Human Health Hazard Assessment Research Articles

Risk surveillance with spatial distribution of Organochlorine Pesticides (OCPs) from sedimentary samples of Chenab River

A pioneering study employed a holistic geostatistical approach to predict the spatial variability of a non sampled area in the Chenab River, Pakistan, using kriging interpolation for organochlorine pesticide (OCP)-polluted risk zones. The Present research intended to investigate the carcinogenic and non-carcinogenic human health risks, contamination levels, and spatial variation of OCPs in the Chenab River, Pakistan. The residual OCP content in sediment samples (n = 120) ranged from 0.056 to 32.14 ng/g. DDE and α-HCH were prevalent among all the samples analyzed, with mean concentrations of 15.84 ± 8.02 and 12.45 ± 6.72 ng/g, respectively. The order of magnitude of OCPs in sediment samples was DDTs > α-HCH > chlorothalonil > heptachlor > endosulfan > aldrin > dieldrin. The findings of the single (SPI) and Nemerow (Nel) pollution index of α-HCH, heptachlor, and aldrin depicted the Chenab River as a serious pollution risk zone. The outcomes of the Pearson correlation coefficient analysis represent the positive correlation among all OCPs, revealing the common origin. Distribution trends showed substantially higher (p < 0.05) contents of analyzed OCPs along the downstream zone. With regards to USEPA human health hazard assessment model, the estimated non-carcinogenic (ΣHI) and non-carcinogenic (ΣTCR) risk ranged from 1.1 × 10−5 to 1.0 × 10−1, 4.0 × 10−8 to 3.2 × 10−4 respectively. TCR >10−4 illustrated a substantial cancer health risk posed by α-HCH, heptachlor, aldrin, and dieldrin in the downstream zone. We recommend the urgent cessation of the ongoing discharge of OCPs into the Chenab River, which needs to be highlighted owing to the significant cancer risk to public health to ensure the good health and wellbeings.

Lead, tin, bismuth or organics: Assessment of potential environmental and human health hazards originating from mature perovskite PV technology

Lead, tin, bismuth or organics: Assessment of potential environmental and human health hazards originating from mature perovskite PV technology

Photovoltaics literature survey (no. 182)

Photovoltaics literature survey (no. 182)

Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro

Cyanobacterial blooms are known sources of environmentally-occurring retinoid compounds, including all-trans and 9-cis retinoic acids (RAs). The developmental hazard for aquatic organisms has been described, while the implications for human health hazard assessment are not yet sufficiently characterized. Here, we employ a human neural stem cell model that can differentiate in vitro into a mixed culture of neurons and glia. Cells were exposed to non-cytotoxic 8–1000 nM all-trans or 9-cis RA for 9–18 days (DIV13 and DIV22, respectively). Impact on biomarkers was analyzed on gene expression (RT-qPCR) and protein level (western blot and proteomics) at both time points; network patterning (immunofluorescence) on DIV22. RA exposure significantly concentration-dependently increased gene expression of retinoic acid receptors and the metabolizing enzyme CYP26A1, confirming the chemical-specific response of the model. Expression of thyroid hormone signaling-related genes remained mostly unchanged. Markers of neural progenitors/stem cells (PAX6, SOX1, SOX2, NESTIN) were decreased with increasing RA concentrations, though a basal population remained. Neural markers (DCX, TUJ1, MAP2, NeuN, SYP) remained unchanged or were decreased at high concentrations (200–1000 nM). Conversely, (astro-)glial marker S100β was increased concentration-dependently on DIV22. Together, the biomarker analysis indicates an RA-dependent promotion of glial cell fates over neural differentiation, despite the increased abundance of neural protein biomarkers during differentiation. Interestingly, RA exposure induced substantial changes to the cell culture morphology: while low concentrations resulted in a network-like differentiation pattern, high concentrations (200–1000 nM RA) almost completely prevented such network patterning. After functional confirmation for implications in network function, such morphological features could present a proxy for network formation assessment, an apical key event in (neuro-)developmental Adverse Outcome Pathways. The described application of a human in vitro model for (developmental) neurotoxicity to emerging environmentally-relevant retinoids contributes to the evidence-base for the use of differentiating human in vitro models for human health hazard and risk assessment.

