Toxicological Risk Assessment Research Articles

The Integrated Environmental Health Impact of emissions from a steel plant in Taranto and from a power plant in Brindisi, (Apulia Region, Southern Italy)

to estimate the environmental and health impact attributable to PM2.5 emissions from the ex-ILVA steel plant in Taranto and the ENEL power plant in Brindisi (Apulia Region, Southern Italy). a SPRAY Lagrangian dispersion model was used to estimate PM2.5 concentrations and population weighted exposures following the requirements of the Integrated Environmental Authorization (IEA) of the two plants under study. Available concentration-response functions (OMS/HRAPIE and updates) were used to estimate the number of attributable premature deaths. residents in the 40 municipalities of the domains of the VDS (assessment of health damage, according to the Regional Law n. 21/2012) of Brindisi (source: Italian National Institute of Statistics 2011 Census) and residents in Taranto, Statte, and Massafra (source: cohort study). mortality from natural causes, cardiovascular and respiratory diseases, and lung cancer attributable to PM2.5. Incremental lifetime cumulative risks (ILCRs) for lung cancer associated to PM2.5 exposure. there was a reduction of the estimated impacts from the pre to the post IEA-scenarios in both Taranto and Brindisi. In Taranto, ILCRs greater than 1x10-4; were estimated in 2010 and 2012; the ILCR was greater than 1x10-4; in the district of Tamburi (near the plant) also for the 2015 scenario. ILCRs estimated for Brindisi were between 1x10-6; and 4x10-5;. the Integrated Environmental Health Impact Assessment confirmed the results of the VDS conducted according to the toxicological risk assessment approach. An unacceptable risk was estimated for Tamburi also for the 2015 scenario, characterized by a production of 4.7 million tons of steel, about half compared to one foreseen by the IEA (8 mt.).

Comparative Genomic Hybridization (CGH) in Genotoxicology.

In the past two decades, comparative genomic hybridization (CGH) and array CGH have become indispensable tools in clinical diagnostics and toxicological risk assessment. Initially developed for the genome-wide screening of chromosomal imbalances, that is, copy-number variations in tumor cells, both CGH and array CGH have been employed in genotoxicology and most recently in toxicogenomics. The latter allows a multi-end point analysis of how particular genes react to toxic agents, revealing changes in signaling pathways and other underlying molecular mechanisms. This chapter provides background on the use of CGH and array CGH in the context of genotoxicology, and also a protocol for conventional CGH, so that the basic principles of this methodology can be better understood. Conventional and array CGH investigate DNA expression patterns, copy-number variations across the whole genome, and loss of heterozygosity after genotoxic damage. Array CGH is still cost-intensive but produces exponentially more data, requiring suitable analytical algorithms and sophisticated bioinformatic analysis. As toxicogenomics is an emerging sub-discipline of toxicology research, effectively evaluating toxicogenomic microarray data can be hugely advantageous for human risk assessment, even though international regulatory guidelines on toxicogenomics have yet to be fully agreed and implemented.

Progress and prospects of marine microplastic research in China

Research on microplastics in China is progressing rapidly. Within recent years, more than 30 research institutes have conducted research on marine microplastic in estuaries, coasts, open sea, and Polar regions. Microplastics have been detected in freshwater systems (lakes, rivers, and wastewater treatment plants) and coastal and marine environments. This paper reviews the research progress of microplastics in China, providing information on topics including the methodology, quantification of microplastics in various habitats, eco-toxicological effect, biodegradation, management, and control of plastic waste and microplastics. This paper discusses the sampling and analysis of microplastic in different media, followed by spatial and temporal distribution of microplastics in marginal seas and coastal and freshwater systems. After summarizing the recent advances on toxicology research and risk assessment of microplastics, this paper provides suggestions for future study to provide baseline information for better risk assessment and improved understanding of the lifecycle of microplastics in the environment.

