Grouping of UVCB substances with new approach methodologies (NAMs) data.

One of the most challenging areas in regulatory science is assessment of the substances known as UVCB (unknown or variable composition, complex reaction products and biological materials). Because the inherent complexity and variability of UVCBs present considerable challenges for establishing sufficient substance similarity based on chemical characteristics or other data, we hypothesized that new approach methodologies (NAMs), including in vitro test-derived biological activity signatures to characterize substance similarity, could be used to support grouping of UVCBs. We tested 141 petroleum substances as representative UVCBs in a compendium of 15 human cell types representing a variety of tissues. Petroleum substances were assayed in dilution series to derive point of departure estimates for each cell type and phenotype. Extensive quality control measures were taken to ensure that only high-confidence in vitro data were used to determine whether current groupings of these petroleum substances, based largely on the manufacturing process and physico-chemical properties, are justifiable. We found that bioactivity data-based groupings of petroleum substances were generally consistent with the manufacturing class-based categories. We also showed that these data, especially bioactivity from human induced pluripotent stem cell (iPSC)-derived and primary cells, can be used to rank substances in a manner highly concordant with their expected in vivo hazard potential based on their chemical compositional profile. Overall, this study demonstrates that NAMs can be used to inform groupings of UVCBs, to assist in identification of repre­sentative substances in each group for testing when needed, and to fill data gaps by read-across.

The Hazardous Level of Heavy Metals in Different Medicinal Plants and Their Decoctions in Water: A Public Health Problem in Brazil.

The determination of Cd, Co, Cr, Cu, Fe, Na, Zn, and Pb by inductively coupled plasma-optical emission spectrometry (ICP OES) was performed on dry matter and decoctions of the medicinal plants Cordia salicifolia, Chiococca alba (L.) Hitchc., and Echites peltata used as an appetite suppressant and diuretic in Brazil. The accuracy of the measurements was analyzed by the spike recovery test. Results showed that the concentration of these seven metals (Cd, Co, Cr, Cu, Fe, Na, and Zn) in dry plant samples is below the oral concentration of elemental impurities established by the United States Pharmacopoeia Convention (USP). However, there are no concentration limits for Fe, Na, and Zn established by the USP in drug substances and excipients. Levels higher than the recommended value by the USP were observed for Pb and the lowest for Cd, Co, Cr, and Cu, both in dried plant samples and their decoctions. In the decoctions prepared from these plants were found elements such as Cd, Co, Cr, Cu, Fe, Na, Zn, and Pb. In the decoction prepared from 40 g C. salicifolia leaves and 40 g C. alba wood, the content of Cd is above the oral daily exposure value set by the USP. Hazard index (HI) for decoctions prepared from these plants exceeded the threshold (1). Given the uncertainties associated with the estimates of toxicity values and exposure factors, futures researches should address the possible toxicity in humans. Uncontrolled selling and long-term ingestion of medicinal plants can cause toxicity and interfere with the effect of drugs. Limited knowledge on the interaction potential of medicinal plants poses a challenge and public health problem in Brazil and other countries.

Exploiting the κ2 -Fashioned Coordination of [Se2 ]-Donor Ligand L3 Se for Facile Hg-C Bond Cleavage of Mercury Alkyls and Cytoprotection against Methylmercury-Induced Toxicity.

The Hg-C bond of MeHgCl, a ubiquitous environmental toxicant, is notoriously inert and exceedingly difficult to cleave. The cleavage of the Hg-C bond of MeHgCl at low temperature, therefore, is of significant importance for human health. Among various bis(imidazole)-2-selones Ln Se (n=1-4, or 6), the three-spacer L3 Se shows extraordinarily high reactivity in the degradation of various mercury alkyls including MeHgCl because of its unique ability to coordinate through κ2 -fashion, in which both the Se atoms simultaneously attack the Hg center of mercury alkyls for facile Hg-C bond cleavage. It has the highest softness (σ) parameter and the lowest HOMO(Ln Se)-LUMO(MeHgX) energy gap and, thus, L3 Se is the most reactive among Ln Se towards MeHgX (X=Cl or I). L3 Se is highly efficient, more than L1 Se, in restoring the activity of antioxidant enzyme glutathione reductase (GR) that is completely inhibited by MeHgCl; 80 % GR activity is recovered by L3 Se relative to 50 % by L1 Se. It shows an excellent cytoprotective effect in liver cells against MeHgCl-induced oxidative stress by protecting vital antioxidant enzymes from inhibition caused by MeHgCl and, thus, does not allow to increase the intracellular reactive oxygen species (ROS) levels. Furthermore, it protects the mitochondrial membrane potential (ΔΨm ) from perturbation by MeHgCl. Major Hg-responsive genes analyses demonstrate that L3 Se plays a significant role in MeHg+ detoxification in liver cells.

