Review of Draft Trichloroethylene Health Risk Assessment:

0,38

MB

Synthesis and Characterization

83

stron

5911

ID

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

2002

rok

TABLE OF CONTENTS

1. EXECUTIVE SUMMARY OF RESPONSES TO CHARGE QUESTIONS . 1

2. INTRODUCTION 4

2.1. Background 4

2.2. Process for Developing this Report 5

3. CHARGE QUESTION 1 6

3.1. Agency Charge Question and Suggested Areas for Inquiry . 6

3.2. Panel Response . 6

4. CHARGE QUESTION 2 10

4.1. Agency Charge Question and Suggested Areas for Inquiry 10

4.2. Panel Response 10

4.2.1. Cancer Classification for TCE . 10

4.2.2. Human Epidemiological Studies 11

4.2.3. Animal Toxicology 13

5. CHARGE QUESTION 3 16

5.1. Agency Charge Question and Suggested Areas for Inquiry 16

5.2. Panel Response 16

6. CHARGE QUESTION 4 18

6.1. Agency Charge Question and Suggested Areas for Inquiry 18

6.2. Panel Response 18

6.2.1. Multiple Critical Effects: Does the draft assessment adequately characterize the data at each

site of toxicity and focus on an appropriate subset of critical effects? . 18

6.2.2. Modes of Action of TCE Toxicity 20

6.2.3. Uncertainty Factors - Areas of Agreement and Differences Within the Panel 20

7. CHARGE QUESTION 5 25

7.1. Agency Charge Question and Suggested Areas for Inquiry 25

7.2.1. Panel Response . 25

7.2.1.1 Clarification of the Cancer Slope Factors 25

7.2.1.2 Suitability and Use of the Cancer Slope Factors 26

7.2.1.3 Improved Mediation of the Cancer Slope Factors . 27

7.2.2. Further Studies to Be Included . 28

7.2.3. Linear or Nonlinear Approach . 28

7.2.4. Sensitive Populations 29

7.2.5. For Further Consideration . 29

8. CHARGE QUESTION 6 30

8.1. Agency Charge Question and Suggested Areas for Inquiry 30

8.2. Panel Response 30

8.2.1. Modeling 31

8.2.2. Uncertainty Analysis . 32

8.2.3. Data Availability 33

8.2.4. Markov-Chain Monte Carlo (MCMC) . 34

9. CHARGE QUESTION 7 35

9.1. Agency Charge Question and Suggested Areas for Inquiry 35

9.2. Panel Response 35

10. CHARGE QUESTION 8 . 38

10.1. Agency Charge Question and Suggested Areas for Inquiry . 38

10.2. Panel Response . 38

11. CHARGE QUESTION 9 . 39

11.1. Agency Charge Question and Suggested Areas for Inquiry . 39

11.2. Panel Response . 39

11.2.1. Major Summary Consensus Points of the Panel . 39

11.2.2 Background to the Panel's Conclusions 40

11.2.3. How the Draft Assessment Can Be Improved 44

REFERENCES . R-1

APPENDIX A

SPECIFIC PANEL COMMENTS ON THE AGENCY'S ASSESSMENT OF NONCANCER

ENDPOINTS . A-1

1. Specific Comments on Hazard Characterization for Noncancer Endpoints A-1

1.1. Liver Effects . A-1

1.2. Kidney Effects . A-1

1.3. Developmental Effects . A-2

1.4. Neurotoxicity Effects A-3

1.5. Endocrine System Effects and Reproductive Toxicity Effects A-3

2. Specific Comments on Uncertainty Factors for NonCancer Endpoints . A-4

2.1. Human Variation A-4

2.2. Animal-to-Human Uncertainty . A-5

2.3. Subchronic-to-Chronic Uncertainty . A-5

2.4. LOAEL-to-NOAEL Uncertainty . A-6

2.5. Other Factors . A-9

APPENDIX B

RECENT RESEARCH ON GENERAL PHARMACOKINETIC DIFFERENCES BETWEEN

CHILDREN OF VARIOUS AGES AND ADULTS . B-1

APPENDIX C

Biosketches of Members of the US EPA Science Advisory Board (SAB) Trichloroethylene Health

Risk Assessment: Synthesis and Characterization Review Panel (TCE Review Panel)C-1