Toxicological Risk Assessment Research Articles

Considering the bioavailability and bioaccessibility of metal(loid)s for risk assessment of soils affected by different non-ferrous metal activities in Southwest China

Toxic metal(loid)s released into the soil by non-ferrous metal mining and smelting activities pose a serious threat to residents and the surrounding ecosystem. Considering only total metal(loid) concentrations likely overestimates routine (eco)toxicological risk assessment of soil. We hypothesize that considering metal(loid) bioavailability/accessibility will improve the accuracy of risk assessment. To test this hypothesis, four mining areas in Southwest China, including mining and surrounding sites, were studied. Bioavailability was determined considering metal(loid)s leached by a simulated strong acid rain (SSAR) treatment. In the four areas, the mining site showed higher cumulative releases of metal(loid)s under SSAR treatment than the agricultural field located in the surrounding sites. Thus, the bioavailable metal(loid)s contents were continuously being released during SSAR treatment and likely increased the environmental risk. Ecological and health risk assessment of soil, calculated using total metal(loid)s content, was corrected considering bioavailable/accessible metal(loid)s, which was determined by the heavy metal(loid)s forms and in vitro simulated intestinal stages. Although the corrected indices indicated that the risk of metal(loid)s-contaminated soil was reduced, unfavorable ecological and health risks remained in the four areas. Our study provides new perspectives to better predict the risk of bioavailable/accessible metal(loid)s in non-ferrous metal contaminated and surrounding soils.

Hazardous Elements in Road Dust from Petrol Stations in Rzeszów (Podkarpackie, Poland): Toxicological Assessment Using Field Portable X-ray Fluorescence (FP-XRF) as ‘White Analytical Technique’

AbstractSamples of road dust (RD) from petrol stations (n = 20) located in Rzeszów (Podkarpackie, Poland) were analysed to find potential markers of traffic-related pollution. The level (μg/g) of: Mo, U, As, Hg, Th, Pb, Ni, Cu, Cr, Be, Sr, Zr, Zn, Mn and Fe were measured using field portable X-ray spectroscopy (FP-XRF) as a direct, rapid and ‘white analytical technique’. Our research demonstrated for the first time the utility of using FP-XRF for environmental toxicological assessment of RD from petrol stations. The qualitative and quantitative composition of the dust samples tested provides valuable research material for creating and updating regulations and finding pollution hotspots such as petrol stations. It was possible to find potential markers of traffic-related pollution (e.g., Zr and Fe forms of disk brakes or brake pads). Certain elements of the study give ambiguous signals related to fuel distribution and road traffic. They can come from various sources of environmental contamination. The adoption of evidence-based policies to minimise pollution, conserve the environment, and protect the well-being of people living or working near gas stations is anticipated to be aided by these findings for policymakers, regulatory authorities, and stakeholders. Incorporating toxicological risk assessment framework, this study pioneers the investigation of human exposure to hazardous elements in RD, an in-depth evaluation of both carcinogenic and non-carcinogenic health risks associated with such exposure including lifetime average daily dose. Our findings contribute novel insights into the environmental toxicology of urban areas, emphasising the need for tailored interventions to mitigate these risks.

The impact of uranium contamination in groundwater on human health: a toxicological risk assessment

ABSTRACT All living beings are exposed to naturally occurring radionuclides. Uranium, a primordial radionuclide forms compounds that are water soluble and enter the human body through food and drinking water. This study conducted a health risk assessment to evaluate the potential dangers associated with consuming uranium through groundwater in the Mansa district of Punjab, India. The uranium concentration varied from 43.43 µg/L to 449.79 µg/L. The biokinetic model of uranium including hair compartment as excretion pathway is used to calculate uranium retention in different organs of the human body. The Pearson correlation and principal component analysis are used for assessing the correlation of uranium with TDS, salinity, conductivity and pH. The high correlation is observed between TDS and uranium. The hazard quotient is 17.42 and excess cancer risk is higher than the permissible limit of 10−4. Owing to the high uranium concentration in Mansa district, periodic monitoring is advised along with clinical investigation of the population.