The 70 year anniversary of the Roczniki Państwowego Zakładu Higieny / Annals of the National Institute of Hygiene

The article presents the genesis of the foundation and development of ‘Roczniki Panstwowego Zakładu Higieny’ [Annals of the National Institute of Hygiene] since 1950 to 2019, scientific peer-reviewed journal devoted to research studies on the food and water safety, nutrition, environmental hygiene, toxicology and health risk assessment, and public health. It also shows the difficulties that this journal had initially to struggle with, and its achievements in recent years, aiming to improve its international position. The article discusses the stages of journal’s development and activity in terms of scientific, editorial and publishing.

Variation in PFAA concentrations and egg parameters throughout the egg-laying sequence in a free-living songbird (the great tit, Parus major): Implications for biomonitoring studies

Over the past decades, there has been growing scientific attention and public concern towards perfluoroalkyl acids (PFAAs), due to their widespread presence in the environment and associations with adverse effects on various organisms. Bird eggs have often been used as less-invasive biomonitoring tools for toxicological risk assessments of persistent organic pollutants, including some PFAAs. Hereby, it is typically assumed that one random egg is representative for the PFAA concentrations of the whole clutch. However, variation of PFAA concentrations within clutches due to laying sequence influences can have important implications for the egg collection strategy and may impede interpretations of the quantified concentrations. Therefore, the main objective of this paper was to study variation patterns and possible laying sequence associations with PFAA concentrations in eggs of the great tit (Parus major). Eight whole clutches (4–8 eggs) were collected at a location in the Antwerp region, situated about 11 km from a known PFAA point source. The ∑ PFAA concentrations ranged from 8.9 to 75.1 ng g−1 ww. PFOS concentrations ranged from 6.7 to 55.1 ng g−1 ww and this compound was the dominant contributor to the total PFAA profile (74%), followed by PFDoA (7%), PFOA (7%), PFDA (5%), PFTrA (4%) and PFNA (3%). The within-clutch variation (70.7%) of the ∑ PFAA concentrations was much larger than the among-clutch variation (29.3%) and concentrations decreased significantly for some PFAA compounds throughout the laying sequence. Nevertheless, PFAA concentrations were positively and significantly correlated between some egg pairs within the same clutch, especially between egg 1 and egg 3. For future PFAA biomonitoring studies, we recommend to consistently collect the same egg along the laying sequence, preferably the first or third egg if maximizing egg exposure metrics is the main objective.

Improving Opioid Management and Resource Utilization in an Internal Medicine Residency Clinic: A Before-After Study over Two Plan-Do-Study-Act Cycles.

Objective Chronic pain and opioid management are challenging in primary care, especially for trainees with discontinuous ambulatory schedules and less practice experience. The study objective was to improve adherence to quality metrics and office visit utilization in a resident clinic. Design Before-after quality improvement intervention over two Plan-Do-Study-Act cycles. Setting Suburban, university-affiliated Internal Medicine resident clinic. Methods During the 2015-2017 academic years, two sequential interventions were implemented: 1) use of electronic pain and opioid management templates and workflow redesign routing opioid renewals through a registered nurse (RN); 2) RN previsit planning and daily nurse-physician huddles before patient visits. Outcomes included adherence to annual toxicology screening, risk assessment and opioid agreements, opioid dose prescribed, and office visit utilization. Results The template and workflow redesign intervention increased annual toxicology from 53% to 81% (P < 0.0015), annual opioid agreement from 13.8% to 53.5% (P < 0.0001), and risk assessment from 0% to 75.9% (P < 0.0001). Average daily morphine milligram equivalents (MME) decreased from 96.6 MME to 67.7 MME (P < 0.0001), and annual office visits decreased from 11.1 to 8.9 (P = 0.0004). Previsit planning and huddles did not show incremental increases in adherence to quality measures but did improve clinic utilization and maintained high levels of adherence to quality measures. Conclusions Quality improvement interventions can improve adherence to quality measures and clinic utilization. A critical role is served by midlevel nursing providers to provide continuity to patients and trainees. Teaching clinics need to develop sustainable systems of care to moderate quality assurance in opioid prescribing.

