experimental field results and literature-based data. This step was followed by a quantitative microbial risk assessment (QMRA) model for pathogenic E. coli based on a literature-based dose-response model. The results showed that the maximum daily HE (HEdaily) is associated with E. coli for unprocessed slurry (treatment T1) on day 1, the worst-case scenario where the simulated mean HEdaily was calculated as 2.84 CFU day -1. The results indicate that the overall annual probability of risk (Pannual) of illness from E. coli is very low or low based on the WHO safe-limit of Pannual as 10 -6. In the worst-case scenario, a moderate risk was estimated with simulated mean Pannual as 1.0 × 10 -5. Unpasteurised digestate application showed low risk on day 1 and 2 (1.651 × 10 -6, 1.167 × 10 -6, respectively). Pasteurised digestate showed very low risk in all scenarios. These results support the restriction imposed on applying bio-based fertiliser if there is any rain forecast within 48 h from the application time. This study proposes a future extension of the probabilistic model to include time, intensity, discharge, and distance-dependant dilution factor. The information generated from this model can help policymakers ensure the safety of surface water sources through the quality monitoring of FIB levels in bio-based fertiliser.

Development of One-Step Non-Solvent Extraction and Sensitive UHPLC-MS/MS Method for Assessment of N-(n-Butyl) Thiophosphoric Triamide (NBPT) and N-(n-Butyl) Phosphoric Triamide (NBPTo) in Milk.

N-(n-butyl) thiophosphoric triamide (NBPT) is a urease inhibitor utilised in urea-based fertilizers. In Ireland, fertilizer treated with NBPT is applied to pasture to mitigate both ammonia and nitrous oxide emissions, but concerns arise as to the potential for residues in milk products. A quick ultrafiltration extraction and ultra-high performance liquid chromatography coupled with mass spectrometry triple quadrupole (UHPLC-MS/MS) quantitation method was developed and validated in this study. The method was applied in the analysis of samples collected from a field study investigating potential transfer of NBPT residues into milk. NBPT and NBPTo residues, were extracted from fortified milk samples and analysed on a UHPLC-MS/MS with recoveries ranging from 74 to 114%. Validation of the UHPLC-MS/MS method at low (0.0020 mg kg-1) and high (0.0250 mg kg-1) concentration levels in line with SANTE/12682/2019 showed overall trueness in the range of 99 to 104% and precision between 1 and 10%, RSD for both compounds. The limit of quantitation (LOQ) was 0.0020 mg kg-1 and other tested parameters (linearity, sensitivity, specificity, matrix effect, robustness, etc.) satisfied acceptance criteria. Stability assessment using spiked samples revealed the compounds were stable in raw and pasteurised milk for 4 weeks at -80 °C storage temperature. Maintaining samples at pH 8.5-9.0 further improved stability. Analysis of 516 milk samples from the field study found that NBPT and NBPTo concentrations were below the LOQ of 0.0020 mg kg-1, thus suggesting very low risk of residues occurring in the milk. The method developed is quick, robust, and sensitive. The method is deemed fit-for-purpose for the simultaneous determination of NBPT and NBPTo in milk.

Antibiotic residues in the aquatic environment - current perspective and risk considerations.

Antimicrobial resistance is a major concern for human and animal health, projected to deteriorate with time and given current trends of antimicrobial usage. Antimicrobial use, particularly in healthcare and agriculture, can result in the release of antimicrobials into surface waters, promoting the development of antibiotic resistance in the environment, and potentially leading to human health risks. This study reviews relevant literature, and investigates current European and Irish antimicrobial usage trends in humans and animals, as well as potential pathways that antibiotics can take into surface waters following use. Reported levels in the aquatic environment are summarized, with particular focus on Ireland. There are relatively few studies examining Irish water bodies or sewage effluent for antibiotic residues, however, five antibiotics, namely azithromycin, ciprofloxacin, clarithromycin, metronidazole, and trimethoprim, have been measured in Irish waters, in concentrations predicted to select for resistance. Numerous isolates of multi-drug resistant bacteria have also been found in water bodies throughout Ireland and Europe. The value of risk assessment methodologies in understanding risks posed by antibiotic residues is reviewed including the advantages and disadvantages of specific approaches. Hazard quotient and bespoke Monte Carlo approaches are predominant risk assessment tools used to examine antimicrobial release and their complex pathways. This study highlights the need for monitoring of antimicrobial releases and the potential for resistance development, persistence and transmission while highlighting the role of risk assessment methodologies in assessing potential human and environmental health impacts.

