A scalable workflow to characterize the human exposome.

Complementing the genome with an understanding of the human exposome is an important challenge for contemporary science and technology. Tens of thousands of chemicals are used in commerce, yet cost for targeted environmental chemical analysis limits surveillance to a few hundred known hazards. To overcome limitations which prevent scaling to thousands of chemicals, we develop a single-step express liquid extraction and gas chromatography high-resolution mass spectrometry analysis to operationalize the human exposome. We show that the workflow supports quantification of environmental chemicals in human plasma (200 µL) and tissue (≤100 mg) samples. The method also provides high resolution, sensitivity and selectivity for exposome epidemiology of mass spectral features without a priori knowledge of chemical identity. The simplicity of the method can facilitate harmonization of environmental biomonitoring between laboratories and enable population level human exposome research with limited sample volume.

Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics.

BACKGROUND: The scope of nanotechnology has been extended to almost every sphere of our daily life. As a result of this, nanocarriers like Carbon Nanotubes (CNTs) are gaining considerable attention for their use in various therapeutic and diagnostic applications. OBJECTIVE: The objective of the current article is to review various important features of CNTs that make them as efficient carriers for anticancer drug delivery in cancer therapeutics. METHODS: In this review article, different works of literature are reported on various prospective applications of CNTs in the targeting of multiple kinds of cancerous cells of different organs via; the loading of various anticancer agents. RESULTS: Actually, CNTs are the 3rd allotropic type of the carbon-fullerenes that are a part of the cylindrical tubular architecture. CNTs possess some excellent physicochemical characteristics and unique structural features that provide an effective platform to deliver anticancer drugs to target specific sites for achieving a high level of therapeutic effectiveness even in cancer therapeutics. For better results, CNTs are functionalized and modified with different classes of therapeutically bioactive molecules via; the formation of stable covalent bonding or by the use of supramolecular assemblies based on the noncovalent interaction(s). In recent years, the applications of CNTs for the delivery of various kinds of anticancer drugs and targeting of tumor sites have been reported by various research groups. CONCLUSION: CNTs represent an emerging nanocarrier material for the delivery and targeting of numerous anticancer drugs in cancer therapeutics.

U.S. Food and Drug Administration's interim reference levels for dietary lead exposure in children and women of childbearing age.

Reducing lead exposure is a public health priority for the US Food and Drug Administration as well as other federal agencies. The goals of this research were to 1) update the maximum daily dietary intake of lead from food, termed an interim reference level (IRL), for children and for women of childbearing age (WOCBA) and 2) to confirm through a literature review that with the exception of neurodevelopment, which was not evaluated here, no adverse effects of lead consistently occur at the blood lead level (BLL) associated with the IRL. Because no safe level of lead exposure has yet been identified for children's health, the IRLs of 3 µg/day for children and 12.5 µg/day for WOCBA were derived from the Centers for Disease Control and Prevention reference value of 5 µg/dL BLL, the level at which public health actions should be initiated. The literature review showed that no adverse effects of lead consistently occurred at the BLL associated with the IRLs (0.5 µg/dL). The IRLs of 3 µg/day for children and 12.5 µg/day for WOCBA should serve as useful benchmarks in evaluating the potential for adverse effects of dietary lead.

Toxicity of cadmium in musculoskeletal diseases.

Epidemiological studies have reported that exposure to toxic metals like cadmium (Cd) may promote the development of musculoskeletal diseases, such as osteoporosis, rheumatoid arthritis (RA), and osteoarthritis (OA), among others. The objective of this review is to summarize the molecular mechanisms of inflammation and oxidative stress activated by Cd at the bone level, particularly in osteoporosis, RA, and OA. Cadmium can increase bone resorption, affect the activity of osteoclasts and calcium (Ca) absorption, and impair kidney function, which favors the development of osteoporosis. In the case of RA, Cd interferes with the activity of antioxidant proteins, like superoxide dismutase (SOD) and catalase (CAT). It also promotes an inflammatory state, inducing the process of citrullination, which affects the proteins of immune response. On the other hand, accumulation of Cd in the tissues and blood of smokers has been related to the development of some musculoskeletal diseases. Therefore, knowing the negative impact of Cd toxicity at the articular level can help understand the damage mechanisms it produces, leading to the development of such diseases.

