AGENDA

Federal Insecticide, Fungicide, and Rodenticide Act

Scientific Advisory Panel Meeting

January 31-February 2, 2012

Scientific Issues Associated with Common Effects Methodology developed by 

the Office of Pesticide Programs and the Office of Water

Docket number: EPA-HQ-OPP-2011-0898 OPP Docket Tel: 703-305-5805

Please note that all times are approximate 

(See note at the end of the Agenda)

Tuesday, January 31, 2012

9:00 A.M. Opening of Meeting and Administrative Procedures – Sharlene Matten, Ph.D. 

Designated Federal Official, Office of Science Coordination and Policy, EPA

9:05 A.M. Introduction and Identification of Panel Members – Janice Chambers, Ph.D., 

DABT, FIFRA Scientific Advisory Panel, Session Chair

9:15 A.M. Opening Remarks – Donald Brady, Ph.D., Director, Environmental Fate and 

Effects Division, Office of Pesticide Programs, EPA and Elizabeth Behl, M.S., 

Director, Health and Ecological Criteria Division, Office of Science and 

Technology, Office of Water, EPA

9:30 A.M. Introduction, Background, Status, and OPP and OW Data Requirements 

and Effects Characterizations – Kristina Garber, M.S., Environmental Fate and 

Effects Division, Office of Pesticide Programs, EPA and Joe Beaman, M.S., 

Health and Ecological Criteria Division, Office of Science and Technology, 

Office of Water, EPA

10:15 A.M. Break

10:30 A.M. Potential Use of Predictive Toxicology Tools in Characterizing Effects of 

Chemical Stressors to Aquatic Animals – Christine Russom, Mid-Continent 

Ecology Division, Office of Research and Development, EPA

11:15 A.M. Analysis of Sensitivity Distributions for Estimation of Acute Hazard 

Concentrations to Aquatic Animals – Matthew Etterson, Ph.D., Mid-Continent 

Ecology Division, Office of Research and Development, EPA

12:15 P.M. Lunch
2

1:15 P.M. Extrapolation Factors for Derivation of Acute Aquatic Life HC5s: Emphasis 

on Acetylcholinesterase Inhibitors – Russell Erickson, Ph.D., Mid-Continent 

Ecology Division, Office of Research and Development, EPA

2:15 P.M. Analysis of Chronic Toxicity Data and Acute Chronic Ratios (ACRs) in 

Support of Deriving Chronic HC5s: Acetylcholinesterase Inhibitors – Russell 

Erickson, Ph.D., Mid-Continent Ecology Division, Office of Research and 

Development, EPA

3:00 P.M. Break

3:15 P.M. Estimating Aquatic Plant Community Hazard Concentrations for Pesticide 

Effects – Glen Thursby, Ph.D., Atlantic Ecology Division, Office of Research and 

Development, EPA

5:00 P.M. Adjournment

Wednesday, February 1, 2012

9:00 A.M. Opening of Meeting and Administrative Procedures – Sharlene Matten, Ph.D., 

Designated Federal Official, Office of Science Coordination and Policy, EPA

9:05 A.M. Introduction and Identification of Panel Members – Janice Chambers, Ph.D., 

DABT, FIFRA Scientific Advisory Panel, Session Chair

9:10 A.M. Follow-up from Previous Day’s Meeting – Kristina Garber, M.S., Office of 

Pesticide Programs, EPA

9:20 A.M. Public Comments 

10:30 A.M. Break

10:45 A.M. Charge Question 1: QSARs for Predicting Acute Toxicity for Aquatic 

Animals

Effect characterizations in both United States Environmental Protection Agency’s (USEPA) Office of 

Water (OW) and Office of Pesticide Programs (OPP) rely on toxicity estimates for various taxa. The 

USEPA investigated the use of some readily available Quantitative Structure Activity Relationship 

(QSAR) tools (described in Appendix A) to predict acute toxicity values to represent sensitive taxa which 

could potentially fill gaps in available empirical toxicity data. Three publicly available QSAR models 

were examined, including: Ecological Structure Activity Relationships (ECOSAR), Toxicity Estimation 

Software Tool (TEST), and the Organization for Economic Cooperation and Development (OECD) 

QSAR Toolbox. These tools are increasingly used by USEPA risk assessors to determine the potential 

toxicity of various chemicals, including pesticide degradates. The white paper’s analyses of ECOSAR, 

