# AGENDA

**Meeting of the Federal Insecticide, Fungicide, and Rodenticide Act**  **Scientific Advisory Panel (FIFRA SAP)** 

**to Consider and Review Scientific Issues Associated with the**  **Proposed Endocrine Disruptor Screening Program (EDSP) Tier Ecotoxicity Tests**  **June 25 -**  **28, 2013 Docket Number: EPA** **- HQ**  **- OPP**  **- 2013**  **- 0182**  **OPP Docket Tel: 703 -**  **305 -**  **5805 Please note that all times are approximate**  **(See note at the end of the Agenda) Tuesday,**  **June 25 , 2013**  **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** 

– Martha Sandy , Ph.D., Session Chair,

F IFRA Scientific Advisory Panel **9: 1**  **5 A.M. Opening Remarks** 

– Steven Knott, Deputy Director, Office of Science Coordination and Policy

and Steven Bradbury, Ph.D. Director, O ffice of Pesticide Programs, EPA **9: 25**  **A.M. Overview of**  **EDSP and Proposed Tier 2 Ecotoxicity Tests** 

– Mary Manibusan, Director,

Exposure Assessment Coordination and Policy Division , Office of Science Coordination and Policy, EPA **10:00 A.M.**  **Break 10:10**  **A.M. Japanese Quail Two**  **- generation Toxicity**  **Test**

**–** Les lie Touart , Ph.D., Exposure Assessment

Coordination and Policy Division, Office of Science Coordination and Policy, EPA **11:10 A.M.**  **Medaka Multigeneration Toxicity Test** 

**–** Rodney Johnson, Ph.D., Mid

- Continent Ecology

Division, National Health and Environmental Effects Research Laboratory

– Duluth, Off ice of Research and Development, EPA **12: 10**  **P.M. Lunch**  **1:10 P**  **.M. Larval Amphibian Growth and Development Assay** 

**–** Sigmund Degitz, Ph.D., Mid

- Continent

Ecology Division, National Health and Environmental Effects Research Laboratory

– Duluth, Office of Research and Development, EPA **2:30 P.M.**  **Break 2:40**  **P.M. Mysid Two**  **- generation Toxicity Test and Harpacticoid Copepod Development &** 

**Reproduction Test**

**–** Leslie Touart, Ph.D., Exposure Assessment Coordination and Policy Division, Office of Science Coordination and Policy, EPA **3:40 P.M.**  **Break 3:45**  **P.M. Public Comments**  **5: 45**  **P.M. Adjournment** 

# AGENDA

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### Wednesday, **June 26 , 2013**  **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 a**  **nd Identification of Panel Members**

– Martha Sandy , Ph.D., Session Chair ,

FIFRA Scientif

ic Advisory Panel **9:10 A.M. Follow**  **- up**  **f rom Previous Day’s Meeting** 

– Mary Manibusan, Director, Exposure Assessment Coordination and Policy Division, Office of Science Coordination and Policy, EPA **9:20 A.M. Additional**  **Public Comments ( if needed** **) 10:2**  **0 A.M. Break**  **10:3 0 A.M.**  **Panel Discussion of Charge Questions JAPANESE QUAIL TWO**  **- GENERATION TEST (JQTT)**  **JQTT Question**  **1** A rationale for the test method should be available, including a clear statement of scientific basis and the regulatory purpo se and need for the test method. The EDSTAC described the Tier 2 tests as having the purpose to “ characterize the n ature, likelihood, and dose

- response relationship of endocrine disruption of estrogen, androgen, and thyroid in humans and wildlife .” Tier 2 tests were designed to be definitive tests that generate sufficient data to characterize the specific hazard of the substance and provide sufficient information on dose

