TOXNET is a group of databases hosted by the National Library of Medicine containing factual information related to the toxicity and other hazards of chemicals. They are structured around chemical records.

 There are four basic groupings of TOXNET databases. Within each of these
 groupings are one or more databases. The first grouping is Toxicology Data
 including factual information on toxicity and other hazards of chemicals. The
 databases included in Toxicology Databases are the following four - Hazardous
 Substances Data Bank (HSDB) providing broad scope in human and animal toxicity,
 safety and handling, environmental fate, and more. Scientifically
 peer-reviewed; the Integrated Risk Information System (IRIS) providing Data
 from the Environmental Protection Agency (EPA) in support of human health risk
 assessment. It, focuses on identifying hazards and assessing the connection
 between dose and response; Chemical Carcinogenesis Research Information System
 (CCRIS) providing carcinogenicity, mutagenicity, tumor promotion, and tumor
 inhibition data provided by the National Cancer Institute (NCI) and GENE-TOX
 providing peer-reviewed mutagenicity test data from the EPA.

 The second grouping is Toxicology Literature. These TOXNET databases contain
 bibliographic information with citations to the scientific literature. You can
 use this information to locate the article in a journal. Many provide
 hyperlinks to Medical Subject Headings (MESH) and other keywords. The
 databases included in Toxicology Literature are the following three - TOXLINE,
 providing an extensive array of references to literature on biochemical,
 pharmacological, physiological, and toxicological effects of drugs and other
 chemicals; Environmental Mutagen Information Center (EMIC) providing current
 and older literature on agents tested for genotoxic activity and Developmental
 and Reproductive Toxicology (DART) and Environmental Teratology Information
 Center (ETIC) providing current and older literature on developmental and
 reproductive toxicology.

 The third grouping is the Toxic Release Information which includes just The
 Toxics Release Inventory (TRI) database created by the Environmental Protection
 Agency and contains data on the estimated quantities of chemicals released to
 the environment or transferred off-site for waste treatment. TRI also holds
 information related to source reduction and recycling. Data for the most recent
 and two prior reporting years is currently available. This particular TRI
 database includes the years 1995 to 1999.

 The fourth grouping is Chemical Information. Chemicals are identified in a
 number of ways, including by name and structural diagram. Using a dictionary or
 a thesaurus can help you find information for a particular substance. SIS
 maintains several chemical online resources to help you determine the identity
 of a substance and point you to files or resources of interest. There are three
 databases within this grouping. The first is ChemIDplus providing Numerous
 chemical synonyms, structures, regulatory list information, and links to other
 databases containing information about the chemicals; HSDB Structures providing
 2D and 3D structural information on the HSDB chemicals and NCI-3D providing 2D
 and 3Dstructural information on compounds tested for anti-tumor activity
 compiled by the National Cancer Institute.

 The TOXNET Basic Search screens are intuitive and straightforward. Most screens
 (except for the TRI database) allow you to place all query information in a
 single input box. For example, you may be looking for a chemical name, a
 particular author, a CAS Registry Number, or any type of concept term. You may
 enter any combination of these into the single input box. In some databases,
 you may also limit your search by author, title or dates.

A toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel.

DART/ETIC is a bibliographic database on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET). It covers teratology and other aspects of developmental and reproductive toxicology. It contains over 90,000 references to literature published since 1965. DART/ETIC is funded by the U.S. Environmental Protection Agency, the National Institute of Environmental Health Sciences, the National Center for Toxicological Research of the Food and Drug Administration, and the NLM.

 Users can search by subject terms, title words, chemical name,
 Chemical Abstracts Service Registry Number (RN), and author. Search
 results can easily be viewed, printed or downloaded. Search results
 are displayed in relevancy ranked order, but may be sorted by
 publication date, author or title.

HSDB is a toxicology data file on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET). It focuses on the toxicology of potentially hazardous chemicals. It is enhanced with information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, and related areas. All data are referenced and derived from a core set of books, government documents, technical reports and selected primary journal literature. HSDB is peer-reviewed by the Scientific Review Panel (SRB) a committee of experts in the major subject areas within the data bank's scope. HSDB is organized into individual chemical records, and contains over 4500 such records.