Heavy Metal Contamination in Leafy Vegetables Grown in Jazan Region of Saudi Arabia: Assessment of Possible Human Health Hazards.

The food chain, through vegetable consumption, is considered to be an important route of heavy metal exposure. Therefore, in this study, heavy metal concentrations in leafy vegetables grown in the Jazan region of Saudi Arabia were assessed using an ICP-MS. Lettuce, radish, mint, parsley and jarjir (Arugula) were selected for study and subjected to digestion using HCl. The results indicated that the Fe level was highest in all vegetables, while jarjir was the most contaminated vegetable. However, no tested metal exceeded the maximum permissible limits set by the FAO/WHO and European Committee. The possible health hazards associated with the exposure to metal contaminants via vegetable consumption were evaluated by estimating target hazard quotient (THQ) values, and the results revealed that the vegetables grown in close proximity of Jazan city were the most contaminated and those in Darb the least. However, the daily intakes of all the tested metals were well below the corresponding oral reference doses (RfDs), and the THQ values were less than unity, suggesting that the vegetables grown in the studied region were safe and the heavy metal exposure via vegetable consumption was unlikely to cause adverse effects to the local inhabitants of the region.

Derivation of human health hazard assessment values of 1,2-dichloroethane under the Japan Chemical Substances Control Law

1,2-Dichloroethane, a priority assessment chemical substance under the Japan Chemical Substances Control Law (CSCL), required a detailed human health hazard assessment under Assessment II. We evaluated its general, reproductive, and developmental toxicities, genotoxicity, and carcinogenicity, based on the hazard information provided by domestic and international risk assessment organizations, and the hazard assessment values (HAVs) for oral and inhalation exposure were proposed. For oral exposure, a 78-week gavage carcinogenicity study (US NCI, 1978) with incidence data of hemangiosarcoma in male rats was selected as a significant toxicological endpoint and the lower confidence limit of benchmark dose (BMD) at 10% benchmark response (BMDL10) of 9.3 mg/kg/day was obtained as a point of departure (POD). A slope factor of 1.07 × 10−2 (mg/kg/day)−1 from which a carcinogenic 10−5 risk of 0.93 µg/kg/day was derived as an oral HAV. For inhalation exposure, a 104-week inhalation exposure carcinogenicity study (Nagano et al., 2006) with a BMDL10 of 11.5 ppm based on the incidence data of mammary gland tumors (adenocarcinoma + adenoma + fibroadenoma, combined) in female rats was obtained, and the human equivalent BMDL10 of 15.7 mg/m3 was calculated. Therefore, a unit risk of 6.40 × 10−6 (µg/m3)−1 from which a carcinogenic 10−5 risk of 1.6 µg/m3 (0.00039 ppm) was derived as an inhalation HAV.

Advancing the science of a read-across framework for evaluation of data-poor chemicals incorporating systematic and new approach methods

The assessment of human health hazards posed by chemicals traditionally relies on toxicity studies in experimental animals. However, most chemicals currently in commerce do not meet the minimum data requirements for hazard identification and dose-response analysis in human health risk assessment. Previously, we introduced a read-across framework designed to address data gaps for screening-level assessment of chemicals with insufficient in vivo toxicity information (Wang et al., 2012). It relies on inference by analogy from suitably tested source analogues to a target chemical, based on structural, toxicokinetic, and toxicodynamic similarity. This approach has been used for dose-response assessment of data-poor chemicals relevant to the U.S. EPA's Superfund program. We present herein, case studies of the application of this framework, highlighting specific examples of the use of biological similarity for chemical grouping and quantitative read-across. Based on practical knowledge and technological advances in the fields of read-across and predictive toxicology, we propose a revised framework. It includes important considerations for problem formulation, systematic review, target chemical analysis, analogue identification, analogue evaluation, and incorporation of new approach methods. This work emphasizes the integration of systematic methods and alternative toxicity testing data and tools in chemical risk assessment to inform regulatory decision-making.