- response and adverse effects to permit risk decisions. **Please comment on the rationale and purpose of the assay as part of the Tier 2 testing in the EDSP, as described in Sections 2.5 and 2.6 of the J**  **QTT ISR. JQTT**  **Question 2**  Test methods and their associated endpoint(s) should be scientifically relevant to the biological processes of interest and should be demonstrated to be responsive to the specific type of effect/toxicity of interest. Each species presents unique characteristics from a biological perspective and allows for specialized endpoints to address a specific toxicological mode of action. **Please comment on the biological and toxicological relevance of the assay in regards to the stated purp ose of**  **characterizing endocrine disruptors, as described in Sections 3 and 4 of the JQTT ISR. JQTT**  **Question 3**  **JQTT Question 3.1** The test protocol should be sufficiently detailed and should include a description of what is measured and how it is measure d. The selection of endpoints within the assay should be reflective of the biological processes of interest and the endpoints should be intrinsically relevant and have established sensitivity. The test protocol should demonstrate the ability to measure the endpoints and provide adequate performance criteria for evaluation. **Please comment on the selection, optim ization and demonstration of the assay endpoints, as outlined in Sections**  **4 and 5 of the JQTT ISR. JQTT Question 3.2**  Pathological evaluation of histological tissue preparations is an established, sensitive and integral endpoint in the assessment of effects in long term in vivo assays. The tissues targeted for histopathological evaluation should be shown to be sensitive to exposure and relevant to a mode of action or pathway determination. Tissue samples from several organs or glands ( e.g. , kidney, liver, thyroid, gonads) underwent histopathological examination in the

# AGENDA

3

JQTT inter

- laboratory validation and a discussion of histopathology as an endpoint is provided in Section 4.1.13 of the JQTT ISR. **Please comment on the value of histopathological analyses in the JQTT assay for each of the tissue types examined and what (if any) critical inform**  **ation is gained from their inclu**  **sion or would be lost if histology were not examined.**  

### 12:00 P.M. **Lunch 1:00 P.M.**  **JQTT Charge Questions (cont’d** **) JQTT**  **Question 4**  Demonstration of the test method performance should be based on the testing of reference chemicals representative of the ty pes of substances for which the test method will be used. Test substances should adequately represent an appropriate range of respons es and physical/chemical properties for which the test method is proposed to be appropriate. The selection of the most appropriate statistical approaches depends in part on the nature of the data and also on the design of the validation study. Statistical and non

- statistical methods used to analyze should be described. **Please comment on the selection of test substances and methods (analytical and statistical where appropriate) chosen for the dem**  **onstration and validation of the JQTT assay. JQTT**  **Question 5**  Considering the variability inherent in biological and chemical test methods, a test method needs to be repeatable and reproducible. A test is robust and reliable if the results are repeatable and reproducible within a laboratory and between different lab oratories, respectively. A test protocol should provide sufficient guidance to ensure proper and consistent performance across labs and chemicals. **Please comment on the test method robustness and reliability and the repeatability and reproducibility of th e results**  **obtained with the JQTT assay. JQTT**  **Question 6**  The test protocol should be descriptive enough to be fully transferable to a competent laboratory. The protocol should describe the methodology of the assay in a clear and concise manner so that a laboratory could comprehend the objective, conduct the assay, observe and measure prescribed endpoints, compile and prepare data for statistical analyses, and report the results. Section 6 of the JQTT ISR outlines the process of and challenges experienced in the inter

- laboratory studies. **Please comment on the tra nsferability across labs and provide any suggestions or recommendations for**  **im provement of the JQTT assay.**  

### 2: **45 P.M.**  **Break 3:00**  **P.M. JQTT Charge Questions (cont’d)**  **JQTT Question**  **7** The purpose of the validation process is to determine the readiness of a test for inclusion in a testing program. A component of readiness of a test is the evaluation of the usefulness and limitations of the test, including the classes and types of te st su bstances that can and cannot be tested. **Please comment on the strengths and/or limitations of the JQTT assay, as described in Section 7 of the JQTT ISR. JQTT**  **Question 8**  There is sufficient evidence to indicate that EDCs can disrupt normal development and reproductive success, however the sensitivity of the F2 generation compared to the P0 or F1 is less clearly defined. In the JQTT, there is an increase in endpoint CVs with each subsequent generation (JQTT ISR Table 6

- 4), which indicates decreased power o f discrimination. **Please comment from a scientific and risk assessment perspective on the value added of m**  **ultiple generations in the JQTT assay.** 

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### 3:55 **P.M. Break**  **4: 00**  **P.M. Panel Discussion of Charge Questions**  **(cont’d)**