 Users can search by chemical or other name, chemical name fragment, Chemical
 Abstracts Service Registry Number (RN), and/or subject terms. Search results
 can easily be viewed, printed or downloaded. Search results are displayed in
 relevancy ranked order. Users may select to display exact term matches,
 complete records, or any combination of data from the groupings listed in the
 keyword section.

 Users can easily conduct their HSDB search strategy against other databases:
 Chemical Carcinogenesis Research Information System, Integrated Information
 System, and GENE-TOX.

As previously reported [Cameron, T. P., Rogers-Back, A. M., Lawlor, T. E., Harbell, J. W., Seifried, H. E., and Dunkel, V. C. (1991) Gentoxicity of multifunctional acrylates in the Salmonella/mammalian-microsome assay and mouse lymphoma TK+/− assay. Environ. Mol. Mutagen. 17, 264−271], the National Cancer Institute (NCI) shares the responsibility of selecting the most significant chemicals for carcinogenicity testing by the National Toxicology Program (NTP) and has used data from Salmonella and mouse lymphoma mutagenicity assays to aid in the selection and prioritization of chemicals to be further evaluated in chronic 2 year rodent studies. In addition, a number of antineoplastic and anti-AIDS drugs in preclinical evaluation were tested for the NCI's Division of Cancer Treatment Toxicology Branch. In the NCI/NTP chemical selection process, it is no longer necessary to test chemicals prior to sending them to the NTP so the NCI program has ceased performing mutagenicity tests. Some of the testing data has been made available in summary form in the Chemical Carcinogenisis Research Information System (CCRIS), which is searchable on the NLM TOXNET system. The limitations in using this source are that only summary results are available and many negative test results are not included. A summary table that presents the results for each compound is provided in the Appendix with raw data provided in the Supporting Information. The Appendix table contains the compound name, CAS number, and a summary of the data from the Ames test and the mouse lymphoma assay.

Toxicology data file of the National Library of Medicine''s (NLM) Toxicology Data Network (TOXNET). It is a scientifically evaluated and fully referenced data bank, developed and maintained by the National Cancer Institute (NCI). It contains over 9,000 chemical records with carcinogenicity, mutagenicity, tumor promotion, and tumor inhibition test results. Data are derived from studies cited in primary journals, current awareness tools, NCI reports, and other special sources. Test results have been reviewed by experts in carcinogenesis and mutagenesis. CCRIS is easily accessible and free of charge. Users can search by chemical or other name, chemical name fragment, Chemical Abstracts Service Registry Number (RN), and/or subject terms. Search results can easily be viewed, printed or downloaded. Search results are displayed in relevancy ranked order. Users may select to display any combination of data from the following broad groupings: (a) Carcinogenicity Studies (b) Tumor Promotion Studies (c) Mutagenicity Studies (d) Tumor Inhibition Studies Users can easily conduct their CCRIS search strategy against other databases: Hazardous Substances Data Bank, Integrated Risk Information System, GENE-TOX, TOXLINE, and ChemIDplus.

