Spatiotemporal variations in soil pollution by polycyclic aromatic hydrocarbons over a 20-year economic boom in different districts of a heavy industrial city in North China.

Urbanization-related human activities, such as population aggregation, rapid industrial expansion, and intensified traffic, are key factors that impact local polycyclic aromatic hydrocarbon emissions and their associated health risks. Consequently, regions with varying degrees of urbanization within a megacity may exhibit diverse spatiotemporal patterns in the presence and distribution of soil polycyclic aromatic hydrocarbons, resulting in different levels of ecological risks for local inhabitants following the same period of development. In this study, we measured the concentrations of 16 polycyclic aromatic hydrocarbons in soil samples collected from industrial district and rural district in Tianjin (China) in 2018, and compared with polycyclic aromatic hydrocarbon data in 2001 from a previous study to characterize these regional variations in occurrence, source, and human risk of polycyclic aromatic hydrocarbons induced by urbanization with time and space. The results indicate the 20-year rapid urbanization and industrialization has differentially affected the composition, distribution and sources of polycyclic aromatic hydrocarbons in soils from different economic functional zones in Tianjin. Additionally, its impact on health risks in rural district appeared to be more significant than that in industrial district.

Assessment of potential environmental and human risks for Bisphenol AF contaminant.

Bisphenol AF (BPAF) is found in high concentrations in aquatic environments due to the increased use of thermal paper and food packaging. However, there have been relatively few toxicological studies and potential risk assessments of BPAF. In this study, the risk quotient (RQ) and hazard quotient (HQ) of BPAF were derived to present the safety standards for environmental risk management and protection in lakes, rivers, bays, and Italian regions. We applied the species sensitivity distribution (SSD) method based on the previous ecotoxicological data and the results of supplementary toxicity tests on BPAF. From the SSD curves, the hazardous concentration for 5 % of the species (HC5) values for the acute and chronic toxicity data were 464.75 µg/L and 3.59 µg/L, respectively, and the acute- and chronic-based predicted no-effect concentration were derived as 154.92 µg/L and 1.20 µg/L, respectively. The acute-based RQ (RQA)values of BPAF in all regions were negligible (RQ < 0.1). The chronic-based RQ (RQC) in the Xitang River (XR) and the Central Italy (CI) showed a considerably high ecological risk (12.77 and 1.29) and the Hangzhou Bay (0.21), the South and North Italy (0.79 and 0.27), and the Tamagawa River (0.13) had a medium ecological risk (0.1 < RQ < 1.0). However, the HQ values based on the tolerable daily intake for BPAF over all age groups in these regions was < 0.1, indicating the low health risk. Nonetheless, the result of this study indicates that BPAF contamination is serious in XR and CI, and their use and emissions require continuous monitoring.

Metal content, bioaccumulation, translocation, and health risk assessment of root vegetables grown in KwaZulu-Natal small-scale farms of South Africa.

Metal uptake by vegetables is becoming a threat to the life of consumers. Therefore, continuous monitoring of metals in vegetables and soils is becoming a necessity. In this study, the occurrence of 18 metals in amadumbe (Colocasia esculenta L.), sweet potatoes (Ipomoea batatas L.), potatoes (Solanum tuberosum L.), and carrots (Daucus carrota L.) grown in small-scale South African agricultural farms was monitored using inductively coupled plasma-optical emission spectroscopy. All the 18 investigated elements were detected in soils and different vegetative plants parts. Bioaccumulation factors indicated the transfer of selected metals from soils into the plant roots. Toxic metals Cd, Cr, and Pb had their concentrations exceeding the maximum permissible levels set by the World Health Organization in the edible parts of all root vegetables. Cd and Pb varied between 18.89 and 19.19 mg kg-1 and 10.46 and 11.46 mg kg-1, respectively, while Cr remained constant at 16.78 mg kg-1. The exact metals together with As and Ni had their total hazard quotients exceeding the threshold value of 1, which indicated that the daily consumption of the investigated root vegetables is likely to pose health risks to both adults and children. Therefore, this study points out to a possibility of toxic health effects that could arise when these vegetables are consumed daily.