Hazard characterization of silver nanoparticles for human exposure routes.

Silver nanoparticles (AgNPs) have been widely used for a multitude of applications without full comprehensive knowledge regarding their safety. In particular, lack of data on hazard characterization may lead to uncertainties regarding potential human health risk. To provide the foundation for human health risk assessment of AgNPs, this study evaluates existing hazard characterization data, including reported pharmacokinetics, symptoms, and their corresponding dose-response relationships. Human equivalent relationships are also provided by extrapolation from animal dose-response relationships. From the data analyzed, it appears that AgNPs may persist for long periods (from days to years) in the human body. It was found that AgNP toxicity on traditional major targets of exogenous substances were generally underestimated. Some omissions of toxicity on sensitive systems in the AgNP toxicity assessment require attention, such as reprotoxicity and neurotoxicity. The necessity of the establishment of toxicity tests specifically for nanomaterials is highlighted. The scientific basis of a toxicity testing strategy is advised by this study, which paves the way for the monitoring and regulation of the ENP utilization in various industries.

Public health risks and benefits associated with breast milk and infant formula consumption.

The safety and quality of infant milk, whether it is breast milk (BM) or infant formula (IF), are a major concern for parents and public health authorities. BM is recommended as the gold standard at WHO level. However, nowadays IF appears as an essential alternative in Western countries, challenging producers to optimize nutritional quality and safety of IF. The aim of the present article is to give an overview on the assessment and comparison of risks and benefits associated with BM and IF consumption. To date, this intensively debated subject has been mainly investigated. It has been shown that both diets could be sources of beneficial health effects in terms of nutrition and also risks in terms of chemical safety. Moreover, microbiologists have demonstrated that IF consumption can cause illness due to product contamination or inappropriate milk preparation. The article concludes on the bottlenecks and gaps that should be investigated to further progress the quantification of the impact of early diet on infant health. Performing a multi-disciplinary risk-benefit assessment with DALY as endpoint might be a future option to help prioritize management options.

Meta-analysis of the reduction of antibiotic-sensitive and antibiotic-resistant Escherichia coli as a result of low- and medium-pressure UV lamps.

It is vital that harmful bacteria are removed from water and wastewater treatment plants to prevent human/environmental exposure. This paper examines the log reduction of antibiotic-sensitive (AS) and antibiotic-resistant (AR) Escherichia coli (E. coli) as a result of low-pressure (LP) and medium-pressure (MP) UV lamps. A meta-analysis was performed and a mixed-effect model was created in which 303 data points on the log reduction of E. coli from UV treatment were collected. The results show that in order to achieve a 6 log reduction using an MP lamp, on average a UV level of 7.3 mJ/cm2 for AS E. coli and 7.5 mJ/cm2 for AR E. coli were required. Using an LP lamp, a UV level of 8.1 mJ/cm2 for AS E. coli and 8.4 mJ/cm2 for AR E. coli were required. The results show there is no significant difference between the inactivation of AR and AS E. coli at different UV levels. The model predicts that AR or AS E. coli will be inactivated at UV levels lower than the recommended UV operation conditions (40 mJ/cm2), but it is important to use this UV level to inactivate other harmful microorganisms.

Measuring Nanoparticle Attachment Efficiency in Complex Systems.