Application of qualitative and quantitative uncertainty assessment tools in developing ranges of plausible toxicity values for 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Increasing interest in characterizing risk assessment uncertainty is highlighted by recent recommendations from the National Academy of Sciences. In this paper we demonstrate the utility of applying qualitative and quantitative methods for assessing uncertainty to enhance risk-based decision-making for 2,3,7,8-tetrachlorodibenzo-p-dioxin. The approach involved deconstructing the reference dose (RfD) via evaluation of the different assumptions, options, models and methods associated with derivation of the value, culminating in the development of a plausible range of potential values based on such areas of uncertainty. The results demonstrate that overall RfD uncertainty was high based on limitations in the process for selection (e.g., compliance with inclusion criteria related to internal validity of the co-critical studies, consistency with other studies), external validity (e.g., generalizing findings of acute, high-dose exposure scenarios to the general population), and selection and classification of the point of departure using data from the individual studies (e.g., lack of statistical and clinical significance). Building on sensitivity analyses conducted by the US Environmental Protection Agency in 2012, the resulting estimates of RfD values that account for the uncertainties ranged from ~1.5 to 179 pg/kg/day. It is anticipated that the range of RfDs presented herein, along with the characterization of uncertainties, will improve risk assessments of dioxins and provide important information to risk managers, because reliance on a single toxicity value limits the information needed for making decisions and gives a false sense of precision and accuracy.

[Rubber granules on synthetic turf pitches: safe or not safe for children?] / Rubbergranulaat op kunstgrasvelden.

Rubber granules from old car tyres used in synthetic turf pitches contain a significant number of carcinogenic and endocrine-disrupting chemicals. In 2017 the Dutch National Institute for Public Health and the Environment (RIVM) and the European Chemical Agency (ECHA) concluded that the risks for children are negligible. However, their reports contain some scientific inaccuracies and omissions which may have led them to underestimate the risks for children. It is therefore premature to conclude that it is safe for children to play on synthetic turf pitches with rubber granules. It is now primarily up to the parents to decide whether or not playing sports is acceptable in these circumstances. The Dutch government should, in accordance with ECHA recommendations, advise parents that their children ought to avoid hand-and-mouth contact with these granules as much as possible.

Recommended acceptable levels of maternal serum typical toxic metals from the perspective of spontaneous preterm birth in Shanxi Province, China.

Preterm birth is an important issue of public reproductive health worldwide. The effects of the toxic metals on the likelihood of spontaneous preterm birth (SPB) are still under discussion. Our study aimed to investigate the association between maternal exposure to the five typical toxic metals or metalloid (i.e. arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb)) and the SPB likelihood. The mothers delivering fetus with SPB (cases) and those with term healthy birth (controls) were chosen from a prospective birth cohort of 3201 women carried out in Shanxi Province, China. A total of 147 SPB cases and 381 controls were included in our nested case-control study. We collected maternal general information by questionnaire and collected their blood sample during recruitment. The serum concentrations of the five toxic metals were measured by inductively coupled-plasma mass spectrometry. We found that the demographic information between the cases and controls were well balanced. The participants in our study had relatively higher serum As concentration. For the other toxic metals (i.e. Cd, Cr, Hg, and Pb), their serum concentrations were overall in the middle range of those from general population. There were no significant associations of the serum concentrations of the five concerned toxic metals with the SPB likelihood. Our study results overall did not support that maternal exposure to As or Cd significantly contribute to the SPB risk in the current exposure level, as well as the other three toxic metals. We further proposed their upper concentration limits in maternal serum from the perspective of SPB likelihood during the early pregnant period, i.e. 18.2 ng/mL of As, 1.05 ng/mL of Cd, 0.96 ng/mL of Cr, 1.07 ng/mL of Hg, and 1.54 ng/mL of Pb.

Explaining variation in elevated blood lead levels among children in Minnesota using neighborhood socioeconomic variables.