2000-2023 over two decades of ICH S7A: has the time come for a revamp?

The ICH S7A guideline on safety pharmacology studies released over 20 years ago largely achieved its objective "to help protect clinical trial participants and patients receiving marketed products from potential adverse effects of pharmaceuticals". Although, Phase I clinical trials are generally very safe, the incidence and severity of adverse events, the safety related attrition and product withdrawal remain elevated during late-stage clinical development and post approval, a proportion of which can be attributed at least in part to safety pharmacology related issues. Considering the latest scientific and technological advancements in drug safety science, the paradigm shift of the drug discovery and development process and the continuously evolving regulatory landscape, we recommend revisiting, adapting and evolving the ICH S7A guideline. This might offer opportunities i) to select and progress optimized drugs with increased confidence in success, ii) to refine and adapt the clinical monitoring at all stages of clinical development resulting in an optimized benefit/risk assessment, iii) to increase likelihood of regulatory acceptance in a way compatible with an expedited and streamlined drug discovery and development process to benefit patients and iv) to avoid the unnecessary use of animals in 'tick-the-box' studies and encourage alternative approaches. As presented in the article, several options could be envisioned to revisit and adapt the ICH S7A taking into consideration several key features.

Organochlorine Pollutants in Human Breast Milk from North of the Far Eastern Region of Russia.

The widespread application of pesticides in the territories of the former USSR still exerts negative impacts on their ecological status. In this regard, dedicated programs for monitoring persistent organic pollutants (POP) in humans are implemented in several countries. Our study aimed to assess the accumulation of organic pollutants in breast milk of women residing the Chukotka Autonomous Okrug (CAO). Organochlorine pesticides (OCP) and polychlorinated biphenyls (PCB) concentrations in breast milk samples were measured by gas chromatography-mass spectrometry (GC-MS). The POP concentrations in the samples varied from 13 ng/g lipid weight (lw) to 620.6 ng/g lw (median 58.3 ng/g lw). An assessment of health risk to infants fed breast milk from CAO women did not show any exceedance of the estimated daily intake (EDI). The results obtained are the indirect evidence of the presence of these compounds in the environment and their negative effects on ecosystems and human health.

Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) in Seawater and Sediments, Human and Ecological Risks, Northern Coastline of Persian Gulf.

This study aimed to assess 13 PAHs concentrations and induced human and ecological risks in seawater and surficial sediments of eight estuaries in the northern coastline of the Persian Gulf, Iran, 2021. The range of Σ13 PAHs concentration was 0.24-8.83 µg L-l and 3.1-11.46 µg g-1 dry weight, and the mean value was 4.99 µg L-l and 6.06 µg g-1 dry weight in seawater and sediment, respectively. Two, three and four rings PAHs were dominant with 29.33% and 41.33% of ΣPAHs in seawater and sediment, respectively. The primary source of PAHs was both pyrolytic and petrogenic. Most PAHs' calculated health (DCR, HQs, TEF, MEF) and ecological risks (SQGs) values in seawater were in the moderate range or high-risk values for damage to the marine environment. It is concluded that the pollution of PAHs should be carefully considered, and the government should make a proper action plan to minimize the pollution.

Human risk assessment of 4-n-nonylphenol (4-n-NP) using physiologically based pharmacokinetic (PBPK) modeling: analysis of gender exposure differences and application to exposure analysis related to large exposure variability in population.