As process-based environmental fate and transport models for engineered nanoparticles are developed, there is a need for relevant and reliable measures of nanoparticle behavior. The affinity of nanoparticles for various surfaces (α) is one such measure. Measurements of the affinity of nanoparticles obtained by flowing particles through a porous medium are constrained by the types of materials or exposure scenarios that can be configured into such column studies. Utilizing glass beads and kaolinite as model collector surfaces, we evaluate a previously developed mixing method for measuring nanoparticle attachment to environmental surfaces, and validate this method with an equivalent static column system over a range of organic matter concentrations and ionic strengths. We found that, while both impacted heteroaggregation rates in a predictable manner when varied individually, neither dominated when both parameters were varied. The theory behind observed nanoparticle heteroaggregation rates (αßB) to background particles in mixed systems is also experimentally validated, demonstrating both collision frequency (ß) and background particle concentration (B) to be independent for use in fate modeling. We further examined the effects of collector particle composition (kaolinite vs glass beads) and nanoparticle surface chemistry (PVP, citrate, or humic acid) on α, and found a strong dependence on both.

Development and Application of a Probabilistic Risk-Benefit Assessment Model for Infant Feeding Integrating Microbiological, Nutritional, and Chemical Components.

A probabilistic and interdisciplinary risk-benefit assessment (RBA) model integrating microbiological, nutritional, and chemical components was developed for infant milk, with the objective of predicting the health impact of different scenarios of consumption. Infant feeding is a particular concern of interest in RBA as breast milk and powder infant formula have both been associated with risks and benefits related to chemicals, bacteria, and nutrients, hence the model considers these three facets. Cronobacter sakazakii, dioxin-like polychlorinated biphenyls (dl-PCB), and docosahexaenoic acid (DHA) were three risk/benefit factors selected as key issues in microbiology, chemistry, and nutrition, respectively. The present model was probabilistic with variability and uncertainty separated using a second-order Monte Carlo simulation process. In this study, advantages and limitations of undertaking probabilistic and interdisciplinary RBA are discussed. In particular, the probabilistic technique was found to be powerful in dealing with missing data and to translate assumptions into quantitative inputs while taking uncertainty into account. In addition, separation of variability and uncertainty strengthened the interpretation of the model outputs by enabling better consideration and distinction of natural heterogeneity from lack of knowledge. Interdisciplinary RBA is necessary to give more structured conclusions and avoid contradictory messages to policymakers and also to consumers, leading to more decisive food recommendations. This assessment provides a conceptual development of the RBA methodology and is a robust basis on which to build upon.

Farm to Fork Quantitative Risk Assessment of Listeria monocytogenes Contamination in Raw and Pasteurized Milk Cheese in Ireland.

The objective of this study was to model and quantify the level of Listeria monocytogenes in raw milk cheese (RMc) and pasteurized milk cheese (PMc) from farm to fork using a Bayesian inference approach combined with a quantitative risk assessment. The modeling approach included a prediction of contamination arising from the farm environment as well from cross-contamination within the cheese-processing facility through storage and subsequent human exposure. The model predicted a high concentration of L. monocytogenes in contaminated RMc (mean 2.19 log10 CFU/g) compared to PMc (mean -1.73 log10 CFU/g). The mean probability of illness (P1 for low-risk population, LR) and (P2 for high-risk population, HR, e.g., immunocompromised) adult Irish consumers following exposure to contaminated cheese was 7 × 10(-8) (P1 ) and 9 × 10(-4) (P2 ) for RMc and 7 × 10(-10) (P1 ) and 8 × 10(-6) (P2 ) for PMc, respectively. In addition, the model was used to evaluate performance objectives at various stages, namely, the cheese making and ripening stages, and to set a food safety objective at the time of consumption. A scenario analysis predicted various probabilities of L. monocytogenes contamination along the cheese-processing chain for both RMc and PMc. The sensitivity analysis showed the critical factors for both cheeses were the serving size of the cheese, storage time, and temperature at the distribution stage. The developed model will allow food processors and policymakers to identify the possible routes of contamination along the cheese-processing chain and to reduce the risk posed to human health.

Development of a screening tool to assess the temporal risk of pesticides leaching to groundwater using the source, target, vector approach. An Irish case study for shallow groundwater.