Biosynthesis, structural characterization of silver nanoparticles synthesized using an eco-friendly method with Mentha spicata L. extract and their antimicrobial activity and toxicological risk assessment

Due to the development of microbial resistance to medicines the development of antiseptics items on AgNPs is a vital task. To assess the efficacy of products based on AgNPs, it is essential to conduct an in-depth study of the activity of AgNPs. Currently,nanomaterialsprepared through ecofriendly procedure has got great interest. In the recent study, the potential ofMentha spicata L. to synthesizeAgNPs is described.The nanoparticleswere characterized by spectroscopic and microscopic tools including UV–Vis, XRD, FT-IR, and SEM techniques. The obtained nanoparticles were assessed against microbes in antibacterial, and antifungal activities along with their biocompatible nature. The preparedAgNPsexhibited outstanding activity against gram-negative and gram-positive bacteria. The highest cleared zone was noted at 20 mg/mL against E. coli (24 mm) followed, P. aeruginosa (22 mm), Klebsiella (21 mm), S. typhi (18 mm) and by S. aureus (17 mm). Similarly, the AgNPs showed antifungal activity at all concentrations but the highest zone of inhibition was observed at 1 mg/mL against A. niger (23 mm) followed by A. alternata (20 mm) and F. oxysporum (18 mm) The biocompatibility activities of the prepared nanoparticles towards RBCs were assessed in the range of 15 to 120 µg/mL. The hemolytic activity confirmed that the bio-inspired AgNPs is a safe as per the standard of American Society for Testing and Materials. The use of silver nanoparticles in drug delivery systems might be the future thrust in the field of medicine. Lastly these must provide highly accurate disease treatments that are eco and patient friendly, safe, dependable and profitable.

Improving predictions of compound amenability for liquid chromatography-mass spectrometry to enhance non-targeted analysis.

Mass-spectrometry-based non-targeted analysis (NTA), in which mass spectrometric signals are assigned chemical identities based on a systematic collation of evidence, is a growing area of interest for toxicological risk assessment. Successful NTA results in better identification of potentially hazardous pollutants within the environment, facilitating the development of targeted analytical strategies to best characterize risks to human and ecological health. A supporting component of the NTA process involves assessing whether suspected chemicals are amenable to the mass spectrometric method, which is necessary in order to assign an observed signal to the chemical structure. Prior work from this group involved the development of a random forest model for predicting the amenability of 5517 unique chemical structures to liquid chromatography-mass spectrometry (LC-MS). This work improves the interpretability of the group's prior model of the same endpoint, as well as integrating 1348 more data points across negative and positive ionization modes. We enhance interpretability by feature engineering, a machine learning practice that reduces the input dimensionality while attempting to preserve performance statistics. We emphasize the importance of interpretable machine learning models within the context of building confidence in NTA identification. The novel data were curated by the labeling of compounds as amenable or unamenable by expert curators, resulting in an enhanced set of chemical compounds to expand the applicability domain of the prior model. The balanced accuracy benchmark of the newly developed model is comparable to performance previously reported (mean CV BA is 0.84 vs. 0.82 in positive mode, and 0.85 vs. 0.82 in negative mode), while on a novel external set, derived from this work's data, the Matthews correlation coefficients (MCC) for the novel models are 0.66 and 0.68 for positive and negative mode, respectively. Our group's prior published models scored MCC of 0.55 and 0.54 on the same external sets. This demonstrates appreciable improvement over the chemical space captured by the expanded dataset. This work forms part of our ongoing efforts to develop models with higher interpretability and higher performance to support NTA efforts.

A Predictive Toxicokinetic Model for Nickel Leaching from Vascular Stents.