As a toxic substance, 4-n-nonylphenol (4-n-NP) or 4-nonylphenol (4-NP) is widely present in the environment. 4-n-NP is a single substance with a linear-alkyl side chain, but 4-NP usually refers to a random mixture containing various branched types. Unfortunately, human risk assessment and/or exposure level analysis for 4-n-NP (or 4-NP) were almost nonexistent, and related research was urgently needed. This study aimed to analyze the various exposures of 4-n-NP (or 4-NP) through development of a physiologically based-pharmacokinetic (PBPK) model considering gender difference in pharmacokinetics of 4-n-NP and its application to human risk assessment studies. A PBPK model was newly developed considering gender differences in 4-n-NP pharmacokinetics and applied to a human risk assessment for each gender. Exposure analysis was performed using a PBPK model that considered gender differences in 4-n-NP (or 4-NP) exposure and high variabilities in several countries. Furthermore, an extended application was attempted as a human risk assessment for random mixture 4-NP, which is difficult to accurately evaluate in reality. External-exposure and margin-of-safety estimated with the same internal exposure amount differed between genders, meaning the need for a differentiated risk assessment considering gender. Exposure analysis based on biomonitoring data confirmed large variability in exposure to 4-n-NP (or 4-NP) by country, group, and period. External-exposures estimated using PBPK model varied widely, ranging from 0.039 to 63.875 mg/kg/day (for 4-n-NP or 4-NP). By country, 4-n-NP (or 4-NP) exposure was higher in females than in males and the margin-of-safety tended to be low. Overall, exposure to 4-n-NP (or 4-NP) in populations was largely not safe, suggesting need for ongoing management and monitoring. Considering low in vivo accumulation confirmed by PBPK model, risk reduction of 4-n-NP is possible by reducing its use.

Human risk assessment of di-isobutyl phthalate through the application of a developed physiologically based pharmacokinetic model of di-isobutyl phthalate and its major metabolite mono-isobutyl phthalate.

Di-isobutyl phthalate (DiBP) is a substance used in the production of objects frequently used in human life. Mono-isobutyl phthalate (MiBP), a major in vivo metabolite of DiBP, is a biomarker for DiBP exposure assessment. Therefore, risk assessment studies on DiBP and MiBP, which have not yet been reported in detail, are needed. The aim of this study was to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for DiBP and MiBP in rats and extend this to human risk assessment based on human exposure. Pharmacokinetic studies were performed in male rats following the administration of 5-100 mg/kg DiBP, and these results were used for the development and validation of the PBPK model. In addition, the previous pharmacokinetic results in female rats following DiBP administration and the pharmacokinetic results in both males and females according to multiple exposures to DiBP were used to develop and validate the PBPK model. The metabolism of DiBP to MiBP in the body was very significant and rapid, and the biodistribution of MiBP was broad and major. Furthermore, the amount of MiBP in the body showed a correlation with DiBP exposure, and from this, a PBPK model was developed to evaluate the external exposure of DiBP from the internal exposure of MiBP. The predicted rat plasma, urine, fecal, and tissue concentrations using the developed PBPK model fitted well with the observed values. The established PBPK model for rats was extrapolated to a human PBPK model of DiBP and MiBP based on human physiological parameters and allometric scaling. The reference dose of 0.512 mg/kg/day of DiBP and external doses of 6.14-280.90 µg/kg/day DiBP for human risk assessment were estimated using Korean biomonitoring values. Valuable insight and approaches to assessing human health risks associated with DiBP exposure were provided by this study.

Toward Rigorous Materials Production: New Approach Methodologies Have Extensive Potential to Improve Current Safety Assessment Practices.

Advanced material development, including at the nanoscale, comprises costly and complex challenges coupled to ensuring human and environmental safety. Governmental agencies regulating safety have announced interest toward acceptance of safety data generated under the collective term New Approach Methodologies (NAMs), as such technologies/approaches offer marked potential to progress the integration of safety testing measures during innovation from idea to product launch of nanomaterials. Divided in overall eight main categories, searchable databases for grouping and read across purposes, exposure assessment and modeling, in silico modeling of physicochemical structure and hazard data, in vitro high-throughput and high-content screening assays, dose-response assessments and modeling, analyses of biological processes and toxicity pathways, kinetics and dose extrapolation, consideration of relevant exposure levels and biomarker endpoints typify such useful NAMs. Their application generally agrees with articulated stakeholder needs for improvement of safety testing procedures. They further fit for inclusion and add value in nanomaterials risk assessment tools. Overall 37 of 50 evaluated NAMs and tiered workflows applying NAMs are recommended for considering safer-by-design innovation, including guidance to the selection of specific NAMs in the eight categories. An innovation funnel enriched with safety methods is ultimately proposed under the central aim of promoting rigorous nanomaterials innovation.

Risk assessment for humans using physiologically based pharmacokinetic model of diethyl phthalate and its major metabolite, monoethyl phthalate.

