Neural Networks in Chemistry

The capabilities of the human brain have always fascinated scientists and led them to investigate its inner workings. Over the past 50 years a number of models have been developed which have attempted to replicate the brain's various functions. At the same time the development of computers was taking a totally different direction. As a result, today's computer architectures, operating systems, and programming have very little in common with information processing as performed by the brain. Currently we are experiencing a reevaluation of the brain's abilities, and models of information processing in the brain have been translated into algorithms and made widely available. The basic building-block of these brain models (neural networks) is an information processing unit that is a model of a neuron. An artificial neuron of this kind performs only rather simple mathematical operations; its effectiveness is derived solely from the way in which large numbers of neurons may be connected to form a network. Just as the various neural models replicate different abilities of the brain, they can be used to solve different types of problem: the classification of objects, the modeling of functional relationships, the storage and retrieval of information, and the representation of large amounts of data. This potential suggests many possibilities for the processing of chemical data, and already applications cover a wide area: spectroscopic analysis, prediction of reactions, chemical process control, and the analysis of electrostatic potentials. All these are just a small sample of the great many possibilities.     

Use of Knowledge Bases and QSARS to Estimate the Relative Ecological Risk of Agrichemicals: A Problem Formulation Exercise

Abstract

Ecological risk assessments can be used to establish the likelihood that an adverse effect will result from exposure to one or more chemicals. When evaluating contaminated sites with many chemicals present, risk assessors must grapple with the problem of quickly identifying the chemicals that are most likely to be of concern, based on effect and exposure assessment information. Many times data gaps exist and the risk assessor is left with decisions on which models to use to estimate the parameter of concern. In the present paper, a procedure is presented for ranking agrichemicals, utilizing the ASTER (ASsessment Tools for the Evaluation of Risk) system. The procedure was employed to rank the relative ecological risk of forty-nine pesticides historically used in agricultural sites in the Walnut Creek watershed near Ames, Iowa, USA. Empirical data from the ASTER system were used when available in the associated data-bases, and quantitative structure-activity relationships and expert systems were invoked when data were lacking. Separate rankings were conducted based on major species taxonomic groupings. Resulting toxic effects thresholds were compared to surface water concentrations.     

Defining the Human-Biota Thresholds of Toxicological Concern for Organic Chemicals in Freshwater: The Proposed Strategy of the LIFE VERMEER Project Using VEGA Tools

Several tons of chemicals are released every year into the environment and it is essential to assess the risk of adverse effects on human health and ecosystems. Risk assessment is expensive and time-consuming and only partial information is available for many compounds. A consolidated approach to overcome this limitation is the Threshold of Toxicological Concern (TTC) for assessment of the potential health impact and, more recently, eco-TTCs for the ecological aspect. The aim is to allow a safe assessment of substances with poor toxicological characterization. Only limited attempts have been made to integrate the human and ecological risk assessment procedures in a “One Health” perspective. We are proposing a strategy to define the Human-Biota TTCs (HB-TTCs) as concentrations of organic chemicals in freshwater preserving both humans and ecological receptors at the same time. Two sets of thresholds were derived: general HB-TTCs as preliminary screening levels for compounds with no eco- and toxicological information, and compound-specific HB-TTCs for chemicals with known hazard assessment, in terms of Predicted No effect Concentration (PNEC) values for freshwater ecosystems and acceptable doses for human health. The proposed strategy is based on freely available public data and tools to characterize and group chemicals according to their toxicological profiles. Five generic HB-TTCs were defined, based on the ecotoxicological profiles reflected by the Verhaar classes, and compound-specific thresholds for more than 400 organic chemicals with complete eco- and toxicological profiles. To complete the strategy, the use of in silico models is proposed to predict the required toxicological properties and suitable models already available on the VEGAHUB platform are listed.     