A review on the potential uses of red mud as amendment for pollution control in environmental media.

Red mud is a solid waste of bauxite processing by Bayer process which involves caustic digestion of Al-containing mineral for alumina production. The global inventory of red mud waste reached an estimated amount of 4 billion tons in 2015, increasing at an approximate rate of 120 million tons per year. Therefore, its management is becoming a global environmental issue for the protection of environment, and the need for awareness in this regard is becoming crucial. Although red mud is not considered as a hazardous material in many countries, its high alkalinity and fine particle size may pose significant environmental threat, and it is found to be an interesting material for environmental remediation purposes due to rich iron content. This paper provides a review of possible remedial applications of red mud in various environmental compartments. Modification of red mud creates novel opportunities for cost-effective and efficient removal of metal ions, inorganic anions, dyes, and phenols from wastewater and acid mine drainage. Re-vegetation of red mud disposal sites, treatment of metal-contaminated acidic soils presents the usefulness of this material but less research has been done so far to investigate its use in the stabilization of polluted sediments. On the other hand, leaching and eco-toxicological tests have also revealed that red mud does not pose high toxicity to the environment making it suitable for the treatment of contaminated media. Nevertheless, neutralization of red mud is recommended for its safe disposal and secure application in any environmental media.

Geochemical Characteristics and Toxic Elements in Alumina Refining Wastes and Leachates from Management Facilities.

A nationwide investigation was carried out to evaluate the geochemical characteristics and environmental impacts of red mud and leachates from the major alumina plants in China. The chemical and mineralogical compositions of red mud were investigated, and major, minor, and trace elements in the leachates were analyzed. The mineral and chemical compositions of red mud vary over refining processes (i.e., Bayer, sintering, and combined methods) and parental bauxites. The main minerals in the red mud are quartz, calcite, dolomite, hematite, hibschite, sodalite, anhydrite, cancrinite, and gibbsite. The major chemical compositions of red mud are Al, Fe, Si, Ca, Ti, and hydroxides. The associated red mud leachate is hyperalkaline (pH > 12), which can be toxic to aquatic life. The concentrations of Al, Cl-, F-, Na, NO32-, and SO42- in the leachate exceed the recommended groundwater quality standard of China by up to 6637 times. These ions are likely to increase the salinization of the soil and groundwater. The minor elements in red mud leachate include As, B, Ba, Cr, Cu, Fe, Ni, Mn, Mo, Ti, V, and Zn, and the trace elements in red mud leachate include Ag, Be, Cd, Co, Hg, Li, Pb, Sb, Se, Sr, and Tl. Some of these elements have the concentration up to 272 times higher than those of the groundwater quality standard and are toxic to the environment and human health. Therefore, scientific guidance is needed for red mud management, especially for the design of the containment system of the facilities.

Highly potent radical scavenging-anti-oxidant activity of biologically reduced graphene oxide using Nettle extract as a green bio-genic amines-based reductants source instead of hazardous hydrazine hydrate.