Ecological and probabilistic human health hazard assessment of heavy metals in Sera Lake Nature Park sediments (Trabzon, Turkey)

Ecological and probabilistic human health hazard assessment of heavy metals in Sera Lake Nature Park sediments (Trabzon, Turkey)

Actinide imaging in environmental hot particles from Chernobyl by rapid spatially resolved resonant laser secondary neutral mass spectrometry

Radioactive particles, so-called hot particles, are of great importance in the risk assessment of environmental pollution and human health hazards. Since most of these particles are only a couple of micrometers in size and thus have correspondingly small atomic inventory, information on origin and composition is difficult to obtain. Many analytical methods do not give insight into isotopic details or require the complete use up of the particle. Resonant laser secondary neutral mass spectrometry (rl-SNMS) has been proven to be a well-suited method for quasi-non-destructive analysis of trace elements. The technique provides high suppression of isobaric interferences and high spatial resolution without necessitating extensive chemical preparation. To measure multiple elements, it is often necessary to switch between laser excitation schemes, requiring elaborate adaptation of the laser setup. Here we present a novel rL-SNMS system capable of multi-element measurements in short succession without any manual adjustment to the laser system. For demonstration, ten micrometer sized hot particles from the Chernobyl Exclusion Zone are analyzed and the obtained isotopic ratios of uranium, plutonium and americium are discussed.

Derivation of human health hazard assessment values for toluene under the Japanese Chemical Substances Control Law

Derivation of human health hazard assessment values for toluene under the Japanese Chemical Substances Control Law

Hazard identification and risk assessment of the organic, inorganic and microbial contaminants in the surface water after the high magnitude of flood event.

The present work has been oriented to the qualitative and quantitative assessments of the aftermath effects of 2014 flood tragedy on the organic, inorganic and microbial contaminants in the floodwater, with a particular emphasis on their relative health risks and microbial infectious hazards to the flood-affected population, using average daily dose, hazard quotient, hazard index (HI), cancer risk (CR) and quantitative microbial risk assessment. Statistical comparison of the organic and inorganic contents was performed using the paired t-tests, while the predominant socio-demographic profiles and health attributes of the respondents to flood-induced health risks (HI) were verified by the chi-square test and binary logistic regression analysis. Among all, Fe, Cu, Pb, Ni, Zn, Cr, Cd, chlorpyrifos, diazinon, polycyclic aromatic hydrocarbons, estriol, 17α-ethinylestradiol, estrone, β-estradiol and bisphenol A were detected at the study area after flooding. The microbiological quality of the floodwater samples has been tracked positive for Escherichia coli, Salmonella typhimurium and Shigella flexneri, with the mean concentrations of 6500, 50 and 180CFU/100mL, respectively. Exposure and health risk assessments revealed that the overall HI value for organic and inorganic contaminants in the water samples was 1.19, exceeding the USEPA maximum limit of 1, after the flood incidence. The largest CR contributors were Ni, Cr and Cd, while the infection risks (Pinf,single) associated with the exposure of E. coli, Salmonella spp. and Shigella spp. were identified to be 3.1×10-2, 1.2×10-4 and 3.2×10-5 for incidental scenario; and 8.3×10-1, 3.9×10-1 and 1.9×10-1 for intentional scenario, respectively. The findings of these integrated tools are critically important to provide a more reliable quantitative assessment of human health hazards and microbial risks for different environmental settings, to safeguard water resource, and preservation of public health and the overall river ecosystem.

High-Throughput Transcriptomic Analysis of Human Primary Hepatocyte Spheroids Exposed to Per- and Polyfluoroalkyl Substances as a Platform for Relative Potency Characterization.