BACKGROUND: Childhood lead exposure is linked to numerous adverse health effects and exposure in the United States is highest among people living in substandard housing, which is disproportionately inhabited by socioeconomically disadvantaged individuals. In this paper, we compared the Vox lead exposure risk score and concentrated disadvantage based on principal component analysis (PCA) to weighted quantile sum (WQS) regression to determine which method was best able to explain variation in elevated blood lead levels (EBLLs). METHODS: We constructed indices for census tracts in Minnesota and used them in Poisson regression models to identify the best socioeconomic measure for explaining EBLL risk. RESULTS: All indices had a significant association with EBLL in separate models. The WQS index had the best goodness-of-fit, followed next by the Vox index, and then the concentrated disadvantage index. Among the most important variables in the WQS index were percent of houses built before 1940, percent renter occupied housing, percent unemployed, and percent African American population. CONCLUSIONS: The WQS approach was best able to explain variation in EBLL risk and identify census tracts where targeted interventions should be focused to reduce lead exposure.

EPA's non-targeted analysis collaborative trial (ENTACT): genesis, design, and initial findings.

In August 2015, the US Environmental Protection Agency (EPA) convened a workshop entitled "Advancing non-targeted analyses of xenobiotic chemicals in environmental and biological media." The purpose of the workshop was to bring together the foremost experts in non-targeted analysis (NTA) to discuss the state-of-the-science for generating, interpreting, and exchanging NTA measurement data. During the workshop, participants discussed potential designs for a collaborative project that would use EPA resources, including the ToxCast library of chemical substances, the DSSTox database, and the CompTox Chemicals Dashboard, to evaluate cutting-edge NTA methods. That discussion was the genesis of EPA's Non-Targeted Analysis Collaborative Trial (ENTACT). Nearly 30 laboratories have enrolled in ENTACT and used a variety of chromatography, mass spectrometry, and data processing approaches to characterize ten synthetic chemical mixtures, three standardized media (human serum, house dust, and silicone band) extracts, and thousands of individual substances. Initial results show that nearly all participants have detected and reported more compounds in the mixtures than were intentionally added, with large inter-lab variability in the number of reported compounds. A comparison of gas and liquid chromatography results shows that the majority (45.3%) of correctly identified compounds were detected by only one method and 15.4% of compounds were not identified. Finally, a limited set of true positive identifications indicates substantial differences in observable chemical space when employing disparate separation and ionization techniques as part of NTA workflows. This article describes the genesis of ENTACT, all study methods and materials, and an analysis of results submitted to date. Graphical abstract ᅟ.

Heavy Metal Accumulation in Water, Soil, and Plants of Municipal Solid Waste Landfill in Vientiane, Laos.

The municipal solid waste (MSW) landfill in Vientiane, Laos, which receives > 300 tons of waste daily, of which approximately 50% is organic matter, has caused serious environmental problems. This study was conducted to investigate the accumulated levels of heavy metals (HMs) (cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), and zinc (Zn)) in water (surface and groundwater), soil, and plants between dry and wet seasons according to the standards of the Agreement on the National Environmental Standards of Laos (ANESs), Dutch Pollutant Standards (DPSs), and the World Health Organization (WHO), respectively. Although no impact of pollution on the surface water was observed, the levels of Cr and Pb in the groundwater significantly exceeded the basics of ANESs and WHO in both seasons. The pollution caused by Cd and Cu reached the eco-toxicological risk level in the landfill soils and its vicinity. The vegetable Ipomoea aquatica, which is consumed by the nearby villagers, was seriously contaminated by Cr, Pb, Cu, and Zn, as the accumulation of these toxic metals was elevated to much greater levels as compared to the WHO standards. For the grass Pennisetum purpureum (elephant grass), the quantities of HMs in all plant parts were extreme, perhaps due to the deeper growth of its rhizome than I. aquatica. This study is the first to warn of serious HM pollution occurring in the water, soil, and plants in the MSW landfill of Vientiane, Laos, which requires urgent phytoremediation. The indication of what sources from the MSW principally cause the pollution of HMs is needed to help reduce the toxicological risks on Lao residents and the environment in Vientiane as well.

Developing Product Environmental Footprint Category Rules (PEFCR) for shampoos: The basis for comparable life cycle assessment.