TEST and the OECD Toolbox suggest that, at this time, 1) the chemical domains for most models within 

these QSAR tools do not include sufficient data for pesticide active ingredients and therefore these 

models are not currently robust estimators of the toxicity for modes of action (MOAs) that are unique to 

pesticides (e.g., acetylcholinesterase (AChE) inhibitors), 2) current models are generally populated with 

data for species for which toxicity data are typically submitted under FIFRA, and generally, could not be 

used to fulfill other taxonomic data requirements defined in the 1985 guidelines, and 3) more 
3

toxicologically relevant molecular descriptors and structural alerts need to be identified for use in building 

models for MOAs associated with pesticide active ingredients. 

a) Appendix A of the white paper includes a review of the utility of ECOSAR, TEST and the OECD 

toolbox for quantifying sensitive acute toxicity values for aquatic animals exposed to pesticides. 

Please comment on the strengths and weaknesses of the methods, results and conclusions 

associated with this review.

b) The analysis discussed in Appendix A of the white paper used empirical toxicity data for AChE 

inhibitors to evaluate the predictions of specific QSAR tools. Please discuss the applicability of 

the conclusions based on AChE inhibitors to other pesticide MOAs. Although not part of the 

current analysis, please comment on the ability of SAR tools to quantitatively predict the toxicity 

of chemicals with non-specific MOAs for sensitive animals (e.g., pesticide degradates and some 

herbicide with a narcosis MOA), that may be within the domain of applicability of these tools. 

c) Please comment on potential modifications to the existing versions of ECOSAR, TEST and the 

OECD toolbox that could improve their quantitative capability relative to estimating acute 

toxicity values for aquatic animals exposed to specific pesticides. For example, expansion of 

QSAR models within existing tools to better include pesticide active ingredients within their 

domain of applicability, expansion of the model training sets to cover taxa associated with data 

gaps, development of models based on MOA, inclusion of parameters other than the logarithm of 

the octanol-water partition coefficient (i.e., log P) to describe toxicity. 

12:00 P.M. Lunch

1:00 P.M. Charge Question 2: Web-ICE for Predicting Acute Toxicity for Aquatic 

Animals

The white paper investigated the use of Web-based Interspecies Correlation Estimation models (WebICE) to predict acute toxicity values and potentially fill data gaps (described in Appendix B). The review 

of the current version of Web-ICE suggests that, when using the minimum acute toxicity data for aquatic 

animals that are typically submitted to fulfill requirements under FIFRA (i.e., data for Daphnia magna, 

rainbow trout and bluegill sunfish), Web-ICE appears to generate the most precise predictions of toxicity 

for closely related fish species (e.g., within the same family). If toxicity data are available for either 

rainbow trout or bluegill sunfish, Web-ICE may be useful for predicting the toxicity of a chemical to 

some species of fish. The current review of this tool indicates that Web-ICE does not have sufficient data 

to fulfill the minimum data requirements across all taxa defined in the 1985 Guidelines when there are 

only acute surrogate data available for rainbow trout, bluegill and D. magna; however, this may change 

with future updates. 

a) Appendix B of the white paper includes a review of the utility of Web-ICE for quantifying 

sensitive acute toxicity values for aquatic animals exposed to pesticides. Please comment on the 

strengths and weaknesses of the methods, results and conclusions associated with this review.

b) Please comment on potential modifications to the existing version of Web ICE that could improve 

its ability to predict the acute toxicity values of pesticides to different species of aquatic animals. 

For example, expansion of the tool to consider MOA, addition of data for infrequently tested 

species that may fulfill the data requirements defined in the 1985 guidelines. 
4

2:00 P.M. Charge Question 3: Use of SSDs to estimate HC5 using varying amounts of 

data

As described in Appendix C, USEPA investigated the use of species sensitivity distributions (SSDs) with 

varying amounts of empirical data to estimate the fifth percentiles of sensitivity distributions of toxicity 

data (termed the “HC5”). Analyses performed by USEPA for this effort suggest that SSDs have limited 

utility when test data points are limited, specifically where biological diversity is not sufficient to 

represent the distribution of taxa sensitivity. The analyses further suggest that SSDs applied to datasets 

that satisfy existing taxonomic requirements with extrapolation constants (as defined in Appendix C) 

would likely result in lower and yet reasonable approximations of the HC5. 

a) Appendix C of the white paper includes a description of the analyses of SSDs. Please comment on 

the strengths and weaknesses of the methods, results and conclusions associated with this 

analysis.

