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ECOTOX: A Foundation for Extrapolation Christine Russom U.S. EPA/ORD/NHEERL/MED Presented at the McKim Conference on the Use of QSARs June 27-29, 2006 What is ECOTOX? ECOTOX is a comprehensive web-based database of effects of single chemicals to aquatic and terrestrial organisms Developed and maintained by U.S. EPA Primary source of data are the studies published in the open literature Information regarding study design and test results are presented in discrete data fields Evaluating Ability of ASTER Toxicity Models to Predict Independent Test Results Predicted log LC50 (moles/L) 2 0 -2 -4 -6 -8 -8 -6 -4 -2 Observed log LC50 (moles/L) 0 2 Brook Trout: Total PCB (ug/g) Total PCB (ug/g ww) 1000 100 10 1 Adults: NOEL Adults: LOEL Juveniles: NOEL Juveniles: LOEL Eggs/Embryos: NOEL Eggs/Embryos: LOEL 0.1 0.01 Biochemical Physiology Reproduction Growth Mortality Population Data Requirements Paper is the primary source of the data Observed effect / no effect responses resulting from a chemical exposure Species and chemical information must be verifiable Single chemical exposures Reports chemical concentration, dose, or application rate Duration of exposure provided Exposure must be to an intact, live organism Sediment studies must include a pore water concentration Database does not include bacteria, viral, and yeast studies Database does not include petroleum (fuel oils) products Database does not include inhalation studies ECOTOX Procedures Develop Literature Search Strategy Conduct Literature Search Identify and Acquire Potentially Applicable Literature Codify / Abstract Relevant Data Release of New Data to Public Website Outreach / Technical Support QA - Verify terms used; test strategy; etc. QA - Assess effectiveness of search; validate exclusion terms; etc. QA – Maintain database of all papers acquired; verify papers identified as nonapplicable; etc. QA – Training procedure; 10% replicate review; electronic checks; verification of species/chemical information; data entry QA; etc. QA – Code verification; Agency IT requirements; beta-testing prior to public release; etc. QA – User support line; data maintenance; web-site documentation / help file; etc. ECOTOX – What is encoded All pertinent data presented by the authors is abstracted from published literature and encoded into the database Species Chemical Test Methods Tests Results Source of information ECOTOX – What is encoded Information Coded for Test Organism Common name Scientific name Taxonomic hierarchy Sex Age Initial weight and length Initial life stage Comments on organism noted by author ECOTOX – What is encoded Information Coded for Test Compound CAS Registry number Collective indices name Synonyms Chemical form Chemical purity Solvent / vehicle used Chemical class / group ECOTOX – What is encoded Test Methods Route of exposure Exposure media Duration of study and/or exposure Application frequency Date and geographic location of field studies Location of study (field vs. laboratory) Water chemistry and physical characteristics of test media Comments on experimental design Control type Whether chemical concentrations are measured vs. nominal ECOTOX – What is encoded Tests Results Observed effect measurements (e.g., P450 enzyme measurements Major effect category (e.g., Enzyme) Any calculated (e.g., BCF) or statistically derived endpoint (e.g., LD50, NOAEL, LOAEL) If the authors do not clearly state the endpoint, but one can be inferred from a statistical presentation of the data (Table or Figure), then the appropriate endpoint is encoded with a flag that the endpoint was assigned by the reviewer Statistical information related to the endpoint is captured including the level of significance Responses studies observed at each dose for terrestrial ECOTOX – Effects Observed Effect Responses Accumulation Behavior (e.g., avoidance and feeding behavior) Biochemical, enzyme and hormonal responses Growth, development and morphological changes Cellular, genetic and histological responses Mortality Physiological changes, injury, immunity, and intoxication Population Effects Reproduction Ecosystem Response Data Mining Can conduct searches on any coded parameters Search on recent updates to the database Taxonomy, common or scientific name, plant vs. animal Independently compiled data sets CAS Registry No., chemical name, chemical group Endpoints (e.g., LC50); effect groups (e.g., mortality, growth); measurement (e.g., time to death, weight) Test conditions: study location (lab vs. field); test media (e.g., freshwater, soil); route of exposure (e.g., diet); chemical analysis (measured vs. nominal) Publication information: ECOTOX reference number; specific publication years; range of publication years ECOTOX – Linkages ECOTOX ASTER System Expert system Chemical Database Species Database Toxic Effects Database (AQUIRE; PHYTOTOX; TERRETOX) Reference Database Evaluated Data : (PCB Effect/Residue data; Toxicity Reference Values; Superfund/Eco-Soil Screening Levels, Endangered species assessments; Water Quality Criteria data) Third-party Data Sources (e.g., OECD, USGS, EPA) Number of Test Results Birds Mammals Fish 80 Percentage of data by endpoint type 60 40 MATC EC50 LT50 BAF/BCF NOEL/NOEC LOEL/LOEC LD50 0 LC50 20 Rainbow trout Fathead minnow Bluegill Common carp Channel catfish Goldfish Guppy Medaka Sheepshead minnow Zebrafish Coho salmon Mosquitofish Brook trout Striped bass Tilapia Carp Atlantic salmon Cutthroat trout Chinook salmon Laregemouth bass 15000 Fish data in ECOTOX with Endpoints reported – Top 20 species 10000 5000 0 Number of Endpoint results by Species Norway rat House mouse Deer mouse Mink Gerbil White-footed mouse Dog European rabbit Pig Antelope 1000 Mammalian data in ECOTOX with Endpoints reported – Top 10 species 100 10 1 Number of Endpoint results by Species Mallard Bobwhite Japanese quail Ring-necked pheasant Bantam chicken European starling House sparrow Common grackle Rock dove Red-winged blackbird American kestral Chukar partridge Helmeted guineafowl Gray partridge Brown-headed cowbird American black duck Mourning dove Red-legged partridge Quail Herring gull 10000 Avian data in ECOTOX with Endpoints reported – Top 20 species 1000 100 10 1 Number of Endpoint Results by Species Copper sulfate Ammonium chloride Zinc sulfate Fenitrothion Thiosulfan Zinc chloride Malathion Endrin Trichlorofon Mercury chloride 2000 Cadmium chloride Pentachlorophenol 3-Trifluoromethyl-4-nitrophenol Potassium dichromate Carbaryl Phenol Lindane Rotenone Diazinon Toxaphene Fish data in ECOTOX with Endpoints reported – Top 20 Chemicals 1500 1000 500 0 Number of Endpoint Results by Chemical Arochlor 1254 Dioxin Kepone Thiophanate-methyl 100 Dieldrin Mirex Nitrofen Carbaryl Lead acetate Triclorofon Mammalian data in ECOTOX with Endpoints reported – Top 10 Chemicals 80 60 40 20 0 Number of Test Results by Chemical Dieldrin Diazinon Strychnine Kepone Methylmercuric dicyandiamide Dicrotophos Endrin Carbofuran Carbaryl Chlorpyrifos 120 100 Fenthion Parathion DDT Mercaptodimethur Arochlor 1254 Mercury bichloride Temephos Paraquat dichloride 1-Naphthylthiourea p,p'-DDE Avian data in ECOTOX with Endpoints reported – Top 25 Chemicals 80 60 40 20 0 Number of Test Results by Chemical Nonpolar narcosis Polar narcosis AChE inhibition Neurotoxicant 60 50 Reactive Ester narcosis Uncoupler of oxidative phosphorylation Respiratory blocker MOA for Organic Chemicals in ECOTOX with concurrent structure information 40 30 20 10 0 Percentage of Chemicals by MOA Summary of Data in ECOTOX Fish, mammals and birds Total Number of Test results in ECOTOX: 502,622 • No. of test results for fish: 111,726 (65% have Endpoints) • No. of test results for mammals: 89,047 (2% have Endpoints) • No. of test results for birds: 36,170 (12% have Endpoints) Total Number of Chemicals in ECOTOX: 10,372 • No. of unique chemicals in fish subset: 5,372 • No. of unique chemicals in mammal subset: 743 • No. of unique chemicals in bird subset: 752 Total Number of Species in ECOTOX: 6,137 • No. of unique fish species: 731 • No. of unique mammal species: 87 • No. of unique bird species: 103 Total number of publications in ECOTOX: 19,551 • No. of papers associated with fish data: 7,876 • No. of papers associated with mammalian data: 652 • No. of papers associated with bird data: 424 Anne Pilli (CSC) Delores Grunwald (CSC) Brian Kinziger (CSC) Amy Puglisi (CSC) Steve Erickson (CSC) Joanne Kobus (CSC) Dan Peterson (CSC) Greg Elonen (CSC) Sue Tranmel (CSC) Brian Ness (CSC) Kraig Hessen (CSC) Wendy Hieb (CSC) Christina Wagner (CSC) Jason Selin (CSC) Anita Pompulin (CSC) Tom Berrisford (CSC) David Burress (CSC) James Niesen (CSC) Sandra Purcell (CSC) Gina Skopinski (CSC) Matt Abel (CSC) Amanda Paul (CSC) Susan Rees (CSC) Pamela Baker (CSC) Donna Swenson (CSC) Gil Veith (formerly EPA) Rosemarie Russo (formerly EPA) Charles Stephan (EPA) Bob Spehar (EPA) Barb Sheedy (EPA) www.epa.gov/ecotox