In 2013, the European Commission launched the Environmental Footprint Rules pilot phase. This initiative aims at setting specific rules for life cycle assessment (LCA: raw material sourcing, production, logistics, use, and disposal phase) studies within 1 product category, called product environmental footprint category rules (PEFCR), and for organizations, called organizational environmental footprint sector rules (OEFSR). Such specific rules for measuring environmental performance throughout the life cycle should facilitate the comparability between LCA studies and provide principles for communicating environmental performance, such as transparency, reliability, completeness, and clarity. Cosmetics Europe, the association representing the cosmetics industry in the European Union, completed a voluntary study into the development of PEFCR for shampoo, generally following the guidelines and methodology developed by the European Commission for its own pilot projects. The study assessed the feasibility and relevance of establishing PEFCR for shampoo. Specifically, the study defines a large number of modeling assumptions and default values relevant for shampoo (e.g., for the functional unit, the system boundaries, default transport distances, rinsing water volumes, temperature differences, life cycle inventory data sources) that can be modified as appropriate, according to the specificities of individual products, manufacturing companies, and countries. The results of the study may be used to support internal decision making (e.g., to identify "hotspots" with high environmental impact and opportunities for improvement) or to meet information requests from commercial partners, consumers, media, or authorities on product environmental characteristics. In addition, the shampoo study also highlighted many of the challenges and limitations of the current product environmental footprint (PEF) methodology, namely its complexity and resource intensiveness. It highlighted 2 areas where improvements are much needed: (1) data quality and availability, and (2) impact assessment methodologies and robustness. Many of the findings are applicable to other rinse-off cosmetic products, such as shower gels, liquid soaps, bath products, and hair conditioners. Integr Environ Assess Manag 2018;14:649-659. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Decision-Making and Environmental Implications under Cap-and-Trade and Take-Back Regulations.

To reduce carbon emissions during production and realize the recycling of resources, the government has promulgated carbon cap-and-trade regulation and take-back regulation separately. This paper firstly analyses the manufacturing, remanufacturing and collection decisions of a monopoly manufacturer under cap-and-trade regulation and take-back regulation conditions, and then explores the environmental impact (i.e., carbon emissions) of both carbon regulation and more stringent take-back regulation. Finally, numerical examples are provided to illustrate the theoretical results. The results indicate that it will do good for the environment once the cap-and-trade regulation is carried out. We also conclude that government’s supervision of carbon trading price plays an important role in reducing the environmental impact. Furthermore, unexpectedly, we prove that if emissions intensity of a remanufactured (vis-á-vis new) product is sufficiently high, the improvement of collection and remanufacturing targets might lead to the deterioration of environment.

The unsteady state and inertia of chemical regulation under the US Toxic Substances Control Act.

After 40 years, the 1976 US Toxic Substances Control Act (TSCA) was revised under the Frank R. Lautenberg Chemical Safety for the 21st Century Act. Its original goals of protecting the public from hazardous chemicals were hindered by complex and cumbersome administrative burdens, data limitations, vulnerabilities in risk assessments, and recurring corporate lawsuits. As a result, countless chemicals were entered into commercial use without toxicological information. Few chemicals of the many identified as potential public health threats were regulated or banned. This paper explores the factors that have worked against a comprehensive and rational policy for regulating toxic chemicals and discusses whether the TSCA revisions offer greater public protection against existing and new chemicals.

Smart Kd-values, their uncertainties and sensitivities - Applying a new approach for realistic distribution coefficients in geochemical modeling of complex systems.

One natural retardation process to be considered in risk assessment for contaminants in the environment is sorption on mineral surfaces. A realistic geochemical modeling is of high relevance in many application areas such as groundwater protection, environmental remediation, or disposal of hazardous waste. Most often concepts with constant distribution coefficients (Kd-values) are applied in geochemical modeling with the advantage to be simple and computationally fast, but not reflecting changes in geochemical conditions. In this paper, we describe an innovative and efficient method, where the smart Kd-concept, a mechanistic approach mainly based on surface complexation modeling, is used (and modified for complex geochemical models) to calculate and apply realistic distribution coefficients. Using the geochemical speciation code PHREEQC, multidimensional smart Kd-matrices are computed as a function of varying (or uncertain) environmental conditions. On the one hand, sensitivity and uncertainty statements for the distribution coefficients can be derived. On the other hand, smart Kd-matrices can be used in reactive transport (or migration) codes (not shown here). This strategy has various benefits: (1) rapid computation of Kd-values for large numbers of environmental parameter combinations; (2) variable geochemistry is taken into account more realistically; (3) efficiency in computing time is ensured, and (4) uncertainty and sensitivity analysis are accessible. Results are presented exemplarily for the sorption of uranium(VI) onto a natural sandy aquifer material and are compared to results based on the conventional Kd-concept. In general, the sorption behavior of U(VI) in dependence of changing geochemical conditions is described quite well.