In Appendix C, several potential avenues for future work on SSDs were described, including i) extension 

of methods for ordered data to all continuous distributions ii) development of stepwise methods, including 

decision points, for data analysis to incorporate information on the relationship of MOA and taxa 

sensitivity, and iii) the use of random effects methods for handling cases in which more than one test 

result is available for a given taxon.

b) Please comment upon additional analyses relative to SSDs that could be considered by USEPA 

that may result in improved confidence in estimates of HC5 values using various amounts of data 

that are typically available for registered pesticides.

3:00 P.M. Break

3:15 P.M. Charge Question 4: Extrapolation Factors for Estimating Acute HC5s with a 

Specified Level of Confidence

The USEPA OW’s aquatic life criteria (ALC) involve calculation of the "Final Acute Value" (FAV) as 

the fifth percentile of acute toxicity values for genera of aquatic animals, and impose certain minimum 

data requirements (MDRs) for such calculations. To provide some assessment of effects when 

insufficient data are available for calculating an FAV, USEPA’s Great Lakes Water Quality Guidance 

(GLWQG) specified extrapolation factors (EFs) by which the acute toxicity value for the most sensitive 

tested aquatic animal genus could be divided to provide a conservative estimate for what the FAV should 

be if sufficient data was available (U.S.EPA 1995). In this case, conservative estimates of the FAV are 

generated by accounting for uncertainty in possible EF values, which generally results in an 

underestimate of the FAV that may be generated using a data set that would be considered complete 

according to the 1985 Guidelines. The EFs incorporated into the GLWQG were based on analyses by 

Host et al. (1995) of toxicity test datasets used in freshwater ALC that existed at that time; these analyses 

involved repeatedly subsampling (resampling) of these datasets to assess the relationship of the lowest 

toxicity values in datasets of a specified size and composition to FAVs based on larger datasets. 

The analyses described in Appendix D of this white paper builds upon the analysis conducted by Host et 

al. (1995) by (a) utilizing more recent aquatic toxicity data and data for chemicals that do not have an 

ALC, (b) developing EFs for different MOAs to reduce uncertainty, (c) paying specific attention to EFs 

for OPP minimum data requirements for acute toxicity testing of aquatic animals, and (d) generating EFs 

using statistical distributions descriptive of acute toxicity values for different taxonomic groups and based 

on multiple chemicals, rather than resampling toxicity data for individual chemicals. These analyses
5

established the feasibility of establishing EFs for certain MOAs, demonstrated how a distributional rather 

than a resampling approach can more effectively exploit data to develop MOA-specific EFs, and 

documented the relationship between OPP and OW benchmarks. In addition, the current efforts 

considered how EF applicability and meaning might be affected, relative to the GLWQG, by different 

strategies for assigning reference HC5 and for summarizing EF distributions. 

a) Please comment on the extent to which consideration of MOA decreases uncertainty associated 

with HC5 values that are estimated using EFs.

b) Please comment on the strengths and limitations of both the resampling and distributional 

methodologies for developing MOA-specific EFs, and provide suggestions on their further 

development and application to other MOAs. Please provide suggestions for deriving EFs for

chemicals with MOAs that have limited amounts of empirical toxicity data. 

c) Please comment on the strengths and limitations of the different approaches in the Host et al. 

(1995) and the current work for assigning reference HC5s and summarizing EF distributions. 

4:30 P.M. Charge Question 5: Use of ACRs to estimate chronic toxicity endpoints or HC5 

values for acutely sensitive species

Chronic toxicity data are generally available for fewer species than are tested to determine acute toxicity. 

Acute-chronic ratios (ACRs) are a common tool used to estimate chronic effect thresholds for taxa 

lacking chronic toxicity data. Both OPP and OW currently use ACRs developed for specific chemicals to 

estimate chronic effect levels. ACR distributions have been developed for broad groups of chemicals 

without consideration of MOA or taxa (e.g., mixed pesticides by TenBrook et al. 2010; all chemicals by 

Host et al. 1995). Appendix E of the white paper considers the application of ACRs developed for 

chemicals within the same MOA to estimate chronic effects for chemicals with the same MOA and 

lacking any chemical-specific ACRs. Analysis of ACR data specifically for AChE inhibitors identified 

patterns in the ACR distributions. Most notably, ACRs for invertebrates were smaller than those for fish. 