**MEDAKA MULTIGENERATION TOXICITY TEST (MMT)**  Section 5 of the MMT ISR outlines the EPA proposed Medaka Reproduction Test (MRT) assay which utilizes the culmination of knowledge and experience gained from many successive U.S. and Japanese studies over multiple years. **MMT Question**  **1** A rationale for the test method should be available, including a clear statement of scientific basis and the regulatory purpose and need for the test method. The EDSTAC introduced the Tier 2 tests as having the purpose to “ characterize the nature, likelihood , and dose

- response relationship of endocrine disruption of estrogen, androgen, and thyroid in humans and wildlife .” Tier 2 tests were designed to be definitive tests which generate sufficient data to characterize the specific hazard of the substance and p rovide sufficient information on dose

- response and adverse effects to permit risk decisions. **Please comment on the rationale and purpose of the assay as part of the Tier 2 testing in the EDSP, as described in Sections 2.1 and 2.2 of the MMT ISR.**  **MMT Que**  **stion 2**  Test methods and their associated endpoint(s) should be scientifically relevant to the biological processes of interest and should be demonstrated to be responsive to the specific type of effect/toxicity of interest. Each species presents unique characteri stics from a biological perspective and allows for specialized endpoints to address a specific toxicological mode of action. **Please comment on the biological and toxicological relevance of the assay in regards to the stated purpose of characterizing endoc**  **rine disruptors, as described in Section 3 of the MMT. MMT**  **Question 3**  The test protocol should be sufficiently detailed and should include a description of what is measured and how it is measured. The selection of endpoints within the assay should be refl ective of the biological processes of interest and the endpoints should be intrinsically relevant and have established sensitivity. The test protocol should demonstrate the ability to measure the endpoints and provide adequate performance criteria for evaluation. **Please comment on the selection, optim ization and demonstration of the assay endpoints, as outlined in Section 3 of**  **the MMT ISR.** 

### 5:30 P.M. **Adjourn ment**  **Thursday, June 27**  **, 2013 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**

– Martha Sandy , Ph.D., Session Chair,

FIFRA Scientific Advisory Panel **9:10 A.M.**  **Follow -**  **up fro m Previous Day’s Meeting** 

– Mary Manibusan, Director, Exposure Assessment

Coordination and Policy Division, Office of Science Coordination and Policy, EPA **9:20 A.M.**  **MMT Test Charge Questions (cont’d)**

# AGENDA

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**MMT Question**  **4** Demonstration of the test method performance should be based on the testing of reference chemicals representative of the ty pes of substances for which the test method will be used. Test substances should adequately represent an appropriate range of responses and physical/chemical properti es for which the test method is proposed to be appropriate. The selection of the most appropriate statistical approaches depends in part on the nature of the data and also on the design of the validation study. Statistical and non

- statistical methods used to analyze should be described. **Please comment on the selection of test substances and methods (analytical and statistical where appropriate) chosen for the dem**  **onstration and validation of the MMT and MRT assays. MMT**  **Question 5**  Considering the variabil ity inherent in biological and chemical test methods, a test method needs to be repeatable and reproducible. A test is robust and reliable if the results are repeatable and reproducible within a laboratory and between different laboratories, respectively. A test protocol should provide sufficient guidance to ensure proper and consistent performance across labs and chemicals. **Please comment on the test method robustness and reliability and the repeatability and reproducibility of the results obtained with t**  **he MTT and MRT assays.** 

### 10:20 **A.M. Break**  **10:30 A**  **.M .**  **MMT Test Charge Questions (cont’d) MMT**  **Question 6**  The test protocol should be descriptive enough to be fully transferable to a functional laboratory. The protocol should describe the methodology of the assay in a clear and concise manner so that a laboratory could comprehend the objective, conduct the ass ay, observe and measure prescribed endpoints, compile and prepare data for statistical analyses, and report the results. Section 4 of the MMT ISR outlines the process of and challenges experienced in the inter