Reduced graphene oxide (rGO) is relied upon to be the most promising candidate for high-proficiency. Hydrazine is the most conventional efficient reducing agent that has been frequently used for reduction of graphene oxide, however, it is not environmentally safe due to its toxic nature, causing unsatisfactory defects on the basal plan of GO. Therefore, employing green and efficient reducing agents from natural sources like plant extracts has become the research interest for obtaining high quality reduced graphene oxide sheets in recent years. Here a one-step, easy, cost-effective and green synthesis method based on Nettle leaves' extract has been introduced as an effective reduction method of graphene oxide compared with the toxic and harmful Hydrazine hydrate substance. In this study, GO and rGO were obtained from various methods and characterized by Raman spectroscopy, field emission scanning electron microscope, high-resolution transmission electron microscope (HR-TEM), X-ray diffraction analysis (XRD) and X-ray photon spectroscopy (XPS) analysis. Results of different analytical techniques revealed that the Nettle leaves' extract could successfully reduce GO sheets to high performance reduced graphene oxide with 79% efficiency in comparison with conventional Hydrazine hydrate. On the other side the rGO obtained by Nettle solution could scavenge the free radicals with 70% inhibition capacity at least concentration. Existence of Histamine and Serotonin and many other polyphenols as a part of Nettle leaves composition by following anti-oxidants mechanisms (H donation or electron transfer) promote the anti-oxidant functionality of Nettle leaves. So the highlighted achievement of this paper is to obtain a highly anti-oxidant green reduced graphene oxide with a wide applications i.e medical and polymer composite with UV-shielding activity.

Preclinical hazard evaluation strategy for nanomedicines.

The increasing nanomedicine usage has raised concerns about their possible impact on human health. Present evaluation strategies for nanomaterials rely on a case-by-case hazard assessment. They take into account material properties, biological interactions, and toxicological responses. Authorities have also emphasized that exposure route and intended use should be considered in the safety assessment of nanotherapeutics. In contrast to an individual assessment of nanomaterial hazards, we propose in the present work a novel and unique evaluation strategy designed to uncover potential adverse effects of such materials. We specifically focus on spherical engineered nanoparticles used as parenterally administered nanomedicines. Standardized assay protocols from the US Nanotechnology Characterization Laboratory as well as the EU Nanomedicine Characterisation Laboratory can be used for experimental data generation. We focus on both cellular uptake and intracellular persistence as main indicators for nanoparticle hazard potentials. Based on existing regulatory specifications defined by authorities such as the European Medicines Agency and the United States Food and Drug Administration, we provide a robust framework for application-oriented classification paired with intuitive decision making. The Hazard Evaluation Strategy (HES) for injectable nanoparticles is a three-tiered concept covering physicochemical characterization, nanoparticle (bio)interactions, and hazard assessment. It is cost-effective and can assist in the design and optimization of nanoparticles intended for therapeutic use. Furthermore, this concept is designed to be adaptable for alternative exposure and application scenarios. To the knowledge of the authors, the HES is unique in its methodology based on exclusion criteria. It is the first hazard evaluation strategy designed for nanotherapeutics.

QSAR modeling of cumulative environmental end-points for the prioritization of hazardous chemicals.

The hazard of chemicals in the environment is inherently related to the molecular structure and derives simultaneously from various chemical properties/activities/reactivities. Models based on Quantitative Structure Activity Relationships (QSARs) are useful to screen, rank and prioritize chemicals that may have an adverse impact on humans and the environment. This paper reviews a selection of QSAR models (based on theoretical molecular descriptors) developed for cumulative multivariate endpoints, which were derived by mathematical combination of multiple effects and properties. The cumulative end-points provide an integrated holistic point of view to address environmentally relevant properties of chemicals.

Development of High Capacity Enterosorbents for Aflatoxin B1 and Other Hazardous Chemicals.

Previously, a calcium montmorillonite clay (NovaSil) included in the diet of animals has been shown to bind aflatoxin B1 (AfB1) and reduce the symptoms of aflatoxicosis. To investigate and improve the capacity and efficacy of clay-based materials as aflatoxin sorbents, we developed and tested calcium and sodium montmorillonite clays amended with nutrients including l-carnitine and choline. Also, we determined the sorption of AfB1 by isothermal analysis and tested the ability of these amended sorbents to protect adult hydra from AfB1 toxicity. The results showed that exchanging montmorillonite clays with l-carnitine and choline inhibited swelling of the clays and increased the sorption capacity and efficacy of clay surfaces for AfB1. Results from dehydroxylated and heat-collapsed clays suggested that AfB1 was primarily adsorbed in the clay interlayer, as predicted from thermodynamic calculations and computational modeling. The hydra bioassay further indicated that the modified clays can significantly protect adult hydra from AfB1 with as low as 0.005% clay inclusion. This enterosorbent therapy may also be applied to screen hazardous chemicals such as pesticides and PAHs based on similar sorption mechanisms. Taken together, enterosorbent therapy could be delivered in nutritional supplements, foods that are vulnerable to aflatoxin contamination, flavored liquids and animal feeds during emergencies and outbreaks of acute aflatoxicosis, and as a screening model for hazardous environmental chemicals.