Per- and poly-fluoroalkyl substances (PFAS) are widely found in the environment because of their extensive use and persistence. Although several PFAS are well studied, most lack toxicity data to inform human health hazard and risk assessment. This study focused on 4 model PFAS: perfluorooctanoic acid (PFOA; 8 carbon), perfluorobutane sulfonate (PFBS; 4 carbon), perfluorooctane sulfonate (PFOS; 8 carbon), and perfluorodecane sulfonate (PFDS; 10 carbon). Human primary liver cell spheroids (pooled from 10 donors) were exposed to 10 concentrations of each PFAS and analyzed at 4 time points. The approach aimed to: (1) identify gene expression changes mediated by the PFAS, (2) identify similarities in biological responses, (3) compare PFAS potency through benchmark concentration analysis, and (4) derive bioactivity exposure ratios (ratio of the concentration at which biological responses occur, relative to daily human exposure). All PFAS induced transcriptional changes in cholesterol biosynthesis and lipid metabolism pathways, and predicted PPARα activation. PFOS exhibited the most transcriptional activity and had a highly similar gene expression profile to PFDS. PFBS induced the least transcriptional changes and the highest benchmark concentration (ie, was the least potent). The data indicate that these PFAS may have common molecular targets and toxicities, but that PFOS and PFDS are the most similar. The transcriptomic bioactivity exposure ratios derived here for PFOA and PFOS were comparable to those derived using rodent apical endpoints in risk assessments. These data provide a baseline level of toxicity for comparison with other known PFAS using this testing strategy.

Human health hazard assessment for high groundwater arsenic and fluoride intact in Malda district, Eastern India

Human health risk assessment is a technique used to estimate the potential impact of a thread on the health of a person, a group of individuals or a community. Agricultural, nuclear, aerospace, oil, rail and military sectors, as well as policy makers, have a long history of risk assessment to address increased health-related issues, such as people exposed to varying amounts of toxic substances. For this work, 288 samples have been collected from the PHE websites, each sample having four ion values (Arsenic, Iron, pH and Fluoride). In this study, the “probability kriging” is a geo-statistical method used to predict the risk magnitude and risk probability of these areas. The risk probability was measured using a semi-variogram, a kriging geo-statistical model. High arsenic risk probability zone is located in the southern and western parts of the district, high iron risk probability zone is scattered, high pH risk probability is located in the southern part of the district, and high fluoride risk zone is located in the eastern part of the district. Finally, a population density map has been used on probability map to better explain the risk to human health. Extremely high human health risks associated with arsenic and pH, while low to medium human health risks associated with fluoride or iron are present in the region. Spatial interpolation results in a risk map for human health which can be easily read and communicated. This may make it possible to consider significant mitigation measures to control drinking water supplies in the Malda district.

Rationale and decision rules behind the ECETOC NanoApp to support registration of sets of similar nanoforms within REACH

New registration requirements for nanomaterials under REACH consider the possibility to form ‘sets of similar nanoforms’ for a joined human health and environmental hazard, exposure and risk assessment. We developed a tool to create and justify sets of similar nanoforms and to ensure that each of the nanoforms is sufficiently similar to all other nanoforms. The decision logic is following the ECHA guidance in a transparent and evidence-based manner. For each two nanoforms the properties under consideration are compared and corresponding thresholds for maximal differences are proposed. In tier1, similarity is assessed based on intrinsic properties that mostly correspond to those required for nanoform identification under REACH: composition, impurities/additives, size, crystallinity, shape and surface treatment. Moreover, potential differences in the agglomeration/aggregation state resulting from different production processes are considered. If nanoforms were not sufficiently similar based on tier1 criteria, additional data from functional assays are required in tier2. In rare cases, additional short-term in vivo rodent data could be required in a third tier. Data required by tier 2 are triggered by the intrinsic properties in the first tier that did not match the similarity criteria. Most often this will be data on dissolution and surface reactivity followed by in vitro toxicity, dispersion stability, dustiness. Out of several nanoforms given by the user, the tool concludes which nanoforms could be justified to be in the same set and which nanoforms are outside. It defines the boundaries of sets of similar nanoforms and generates a justification for the REACH registration.