废弃感光化学品的环境风险分析

利用感光材料产量、彩扩店数量等统计数据,结合常用感光化学品的危害数据和进入环境的途径,根据我国对废弃感光化学品的管理和研究的现状,参考美国环保局的健康风险评价方法,分析了我国废弃感光化学品可能存在的环境风险,强调了加强感光化学品监控技术的开发、环境友好替代品研究和提高防范意识的重要性。     

Comparison of three fish bioaccumulation models for ecological and human risk assessment and validation with field data

This article compares two bioconcentration Quantitative Structure Activity Relationships (QSARs) for fish applied in human risk assessments with the mechanistic bioaccumulation model OMEGA and field data. It was found that all models are virtually similar up to a Kow of 10(6). For substances with a Kow higher than 10(6), the fish bioconcentration curve in the risk assessment model EUSES decreases parabolically. In contrast, OMEGA bioaccumulation outcomes approximately show a linear increase, based on mechanistic bioconcentration and biomagnification properties of chemicals. The OMEGA-outcomes are close to the fish bioconcentration outcomes of the risk assessment model CalTOX. For very hydrophobic substances, field accumulation data in freshwater and marine fish species are closer to OMEGA- and CalTOX-outcomes compared to EUSES. The results also show that it is important to include biomagnification in fish and lipid content of fish in human exposure models.     

Fish freshness detection by a computer screen photoassisted based gas sensor array

In the last years a large number of different measurement methodologies were applied to measure the freshness of fishes. Among them the connection between freshness and headspace composition has been considered by gas chromatographic analysis and from the last two decades by a number of sensors and biosensors aimed at measuring some characteristic indicators (usually amines). More recently also the so-called artificial olfaction systems gathering together many non-specific sensors have shown a certain capability to transduce the global composition of the fish headspace capturing the differences between fresh and spoiled products. One of the main objectives related to the introduction of sensor systems with respect to the analytical methods is the claimed possibility to distribute the freshness control since sensors are expected to be “portable” and “simple”. In spite of these objectives, until now sensor systems did not result in any tool that may be broadly distributed. In this paper, we present a chemical sensor array where the optical features of layers of chemicals, sensitive to volatile compounds typical of spoilage processes in fish, are interrogated by a very simple platform based on a computer screen and a web cam. An array of metalloporphyrins is here used to classify fillets of thawed fishes according to their storage days and to monitor the spoilage in filleted anchovies for a time of 8 h. Results indicate a complete identification of the storage days of thawed fillets and a determination of the storage time of anchovies held at room temperature with a root mean square error of validation of about 30 min.The optical system produces a sort of spectral fingerprint containing information about both the absorbance and the emission of the sensitive layer. The system here illustrated, based on computer peripherals, can be easily scaled to any device endowed with a programmable screen and a camera such as cellular phones offering for the first time the possibility to fulfil the sensor expectation of diffused and efficient analytical capabilities.     

Risk assessment, remedial decisions and the challenge to protect public health: the perchlorate case study

While scientists have a responsibility to defer judgment in the absence of conclusive data, public health and ecological protection require that government regulators make decisions based on available information. The risk assessment paradigm has evolved to help risk managers balance risks to public health with the cost of pollution control and remediation. Risk assessments are designed to be reasonably protective of public health, however the time and money required to develop and evaluate a robust scientific database can significantly delay regulatory action while exposures continue. The federal assessment of perchlorate, a component of rocket fuel and a thyroid toxicant, is presented here as a case study that demonstrates some of the limitations of risk assessment in protecting public health. Perchlorate was detected in a city well field that lies beneath a military training range at Aberdeen Proving Ground, a U.S. Army garrison in Maryland. Cleanup was put on hold, pending promulgation of a national drinking water standard for perchlorate. This case study (1) illustrates the challenge of preventing chemical exposures in the absence of promulgated standards, and (2) makes recommendations for approaches to preventing exposures to chemicals of unknown, or uncertain toxicity before they occur.     

Development of non-invasive Raman spectroscopy for in vivo evaluation of bone graft osseointegration in a rat model

The use of bone structural allografts for reconstruction following tumor resection is widespread, although successful incorporation and regeneration remain uncertain. There are few non-invasive methods to fully assess the progress of graft incorporation. Computed tomography and MRI provide information on the morphology of the graft/host interface. Limited information is also available from DXA and ultrasound. Only few techniques can provide information on the metabolic status of the graft, such as the mineral and matrix composition of the regenerated tissue that may provide early indications of graft success or failure. To address this challenge, we discuss here the implementation of Raman spectroscopy for in vivo assessment of allograft implantation in a rat model. An array of optical fibers was developed to allow excitation and collection of Raman spectra through the skin of rat at various positions around the rat's tibia. The system is calibrated against locally constructed phantoms that mimic the morphology, optics and spectroscopy of the rat. The system was evaluated by carrying out transcutaneous Raman measurement on rat. Bone mineral and matrix Raman bands are successfully recovered. This new technology provides a non-invasive method for in vivo monitoring of bone graft osseointegration.     