Application of Bayesian networks for hazard ranking of nanomaterials to support human health risk assessment.

In this study, a Bayesian Network (BN) was developed for the prediction of the hazard potential and biological effects with the focus on metal- and metal-oxide nanomaterials to support human health risk assessment. The developed BN captures the (inter) relationships between the exposure route, the nanomaterials physicochemical properties and the ultimate biological effects in a holistic manner and was based on international expert consultation and the scientific literature (e.g., in vitro/in vivo data). The BN was validated with independent data extracted from published studies and the accuracy of the prediction of the nanomaterials hazard potential was 72% and for the biological effect 71%, respectively. The application of the BN is shown with scenario studies for TiO2, SiO2, Ag, CeO2, ZnO nanomaterials. It is demonstrated that the BN may be used by different stakeholders at several stages in the risk assessment to predict certain properties of a nanomaterials of which little information is available or to prioritize nanomaterials for further screening.

Enantioselective Phytotoxicity and the Relative Mechanism of Current Chiral Herbicides.

BACKGROUND: Regardless of the achievable of chiral switch, most of the chiral nature agrochemical is still sold as racemate or enantiomer-enriched pesticides. Herbicides, accounted for a large proportion in pesticide market, are of great concern due to the frequent occurrence in environment and the structure selective phyto-biochemical impact on plants. METHODS: We give a systematic search on the literature database and included approximately 50 papers which were related to the review. We do careful categories for the chiral herbicides according to their structure and listed out the acute phytotoxicity endpoints. The potential mechanism for the enantioselective toxicity was concluded into 5 main points. RESULTS: The enantiomer-specific toxicity on plant growth and flowers are limited on phenoxyalkanoic acid herbicide, aryloxyphenoxypropanoic acid, imidazolinone herbicide, and acetamide pesticide. Data available on the potential mechanism explanation of enantioselective phytotoxicity has been concerned on the genetic transcription, oxidative stress, and photosynthesis disruption, etc. A comparison between the two enantiomers' enantioselective effects identified an organ-specific and species-specific phenomenon for several herbicides. Moreover, a more herbicidal activity enantiomer is also displayed the more toxicity than its antipode. CONCLUSION: The review elucidated a paucity of information on the enantioselective effect research on various types of plants at the different life stages. It appealed us to conduct a more holistic approach to balance the benefit between herbicidal activity and phytotoxicity when try to develop an enantio-pure herbicide.

Nondestructive detection of lead chrome green in tea by Raman spectroscopy.

Raman spectroscopy was first adopted for rapid detecting a hazardous substance of lead chrome green in tea, which was illegally added to tea to disguise as high-quality. 160 samples of tea infusion with different concentrations of lead chrome green were prepared for Raman spectra acquirement in the range of 2804 cm(-1)-230 cm(-1) and the spectral intensities were calibrated with relative intensity standards. Then wavelet transformation (WT) was adopted to extract information in different time and frequency domains from Raman spectra, and the low-frequency approximation signal (ca4) was proved as the most important information for establishment of lead chrome green measurement model, and the corresponding partial least squares (PLS) regression model obtained good performance in prediction with Rp and RMSEP of 0.936 and 0.803, respectively. To further explore the important wavenumbers closely related to lead chrome green, successive projections algorithm (SPA) was proposed. Finally, 8 characteristic wavenumbers closely related to lead chrome green were obtained and a more convenient and fast model was also developed. These results proved the feasibility of Raman spectroscopy for nondestructive detection of lead chrome green in tea quality control.

Assessment of water quality and identification of polluted risky regions based on field observations & GIS in the Honghe River watershed, China.