In vitro testing methods offer valuable insights into the corrosion vulnerability of metal implants and enable prompt comparison between devices. However, they fall short in predicting the extent of leaching and the biodistribution of implant byproducts under in vivo conditions. Physiologically based toxicokinetic (PBTK) models are capable of quantitatively establishing such correlations and therefore provide a powerful tool in advancing nonclinical methods to test medical implants and assess patient exposure to implant debris. In this study, we present a multicompartment PBTK model and a simulation engine for toxicological risk assessment of vascular stents. The mathematical model consists of a detailed set of constitutive equations that describe the transfer of nickel ions from the device to peri-implant tissue and circulation and the nickel mass exchange between blood and the various tissues/organs and excreta. Model parameterization was performed using (1) in-house-produced data from immersion testing to compute the device-specific diffusion parameters and (2) full-scale animal in situ implantation studies to extract the mammalian-specific biokinetic functions that characterize the time-dependent biodistribution of the released ions. The PBTK model was put to the test using a simulation engine to estimate the concentration-time profiles, along with confidence intervals through probabilistic Monte Carlo, of nickel ions leaching from the implanted devices and determine if permissible exposure limits are exceeded. The model-derived output demonstrated prognostic conformity with reported experimental data, indicating that it may provide the basis for the broader use of modeling and simulation tools to guide the optimal design of implantable devices in compliance with exposure limits and other regulatory requirements.

A Comprehensive Review of the Nutritional Composition and Toxicological Profile of Date Seed Coffee (Phoenix dactylifera)

Approximately 8 million tons of dates (Phoenix dactylifera) are produced globally each year. The seeds of the fruit, which make up 10–15% of its weight, are typically discarded. Date seed coffee is a sustainable food system innovation rooted in the traditions of high date-producing regions. Dating back to the late 19th century, date seed coffee has evolved from a historical coffee substitute to a modern caffeine-free alternative. Date seed coffee has a long history of consumption in the European Union (EU). This indicates that it may not require novel food authorization. The composition of date seeds is evaluated in this review and a toxicological risk assessment for date seed coffee is conducted. Subchronic studies show that consuming date seed or date seed coffee has no adverse effects. Therefore, currently unavailable chronic toxicity, carcinogenicity, and reproductive toxicity studies may be unnecessary. However, for a comprehensive evaluation, it is recommended to conduct an in vitro mutagenicity test. This review provides information on the safety of date seed coffee and highlights the need for further research.

New approach methodologies (NAMs): identifying and overcoming hurdles to accelerated adoption.

New approach methodologies (NAMs) can deliver improved chemical safety assessment through the provision of more protective and/or relevant models that have a reduced reliance on animals. Despite the widely acknowledged benefits offered by NAMs, there continue to be barriers that prevent or limit their application for decision-making in chemical safety assessment. These include barriers related to real and perceived scientific, technical, legislative and economic issues, as well as cultural and societal obstacles that may relate to inertia, familiarity, and comfort with established methods, and perceptions around regulatory expectations and acceptance. This article focuses on chemical safety science, exposure, hazard, and risk assessment, and explores the nature of these barriers and how they can be overcome to drive the wider exploitation and acceptance of NAMs. Short-, mid- and longer-term goals are outlined that embrace the opportunities provided by NAMs to deliver improved protection of human health and environmental security as part of a new paradigm that incorporates exposure science and a culture that promotes the use of protective toxicological risk assessments.

Non-pyrogenicity and biocompatibility of parylene-coated magnetic bead implants.

Clinical grade magnetic bead implants have important applications in interfacing with the human body, providing contactless mechanical attachment or wireless communication through human tissue. We recently developed a new strategy, magnetomicrometry, that uses magnetic bead implants as passive communication devices to wirelessly sense muscle tissue lengths. We manufactured clinical-grade magnetic bead implants and verified their biocompatibility via intramuscular implantation, cytotoxicity, sensitization, and intracutaneous irritation testing. In this work, we test the pyrogenicity of the magnetic bead implants via a lagomorph model, and we test the biocompatibility of the magnetic bead implants via a full chemical characterization and toxicological risk assessment. Further, we test the cleaning, sterilization, and dry time of the devices that are used to deploy these magnetic bead implants. We find that the magnetic bead implants are non-pyrogenic and biocompatible, with the insertion device determined to be safe to clean, sterilize, and dry in a healthcare setting. These results provide confidence for the safe use of these magnetic bead implants in humans.