EFSA Scientific Colloquium 24 – 'omics in risk assessment: state of the art and next steps

In recent years, the development of innovative tools in genomics, transcriptomics, proteomics and metabolomics (designated collectively as 'omics technologies) has opened up new possibilities for applications in scientific research and led to the availability of vast amounts of analytical data. The interpretation and integration of 'omics data can provide valuable information on the functional status of an organism and on the effect of external factors such as stressors. The European Food Safety Authority's (EFSA) 24th Scientific Colloquium on 'omics in risk assessment: state of the art and next steps explored the opportunities for integration of datasets produced via specific 'omics tools within the remit of EFSA's risk assessment approaches and tried to build further towards concrete paths of implementation. Discussions focused on genomics in microbial strain characterisation, metabolomics for the comparative assessment of GM plants and the use of 'omics for toxicological and environmental risk assessment. From the Colloquium it became clear that 'omics technologies are a valuable addition in some aspects of risk assessment of food and feed products and the environment, especially now that this technology is almost mature and stable. However, a consistent reporting framework for data collection, processing, interpretation, storage and curation should be further drawn up together with national and international organisations before 'omics technologies can be routinely used in risk assessment. For 'omics datasets in chemical and environmental risk assessments, the use of 'omics technologies alongside current toxicological or environmental risk assessment approaches is needed to re-inforce confidence and expertise before implementation of these datasets as a standalone tool in risk assessment. Test cases could be worked out to enhance confidence in the use of 'omics datasets in risk assessment.

Toxicological risk assessment of protracted ingestion of uranium in groundwater.

Groundwater samples have been collected from far-reaching locations in Solan and Shimla districts of Himachal Pradesh, India, and studied for uranium concentration using LED fluorimetry. In this region, uranium in groundwater varies from 0.12 to 19.43μgL-1. Radiological and chemical toxicity is accounted for different uranium isotopes. The average mortality risk for uranium isotopes 234U, 235U, and 238U are 2.6 × 10-12, 3.5 × 10-10, and 5.9 × 10-8, respectively. Similarly, the mean morbidity risk for 234U, 235U and 238U are 4.1 × 10-12, 5.6 × 10-10 and 9.5 × 10-8, respectively. An attempt has also been made to calculate doses for different age-groups. Highest doses, ranging from 0.30 to 48.23µSvyear-1, are imparted to infants of 7-12months of age which makes them the most vulnerable group of population. Using Hair Compartmental Model for uranium and mean daily uranium intake of 3.406μg for 60-year exposure period, organ-specific doses due to uranium radioisotopes, retention in prime organs/tissues and excretion rates via urine, feces and hair pathway are estimated. In this manuscript, the transfer coefficients for kidney, liver, skeleton, GI tract, soft tissues, urinary bladder, and blood are analyzed. Hair compartment model and ICRP's biokinetic model are compared in terms of uranium load in different organs after 60years of protracted ingestion. The study on biokinetic behavior of uranium is the first of its kind in the area which is dedicated to environmental and social cause.

Non-oxidative hair dye products on the European market: What do they contain?

Hair dyeing is very common and may cause allergic contact dermatitis. Oxidative (often termed permanent or semi-permanent) hair dye products have constituted the focus of market surveys and toxicological risk assessments, while non-oxidative (semi-permanent, temporary or direct) products have not been assessed. To identify the hair dye substances presently used in non-oxidative hair dye products in Europe. Ingredient label data on eligible products in 5 European countries were collected, and 289 different non-oxidative hair dye products were included in this study. Up to 9 hair dye substances were present in each product. Sixty-eight individual hair dye substances were identified on the 289 product labels, and their occurrence ranged from 0.3% to 34%. There were differences concerning substances used and their number per product between products of different consistency and colour. The hair dye substances in non-oxidative hair dye products are different from those in oxidative hair dye products, and are currently not covered by patch test series. The toxicological and skin-sensitizing profile of the substances in non-oxidative hair dye products, as well as their concentrations, should be further investigated.

