Browsing by Subject "Molecular similarity"

Now showing 1 - 5 of 5
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    Computational Techniques to Quantify Chemical Similarity: Tools for Risk Assessment
    (University of Minnesota Duluth, 1995) Basak, Subhash C; Niemi, Gerald J; Host, George E
    The principal goal of the cooperative agreement was to develop new molecular similarity methods and apply them to the risk assessment of environmental chemicals. To this end, our strategy had the following three-fold objectives: 1. Conduct an International workshop on " MOLECULAR SIMILARITY IN RISK ASSESSMENT " where internationally known experts in toxicology, computational chemistry, mathematical chemistry, structure-activity relationships and risk assessment of chemicals were brought together. These experts provided their opinions about how MOLECULAR SIMILARITY methods should be developed and used for risk assessment of chemicals. Ten experts were interviewed by the NRRI team and subsequently their input was summarized in a technical report submitted to USEPA. The workshop was part of QSAR ’92, an international conference held in Duluth, Minnesota jointly by the Natural Resources Research Institute-University of Minnesota and U S Environmental Protection Agency. The experts also submitted written manuscripts as part of the workshop. The workshop report reflected on different aspects of hazard assessment and molecular similarity. 2. Develop molecular similarity methodology by incorporating the inputs of the experts mentioned in item 1 above, along with our expertise in these methods. Special attention was given to the use of NONEMPIRICAL PARAMETERS (e.g., values calculated directly from the chemical structure) as opposed to empirical (or experimental) parameters because most chemicals used in the environment do not have experimental data necessary for detailed hazard assessment. 3. Apply the computational molecular similarity methods developed during the project in the selection of analogs and in estimation of environmentally important properties of these chemicals.
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    Predicting Toxicity and Degradability of Quadricyclane, Fluorocarbon Ethers and their Analogs (1994-1995)
    (University of Minnesota Duluth, 1995) Basak, Subhash C; Lodge, Keith B; Schubauer-Berigan, Joseph
    In a large number of cases, we have to assess the risk of chemicals and predict the toxic potential of molecules in the face of limited experimental data. Structural criteria and functional criteria (if available) are routinely used to estimate the possible hazard posed by a chemical to the environment and ecosystem. Frequently, no biological or relevant physicochemical properties of the chemical species of interest are available to the risk assessor. In the proposed project, we will develop and implement a number of methods of quantifying molecular similarity of chemicals using techniques of computational and mathematical chemistry. Some of the methods are new and will be based on our own research on the theoretical development and implementation of molecular similarity methods. These techniques will be implemented in a user friendly computer environment of the Silicon Graphics workstation. The similarity methods will be used to select analogs of chemicals of interest to the Air Force, viz., QUADRICYCLANE, FLUOROCARBON ETHERS AND THEIR ANALOGS, from databases containing high quality physicochemical data and toxicity endpoints for large number of chemicals. The databases used in the project will come from three sources: a) public domain databases, b) our own in-house databases, and c) databases acquired from commercial vendors. The set of selected analogs, called probe-induced subsets, will be used to: a) develop structure-activity relationships (SAR), and b) carry out ranking of chemicals. Both of these methods will be used to estimate the hazard of the chemicals of interest. A set of chemicals (five to ten) will be chosen for experimental work with the purpose of evaluating and refining computer models. The set will include quadricyclane and fluorocarbon ethers of interest to the Air Force. It will also include a selection of analogs (probe-induced subset) that are readily available, suitable for experimentation, and for which data are lacking. Experiments will be performed to assess the biodegradability and photochemical degradability of the members of the set. Their toxicity will be tested by MicroTox and MutaTox. In cases where significant degradation is observed, the toxicity of the degradation products will also be tested. Direct measurement of the hydrophobicity (octanol-water partition coefficient) will be performed on the members of the set.