Recombinant cell bioassay systems for the detection and relative quantitation of halogenated dioxins and related chemicals

Proper epidemiological, risk assessment and exposure analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related halogenated aromatic hydrocarbons (HAHs) requires accurate measurements of these chemicals both in the species of interest and in various exposure matrices (i.e. biological, environmental, food and feed). High-resolution instrumental analysis techniques are established for these chemicals, however, these procedures are very costly and time-consuming and as such, they are impractical for large scale sampling studies (i.e. for epidemiological studies and assessment of areas with widespread contamination). Accordingly, numerous bioanalytical methods have been developed for the detection of these chemicals in extracts from a variety of matrices, the majority of which take advantage of the ability of these chemicals to activate the aromatic hydrocarbon receptor (AhR) and the AhR signal transduction pathway. Here we review the currently available in vitro AhR-based cell bioassay systems with a focus on recent recombinant reporter gene cell lines that have been developed for detection and relative quantitation of TCDD and related HAHs. Comparison of the relative sensitivities of the various cell bioassays and examples of their use in screening and analysis of environmental, biological, and food and feed samples are presented. Currently available experimental results and validation studies demonstrate the utility of these cell bioassay systems to provide a relatively rapid, accurate, and cost effective screening approach for the detection of TCDD and related HAHs in a variety of environmental, biological, food and feed samples. The availability of these cell bioassay systems will not only facilitate the large scale sampling studies needed for accurate assessment of contamination and exposure to these environmental chemicals, but they provide avenues for the identification of novel classes of TCDD-like chemicals.     

Bromine,arsenic, cadmium,and lead in several key food groups: an assessment of relative risk

ABSTRACT

This study endeavoured to provide an overview of the bromine, Br, arsenic (As, a metalloid) and metal (cadmium, Cd, and lead, Pb) relative risk associated with the consumption of relevant food groups (lean fish, fatty fish, bivalves, cephalopods, fresh fruit, dried fruit, and green vegetables) in Portugal. Though As, Cd, and Pb have been frequently studied, a comprehensive overview applying the same state-of-the-art methodology to a wide array of foods is missing. Besides, there is a large deficit of content information and risk assessment studies on Br. Thus, it is important to apply a mathematically realistic and innovative methodology (extreme value theory) to recent and accurate databases for the aforementioned food groups and elements.

Best fits to Br, As (total), Cd, and Pb concentrations were attained through different functions, ranging from the normal distribution to the Weibull distribution. A semi-probabilistic risk assessment approach on the basis of four alternative scenarios (one monthly meal; one weekly meal; three weekly meals; one daily meal) showed low relative risk regarding Br and Pb in the selected food groups, including bivalves, which contained the highest Br and Pb contents. With respect to total As, high relative risk values were calculated for seafood, but it should be emphasized that this As is overwhelmingly organic, thus presenting low risk. For Cd, substantial relative risk associated with bivalves’ and cephalopods’ consumption, particularly with one or more weekly meal(s), was found. However, the current study enables us to compare between the relative risk of the studied food groups and scenarios, and other studies encompassing the whole diet and following long-term dietary patterns are needed for the assessment of absolute risk.     

Effect of gating currents of ion channels on the collective spiking activity of coupled Hodgkin-Huxley neurons

Based on the coupled stochastic Hodgkin-Huxley neurons, we numerically studied the effect of gating currents of ion channels, as well as coupling and the number of neurons, on the collective spiking rate and regularity in the coupled system. It was found, for a given coupling strength and with a relatively large number of neurons, when gating currents are applied, the collective spiking regularity decreases; meanwhile, the collective spiking rate increases, indicating that gating currents can aggravate the desynchronization of the spikings of all neurons. However, gating currents caused hardly any effect in the spiking of any individual neuron of the coupled system. This result, different from the reduction of the spiking rate by gating currents in a single neuron, provides a new insight into the effect of gating currents on the global information processing and signal transduction in real neural systems. Supported by the Science Foundation of Ludong University (Grant Nos. 23140301, L20072805)     

Experiences with the Application of QSAR in the Routine of the Notification Procedure