During this study, a groundwater screening tool was developed to assess the temporal risk of groundwater contamination from the use of pesticides. It is based on a source, vector, target approach. The method utilised in this study uses a semi-quantitative probabilistic risk assessment where the input parameters were classified and assigned a relative score from 1 to 5 (i.e. 1 = no risk and 5 = high risk). The model was parameterised by using national data and calibrated with 2 years of national pesticide groundwater monitoring data. After calibration, two specific sites were selected for model validation. Based on the presence of the source, vector and target, the evaluation indicated that the temporal risk is site specific (i.e. May to December for the country model, June to September for the Oak Park site and September for the Castledockrell site). A sensitivity analysis performed on the national scale revealed that the groundwater vulnerability category (gv), the clay content (cc%), the persistence of pesticides in soil (DT50) and the rainfall represented by wet day (wd) were the most important parameters that affected model predictions (correlation coefficients of 0.54, -0.39, 0.35 and 0.31, respectively), highlighting the importance of soil hydrogeological conditions, soil type and rainfall in influencing water model predictions. The model developed can help to identify the temporal risk from pesticides to groundwater and guide regulators in highlighting at-risk periods, therefore allowing more focused monitoring programmes.

Assessing the vulnerability of groundwater to pollution in Ireland based on the COST-620 Pan-European approach.

The aim of the analysis was to assess the intrinsic and specific vulnerability of groundwater to pollution from pesticides in Ireland at the national scale. A methodology to incorporate the effect of groundwater recharge in vulnerability assessment is described which can be particularly useful for the evaluation of dilution of groundwater pollutants. A sensitivity analysis using Monte-Carlo simulation revealed that the most important parameters of the model were subsoil (ρ = 0.79) and topsoil (ρ = 0.72), which is in agreement with the current knowledge of the parameters that have a significant effect on groundwater vulnerability in Ireland. The intrinsic vulnerability assessment was verified using total organic carbon (TOC) concentration in groundwater, a novel approach for the validation of groundwater vulnerability methods at regional scales. A statistical analysis showed that TOC concentration was significantly different (p < 0.001) between watersheds classified as highly vulnerable and watersheds classified as less vulnerable, providing evidence that the developed method can effectively classify karst areas in terms of groundwater vulnerability.

Prevalence and concentration of mycotoxins in bovine feed and feed components: A global systematic review and meta-analysis.

Mycotoxins are secondary metabolites produced by fungi and identified as contaminants in animal feed. They have potentially harmful effects, including carcinogenicity, mutagenicity, and repro-toxicity in animals and humans. As a result of climate change, there is the potential for a change in the prevalence and concentration of mycotoxins in animal feed components. This necessitates an assessment of the present and emerging threats to the food supply chain from mycotoxins. This systematic review and meta-analysis study synthesised studies on mycotoxin contamination and prevalence in cattle feed components. The studies were collected from scientific databases Web of Knowledge, Scopus, and Embase between 2011 and 2022. The meta-analysis synthesised 97 studies on the prevalence and the concentration of aflatoxins, ochratoxin A, deoxynivalenol, zearalenone, fumonisin and T-2/HT-2 toxins in feed components. Aflatoxin was highly prevalent (59 %), with a concentration of 2.58-3.92 µg kg-1 in feed components. Ochratoxin A had a global prevalence of 31 % with a concentration of 5.56-12.41 µg kg-1. Deoxynivalenol had a global concentration of 233.17-327.73 µg kg-1 and a prevalence of 74 %. Zearalenone had a prevalence of 70 % and a concentration of 42.47-66.19 µg kg-1. The concentration and prevalence of fumonisins was 232.19-393.07 µg kg-1 and 65 %, respectively. The prevalence and concentration of T-2/HT-2 toxins were 45 % and 23.54-35.12 µg kg-1, respectively. The synthesised concentration of the mycotoxins in the overall feed components was lower than the regulated and guidance values set by the European Union. However, in a few cases, the 95th percentile exceeded these concentration values due to high levels of uncertainty attributed to lower sample size, and thus, need to be considered while conducting risk assessments. The study highlights climates and regions likely to be conducive to the emergence of mycotoxin risk, especially considering the potential influences of climate change.