Regulating human safety: How dose selection in toxicity studies impacts human health hazard assessment and subsequent risk management options

In the EU, one of the key determinants in the regulation and management of substances to ensure adequate protection of human health is the outcome of toxicity studies. These studies should therefore be performed in a way that the data generated are adequate to fulfil all regulatory requirements. However, in recent years, an increasing number of toxicity studies use dose levels that induce only slight, or even no toxicity, while the top dose lies well below the limit dose of 1000 mg/kg bw/d. The results of these studies have limited value for the hazard and subsequent risk assessment and risk management of substances. This paper shows why conducting toxicity studies with too low doses has severe consequences for among others classification and labelling, identification of endocrine disruptors, health impact assessment, and incident management.With this paper we aim to raise awareness on this issue and want to stress the importance of the use of sufficiently high dosing in toxicity studies. Given their central role in toxicity testing, it is therefore key to adapt where necessary the descriptions in OECD test guidelines and guidance documents on requirements for dose level setting, to make sure they are as explicit and unambiguous as possible.

Residues, bioaccumulation, and trophic transfer of pharmaceuticals and personal care products in highly urbanized rivers affected by water diversion

Little information is available on the bioaccumulation and trophic transfer of pharmaceuticals and personal care products (PPCPs) in urban rivers system, particularly for those affected by water transfer. Herein, a comprehensive study was conducted to investigate the biological residues, bioaccumulation and trophic transfer of 45 PPCPs in the Nanjing Qinhuai River system under the background of water diversion projects. A total of 30 compounds were detected with a descending order of overall concentration as plankton > benthic mollusc > fish (except grass carp). Higher biological residues were observed in the downstream than those in the upstream, with the largest increase for fish (136.4 %) and the lowest increase for phytoplankton (5.4 %). However, the bioaccumulation classifications of most PPCPs were unchanged among the three different water-diversion regions. Trophic magnification factors (TMFs) of organic UV filters (homosalate, oxybenzone, ethylhexyl methoxycinnamate and octocrylene) ranged from 1.23 to 2.04, suggesting trophic magnification potential, while trophic dilution for pharmaceuticals (sertraline, citalopram, caffeine and roxithromycin) with TMFs of 0.42 to 0.50 were observed. A notable positive correlation was observed between the pH-dependent distribution coefficient (logDow) and the TMFs of the PPCPs (P < 0.05). Although the human health hazard assessment indicated no immediate health risk via the consumption of freshwater food, attention should be paid to the joint effects of PPCPs.

Multi-Target Risk Assessment of Potentially Toxic Elements in Farmland Soil Based on the Environment-Ecological-Health Effect.

There are potential impacts of Potentially Toxic Elements (PTEs) (e.g., Cd, Cr, Ni, Cu, As, Zn, Hg, and Pb) in soil from the perspective of the ecological environment and human health, and assessing the pollution and risk level of soil will play an important role in formulating policies for soil pollution control. Lingyuan, in the west of Liaoning Province, China, is a typical low-relief terrain of a hilly area. The object of study in this research is the topsoil of farmland in this area, of which 71 soil samples are collected. In this study, research methods, such as the Nemerow Index, Potential Ecological Hazard Index, Ecological Risk Quotient, Environmental Exposure Hazard Analysis, Positive Matrix Factorization Model, and Land Statistical Analysis, are used for systematical assessment of the pollution scale, pollution level, and source of PTEs, as well as the ecological environmental risks and health risks in the study area. The main conclusions are: The average contents of As, Cd, Cr, Cu, Hg, Zn, Ni, and Pb of the soil are 5.32 mg/kg, 0.31 mg/kg, 50.44 mg/kg, 47.05 mg/kg, 0.03 mg/kg, 79.36 mg/kg, 26.01 mg/kg, and 35.65 mg/kg, respectively. The contents of Cd, Cu, Zn, and Pb exceed the background value of local soil; Cd content of some study plots exceeds the National Soil Environmental Quality Standard Value (0.6 mg/kg), and the exceeding standard rate of study plots is 5.63%; the comprehensive potential ecological hazard assessment in the study area indicates that the PTEs are at a slight ecological risk; probabilistic hazard quotient assessment indicates that the influence of PTEs on species caused by Cu is at a slight level (p = 10.93%), and Zn, Pb, and Cd are at an acceptable level. For the ecological process, Zn is at a medium level (p = 25.78%), Cu is at a slight level (19.77%), and the influence of Cd and Pb are acceptable; human health hazard assessment states that the Non-carcinogenic comprehensive health hazard index HI = 0.16 < 1, indicating that PTEs in soil have no significant effect on people’s health through exposure; the PMF model (Positive Matrix Factorization) shows that the contribution rates of agricultural source, industrial source, atmospheric dust source, and natural source are 13.15%, 25.33%, 18.47%, and 43.05%, respectively.