Abstract

On behalf of the Umweltbundesamt the Fraunhofer Gesellschaft has developed a software system (SAR-system) comprising more than 90 estimation models for endpoints relevant in environmental risk assessment. These estimation models are based on the approach of quantitative structure-activity relationships (QSAR). All models were checked for their validity and application range. In the last months the Umweltbundesamt started to test the applicability of some models concerning the endpoints fish acute toxicity, daphnia acute toxicity and ready (i.e., ultimate) biodegradability in the daily routine of the notification procedure. For testing these models the corresponding confidential data given in the dossiers of substances notified 1993 in Germany, were used. We were able to make calculations for 36% of the notified substances. For the remaining 64% of the chemicals it was impossible to accomplish SAR estimations due to several reasons, e.g., ionic structure of the compounds. Different results for the applicability of the mentioned endpoints are obtained. The predictions of the fish and Daphnia toxicity are in sufficient agreement with the experimental results, in case of the fish toxicity we receive 58% agreement, for the Daphnia toxicity 56% The corresponding values which were obtained in the US EPA/E.C. Joint Project on the evaluation of (quantitative) structure activity relationships were 82.3% and 70.9% About 300 different models were used for the calculations of these endpoints within the framework of the EPA/EC project. The SAR-system presented here contains 8 models for estimating the fish toxicity and 6 models for the Daphnia toxicity. For the prediction of the biodegradability the results obtained with the SAR-system are rather poor and have to be improved. Meanwhile the SAR-system is commercially available and can be ordered at the Fraunhofer Institute for Environmental Chemistry and Ecotoxicology, Schmallenberg (Germany).     

Human and environmental risk assessment of pharmaceuticals: differences,similarities, lessons from toxicology

The presence of human and veterinary pharmaceuticals in the environment has caused increasing concern due their effects on ecological receptors. Improving the risk assessment of these compounds necessitates a quantitative understanding of their metabolism and elimination in the target organism (toxicokinetics), particularly via the ubiquitous cytochrome P-450 (CYP) system and their mechanisms of toxicity (toxicodynamics). This review focuses on a number of pharmaceuticals and veterinary medicines of environmental concern, and the differences and similarities between ecological and human risk assessment. CYP metabolism is discussed with particular reference to its ubiquity in species of ecological relevance. The important issue of pharmaceutical mixtures is discussed to assess how emerging technologies such as ecotoxicogenomics may assist in moving towards a more mechanism-based environmental risk assessment of pharmaceuticals.     

Improving confidence in (Q)SAR predictions under Canada’s Chemicals Management Plan – a chemical space approach$

Abstract

One of the key challenges of Canada’s Chemicals Management Plan (CMP) is assessing chemicals with limited/no empirical hazard data for their risk to human health. In some instances, these chemicals have not been tested broadly for their toxicological potency; as such, limited information exists on their potential to induce human health effects following exposure. Although (quantitative) structure activity relationship ((Q)SAR) models are able to generate predictions to address data gaps for certain toxicological endpoints, the confidence in predictions also needs to be addressed. One way to address this issue is to apply a chemical space approach. This approach uses international toxicological databases, for example, those available in the Organisation for Economic Co-operation and Development (OECD) QSAR Toolbox. The approach,assesses a model’s ability to predict the potential hazards of chemicals that have limited hazard data that require assessment under the CMP when compared to a larger, data-rich chemical space that is structurally similar to chemicals of interest. This evaluation of a model’s predictive ability makes (Q)SAR analysis more transparent and increases confidence in the application of these predictions in a risk-assessment context. Using this approach, predictions for such chemicals obtained from four (Q)SAR models were successfully classified into high, medium and low confidence levels to better inform their use in decision-making.     

Lessons Learned from the Grouping of Chemicals to Assess Risks to Human Health

In analogy to the periodic system that groups elements by their similarity in structure and chemical properties, the hazard of chemicals can be assessed in groups having similar structures and similar toxicological properties. Here we review case studies of chemical grouping strategies that supported the assessment of hazard, exposure, and risk to human health. By the EU-REACH and the US-TSCA New Chemicals Program, structural similarity is commonly used as the basis for grouping, but that criterion is not always adequate and sufficient. Based on the lessons learned, we derive ten principles for grouping, including: transparency of the purpose, criteria, and boundaries of the group; adequacy of methods used to justify the group; and inclusion or exclusion of substances in the group by toxicological properties. These principles apply to initial grouping to prioritize further actions as well as to definitive grouping to generate data for risk assessment. Both can expedite effective risk management.     

