Transcript ecotox - McKim Conferences

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