Diethyl phthalate (DEP) belongs to phthalates with short alkyl chains. It is a substance frequently used to make various products. Thus, humans are widely exposed to DEP from the surrounding environment such as food, soil, air, and water. As previously reported in many studies, DEP is an endocrine disruptor with reproductive toxicity. Monoethyl phthalate (MEP), a major metabolite of DEP in vivo, is a biomarker for DEP exposure assessment. It is also an endocrine disruptor with reproductive toxicity, similar to DEP. However, toxicokinetic studies on both MEP and DEP have not been reported in detail yet. Therefore, the objective of this study was to evaluate and develop physiologically based pharmacokinetic (PBPK) model for both DEP and MEP in rats and extend this to human risk assessment based on human exposure. This study was conducted in vivo after intravenous or oral administration of DEP into female (2 mg/kg dose) and male (0.1-10 mg/kg dose) rats. Biological samples consisted of urine, plasma, and 11 different tissues. These samples were analyzed using UPLC-ESI-MS/MS method. For DEP, the tissue to plasma partition coefficient was the highest in the kidney, followed by that in the liver. For MEP, the tissue to plasma partition coefficient was the highest in the liver. It was less than unity in all other tissues. Plasma, urine, and fecal samples were also obtained after IV administration of MEP (10 mg/kg dose) to male rats. All results were reflected in a model developed in this study, including in vivo conversion from DEP to MEP. Predicted concentrations of DEP and MEP in rat urine, plasma, and tissue samples using the developed PBPK model fitted well with observed values. We then extrapolated the PBPK model in rats to a human PBPK model of DEP and MEP based on human physiological parameters. Reference dose of 0.63 mg/kg/day (or 0.18 mg/kg/day) for DEP and external doses of 0.246 µg/kg/day (pregnant), 0.193 µg/kg/day (fetus), 1.005-1.253 µg/kg/day (adults), 0.356-0.376 µg/kg/day (adolescents), and 0.595-0.603 µg/kg/day (children) for DEP for human risk assessment were estimated using Korean biomonitoring values. Our study provides valuable insight into human health risk assessment regarding DEP exposure.

Dynamics of (total and methyl) mercury in sediment, fish, and crocodiles in an Amazonian Lake and risk assessment of fish consumption to the local population.

Increasing concerns have been raised about the toxicity of mercury (Hg) to humans, especially for those that consume a great amount of fish. High Hg concentrations have previously been measured in Amazonian waterbodies, both resulting from natural and anthropogenic sources. However, few studies have been conducted so far in Amazonian lakes that are fished by local populations. In addition, few of those studies included methylmercury (MeHg), the most toxic and bioaccumulative Hg form, and evaluated the influence of physico-chemical conditions and season on Hg dynamics. In the present study, total Hg (THg) and MeHg concentrations were measured in bottom sediment as well as in two fish and two crocodile species of the Amazonian Cuniã Lake. Bottom sediment MeHg concentrations were higher in the dry season than in the wet season, which is related to differences in physico-chemical (pH and electrical conductivity) conditions. Diet appeared to be related with animal tissue MeHg concentrations, with the herbivorous fish having lower MeHg levels than the predatory fish and crocodiles. Based on the measured tissue concentrations and published data on local person weight and fish consumption, MeHg risk to Cuniã Lake populations was estimated. Although the MeHg fish tissue concentrations did not exceed national and international standards, a significant risk to the local population is anticipated due to their high fish consumption rates. Graphical abstract.

Comparisons of human risk assessment models for heavy metal contamination within abandoned metal mine areas in Korea.