Simulation of chemical metabolism for fate and hazard assessment. I. Approach for simulating metabolism

Information regarding the metabolism of xenobiotic chemicals plays a central role in regulatory risk assessments. In regulatory programmes where metabolism studies are required, the studies of metabolic pathways are often incomplete and the identification of activated metabolites and important degradation products are limited by analytical methods. Because so many more new chemicals are being produced than can be assessed for potential hazards, setting assessment priorities among the thousands of untested chemicals requires methods for predictive hazard identification which can be derived directly from chemical structure and their likely metabolites. In a series of papers we are sharing our experience in the computerized management of metabolic data and the development of simulators of metabolism for predicting the environmental fate and (eco)toxicity of chemicals. The first paper of the series presents a knowledge-based formalism for the computer simulation of non-intermediary metabolism for untested chemicals, with an emphasis on qualitative and quantitative aspects of modelling metabolism.     

POPs: a QSAR system for developing categories for persistent, bioaccumulative and toxic chemicals and their metabolites

This paper presents the framework of a QSAR-based decision support system which provides a rapid screening of potential hazards, classification of chemicals with respect to risk management thresholds, and estimation of missing data for the early stages of risk assessment. At the simplest level, the framework is designed to rank hundreds of chemicals according to their profile of persistence, bioaccumulation potential and toxicity often called the persistent organic pollutant (POP) profile or the PBT (persistent bioaccumulative toxicant) profile. The only input data are the chemical structure. The POPs framework enables decision makers to introduce the risk management thresholds used in the classification of chemicals under various authorities. Finally, the POPs framework advances hazard identification by integrating a metabolic simulator that generates metabolic map for each parent chemical. Both the parent chemicals and plausible metabolites are systematically evaluated for metabolic activation and POPs profile.     

Recent advances of use of the supercritical carbon dioxide for the biomass pre-treatment and extraction: A mini-review

Biomass is considered as the most sustainable and renewable resource for the synthesis of value added potential platform chemicals. Various techniques are utilized to extract or to pre-treat or to isolate various value added chemicals from biomass. Pre-treatment of the biomass is a very essential aspect to enhance the biomass processing yield which is attributed to reduced lignin content/delignification, cellulose crystallinity and hemi-cellulose hydration. In search of efficient extraction and processing for biomass treatment, supercritical fluid (SCF) has been considered as the green technique to obtain the value added chemicals with higher efficiency than conventional technique. The use of the supercritical carbon dioxide (SC–CO₂) pre-treatment on biomass not only enhances glucose yield effectively but also delignify, hydrolyse hemi-cellulose component and allows extraction of various compounds from the biomass. However, very limited research articles are available for the use of SC-CO₂ for biomass processing to obtain value-added chemicals. In view of this, the present review article focus on the recent advances of applications of SC-CO₂ in (i) extraction of value added chemicals from biomass processing, (ii) biomass pre-treatment, (iii) factors affecting SC-CO₂ processing efficiency, (iv) scale-up scenario (v) challenges and opportunities in this field.     

The physicochemical basis of QSARs for baseline toxicity

The physico-chemical properties relevant to the equilibrium partitioning (bioconcentration) of chemicals between organisms and their respired media of water and air are reviewed and illustrated for chemicals that range in hydrophobicity. Relationships are then explored between freely dissolved external concentrations such as LC50s and chemical properties for one important toxicity mechanism, namely baseline toxicity or narcosis. The ‘activity hypothesis’ proposed by Ferguson in 1939 provides a coherent and compelling explanation for baseline toxicity of chemicals in both water- and air-respiring organisms, as well as a reference point for identifying more specific toxicity pathways. From inhalation studies with fish and rodents, narcosis is shown to occur at a chemical activity exceeding approximately 0.01 and there is no evidence of narcosis at activities less than 0.001. The activity hypothesis provides a framework for directly comparing the toxic potency of chemicals in both air- and water-breathing animals. The activity hypothesis is shown to be consistent with the critical body residue concept, but it has the advantage of avoiding the confounding effect of lipid content of the test organism. It also provides a theoretically sound basis for assessing the baseline toxicity of mixtures. It is suggested that since activity is readily calculated from fugacity, observed or predicted environmental abiotic and biotic fugacities can be used to evaluate the potential for baseline toxicity. Further, models employing fugacity or activity can be used to improve the experimental design of bioassays, thus possibly reducing unnecessary animal testing.