Although fish had larger ACRs, this did not translate to higher chronic sensitivity of fish to AChE 

inhibitors, because of their very low acute sensitivity. In fact, analyses showed that concentrations 

protective of acute toxicity to invertebrates would simultaneously protect fish from chronic effects. By 

extension, for AChE inhibitors, applying an invertebrate-based ACR to the acute HC5 (i.e., fifth 

percentile of a sensitivity distribution) should provide a chronic HC5 protective of both fish and 

invertebrates. When comparing ACRs developed for broad groups of chemicals and taxa to ACRs for 

aquatic invertebrates exposed to AChE inhibitors, they were approximately 2 fold different. 

a) Please comment on the strengths and weaknesses of using chemical-specific ACRs to estimate 

chronic effect thresholds for other species and taxa.

b) Please comment on the strengths and weakness of applying “default” ACRs derived from other 

chemicals to extrapolate from an acute HC5 to a chronic HC5, including the relative merits of 

values derived for MOA-specific (e.g., for AChE inhibitors) or more generalized (e.g., Host et al. 

1995) distributions.

c) Are there other methods for estimating a chronic HC5 that the panel believes would be 

technically superior to ACR-based approaches? For example, TCE models (described in USEPA 

2010a), distributional approaches (e.g., de Zwart 2002, Douboudin et al. 2004; described in 

USEPA 2010b).

5:30 P.M. Adjournment
6

Thursday, February 2, 2012

9:00 A.M. Opening of Meeting and Administrative Procedures – Sharlene Matten, Ph.D., 

Designated Federal Official, Office of Science Coordination and Policy, EPA

9:05 A.M. Introduction and Identification of Panel Members – Janice Chambers, Ph.D., 

DABT, FIFRA Scientific Advisory Panel, Session Chair

9:10 A.M. Follow-up From Previous Day’s Meeting – Kristina Garber, M.S., Office of 

Pesticide Programs, EPA

9:20 A.M. Panel Discussion of Charge Question 5 cont’d

10:30 A.M. Break

10:45 A.M. Charge Question 6: Estimating the HC5 for Aquatic Plants

As with animals, there has been uncertainty regarding the extent to which available data reflect the range 

of sensitivities that may be present for aquatic plants. This effort focuses on the potential uses of EFs and 

SSDs to estimate the HC5 relevant to aquatic plants. As described in Appendix F, the primary analyses 

investigated the use of the standard aquatic plant species submitted to fulfill FIFRA data requirements in 

estimating the HC5. These species, which are referred to in the white paper as “the FIFRA-5” include: 

Pseudokirchneriella subcapitata (a freshwater green alga), Anabaena flos-aquae (a freshwater 

cyanobacterium), Navicula pelliculosa (a freshwater diatom), Skeletonema costatum (a saltwater diatom) 

and Lemna gibba (the aquatic vascular plant, duckweed). The analysis described in Appendix F

suggested that estimating the HC5 using the FIFRA-5 will result in a reasonable approximation of the 

HC5 of an aquatic plant community. 

a) Appendix F of the white paper includes an analysis of the use of EFs and SSDs combined with the 

FIFRA-5 to estimate the HC5 for aquatic plants. Please comment on the strengths and 

weaknesses of the methods, results and conclusions associated with this analysis.

b) Please comment on other aquatic plant species or test endpoints that may be considered in order 

to generate more certain estimates of the HC5 for aquatic plants.

c) Please comment on the strengths and limitations of normalizing plant toxicity endpoints to a 

standard metric (i.e., EC50 for growth rate).

d) Please comment on the extent to which consideration of MOA may decrease uncertainty 

associated with HC5 values for aquatic plants. 

12:30 P.M. Lunch

1:30 P.M. Continued Panel Discussion (as necessary)

3:00 P.M. Adjournment

Please be advised that agenda times are approximate; when the discussion for one topic is completed, 

discussions for the next topic will begin. For further information, please contact the Designated Federal 

Official for this meeting, Dr. Sharlene Matten, telephone: (202)-564-0130, fax: (202) 564-8382, or email: 

matten.sharlene@epa.gov.