- laboratory studies and Section 5 presents the optimization and proposed Medaka Reproduction Test (MRT) protocol. **Please comment on the transferability across labs and provide any suggestions or recommendations for im** **provement of the.MMT and MRT assays. MMT**  **Question 7**  The purpose of the validation process is to determine the readiness of a test for inclusion in a testing program. A component of readiness of a test is the evaluation of the usefulness and limitations of the test, including the classes and types of te st substances that can and cannot b e tested. **Please comment on the strengths and/or limitations of the MMT and MRT assays. MMT**  **Question 8**  There is sufficient evidence to indicate that EDCs can disrupt normal development and reproductive success, however the value added of the F2 generation compared to the P0 or F1 is less clearly defined. The EPA is proposing the Medaka Reproduction Test (MRT) as an EDSP Tier 2 assay. The MRT test terminates after the F2 embryo hatch, and a rationale for the proposed protocol is provided in Section 5 of the MMT ISR. **Please comment on the Agency’s rationale that the value added by the F2 generation is not sufficient to warrant its inclusion in the Tier 2 fish test protocol.**  **MMT Question**  **9** It is the Agency’s opinion that the outcomes of the various MMT trials have pro vided enough information to recommend a medaka reproduction test (MRT) for use as the fish test in Tier 2 of the EDSP. T wo major changes from the MMT are proposed, i.e., an increase in the number of replicates per treatment for evaluating effects on reproduction, and terminating the test after the embryos hatch in F2. Other proposed changes include minimizing the collection of endpoint data from F0, and evaluating pathology in only the F1 adults sampled after the assessment of reproduction.

# AGENDA

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Overall, the authors conclude that both the MMT and the MRT are transferable methods and are capable of adequately characterizing potential disruption of the endocrine system by putative endocrine disrupting chemicals. However, the MRT is recommended as the preferred ED SP Tier 2 test method for fish because it is less resource intensive with improved statistical power, appears to be as sensitive, and is better able to ensure consistent findings when performed routinely by testing laboratories. **Please comment on the scie ntific rationale of the Agency’s proposed Tier 2 fish test, the MRT, with respect to**  **statistical power, sensitivity, and consistency in perform ance across laboratories. In addition, please comment on the**  **adequacy of the MRT to characterize potential endocr ine disruption, a require**  **ment of Tier 2 of the EDSP.** 

### 12:15 **P.M. Lunch**  **1:15 P.M**  **. Panel Discussion of Charge Questions** 

**LARVAL AMPHIBIAN GROWTH AND DEVELOPMENT ASSAY (LAGDA) LAGDA**  **Question 1**  A rationale for the test method should be available, including a clear statement of scientific basis and the regulatory purpose and need for the test method. The EDSTAC introduced the Tier 2 tests as having the purpose to “ characterize the nature, likelihood, and dose

- response relationship of endocrine disruption of estrogen, androgen, and thyroid in humans and wildlife .” Tier 2 tests were designed to be definitive tests which generate sufficient data to characterize the specific hazard of the substance and provide sufficient information on dose

- response and adverse ef fects to permit risk decisions. **Please comment on the rationale and purpose of the assay as part of the Tier 2 testing in the EDSP, as described in Section 3 of the LAGDA ISR.**  **LAGDA Question**  **2** Test methods and their associated endpoint(s) should be sci entifically relevant to the biological processes of interest and should be demonstrated to be responsive to the specific type of effect/toxicity of interest. Each species presents unique characteristics from a biological perspective and allows for speciali zed endpoints to address a specific toxicological mode of action. **Please comment on the biological and toxicological relevance of the assay in regards to the stated purpose of characterizing endocrine disruptors, as described in Sections 3 and 4 of the LAG** **DA ISR. LAGDA**  **Question 3 LAGDA Question 3.1**  The test protocol should be sufficiently detailed and should include a description of what is measured and how it is measured. The selection of endpoints within the assay should be reflective of the biological processes of interest and the endpoints should be intrinsically relevant and have established sensitivity. The test protocol should demonstrate the ability to measure the endpoints and provide adequate performance criteria for evaluation. **Please comment on the selection, optim** **ization and demonstration of the assay endpoints, as outlined in Sections 3 and 4 of the LAGDA ISR.**  **LAGDA Question 3.2** Three of the four labs in the inter

- laboratory validation of the LAGDA were unsuccessful in properly performing the thyroxine (T4) analyses using commercially available enzyme

- linked Immunosorbent assay (ELISA) kits with antibodies specific for human or canine T4. Subsequently, the EPA developed an extraction method (Section 5.3.2) and presents a revised ELISA metho d for measuring T4 in amphibian samples in Appendix 7 of the LAGDA ISR. **Please comment on the technical feasibility, reproducibility, and accuracy of the revised ELISA T4 measurement method. Provide any recommendations regarding additional guidance to ens**  **ure the reproducibility of T4 m**  **easurem ents.**  