Simulation model to predict the fate of ciprofloxacin in the environment after wastewater treatment.

The extent hospital effluent contributes to antimicrobial presence in the environment and its impact on resistance dissemination remains unknown. To investigate the fate of the antimicrobial ciprofloxacin in hospital effluent a Monte Carlo simulation model was developed to model levels from hospital use to wastewater treatment plant (WWTP) effluent release, in addition to modeling resistance formation potential, hazard quotient (HQ) and swimmer exposure. The mean predicted concentration (PC) of ciprofloxacin in hospital effluent, urban effluent, WWTP effluent, sludge, soil and sea water was 579, 6.06, 2.59, 3.48, 0.006 and 0.15 mg/m(3), respectively. A parallel surveillance study confirmed levels of ciprofloxacin above or below the limit of detection. The model predicted levels would never exceed the ECOSAR toxicity value. The model predicted a 98% probability of ciprofloxacin exhibiting a HQ > 1 (low toxicity concern). The mean ciprofloxacin PC in WWTP effluent was less than the minimum inhibitory concentration (MIC). The probability of conditions in WWTP effluent being favorable for resistance at 20% and 80% of the MIC was 3% and 72%, respectively. In all instances, when the MIC was bound, the probability for resistance formation within soil and sea water was < 1%. The probability of a swimmer being exposed to a level of ciprofloxacin greater than the acceptable daily intake was negligible. The study concluded that release of hospital effluent into the environment may lead to concentrations of ciprofloxacin which are of low toxicity concern but may be conducive to resistance formation and allow for the dissemination of resistance.

Risk ranking of macrolide antibiotics - Release levels, resistance formation potential and ecological risk.

Antibiotic resistance (AR) development in natural water bodies is a significant source of concern. Macrolide antibiotics in particular have been identified as pollutants of concern for AR development throughout the literature, as well as by state and international authorities. This study utilises a probabilistic model to examine the risk of AR development arising from human-use macrolide residues, utilising administration rates from Ireland as a case study. Stages modelled included level of administration, excretion, degradation in wastewater, removal in wastewater treatment, assuming conventional activated sludge (CAS) treatment, and dilution. Release estimates per day, as well as risk quotient values for antibiotic resistance development and ecological impact, are generated for erythromycin, clarithromycin, and azithromycin. In the modelled scenario in which conventional activated sludge treatment is utilised in wastewater treatment, this model ranks risk of resistance development for each antibiotic in the order clarithromycin > azithromycin > erythromycin, with mean risk quotient values of 0.50, 0.34 and 0.12, respectively. A membrane bioreactor scenario was also modelled, which reduced risk quotient values for all three macrolides by at least 50 %. Risk of ecological impact for each antibiotic was also examined, by comparing environmental concentrations predicted to safety limits based on toxicity data for cyanobacteria and other organisms from the literature, with azithromycin being identified as the macrolide of highest risk. This study compares and quantifies the risk of resistance development and ecological impact for a high-risk antibiotic group in the Irish context, and demonstrates the potential for risk reduction achieved by adoption of alternative (e.g. membrane bioreactor) technology.

Multilevel meta-analysis and dose-response analysis for bisphenol A (BPA) exposure on metabolic and neurobehavioral effects.