Occurrence and Toxicological Risk Assessment of Polycyclic Aromatic Hydrocarbons and Heavy Metals in Drinking Water Resources of Southern China.

Polycyclic aromatic hydrocarbons (PAHs) and heavy metals exposure is related to a variety of diseases and cancer development, posing a great health risk to humans. In this study, water samples were collected from nine important water sources in Guangdong, Guangxi and Hainan provinces to determine the degree of PAHs and heavy metals contamination. Overall, the total contents of 16 PAHs and heavy metals were found within the permissible levels. In human health risk assessment, the benzo(a)pyrene equivalent concentration (BaPeq) presented a much lower level than the guideline values announced by Chinese Environmental Protection Agency (CEPA) and United States Environmental Protection Agency (US EPA), demonstrating that the PAHs contamination level in drinking water was mostly acceptable. For heavy metals, the Chronic daily intake (CDI), hazard quotient (HQ) or hazard index (HI) suggested that the water quality in nine water sources was desirable and did not present a risk to human health.

Biomarkers in Human and Environmental Health Risk Studies

Uncertainties in human health risk assessment, and the measuring on the impacts of contaminants have attracted great concern. Uncertainties, source-to-outcome, exposure assessment, hazard and risk characterisations are a number of techniques that have been applied to maximize results. Experts’ opinions and quantitative tools have been applied to narrow the gap between data and rules for regulatory purposes. Bio monitoring information, in vitro data streams and computational toxicology are major areas for human health risk assessment. A need for a biomarkers data bank is of utmost need to minimize uncertainties in the toxicological environmental human health risk assessment field.

Toxicological risk assessment and prioritization of drinking water relevant contaminants of emerging concern

Toxicological risk assessment of contaminants of emerging concern (CEC) in (sources of) drinking water is required to identify potential health risks and prioritize chemicals for abatement or monitoring. In such assessments, concentrations of chemicals in drinking water or sources are compared to either (i) health-based (statutory) drinking water guideline values, (ii) provisional guideline values based on recent toxicity data in absence of drinking water guidelines, or (iii) generic drinking water target values in absence of toxicity data. Here, we performed a toxicological risk assessment for 163 CEC that were selected as relevant for drinking water. This relevance was based on their presence in drinking water and/or groundwater and surface water sources in downstream parts of the Rhine and Meuse, in combination with concentration levels and physicochemical properties. Statutory and provisional drinking water guideline values could be derived from publically available toxicological information for 142 of the CEC. Based on measured concentrations it was concluded that the majority of substances do not occur in concentrations which individually pose an appreciable human health risk. A health concern could however not be excluded for vinylchloride, trichloroethene, bromodichloromethane, aniline, phenol, 2-chlorobenzenamine, mevinphos, 1,4-dioxane, and nitrolotriacetic acid. For part of the selected substances, toxicological risk assessment for drinking water could not be performed since either toxicity data (hazard) or drinking water concentrations (exposure) were lacking. In absence of toxicity data, the Threshold of Toxicological Concern (TTC) approach can be applied for screening level risk assessment. The toxicological information on the selected substances was used to evaluate whether drinking water target values based on existing TTC levels are sufficiently protective for drinking water relevant CEC. Generic drinking water target levels of 37 μg/L for Cramer class I substances and 4 μg/L for Cramer class III substances in drinking water were derived based on these CEC. These levels are in line with previously reported generic drinking water target levels based on original TTC values and are shown to be protective for health effects of the majority of contaminants of emerging concern evaluated in the present study. Since the human health impact of many chemicals appearing in the water cycle has been studied insufficiently, generic drinking water target levels are useful for early warning and prioritization of CEC with unknown toxicity in drinking water and its sources for future monitoring.