### 2: **45 P.M.**  **Break**

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### 3:00 **P.M. LAGDA Charge Questions (cont’d)**  **LAGDA Question 3.3** Vitellogenin (VTG) is an established biomarker of estrogenic exposure and is used as a key endpoint in endocrine disruptor testing. There is currently not a standardized commercial source for Xenopus laevis VTG antibodies for an ELISA. **Please comment on t he protocol for m**  **easuring and reporting VTG levels. Provide any recommendations regarding additional guidance to ensure the consistency, repeatability and reproducibility of VTG**  **measurements. LAGDA**  **Question 4**  Demonstration of the test method performance s hould be based on the testing of reference chemicals representative of the ty pes of substances for which the test method will be used. Test substances should adequately represent an appropriate range of responses and physical/chemical properties for which the test method is proposed to be appropriate. The selection of the most appropriate statistical approaches depends in part on the nature of the data and also on the design of the validation study. Statistical and non

- statistical methods used to analyze sh ould be described. **Please comment on the selection of test substances and methods (analytical and statistical where appropriate) chosen for the dem**  **onstration and validation of the LAGDA assay. LAGDA**  **Question 5**  Considering the variability inherent in bi ological and chemical test methods, a test method needs to be repeatable and reproducible. A test is robust and reliable if the results are repeatable and reproducible within a laboratory and between different laboratories, respectively. A test protocol sh ould provide sufficient guidance to ensure proper and consistent performance across labs and chemicals. **Please comment on the test method robustness and reliability and the repeatability and reproducibility of the results obtained with the LAGDA assay.**  **LAGDA Question**  **6** The test protocol should be descriptive enough to be fully transferable to a functional laboratory. The protocol should describe the methodology of the assay in a clear and concise manner so that a laboratory could comprehend the objective , conduct the assay, observe and measure prescribed endpoints, compile and prepare data for statistical analyses, and report the results. Sections 5 and 6 of the LAGDA ISR outline the process of and challenges experienced in the inter

- laboratory studies. **Please comment on the transferability across labs and provide any suggestions or recommendations for im** **provement of the LAGDA assay. LAGDA**  **Question 7**  The purpose of the validation process is to determine the readiness of a test for inclusion in a testing program. A component of readiness of a test is the evaluation of the usefulness and limitations of the test, including the classes and types of te st su bstances that can and cannot be tested. **Please comment on the strengths and/or limitations of the LAGDA assay.** 

### 5:30 P.M. **Adjournment**

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### Friday, **June 28 , 2013**  **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**

– Martha Sandy, Ph.D., Session Chair,

FIFRA Scientific Advisory Panel **9:10 A.M. Follow**  **- up from Previous Day’s Meeting** 

– Mary Manibusan, Director, Exposure Assessment

Coordination and Policy Division, Office of Science Coordination and Policy, EPA **9: 20**  **A.M. Panel Discussion of Charge Questions (cont’d)**  **MYSID TWO -**  **GENERATION TOXICITY TEST (MTTT) AND HARPACTICOID COPEPOD**

**DEVELOPMENT & REPRODUCTION TEST (HCDRT) MT**  **TT Question**  **1** A rationale for the test method should be available, including a clear statement of scientific basis and the regulatory purpo se and need for the test method. The EDSTAC introduced the Tier 2 tests as having the purpose to “ characterize the nature, likelihood, and dose

- response relationship of endocrine disruption of estrogen, androgen, and thyroid in humans and wildlife .” Although the hormones produced and used by invertebrates are not directly analogous to those of vertebrates (e.g., estrogen, androgen, and thyroid), growth, reproduction, development, and other aspects of invertebrate physiology and life cycle are known to be under endocrine control. EDSTAC went on to note that “ chemicals that affect these vertebrate hormones may also affect invertebrate hormones resulting in altered reproduction, development, and growth .” Tier 2 tests were designed to be definitive tests which generat e sufficient data to characterize the specific hazard of the substance and provide sufficient information on dose