This study was initiated to develop a model specialized to conduct human risk assessments (HRAs) of abandoned metal mine areas in Korea. The Korean guideline (KG) model used in study was formulated via modification of the original Korean guidelines on HRAs of soil contamination. In addition, the newly developed model was applied to the HRAs of two abandoned metal mines contaminated with arsenic (As) and heavy metals (Cd, Cu, Pb, and Zn). The results of the KG model were compared with those of two internationally renowned models [Contaminated land exposure assessment (CLEA) and CSOIL models]. The HRA results of the three models indicated that the areas of concern were unsafe when it came to both carcinogenic and non-carcinogenic hazards. Furthermore, the hazards in both areas were mostly attributed to As and the predominant exposure pathways were identified as crop intake in the KG model and surface soil dermal contact in CLEA and CSOIL models. Accordingly, measures to protect against As exposure should be established immediately to prevent adverse health effects on inhabitants in these areas. A comparison of HRA results revealed significant differences between KG, CLEA, and CSOIL models due to the various types of exposure pathways, contaminants, and input data, such as exposure factors and receptor parameters. This study suggests that set-up of an exposure scenario is crucial for the successful performance of HRAs, and the most relevant HRA model should be deliberately selected to attain risk assessment goals.

Persistent organic pollutants in fish from Charleston Harbor and tributaries, South Carolina, United States: A risk assessment.

Fish consumption is an important route of exposure to persistent organic pollutants (POPs) in dolphins as well as humans. In order to assess the potential risks associated with these contaminants, 39 whole fish and 37 fillets from fish representing species consumed by dolphins and humans captured from Charleston Harbor and tributaries, South Carolina, USA, were measured for a suite of POPs. Polychlorinated biphenyls (PCBs) were the predominant contaminant with concentrations ranging from 5.02 to 232.20 ng/g in whole fish and 5.42-131.95 ng/g in fillets (weight weight ww) followed by total organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). Total POPs levels varied by location and species with general trends indicating significantly higher levels in fish from the Cooper (93.4 ng/g ww) and Ashley Rivers (56.2 ng/g ww) compared to Charleston Harbor (31.6 ng/g ww). Mullet and spot were found to have significantly higher PCBs, OCPs and total POPs, 2-3 times higher than red drum; mullet were also significantly higher in OCPs compared to seatrout. PCB concentrations in whole fish and fillets exceeded EPA human screening values for cancer risk in all fish sampled. For PCBs in fillets, all samples had values of maximum allowable meals per month that were less than the EPA, FDA guidelines for recommended fish meals per month, suggesting lower (more stringent) allowable fish meals per month. All fish exceeded PBDE wildlife values and all fish except two exceeded the level where 95% of the dolphin population would have tissue levels below the health effect threshold. Considering that POP concentrations in fish potentially consumed by humans exceed human health effect thresholds levels, consumption advisories should be considered as a prudent public health measure.

An integrated approach to study the risk from landfill soil of Delhi: Chemical analyses, in vitro assays and human risk assessment.

In the present study, landfill soil of three municipal solid waste landfill sites of Delhi, India were toxico-chemically analyzed for human risk assessment as inadequate information is available on the possible health effects of the contaminants present in landfill soil. The landfill soil samples were prepared for analyzing heavy metal concentration, organic contaminants and toxicity analysis separately. Composite soil sample collected from three landfill sites were analyzed for heavy metal by ICP-AES. Metal concentration so obtained was below the permissible limit of soil but higher than the set limits for effluent. Some of the persistent organic contaminants like phthalates, benzene derivatives, halogenated aliphatic compounds and PAHs derivatives were detected by scan mode GC-MS. Further, concentration of 17 polycyclic aromatic hydrocarbons (PAHs) in landfill soil of Delhi was evaluated by selective ion monitoring GC-MS in order to ascertain their contamination levels and potential health risk. The concentration of total PAHs in the samples ranged from 192 to 348µg/kg. The maximum concentrations of PAHs were found in Ghazipur landfill site followed by Okhla and Bhalswa landfills. Cancer risk (CR) values of sampling sites were within the acceptable range for adults, adolescents and children (both male and female) suggesting that PAHs present in landfill soil are unlikely to pose any cancer risk for population based on dermal contact, ingestion and inhalation exposure pathways. However, landfill soil organic extract showed significant cytotoxic and genotoxic effects on HepG2 cell line as revealed by MTT and Comet assays respectively. The observed MTT EC50 values ranged from 7.58 to 12.9g SedEq/Lalong with statistically significant DNA damage. Thus, although the soil organic extract contained low concentrations of PAHs with negligible carcinogenic potential, but the mixture of organic pollutants present in soil were found to be toxic enough to affect human health due to their synergistic or additive actions.