Assessment of environmental pollution and human health risks of mine tailings in soil: after dam failure of the Córrego do Feijão Mine (in Brumadinho, Brazil).

The dam failure of the Córrego do Feijão Mine (CFM) located in Minas Gerais State,Brazil, killed at least 278 people. In addition, large extensions of aquatic and terrestrial ecosystems were destroyed, directly compromising the environmental and socioeconomic quality of the region. This study assessed the pollution and human health risks of soils impacted by the tailing spill of theCFM dam, along a sample perimeter of approximately 200km. Based on potential ecological risk and pollution load indices, the enrichments of Cd, As, Hg, Cu, Pb and Ni in soils indicated thatthe Brumadinho, Mário Campos, Betim and São Joaquim de Bicas municipalities were the most affected areas by the broken dam. Restorative and reparative actions must be urgently carried out in these areas. For all contaminated areas, the children's group indicated anexacerbated propensity to the development of carcinogenic and non-carcinogenic diseases, mainly through theingestion pathway. Toxicological risk assessments, including acute, chronic and genotoxic effects, on people living and working in mining areas should be a priority for public management and mining companies to ensure effective environmental measures that do not harm human health and well-being over time.

Enhanced vermicomposting of rice straw and pressmud with biogas slurry employing Eisenia fetida: Production, characterization, growth, and toxicological risk assessment

The biogas plant plays a dual role: it directly provides energy and indirectly promotes organic farming through outlet slurry. However, agricultural biomass wastes such as rice straws (RS) and pressmud (PM), which can't be used as fertilizers on their own, were vermicomposted (60 days) with biogas slurry (BS), using earthworm, into four blends: T1(BS, 100%), T2(3:2, BS: RS), T3(3:2, BS: PM), and T4(3:1:1, BS: RS: PM). The characterization, elemental analysis, and toxicological risk assessment of derived vermimanure were carried out using various analytical tools, such as an organic elemental analyzer such as CHNS, FT-IR, FESEM-EDXA, XPS, and ICP-OES. The pH, electrical conductivity, and C/N values were within 7.1–7.8, 3.2–6.0 dSm−1, and 12–15, respectively, for all treatments. The proportions of N (38%), P (70%), K (58%), Mg (67%), Ca (42%), and ash (44%), increased significantly (P < 0.05) over the initial feedstocks. The ecological risks of heavy metals (Zn, Cu, Ni, Pb, Cd, and Cr) in all feedstocks were found to be under WHO-permitted levels. The growth performance of earthworms was also considerably higher (P < 0.05) over the control feedstock group. The analytical methods verified that feedstock T4 (3:1:1, BS: RS: PM) was more porous, containing NH4+, PO43−, K+, and other nutrients. Pellets of all vermimanure groups keep 65–75% of the original volume. As well, when these pellets have been employed for agronomy and dispersed in the field, they will cause less dust than traditional or powdered compost or manure. In comparison to the control group, the synergistic approach of RS, PM, and BS in vermimanure significantly (P < 0.05) enhanced seed germination (83%), vigour index (42.5%), and decreased mean germination time by 27%. Furthermore, pot trials with Abelmoschus esculentus seed indicated that seedlings cultivated with 40% vermimanure of T4 (3:1:1, BS: RS: PM) mixed soil showed high growth in shoot, root, and plant yield.

Toxicological Risk Evaluation of Polycyclic Aromatic Hydrocarbons in Soils from a Petroleum Spillage Site at Kokori in the Niger Delta Region of Nigeria

