Christine Russom U.S. EPA/ORD/NHEERL/MED Presented at the McKim Conference on the Use of QSARs June...

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Christine RussomChristine Russom

U.S. EPA/ORD/NHEERL/MEDU.S. EPA/ORD/NHEERL/MED

Presented at the McKim Conference Presented at the McKim Conference

on the Use of QSARson the Use of QSARs

June 27-29, 2006 June 27-29, 2006

ECOTOX: A Foundation ECOTOX: A Foundation for Extrapolationfor Extrapolation

What is ECOTOX?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

-8 -6 -4 -2 0 2-8

Observed log LC50 (moles/L)

Evaluating Ability of ASTER Toxicity Models to Predict Independent Test Results

Brook Trout: Total PCB (ug/g)T

Biochemical Growth MortalityPopulationReproductionPhysiology

Adults: NOEL

Adults: LOEL

Juveniles: NOEL

Juveniles: LOEL

Eggs/Embryos: NOELEggs/Embryos: LOEL

Data RequirementsData 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

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

ECOTOX ProceduresECOTOX ProceduresQA - 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 non-applicable; 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 ECOTOX – What is encodedencoded

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

Information Coded for Test Organism Common nameScientific nameTaxonomic hierarchySex Age Initial weight and length Initial life stage Comments on organism noted by author

Information Coded for Test CompoundCAS Registry numberCollective indices nameSynonymsChemical formChemical puritySolvent / vehicle used Chemical class / group

Test MethodsRoute of exposureExposure mediaDuration of study and/or exposureApplication frequencyDate and geographic location of field studiesLocation of study (field vs. laboratory)Water chemistry and physical characteristics of

test mediaComments on experimental designControl typeWhether chemical concentrations are

measured vs. nominal

Tests ResultsObserved effect measurements (e.g., P450

enzyme measurementsMajor 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 observed at each dose for terrestrial studies

ECOTOX – EffectsECOTOX – 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 MiningData 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

ECOTOXChemical DatabaseSpecies Database

Toxic Effects Database(AQUIRE; PHYTOTOX; TERRETOX)

Reference Database

ASTER SystemExpert system

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)

ECOTOX – LinkagesECOTOX – Linkages

N u m b e r o f T e s t R e s u lt s

B ir d s M a m m a ls F is h

Percentage of data by endpoint type

5 0 0 0

1 0 0 0 0

1 5 0 0 0

N u m b e r o f E n d p o i n t r e s u l t s b y S p e c i e s

R a i n b o w t r o u t F a t h e a d m i n n o w B l u e g i l l

C o m m o n c a r p C h a n n e l c a t fi s h G o l d fi s h

G u p p y M e d a k a S h e e p s h e a d m i n n o w

Z e b r a fi s h C o h o s a l m o n M o s q u i t o fi s h

B r o o k t r o u t S t r i p e d b a s s T i l a p i a

C a r p A t l a n t i c s a l m o n C u t t h r o a t t r o u t

C h i n o o k s a l m o n L a r e g e m o u t h b a s s

Fish data in ECOTOX with Endpoints reported – Top 20 species

1 0 0 0

N u m b e r o f E n d p o in t r e s u lt s b y S p e c ie s

N o r w a y r a t H o u s e m o u s e D e e r m o u s e

M i n k G e r b i l W h i t e - f o o t e d m o u s e

D o g E u r o p e a n r a b b i t P i g

A n t e l o p e

Mammalian data in ECOTOX with Endpoints reported – Top 10 species

1 0 0 0

1 0 0 0 0

N u m b e r o f E n d p o i n t R e s u l t s b y S p e c i e s

M a l l a r d B o b w h i t e J a p a n e s e q u a i l

R i n g - n e c k e d p h e a s a n t B a n t a m c h i c k e n E u r o p e a n s t a r l i n g

H o u s e s p a r r o w C o m m o n g r a c k l e R o c k d o v e

R e d - w i n g e d b l a c k b i r d A m e r i c a n k e s t r a l C h u k a r p a r t r i d g e

H e l m e t e d g u i n e a f o w l G r a y p a r t r i d g e B r o w n - h e a d e d c o w b i r d

A m e r i c a n b l a c k d u c k M o u r n i n g d o v e R e d - l e g g e d p a r t r i d g e

Q u a i l H e r r i n g g u l l

Avian data in ECOTOX with Endpoints reported – Top 20 species

1 0 0 0

1 5 0 0

2 0 0 0

N u m b e r o f E n d p o i n t R e s u l t s b y C h e m i c a l

C o p p e r s u lf a te C a d m iu m c h lo r id eA m m o n iu m c h lo r id e P e n ta c h lo r o p h e n o l Z in c s u lf a te 3 - T r ifl u o r o m e th y l- 4 - n it r o p h e n o lF e n it r o th io n P o ta s s iu m d ic h r o m a teT h io s u lf a n C a r b a r y lZ in c c h lo r id e P h e n o lM a la th io n L in d a n eE n d r in R o te n o n eT r ic h lo r o f o n D ia z in o nM e r c u r y c h lo r id e T o x a p h e n e

Fish data in ECOTOX with Endpoints reported – Top 20 Chemicals

N u m b e r o f T e s t R e s u l t s b y C h e m i c a l

A r o c h lo r 1 2 5 4 D ie ld r in C a r b a r y l

D io x in M ir e x L e a d a c e ta te

K e p o n e N it r o f e n T r ic lo r o f o nT h io p h a n a te - m e th y l

Mammalian data in ECOTOX with Endpoints reported – Top 10 Chemicals

N u m b e r o f T e s t R e s u l t s b y C h e m i c a l

D ie ld r in F e n th io nD ia z in o n P a r a th io nS tr y c h n in e D D TK e p o n e M e r c a p to d im e th u r M e th y lm e r c u r ic d ic y a n d ia m id e A r o c h lo r 1 2 5 4D ic r o to p h o s M e r c u r y b ic h lo r id eE n d r in T e m e p h o sC a r b o f u r a n P a r a q u a t d ic h lo r id eC a r b a r y l 1 - N a p h th y lth io u r e aC h lo r p y r if o s p , p '- D D E

Avian data in ECOTOX with Endpoints reported – Top 25 Chemicals

P e r c e n t a g e o f C h e m i c a l s b y M O A

N o n p o la r n a r c o s is R e a c t iv eP o la r n a r c o s is E s te r n a r c o s isA C h E in h ib it io n U n c o u p le r o f o x id a t iv e p h o s p h o r y la t io nN e u r o to x ic a n t R e s p ir a to r y b lo c k e r

MOA for Organic Chemicals in ECOTOX with concurrent structure information

Summary of Data in ECOTOXSummary of Data in ECOTOXFish, mammals and birdsFish, 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/ecotoxwww.epa.gov/ecotox

Christine Russom U.S. EPA/ORD/NHEERL/MED Presented at the McKim Conference on the Use of QSARs June...

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