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    Predicting Toxicity and Degradability of Quadricyclane, Fluorocarbon Ethers and their Analogs (1996-1997)
    (University of Minnesota Duluth, 1997) Basak, Subhash C; Lodge, Keith B; Schubauer-Berigan, Joseph
    In a large number of cases, we have to assess the risk of chemicals and predict the toxic potential of molecules in the face of limited experimental data. Structural criteria and functional criteria (if available) are routinely used to estimate the possible hazard posed by a chemical to the environment and ecosystem. Frequently, no biological or relevant physicochemical properties of the chemical species of interest are available to the risk assessor. In the proposed project, we will develop and implement a number of methods of quantifying molecular similarity of chemicals using techniques of computational and mathematical chemistry. Some of the methods are new and will be based on our own research on the theoretical development and implementation of molecular similarity methods. These techniques will be implemented in a user friendly computer environment of the Silicon Graphics workstation. The similarity methods will be used to select analogs of chemicals of interest to the Air Force, viz., QUADRICYCLANE, FLUOROCARBON ETHERS AND THEIR ANALOGS, from databases containing high quality physicochemical data and toxicity endpoints for large number of chemicals. The databases used in the project will come from three sources: a) public domain databases, b) our own in-house databases, and c) databases acquired from commercial vendors. The set of selected analogs, called probe-induced subsets, will be used to: a) develop structure-activity relationships (SAR), and b) carry out ranking of chemicals. Both of these methods will be used to estimate the hazard of the chemicals of interest. A set of chemicals (five to ten) will be chosen for experimental work with the purpose of evaluating and refining computer models. The set will include quadricyclane and fluorocarbon ethers of interest to the Air Force. It will also include a selection of analogs (probe-induced subset) that are readily available, suitable for experimentation, and for which data are lacking. Experiments will be performed to assess the biodegradability and photochemical degradability of the members of the set. Their toxicity will be tested by MicroTox and MutaTox. In cases where significant degradation is observed, the toxicity of the degradation products will also be tested. Direct measurement of the hydrophobicity (octanol-water partition coefficient) will be performed on the members of the set.
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    Report of the Internal Workshop on Molecular Similarity in Risk Assessment
    (University of Minnesota Duluth, 1993) Basak, Subhash C; Hunter, Bob; Niemi, Gerald J; Host, George E
    In an attempt to adequately capture the different aspects of molecular similarity, our group thought it would be appropriate to solicit, a variety of opinions regarding chemical similarity and its uses in different situations. While we have some experience and expertise in this field, we felt it important to consider a variety of opinions of internationally known experts about the concept of chemical similarity and its uses. Along those lines, we were fortunate enough to be able to access many researchers and regulators who had intended to participate in the QSAR 92 Conference held in Duluth, MN during July 19-23, 1992. In fact, we felt it essential that we take advantage of the collective body of expertise. To that end, we, in conjunction with United States Environmental Protection Agency (USEPA), sponsored nine key speakers and presenters who, we felt, had broad background in their area of expertise and could share with us their perspectives of what it means for two chemicals to be similar. After selecting our key speakers, we. arranged for many of them to be present at QSAR 92. During the course of the conference, we made arrangements to meet and have open discussions regrading chemical similarity with these speakers. The participants were questioned about what they thought were the critical elements or processes relevant to their subject area and the relevancy or uses of chemical similarity in their field of expertise. Many of these participants provided papers, which were reviewed for content relevant to chemical similarity and are provided in Appendix A. The goal of this exercise was to distill the common elements critical to operationalizing a method or system of components to formulate, implement, test, and validate chemical similarity models. This would lead to the development of a computer system design that incorporates many of the essential elements together under a common interface. We felt that it was essential that regulatory, toxicological, and computational perspectives of chemical similarity be taken into account during the course of this project. The remainder of this report will detail these different perspectives, and then discuss and review the common features to be used, with the hope that this will facilitate a computer software system design to accomplish the objectives of this project.
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    Stereo-electronic Factors in Molecular Similarity and Risk Assessment
    (University of Minnesota Duluth, 1994) Basak, Subhash C; Hunter, Bob; Niemi, Gerald J; Host, George E
    Three strategic tasks for the risk assessment of the chemicals can be defined nowadays. The first one is related to the critical evaluation of the existing test data. For example, in the area of industrial chemicals, after exploration the availability of toxicity endpoints, the National Research Council concluded that for many of these chemicals minimum of tests or, in many cases, no tests at all are performed [1]. On the other hand, the available test data mostly consist of acute toxicity and eye/skin irritation tests. Recently, an analysis of an environmental database of more than 30,000 chemicals showed [2] that the total number of chemicals possessing measured values of either boiling/melting points or vapor pressure is only 3,692. The second task should handle the identification problem of potential analogues of chemicals. An effective solution of this problem based on similarity methods can allow the selection of analogues of a query chemical possessing similar (hazardous) properties. The third task is closely related with the second one and is directed to estimating the properties of chemicals by using quantitative structure-activity relationships (QSAR) models.