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that are produced by the incomplete combustion of organic sources and are widely found in soils. This present research was carried out to evaluate the concentrations and toxicological risk assessment of the United States Environmental Protection Agency's sixteen priority polycyclic aromatic hydrocarbons (16 priority PAHs) in soils from the vicinity of an oil spillage site in Delta State of Nigeria. The level of pollution and potential toxicological health hazards of the PAHs were assessed in surface soil samples using soxhlet extraction of and Gas Chromatography-Mass Spectrometry (GC-MS). Thirteen out of the sixteen USEPA priority PAHs were detected in the soil sample. The concentrations of PAHs in the petroleum-contaminated soils in this investigation ranged from 0.01181 ppm to 1.16054 ppm, with the total estimated concentration of the 16 priority PAHs being 5.6713 ppm. Furthermore, the distribution of the PAHs in the study area was predominated by LMW PAHs (62%) over HMW PAHs (38%). Additionally, the total toxicity equivalency quotients TEQ (B[a]Peq) result of the carcinogenic potency of the USEPA priority PAHs was calculated as 0.08689 ppm (8.689%) and was discovered to be within the Canadian TEQ (B[a]Peq) threshold of 0.6 ppm. This suggests that the soil in the study area is safe based on the Canadian TEQ (B[a]Peq) standard and does not constitute a carcinogenic risk. However, the long-term bioaccumulation of these low quantities of PAHs in human has been found to constitute a potential health concern due to bioaccumulation in living systems.

Fine particulate matter (PM2.5) exposure assessment among active daily commuters to induce behaviour change to reduce air pollution

Fine particulate matter (PM2.5), a detrimental urban air pollutant primarily emitted by traffic and biomass burning, poses disproportionately significant health risks at relatively limited exposure during commuting. Previous studies have mainly focused on fixed locations when assessing PM2.5 exposure, while neglecting pedestrians and cyclists, who often experience higher pollution levels. In response, this research aimed to independently validate the effectiveness of bicycle-mounted low-cost sensors (LCS) adopted by citizens, evaluate temporal and spatial PM2.5 exposure, and assess associated health risks in Ljubljana, Slovenia. The LCS quality assurance results, verified by co-location field tests by air quality monitoring stations (AQMS), showed comparable outcomes with an average percentage difference of 21.29 %, attributed to humidity-induced nucleation effects. The colder months exhibited the highest air pollution levels (μ = 32.31 μg/m3) due to frequent thermal inversions and weak wind circulation, hindering vertical air mixing and the adequate dispersion of pollutants. Additionally, PM2.5 levels in all sampling periods were lowest in the afternoon (μ = 12.09 μg/m3) and highest during the night (μ = 61.00 μg/m3) when the planetary boundary layer thins, leading to the trapping of pollutants near the surface, thus significantly affecting diurnal and seasonal patterns. Analysis of exposure factors revealed that cyclists were approximately three times more exposed than pedestrians. However, the toxicological risk assessment indicated a minimal potential risk of PM2.5 exposure. The collaborative integration of data from official AQMS and LCS can enhance evidence-based policy-making processes and facilitates the realignment of effective regulatory frameworks to reduce urban air pollution.

Identification of nonvolatile organic compounds (NVOCs) in biopharmaceuticals through non-target analysis and quantification using complexation-precipitation extraction

Single-use systems in biopharmaceutical manufacturing can potentially release chemical constituents (leachables) into drug products. Prior to conducting toxicological risk assessments, it is crucial to establish the qualitative and quantitative methods for these leachables. In this study, we conducted a comprehensive screening and structure elucidation of 23 leachables (nonvolatile organic compounds, NVOCs) in two antibody drugs using multiple (self-built and public) databases and mass spectral simulation. We identified 7 compounds that have not been previously reported in medical or medicinal extractables and leachables. The confidence levels for identified compounds were classified based on analytical standards, literature references, and fragment assignments. Most of the identified leachables were found to be plasticizers, antioxidants, slip agents or polymer degradants. Polysorbate (namely Tween) is commonly used as an excipient for protein stabilization in biopharmaceutical formulations, but its ionization in liquid chromatography-electrospray ionization mass spectrometry can interfere with compound quantification. To address this, we employed a complexation-precipitation extraction method to reduce polysorbate content and quantify the analytes. The developed quantitative method for target NVOCs demonstrated high sensitivity (limit of quantification: 20 or 50 μg/L), accuracy (recoveries: 77.2 to 109.5 %) and precision (RSD ≤ 8.2 %). Overall, this established method will facilitate the evaluation of NVOC safety in drug products.