Comprehensive and comparative ecotoxicological and human risk assessment of polycyclic aromatic hydrocarbons (PAHs) in reef surface sediments and coastal seawaters of Iranian Coral Islands, Persian Gulf.

The concentration and spatial distribution along with ecotoxicological risk of 30 polycyclic aromatic hydrocarbons were investigated in the reef surface sediments (RSSs) and coastal seawater (CSW) of ten coral Islands from the Persian Gulf, Iran, in January 2015. For all sampling sites, assessment of ecological risk was undertaken using several approaches. Mean concentration of ∑30PAHs varied between 70 and 884ngL-l with an overall mean value of 464ngL-l in the CSW, while the RSS ranged from 274 to 1098ngg-1dw with a total average of 619ngg-1dw. The results showed a gradient in PAH concentration and toxicity estimates from the northern Hormoz site increasing to the eastern Kharg site. Most of the toxicity estimates were in the moderate range or less than risk values for damage to the marine environment. The calculated Dermal Hazard Quotient (HQs), the sum of HQs (HI) and other cancer risk values of most compounds were less than safety values at most sites. It means that the possibility of negative effects of PAHs via dermal absorption from sediments for children and adults is low. Some sampling sites studied have already been impacted with hazardous pollutants for an extended period of time and evidence from this investigation demonstrates that mixtures of PAHs may be carcinogenic to humans, especially in the western part of the Gulf.

Evaluation of relative effect potencies (REPs) for dioxin-like compounds to derive systemic or human-specific TEFs to improve human risk assessment.

Toxic equivalency factors (TEFs) are generally applied for estimating human risk of dioxins and dioxin-like compounds using systemic (e.g., blood) levels, even though these TEFs are established based on intake doses in rodent studies. This review shows that systemic relative effect potencies (REPs) can deviate substantially from intake REPs, but are similar to in vitro-derived REPs. Interestingly, the in vitro REPs for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) and 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) are up to one order of magnitude higher than their in vivo REPs and WHO-TEFs, based on oral intake. In addition, clear species-differences in in vitro REPs were apparent for some congeners. Especially the human-derived REP for polychlorinated biphenyl 126 is one to two orders of magnitude lower than rodent REPs and its current WHO-TEF. Next, suggested adapted systemic or human-specific TEFs for these congeners were applied to calculate changes in systemic TEQ concentrations in studies from the USA, Germany and Japan and compared with either the JECFA TDI or USEPA RfD of TCDD. Overall, the effect of such TEF changes for these three congeners on total TEQ roughly balances each other out in the general population. However, results may be different for situations in which a specific group of congeners dominates. For those congeners that show a distinct deviation between either intake and systemic REPs or between rodent- and human-based in vitro REPs, we propose that especially REPs derived from human-based in vitro models are weighted more heavily in establishing systemic or human-specific TEF values to improve human health risk assessment.

Human health risk assessment of heavy metals in a replaced urban industrial area of Qingdao, China.

The aim of this study was risk characterization of a replaced urban industrial land located north of Qingdao, in relation to heavy metals values. Soil concentrations of Cd, Pb, Cu, Ni, Cr, and Zn were analyzed. It was observed that the components of Cd, Pb, Cu, Ni, Cr, and Zn are about 2.22, 8.07, 4.70, 6.81, 2.65, and 3.0-folds, respectively, when compared with the local natural background values in Qingdao. The spatial distribution of heavy metals indicated that these hotspots for Cr and Zn located in the southwestern part, Ni and Cd in the middle of the south area, Pb in the northwest, and Cu in the middle of the east area. The values of pollution index and Nemerow integrated pollution index revealed that 100 % of soil samples were moderately or heavily contaminated by six heavy metals. From these results, human health risk assessment for sensitive population was performed according to two different land uses. For non-carcinogenic risk, the direct oral ingestion appeared to be the main exposure pathway followed by dermal and inhalation absorption. The HI values of Pb and Cr characterized for children were larger than 1, while HI values of each metal for adults in two scenarios were lower than 1. Besides, carcinogenic risk from inhalation exposure to Cr for children and adults in two scenarios all exceeded the safety limit.