Raphidocelis subcapitata (=Pseudokirchneriella subcapitata) provides an insight into genome evolution and environmental adaptations in the Sphaeropleales

The Sphaeropleales are a dominant group of green algae, which contain species important to freshwater ecosystems and those that have potential applied usages. In particular, Raphidocelis subcapitata is widely used worldwide for bioassays in toxicological risk assessments. However, there are few comparative genome analyses of the Sphaeropleales. To reveal genome evolution in the Sphaeropleales based on well-resolved phylogenetic relationships, nuclear, mitochondrial, and plastid genomes were sequenced in this study. The plastid genome provides insights into the phylogenetic relationships of R. subcapitata, which is located in the most basal lineage of the four species in the family Selenastraceae. The mitochondrial genome shows dynamic evolutionary histories with intron expansion in the Selenastraceae. The 51.2 Mbp nuclear genome of R. subcapitata, encoding 13,383 protein-coding genes, is more compact than the genome of its closely related oil-rich species, Monoraphidium neglectum (Selenastraceae), Tetradesmus obliquus (Scenedesmaceae), and Chromochloris zofingiensis (Chromochloridaceae); however, the four species share most of their genes. The Sphaeropleales possess a large number of genes for glycerolipid metabolism and sugar assimilation, which suggests that this order is capable of both heterotrophic and mixotrophic lifestyles in nature. Comparison of transporter genes suggests that the Sphaeropleales can adapt to different natural environmental conditions, such as salinity and low metal concentrations.

Advances in toxicological research and risk assessment.

Advances in toxicological research and risk assessment.

Spatial variation of polycyclic aromatic hydrocarbons (PAHs) in surface sediments from rivers in hilly regions of Southern China in the wet and dry seasons

Seasonal variations of polycyclic aromatic hydrocarbons (PAHs) in the surface sediments from 13 rivers in hilly regions of southern China were studied. Concentrations of PAHs analyzed in the wet season were higher than those analyzed in the dry season, with residues ranging from 74.3 to 1930.9 ng g−1 dw in the wet season and from 96.9 to 1388.9 ng g−1 dw in the dry season. The primary contributors were 3- and 4-ringed congeners accounting for 59.8% ± 10.1% and 58.3% ± 9.3% of the identified PAHs in the wet and the dry seasons, respectively. Proximity to sources and locations susceptible to high atmospheric depositional inputs results in high concentrations of PAH. Diagnostic ratios have indicated that the sources of PAHs in different seasons make no apparent difference. Furthermore, a principal component analysis and multiple linear regression (PCA-MLR) studies indicate that combustion sources such as vehicle emissions and coal combustion are the primary sources of PAHs. Toxicological risk assessments based on TEQcare suggested that Benzo[a]pyrene, benz[a]anthracene, dibenz[a,h]anthracene could pose high ecological risks in this area.

Advances in toxicological research and risk assessment

Advances in toxicological research and risk assessment

Gut microbiota in toxicological risk assessment of drugs and chemicals: The need of hour

ABSTRACTThe advent of industrial revolution caused a large inflow of synthetic chemicals for medical, agricultural, industrial and other purposes in the world. In general, these chemicals were subjected to toxicological risk assessment for human health and ecology before release for public use. But today we are witnessing a negative impact of some of these chemicals on human health and environment indicating an underestimation of toxic effects by current risk assessment protocol. Recent studies established gut microbiota as one of the key player in intercession of toxicity of drugs and synthetic chemicals. Hence, the need of the hour is to include the assessment for microbiota specifically gut microbiota in human toxicological risk assessment protocol. Herewith we are proposing a framework for assessment of gut microbiota upon exposure to drugs or chemicals.

Laboratory and Benchtop Performance of a Mealtime Insulin-Delivery System.