Background: Pregnancy-induced Hypertension (PIH) is a disease that causes serious maternal and fetal morbidity and mortality. Alisma Orientale (AO) has a long history of use as traditional Chinese medicine therapy for PIH. This study explores its potential mechanism and biosafety based on network pharmacology, network toxicology, molecular docking and molecular dynamics simulation.Methods: Compounds of AO were screened in TCMSP, TCM-ID, TCM@Taiwan, BATMAN, TOXNET and CTD database; PharmMapper and SwissTargetPrediction, GeneCards, DisGeNET and OMIM databases were used to predict the targets of AO anti-PIH. The protein-protein interaction analysis and the KEGG/GO enrichment analysis were applied by STRING and Metascape databases, respectively. Then, we constructed the “herb-compound-target-pathway-disease” map in Cytoscape software to show the core regulatory network. Finally, molecular docking and molecular dynamics simulation were applied to analyze binding affinity and reliability. The same procedure was conducted for network toxicology to illustrate the mechanisms of AO hepatotoxicity and nephrotoxicity.Results: 29 compounds with 78 potential targets associated with the therapeutic effect of AO on PIH, 10 compounds with 117 and 111 targets associated with AO induced hepatotoxicity and nephrotoxicity were obtained, respectively. The PPI network analysis showed that core therapeutic targets were IGF, MAPK1, AKT1 and EGFR, while PPARG and TNF were toxicity-related targets. Besides, GO/KEGG enrichment analysis showed that AO might modulate the PI3K-AKT and MAPK pathways in treating PIH and mainly interfere with the lipid and atherosclerosis pathways to induce liver and kidney injury. The “herb-compound-target-pathway-disease” network showed that triterpenoids were the main therapeutic compounds, such as Alisol B 23-Acetate and Alisol C, while emodin was the main toxic compounds. The results of molecular docking and molecular dynamics simulation also showed good binding affinity between core compounds and targets.Conclusion: This research illustrated the mechanism underlying the therapeutic effects of AO against PIH and AO induced hepato-nephrotoxicity. However, further experimental verification is warranted for optimal use of AO during clinical practice.

CCRIS is a toxicology data file of the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET). It is a scientifically evaluated and fully referenced data bank, developed and maintained by the National Cancer Institute (NCI). It contains some 8000 chemical records with carcinogenicity, mutagenicity, tumor promotion, and tumor inhibition test results. Data are derived from studies cited in primary journals, current awareness tools, NCI reports, and other special sources. Test results have been reviewed by experts in carcinogenesis and mutagenesis.

    Users can search by chemical or other name, chemical name fragment,
    Chemical Abstracts Service Registry Number (RN), and/or subject
    terms. Search results can easily be viewed, printed or downloaded.
    Search results are displayed in relevancy ranked order. Users may
    select to display any combination of data from the broad groupings
    listed in the keyword section.

    Users can easily conduct their CCRIS search strategy against other
    databases: Hazardous Substances Data Bank, Integrated Risk Information
    System, and GENE-TOX.

In this study, a major effort was undertaken to compile a large genotoxicity dataset (54,805 records for 9299 substances) from several public sources (e.g., TOXNET, COSMOS, eChemPortal). The names and outcomes of the different assays were harmonized, and assays were annotated by type: gene mutation in Salmonella bacteria (Ames assay) and chromosome mutation (clastogenicity) in vitro or in vivo (chromosome aberration, micronucleus, and mouse lymphoma Tk+/- assays). This dataset was then evaluated to assess genotoxic potential using a categorization scheme, whereby a substance was considered genotoxic if it was positive in at least one Ames or clastogen study. The categorization dataset comprised 8442 chemicals, of which 2728 chemicals were genotoxic, 5585 were not and 129 were inconclusive. QSAR models (TEST and VEGA) and the OECD Toolbox structural alerts/profilers (e.g., OASIS DNA alerts for Ames and chromosomal aberrations) were used to make in silico predictions of genotoxicity potential. The performance of the individual QSAR tools and structural alerts resulted in balanced accuracies of 57-73%. A Naïve Bayes consensus model was developed using combinations of QSAR models and structural alert predictions. The ‘best’ consensus model selected had a balanced accuracy of 81.2%, a sensitivity of 87.24% and a specificity of 75.20%. This in silico scheme offers promise as a first step in ranking thousands of substances as part of a prioritization approach for genotoxicity. This dataset is associated with the following publication: Pradeep, P., R. Judson, D. DeMarini, N. Keshava, T. Martin, J. Dean, C. Gibbons, A. Simha, S. Warren, M. Gwinn, and G. Patlewicz. An Evaluation of Existing QSAR Models and Structural Alerts and Development of New Ensemble Models for Genotoxicity Using a Newly Compiled Experimental Dataset. Computational Toxicology. Elsevier B.V., Amsterdam, NETHERLANDS, 18: 100167, (2021).

Key:(*)from Chemical Identification/Dictionary database at http://toxnet.nlm.nih.gov/cgibin/sis/search/;(#)from [36].