- response and adverse effects to permit risk decisions. **Please comment on the rationale and purpose of the assay as part of the Tier 2 testing in the EDSP, as described in**  **Sections 2.1 and 2.2 of the MTTT ISR. MT**  **TT Question**  **2** Test methods and their associated endpoint(s) should be scientifically relevant to the biological processes of interest and should be demonstrated to be responsive to the specific type of effect/toxicity of interest. Each species presents unique characteristics from a biological perspective and allows for specialized endpoints to address a specific toxicological mode of action. **Please comment on the biological and toxicol ogical relevance of the assay in regards to the stated purpose of**  **characterizing endocrine disruptors, as described in Section 2 of the MTTT ISR.** 

### 10:20 A.M. **Break 10:30 A.M.**  **MTTT and HCDRT Charge Questions (cont’d) MT**  **TT Question**  **3** The test protocol should be sufficiently detailed and should include a description of what is measured and how it is measured. The selection of endpoints within the assay should be reflective of the biological processes of interest and the endpoints should be intrinsically relevant and have established sensitivity. The test protocol should demonstrate the ability to measure the endpoints and provide adequate performance criteria for evaluation. **Please comment on the selection, optim ization and demonstratio**  **n of the assay endpoints, as outlined in Sections 3 and 4 of the MTTT ISR.** 

# AGENDA

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**MT TT**  **Question 4**  **MT TT Question 4.1**  Demonstration of the test method performance should be based on the testing of reference chemicals representative of the types of substances for which the test method will be used. Test substances should adequately represent an appropriate range of responses and physical/chemical properties for which the test method is proposed to be appropriate. The selection of the most appropriate statistical approaches depends in part on the nature of the data and also on the design of the validation study. Statistical and non

- statistical methods used to analyze should be described. **Please comment on the selection of test substances and methods (analytical a nd statistical where appropriate)**  **chosen for the dem onstration and validation of the MTTT assay.**  **MT TT Question 4.2**  The proposed MTTT study design uses three replicates per control and treatment group and additional replicates require greater resources. **P lease comment on the proposed level of replication and the subsequent statistical analysis of the data.**  **MT TT**  **Question 5**  Considering the variability inherent in biological and chemical test methods, a test method needs to be repeatable and reproducible. A test is robust and reliable if the results are repeatable and reproducible within a laboratory and between different laboratories, respectively. A test protocol should provide sufficient guidance to ensure proper and consistent performance across labs and chemicals. **Please comment on the test method robustness and reliability and the repeatability and reproducibility of the results obtained with the MTTT assay.**  

### 12:00 P.M. **Lunch 1:00 P.M**  **MTTT and HCDRT Charge Questions (cont’d) MT**  **TT Question**  **6 MT**  **TT Question 6.1**  The test protocol should be descriptive enough to be fully transferable to a functional laboratory. The protocol should describe the methodology of the assay in a clear and concise manner so that a laboratory could comprehend the objective, co nduct the assay, observe and measure prescribed endpoints, compile and prepare data for statistical analyses, and report the results. Section 5 of the MTTT ISR outlines the process of and challenges experienced in the inter

- laboratory studies. **Please comme nt on the transferability across labs and provide any suggestions or**  **recommendations for improvem ent of the MTTT assay.**  **MT TT Question 6.2**  Based on the validation results using the two different invertebrate species, mysid (MTTT) and copepod (HCDRT), the EPA is proposing the mysid protocol as the preferred Tier 2 assay. **Please comment on the rationale to recommend the my**  **sid protocol as the preferred Tier 2 invertebrate assay, as described in Section 6.4 of the MTTT ISR.**  **MT TT**  **Question 7**  The purpose of the validation process is to determine the readiness of a test for inclusion in a testing program. A component of readiness of a test is the evaluation of the usefulness and limitations of the test, including the classes and types of te st su bstances that can and cannot be tested. **Please comment on the strengths and/or limitations of the assay, as described in Section 6 of the MTTT ISR.**

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**MT TT**  **Question 8**  There is sufficient evidence to indicate that EDCs can disrupt normal development and reproductive success, however the sensitivity of the F1 generation compared to the F0 is less clearly defined. **Please comment from a scientific and risk assessment perspective on the value added of m**  **ultiple generations in the MT**  **TT assay .**  

### 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 , t elephone: (202)

- 564
- 0130, fax: (202) 564

- 8382, or email: matten.sharlene@epa.gov.