Accurate or Protective: What is the Goal of Non-targeted Extractables and Leachables Quantitation and Identification?

Leachables are quantified and identified to enable their quantitative toxicological safety risk assessment (qTSRA). The leachable's reported concentration and identity must meet certain quality expectations to be suitable for qTSRA. In this Correspondence, the author considers accuracy and protectiveness as competing key quality attributes and suggests that protectiveness is the proper quality attribute for qTSRA as qTSRA is based on the foundation that a leachable's potential adverse effect on patient health and safety must not be under-estimated. Considering this conclusion, means of making concentration estimates and proposed identities protective are discussed.

Use of the TD50 99 % CI for single dose rodent carcinogenicity studies

The Tumorigenic dose 50 (TD50) is a widely used measure of carcinogenic potency representing the dosage at which 50 % of animals exposed to a compound will develop tumours. The popularity of the TD50 is in part due to the large amount of publicly available data. TD50s were calculated for a large number of compounds in the Carcinogenic Potency Database, which has since been extended in the freely available Lhasa Carcinogenicity database, containing TD50s from over 7500 studies and 1700 compounds. However, due to the age of these studies many are of low quality, often comprising only a single test dosage, therefore raising questions about the applicability of such TD50 sfor toxicological risk assessment. We investigate whether the lower 99 % confidence interval is sufficient to produce conservative TD50 estimates for these studies.

Ecological and economic evaluation of conventional and new weed control techniques in row crops

The Farm to Fork strategy of the European Union aims to reduce pesticide use. In weed control, chemical measures are to be replaced mainly by mechanical ones. However, a comprehensive evaluation of mechanical methods with respect to ecological and economic parameters is not yet available. The aim of the study was to quantify relevant ecological and economic parameters of mechanical, mechanical-chemical and chemical weed control in sugar beet as a model crop. An overall consideration of the multidimensional risks for different conventional and new methods revealed that currently no method can be appraised as fully environmentally friendly. Toxicological risk assessment using the model SYNOPS-GIS indicated that broadcast spraying of conventional herbicides is associated with low toxicological risks in most soil-climate-regions and years. Broadcast spraying with herbicides such as CONVISO ONE, while beneficial for energy use, climatic effects, and toxicity to soil organisms, has the highest acute aquatic toxicity. Conventional mechanical methods, while toxicologically safe and, according to field trials, without negative effects on soil biota, soil erosion, or sugar yield, are associated with 100–150% higher greenhouse gas emissions compared to conventional herbicide application. Overall, hoeing with a solar powered robot combined with herbicide spot spraying has the greatest advantages. This technique requires relatively low resource and energy consumption, produces about 5% lower greenhouse gas emissions and has by 87% lower toxicological risk than conventional herbicide spraying. Among pure mechanical techniques, the combination of a solar-driven hoe robot with hand-hoeing appears to be most economic and environmentally sustainable.

OZONE-INDUCED NEUROTOXICITY: IN VITRO AND IN VIVO EVIDENCE.

Together with cities in higher-income nations, it is anticipated that the real global ozone is rising in densely populated areas of Asia and Africa. This review aims to discuss the possible neurotoxic pollutants and ozone-induced neurotoxicity: in vitro and in vivo, along with possible biomarkers to assess ozone-related oxidative stress. As a methodical and scientific strategy for hazard identification and risk characterization of human chemical exposures, toxicological risk assessment is increasingly being implemented. While traditional methods are followed by in vitro toxicology, cell culture techniques are being investigated in modern toxicology. In both human and rodent models, aging makes the olfactory circuitry vulnerable to spreading immunological responses from the periphery to the brain because it lacks the blood-brain barrier. The ozone toxicity is elusive as it shows ventral and dorsal root injury cases even in the milder dose. Its potential toxicity should be disclosed to understand further the clear mechanism insights of how it acts in cellular aspects. Human epidemiological research has confirmed the conclusions that prenatal and postnatal exposure to high levels of air pollution are linked to behavioral alterations in offspring. O3 also enhances blood circulation. It has antibacterial action, which may have an impact on the gut microbiota. It also activates immunological, anti-inflammatory, proteasome, and growth factor signaling Prolonged O3 exposure causes oxidative damage to plasma proteins and lipids and damages the structural and functional integrity of the mitochondria. Finally, various studies need to be conducted to identify the potential biomarkers associated with ozone and the brain.