Water quality assessment at the watershed scale requires not only an investigation of water pollution and the recognition of main pollution factors, but also the identification of polluted risky regions resulted in polluted surrounding river sections. To realize this objective, we collected water samplings from 67 sampling sites in the Honghe River watershed of China with Grid GIS method to analyze six parameters including dissolved oxygen (DO), ammonia nitrogen (NH3-N), nitrate nitrogen (NO3-N), nitrite nitrogen (NO2-N), total nitrogen (TN) and total phosphorus (TP). Single factor pollution index and comprehensive pollution index were adopted to explore main water pollutants and evaluate water quality pollution level. Based on two evaluate methods, Geo-statistical analysis and Geographical Information System (GIS) were used to visualize the spatial pollution characteristics and identifying potential polluted risky regions. The results indicated that the general water quality in the watershed has been exposed to various pollutants, in which TP, NO2-N and TN were the main pollutants and seriously exceeded the standard of Category III. The zones of TP, TN, DO, NO2-N and NH3-N pollution covered 99.07%, 62.22%, 59.72%, 37.34% and 13.82% of the watershed respectively, and they were from medium to serious polluted. 83.27% of the watershed in total was polluted by comprehensive pollutants. These conclusions may provide useful and effective information for watershed water pollution control and management.

Characterization of the noncancer hazards of gas oils.

Gas oils, used to manufacture diesel fuel and residential heating oil, are complex hydrocarbon substances with carbon numbers of C9-C30 and boiling ranges of approximately 150 °C to 450 °C. Target organ (liver enlargement, reduced thymus weights, and reductions in hematological parameters) and developmental (reduced fetal viability, increased resorption frequency, and reduced fetal weights) effects are associated with aromatic constituents present in some gas oils. Two types of gas oils were tested for repeated-dose and developmental toxicity following repeated dermal administration. A blend of commercial diesel fuels containing 26% aromatics, primarily single-ring compounds, did not cause either target organ or developmental effects at levels up to 600 mg/kg/d. "Cracked" gas oils containing higher levels of aromatic constituents were also tested. Because of limited sample availability, 2 cracked gas oil samples were tested, one for systemic effects and the other for developmental toxicity. The sample tested in the repeated-dose toxicity study (81% aromatics including approximately 10% 3-ring compounds) produced increased liver weights, reduced thymus weights, and reductions in hematological parameters. The overall no observed adverse effect level (NOAEL) was 100 mg/kg/d. The sample tested for developmental toxicity (65% aromatics including approximately 5% 3-ring compounds) resulted in significant reductions in fetal survival, significant increases in resorption frequency, and significant reductions in fetal weights with an overall NOAEL of 100 mg/kg/d. In summary, gas oils may or may not cause target organ and/or developmental effects depending on the levels and types of aromatic constituents that they contain.

Degradation of polychlorinated naphthalene by mechanochemical treatment.

Polychlorinated naphthalene (PCN) is a hazardous compound that is listed as a new persistent organic pollutants candidate by the United Nations Environment Program. The production, import and use of PCNs are prohibited by the Chemical Substances Control Law in Japan. PCN was milled with calcium oxide as an additive to investigate the feasibility of its degradation by mechanochemical treatment. The milling process cleaved the C-C and C-Cl bonds by the mechanically induced solid-state reaction. Gas chromatography/mass spectrometry analysis confirmed that the PCN was decomposed after 1h milling. The yield of chloride ions reached 100% after 3h milling. This indicates that all PCN was broken down into inorganic compounds after milling, thereby maintaining the chlorine mass balance through the reaction. This experiment, for the first time, exhibited the effectiveness of mechanochemical treatment as a PCN degradation method.

A GHS-consistent approach to health hazard classification of petroleum substances, a class of UVCB substances.

The process streams refined from petroleum crude oil for use in petroleum products are among those designated by USEPA as UVCB substances (unknown or variable composition, complex reaction products and biological materials). They are identified on global chemical inventories with unique Chemical Abstract Services (CAS) numbers and names. The chemical complexity of most petroleum substances presents challenges when evaluating their hazards and can result in differing evaluations due to the varying level of hazardous constituents and differences in national chemical control regulations. Global efforts to harmonize the identification of chemical hazards are aimed at promoting the use of consistent hazard evaluation criteria. This paper discusses a systematic approach for the health hazard evaluation of petroleum substances using chemical categories and the United Nations (UN) Globally Harmonized System (GHS) of classification and labeling. Also described are historical efforts to characterize the hazard of these substances and how they led to the development of categories, the identification of potentially hazardous constituents which should be considered, and a summary of the toxicology of the major petroleum product groups. The use of these categories can increase the utility of existing data, provide better informed hazard evaluations, and reduce the amount of animal testing required.