Thresholds of Toxicological Concern - Setting a threshold for testing below which there is little concern.

Low dose, low risk; very low dose, no real risk. Setting a pragmatic threshold below which concerns become negligible is the purpose of thresholds of toxicological concern (TTC). The idea is that such threshold values do not need to be established for each and every chemical based on experimental data, but that by analyzing the distribution of lowest or no-effect doses of many chemicals, a TTC can be defined - typically using the 5th percentile of this distribution and lowering it by an uncertainty factor of, e.g., 100. In doing so, TTC aims to compare exposure information (dose) with a threshold below which any hazard manifestation is very unlikely to occur. The history and current developments of this concept are reviewed and the application of TTC for different regulated products and their hazards is discussed. TTC lends itself as a pragmatic filter to deprioritize testing needs whenever real-life exposures are much lower than levels where hazard manifestation would be expected, a situation that is called "negligible exposure" in the REACH legislation, though the TTC concept has not been fully incorporated in its implementation (yet). Other areas and regulations - especially in the food sector and for pharmaceutical impurities - are more proactive. Large, curated databases on toxic effects of chemicals provide us with the opportunity to set TTC for many hazards and substance classes and thus offer a precautionary second tier for risk assessments if hazard cannot be excluded. This allows focusing testing efforts better on relevant exposures to chemicals.

Anatomy of a decision II: Potential effects of changes to Tier I chemical approaches in Canadian Disposal at Sea program sediment assessment protocols.

The effects of possible changes to the Canadian 2-tiered assessment framework for dredged material based on outcomes of the 2006 Contaminated Dredged Material Management Decisions Workshop (CDMMD) are evaluated. Expanding on the "data mining" approach described in a previous paper, which focused solely on chemical lines of evidence, the efficacy of Tier 1 approaches (increases to the number of chemical analytes, use of mean hazard quotients, and the use of a screening bioassay) in predicting toxicity are evaluated. Results suggest value in additional work to evaluate the following areas: 1) further expanding minimum chemical requirements, 2) using more advanced approaches for chemical interpretation, and 3) using a screening-level bioassay (e.g., Canadian solid-phase photoluminescent bacteria test) to determine whether it would complement Tier 1 chemistry as well as or better than the solvent-based Microtox™ test method evaluated in the present study. Integr Environ Assess Manag 2017;13:1072-1085. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Towards a proportionality assessment of risk reduction measures aimed at restricting the use of persistent and bioaccumulative substances.

International chemicals legislation aims at adequately controlling persistent organic pollutants (POPs) and substances of very high concern (SVHCs), such as persistent, bioaccumulative, and toxic (PBT) and very persistent and very bioaccumulative (vPvB) substances, with a view to progressively substitute these substances with suitable less-hazardous alternatives. Using cost-effectiveness analysis (CEA) to assess the (dis)proportionality of measures to control such substances (collectively called "PBT" in the present paper) requires benchmarks. The present paper provides building blocks for possible benchmarks by looking at the cost-effectiveness estimates for regulatory measures that have been applied or considered for various PBT substances. These cost-effectiveness estimates vary widely, and the main factors possibly explaining this variation are discussed. The available cost estimates currently do not allow deriving a value for society's willingness to pay to reduce PBT presence, use, and emissions because decisions referring explicitly to these estimates are scarce. Roughly speaking, the available evidence suggests that measures costing less than €1000 per kilogram PBT use or emission reduction will usually not be rejected for reasons of disproportionate costs, whereas for measures with costs above €50 000 per kilogram PBT such a rejection is likely. More research is needed to strengthen the evidence base and further elaborate a systematic approach toward proportionality benchmarking. Integr Environ Assess Manag 2017;13:1100-1112. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).