Distribution and toxicological risk assessment of metals in commercial fish species from a lentic ecosystem in Nigeria

Background of StudyThe increasing exposure of lentic water bodies to pollutants and the ability of aquatic organisms to bioaccumulate heavy metals in its edible body parts has raised concerns on the food safety of aquatic animals harvested from them. This study investigated the distribution of metals in the organs of C. gariepinus and T. zillii from Ikpoba reservoir and evaluated the potential human health risk associated with their consumption. MethodologyFish samples of Clarias gariepinus and Tilapia zillii were collected for a period of six months (January 2019 to June 2019) from Ikpoba reservoir using a drag net with the assistance of artisanal fishermen. Fish samples were properly identified and heavy metal content in the gills, liver and muscles were determined using atomic absorption spectrophotometer. FindingsThe results showed that C. gariepinus had higher mean concentration of metals and metalloids than T. zillii in all the organs examined. The order of accumulation of metals in the gills and muscles of C. gariepinus and T. zillii was Fe > Zn > Mg > Cu > Pb > Cd, while order in the liver for both fish species was Fe > Zn > Cu > Mg > Pb > Cd. Human health risk assessment for metals in C. gariepinus and T. zillii indicated no significant health risk to the adults (HI < 1), whereas children were predisposed to health risk of non-carcinogenic effect (HI > 1). Carcinogenic risk values for Pb and Cd in adults and children did not exceed the acceptable carcinogenic risk value for humans. The integrated carcinogenic risk (ICR) values classified the consumption of C. gariepinus and T. zillii as low – medium risk (Grade III). ConclusionThe study has shown that the consumption of the selected fish species is not safe for children. Also, the consumption of the gills of C. gariepinus along with the head portion of the fish should be discouraged to reduce exposure to heavy metal toxicity. The continuous monitoring of activities within the reservoir watershed to mitigate heavy metal pollution of the reservoir is recommended.

Use of in silico and in vitro methods as a potential new approach methodologies (NAMs) for (photo)mutagenicity and phototoxicity risk assessment of agrochemicals

The increased use of agrochemicals raises concerns about environmental, animal, and mainly human toxicology. The development of New Approach Methodologies (NAMs) for toxicological risk assessment including new in vitro tests and in silico protocols is encouraged. Although agrochemical mutagenicity testing is well established, a complementary alternative approach may contribute to increasing reliability, with the consequent reduction of false-positive results that lead to unnecessary use of animals in follow-up in vivo testing. Additionally, it is unreasonable to underestimate the phototoxic effects of an accidental dermal exposure to agrochemicals during agricultural work or domestic application in the absence of adequate personal protection equipment, especially in terms of photomutagenicity. In this scenario, we addressed the integration of in vitro and in silico techniques as NAMs to assess the mutagenic and phototoxic potential of agrochemicals. In the present study we used the yno1 S. cerevisiae strain as a biomodel for in vitro assessment of agrochemical mutagenicity, both in the absence and in the presence of simulated sunlight. In parallel, in silico predictions were performed using a combination of expert rule-based and statistical-based models to assess gene mutations and phototoxicity. None of the tested agrochemicals showed mutagenic potential in the two proposed approaches. The Gly and 2,4D herbicides were photomutagenic in the in vitro yeast test despite the negative in silico prediction of phototoxicity. Herein, we demonstrated a novel experimental approach combining both in silico and in vitro experiments to address the complementary investigation of the phototoxicity and (photo)mutagenicity of agrochemicals. These findings shed light on the importance of investigating and reconsidering the photosafety assessment of these products, using not only photocytotoxicity assays but also photomutagenicity assays, which should be encouraged.