Application of Caenorhabditis elegans (nematode) and Danio rerio embryo (zebrafish) as model systems to screen for developmental and reproductive toxicity of Piperazine compounds

To enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement).In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This is because they often lack biotransformation capacity, multicellular or multi- organ complexity, for example, the hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms.To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode) and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals being considered for a new commercial application. Nematodes exposed to Piperazine and one of the analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental delays. Malformations and mortality in individual fish were also scored. Significant malformations were most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish.The results of the nematode and zebrafish studies were in alignment with data obtained from conventional mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems. The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications.

Suburban air quality: Human health hazard assessment of potentially toxic elements in PM10

PM10 samples were collected at two suburban locations in northern Spain, a traffic-industrial suburban (TIS) station located in the coastal city of Gijón and an industrial suburban (IS) station in Langreo, about 25 km inland. The aerosol samples were chemically analysed to determine ambient air concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se, V and Zn. The results showed that the mean levels of As, Co, Cu, Fe, Mn, Ni, Pb and Se recorded at the IS location were higher than those at the TIS station. Mean levels of Fe and Zn in PM10 were higher than all other species at both the TIS and IS sampling sites (467 and 353 ng Fe/m3 and 46 and 282 ng Zn/m3, respectively). Human exposure to these twelve potentially toxic elements through PM10 was assessed for both children and adults using the U.S.EPA method, considering three pathways: ingestion, dermal contact and inhalation. In general, the IS location presented higher non-cancer risks than the TIS site. However, at both suburban locations, cancer and non-cancer risk values were in the acceptable range for adults, some exceptions being found. Greater health risk was estimated in the case of children. For this sector of the population, ingestion, dermal contact and/or inhalation of As, Pb and Zn in PM10 may pose a health hazard owing to possible carcinogenic/non-carcinogenic effects.

Mycotoxin Contamination of Rice in China

Mycotoxin contamination in rice is generally lower than in other cereals such as corn or wheat. However, over 65% of the population in China consumes rice as a staple food. Due to the diversity of the climate across China, the southern region is characterized by high temperatures and humidities, especially in rainy season. Such conditions are optimal for the growth of fungi. The accumulative and transferrable characteristics of fungi mycotoxins pose a great potential threat as confirmed by high incidences of liver cancer in the Yangtze delta region. Major mycotoxins identified in China are aflatoxins and ochratoxin A, as well as fumonisins. The contents of aflatoxin B1 (AFB1 ) in rice are varied among different provinces and regions and generally less than 5 μg/kg. Although high incidences of positive aflatoxins samples have widely been detected, few samples were detected as exceeding the national's maximum residue limit (10 μg/kg). Limited information is available on risk assessment of human health hazards of mycotoxins in rice, children should be paid more attention to due to their having the highest mycotoxins exposure level, although the risks are generally at low levels from rice. Mycotoxins are mainly distributed in the outer layer of the paddy rice (also called rough rice, referring to whole rice grain with the hulls), and the AFB1 content in bran is 8.4 times greater than that in brown rice (hulled rice). Further investigation should focus on isolation and identification of mycotoxins-producing fungal strains, especially unknown mycotoxigenic fungal strains determination. Infection resistant rice breeding of mycotoxigenic fungal species may be a fundamental approach to guaranteeing rice safety in China.