A basal bolus insulin regimen requires multiple daily insulin injections, which might discourage patient adherence. As a potential solution, a mealtime insulin-delivery system-a 3-day wearable bolus-only patch-was designed to manually administer mealtime insulin discreetly by actuating buttons through clothing, without the need for multiple needle sticks. Extensive functional testing of the patch included dose accuracy (from initial fill of the device to empty), pressure-vacuum leak testing, last-dose lockout and occlusion detection (safety alert features that lock the dosing buttons when no insulin is delivered), assessments of insulin drug stability, toxicological risk (including chemical testing), and system biocompatibility. Dosing accuracy was 2 units ±10% (with U-100 insulin) over a range of environmental conditions, with ≥95% reliability and confidence. The fluid seal performance and the safety alert features performed with ≥95% reliability and ≥95% confidence. The system met acceptable standards for insulin (U-100 lispro and aspart) stability for its intended 3-day use, in addition to the operational requirements. The toxicological risk assessment and demonstrated biocompatibility suggested that the patch is safe for human use. Benchtop performance showed that the bolus-only patch is a safe, accurate, and reliable device for mealtime insulin delivery.

Immunological and toxicological risk assessment of e-cigarettes.

Knowledge of the long-term toxicological and immunological effects of e-cigarette (e-cig) aerosols remains elusive due to the relatively short existence of vaping. Therefore, we performed a systematic search of articles published in public databases and analysed the research evidence in order to provide critical information regarding e-cig safety. Electronic nicotine delivery systems (or e-cigs) are an alternative to traditional cigarettes for the delivery of nicotine and are typically filled with glycerol or propylene glycol-based solutions known as e-liquids. Though present in lower quantities, e-cig aerosols are known to contain many of the harmful chemicals found in tobacco smoke. However, due to the paucity of experimental data and contradictory evidence, it is difficult to draw conclusive outcomes regarding toxicological, immunological and clinical impacts of e-cig aerosols. Excessive vaping has been reported to induce inflammatory responses including mitogen-activated protein kinase, Janus tyrosine kinase/signal transducer and activator of transcription and nuclear factor-κB signalling, similar to that induced by tobacco smoke. Based on recent evidence, prolonged exposure to some constituents of e-cig aerosols might result in respiratory complications such as asthma, chronic obstructive pulmonary disease and inflammation. Future studies are warranted that focus on establishing correlations between e-cig types, generations and e-liquid flavours and immunological and toxicological profiles to broaden our understanding about the effects of vaping.

The impact of nanomaterial characteristics on inhalation toxicity.

During the last few decades, nanotechnology has evolved into a success story, apparent from a steadily increasing number of scientific publications as well as a large number of applications based on engineered nanomaterials (ENMs). Its widespread uses suggest a high relevance for consumers, workers and the environment, hence justifying intensive investigations into ENM-related adverse effects as a prerequisite for nano-specific regulations. In particular, the inhalation of airborne ENMs, being assumed to represent the most hazardous type of human exposure to these kinds of particles, needs to be scrutinized. Due to an increased awareness of possible health effects, which have already been seen in the case of ultrafine particles (UFPs), research and regulatory measures have set in to identify and address toxic implications following their almost ubiquitous occurrence. Although ENM properties differ from those of the respective bulk materials, the available assessment protocols are often designed for the latter. Despite the large benefit ensuing from the application of nanotechnology, many issues related to ENM behavior and adverse effects are not fully understood or should be examined anew. The traditional hypothesis that ENMs exhibit different or additional hazards due to their "nano" size has been challenged in recent years and ENM categorization according to their properties and toxicity mechanisms has been proposed instead. This review summarizes the toxicological effects of inhaled ENMs identified to date, elucidating the modes of action which provoke different mechanisms in the respiratory tract and their resulting effects. By linking particular mechanisms and adverse effects to ENM properties, grouping of ENMs based on toxicity-related properties is supposed to facilitate toxicological risk assessment. As intensive studies are still required to identify these "ENM classes", the need for alternatives to animal studies is evident and advances in cell-based test systems for pulmonary research are presented here. We hope to encourage the ongoing discussion about ENM risks and to advocate the further development and practice of suitable testing and grouping methods.