Minimal inflammogenicity of pristine single-wall carbon nanotubes.

Carbon nanotubes (CNTs) are a novel synthetic material comprising only carbon atoms. Based on its rigidity, its electrical and heat conductivity and its applicability to surface manufacturing, this material is expected to have numerous applications in industry. However, due to the material's dimensional similarity to asbestos fibers, its carcinogenicity was hypothesized during the last decade, and indeed, we have shown that multi-wall CNTs (MWCNTs) of 50 nm in diameter are potently carcinogenic to mesothelial cells after intraperitoneal injection. Additionally, we suggested that inflammogenicity after intraperitoneal injection can predict mesothelial carcinogenesis. However, few data have been published on the intraperitoneal inflammogenicity of single-wall CNTs (SWCNTs). Here, we conducted a series of studies on SWCNTs using both intraperitoneal injection into rats and MeT5A mesothelial cells. Intraperitoneal injection of 10 mg SWCNTs caused no remarkable inflammation in the abdominal cavity, and the exposure of MeT5A cells to up to 25 µg/cm(2) SWCNTs did not alter proliferation. MWCNTs of 50 nm in diameter were used as a positive control, and tangled MWCNTs of 15 nm in diameter were used as a negative control. The results suggest that SWCNTs are a low-risk material with respect to mesothelial carcinogenesis.

Reassessing the two-year rodent carcinogenicity bioassay: a review of the applicability to human risk and current perspectives.

The 2-year rodent carcinogenicity test has been the regulatory standard for the prediction of human outcomes for exposure to industrial and agro-chemicals, food additives, pharmaceuticals and environmental pollutants for over 50 years. The extensive experience and data accumulated over that time has spurred a vigorous debate and assessment, particularly over the last 10 years, of the usefulness of this test in terms of cost and time for the information obtained. With renewed interest in the United States and globally, plus new regulations in the European Union, to reduce, refine and replace sentinel animals, this review offers the recommendation that reliance on information obtained from detailed shorter-term, 6 months rodent studies, combined with genotoxicity and chemical mode of action can realize effective prediction of human carcinogenicity instead of the classical two year rodent bioassay. The aim of carcinogenicity studies should not be on the length of time, and by obligation, number of animals expended but on the combined systemic pathophysiologic influence of a suspected chemical in determining disease. This perspective is in coordination with progressive regulatory standards and goals globally to utilize effectively resources of animal usage, time and cost for the goal of human disease predictability.

Microplastic prevalence and human exposure in the bottled drinking water in the west Godavari region of Andhra Pradesh, India.

Microplastics (MPs) are widespread, minute plastic particles present in various aquatic environments, raising concerns about their effect on human health and ecosystems. The detrimental effects of MPs on the environment, include the contamination of ecosystems, harm to aquatic life through ingestion, potential disruption of food chains, and long-term ecological consequences. Despite numerous studies confirming the MP's presence in aquatic environments, research specifically focused on MPs in bottled drinking water (BDW) is limited. Research on MPs in drinking water is vital to assess potential health risks and develop strategies for ensuring water safety and quality. This study fills a research gap by investigating microplastics (MPs) in nine brands of BDW in the West Godavari region of Andhra Pradesh, India. The average MP concentration in BDW was found to be 2.89 ± 0.48 items/L, with fibers being the predominant shape and sizes ranging from 500 to 1000 µm. Transparent and blue were the most common colors. From ATR-FTIR analysis, the dominant polymer found was polypropylene (PP) followed by polyethylene terephthalate (PET). The human risk assessment was also calculated using the formula of Estimated daily intake (EDI) and Lifetime intake (LTI). The calculation found that the EDI of MPs for children and adults ranged from 0.041 to 0.291 MPs per kilogram per day and 0.019 to 0.133 MPs per kilogram per day, respectively. The mean LTI of MP consumption of an individual, ranged from 17,958 to 2,54,861 MPs, considering an average age of 75 years. The current findings offer valuable information for ongoing evaluations of the potential human risks linked to MP exposure.