Evidence suggests that oral exposure to bisphenol A (BPA) may result in adverse metabolic and neurobehavioral effects. The aim of the present meta-analysis is to examine this association based on systematically selected laboratory rodent studies published from 2012 to 2021 and sourced from Scopus, Web of Science, EmBase, and PubMed. Articles satisfying eligibility and inclusion criteria were included for the calculation of the summary standardised mean difference (SMD). Subgroup analysis and subsequent dose-response analysis were conducted if applicable. In total, 32 studies were analysed for 6 metabolic endpoints (cholesterol, triglycerides, insulin, glucose, leptin, and adiponectin) and 6 neurobehavioral endpoints (locomotor activity, exploratory, anxiety, depression, spatial learning and memory, non-spatial learning and memory). Summary SMDs implied that no significant effects were observed in endpoints considered. The dose was not determined as a significant moderator with regards to medium or high heterogeneity; however, there was significant impairment of spatial learning and memory at health-based guidance value ('HBGV') (0.05-9 mg (kg bw)-1 day-1) and 'High' (>9 mg (kg bw)-1 day-1) dose group. As a result, an indicative toxicological reference dose value of 0.034 mg (kg bw)-1 day-1 was proposed due to large variability. Potential harm to spatial learning and memory from BPA exposure requires further investigation. This study has provided some additional information on potential adverse metabolic and neurobehavioral effects of BPA from the perspective of meta-analysis which can inform the public, regulatory authorities, and policymakers.

Hazard characterization of bisphenol A (BPA) based on rodent models - Multilevel meta-analysis and dose-response analysis for reproductive toxicity.

Bisphenol A (BPA) is a widely used synthetic industrial compound frequently detected in food. Dietary exposure to BPA has been recognised as a potential health concern. However, there are uncertainties regarding BPA toxicity. The primary objective of this study was to summarise and analyse multiple toxicity endpoints of adverse reproductive effects caused by BPA exposure in rodent models. Therefore, a multilevel meta-analysis and subsequent dose-response analysis were conducted. Relevant articles published in English between 2012 and 2021 were collected from online databases, viz. Scopus, EmBase, Web of Science, and PubMed. In total, 41 studies were included for statistical analysis. All statistical analyses were performed using open-source RStudio packages. Summary effects indicated the statistical significance of BPA exposure on decreased sperm concentration (Hedges' g: -1.35) and motility (Hedges' g: -1.12) on average, while no significant effects were observed on the absolute and relative weight of male and female reproductive organs. The lowest mean toxicological reference dose values of 0.0011 mg (kg bw)-1 day-1 was proposed for BPA exposure on sperm concentration from the dose-response model. In conclusion, potential health risks from BPA exposure were shown with regards to reproductive toxicity, especially that sperm concentration and sperm motility require further attention.

Modelling potential human exposure to the urease inhibitor NBPT through the environment-food pathway.

The urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) has recently attracted a lot of attention attributing to its efficiency in reducing ammonia loss from urea fertiliser applied to temperate grassland soils. Ammonia gas lost to the environment causes soil acidification, eutrophication and contributes to global warming through increased greenhouse gas emissions and ozone layer depletion. The active chemical NBPT blocks the soil microbial enzyme (urease) and reduces ammonia emission. Furthermore, NBPT's use in agriculture might benefit farmers by reducing reliance on expensive nitrate fertiliser and aiding in a shift to more urea-based fertiliser (using NBPT co-applied with urea is more cost-effective). The present study was carried out to characterise the potential transfer of NBPT from grass to liquid milk and compute the associated human health risks. Using probabilistic risk assessment techniques, an exposure assessment model was developed to calculate the Estimated Daily Intake (EDI) of NBPT from milk, following co-application of NBPT with a urea N-fertiliser. Results show that the predicted mean concentration of NBPT in milk is 2.5 × 10-8 mg NBPT/kg milk, while the mean daily intake (EDI) of NBPT is 5 × 10-11 mg NBPT /kg BW/day). Back-calculations revealed that, under the studied conditions, for the EDI to exceed ADI of 3 × 10-2 mg NBPT/kg BW/ day, the NBPT application rate would need to exceed the NBPT fertiliser limit (0.09-0.2% by mass of urea nitrogen) set in the Commission Regulation (EC) No 1107/2008, and the bio-transfer factor would need to be over 100% (implausible). Sensitivity analysis revealed soil pH (SPH), phytoaccumulation factor (PF), NBPT permissible levels in fertiliser (NBPT%), pasture cover (P), and grazing rotation length (t) as critical factors influencing the EDI of NBPT. The present study concludes that NBPT presents negligible risk to human health under the conditions and assumptions studied.