GUIDELINES FOR SETTING SPECIFIC CONCENTRATION LIMITS FOR

0,13

MB

CARCINOGENS IN ANNEX I OF DIRECTIVE 67/548/EEC - INCLUSION OF

29

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POTENCY CONSIDERATIONS

4397

ID

Scientific Committee for Toxicity, Ecotoxicity and the Environment

2003

rok

TABLE OF CONTENTS

1. EXECUTIVE SUMMARY 3

2. INTRODUCTION 3

2.1 General description of the EU classification system for carcinogens 3

2.2 Need for considering potency in setting specific concentration limits for carcinogens 4

2.3 Descriptors of tumorigenic dose 5

2.4 Procedure 7

2.5 Cases where potency evaluation are difficult or unfeasible 8

3. DETERMINATION OF THE CARCINOGENIC POTENCY 8

3.1 Determination of the T25 value 8

3.2 When to use T25 11

3.3 Human data 11

3.4 Provisional evaluation of potency classification 11

4. ELEMENTS THAT MAY MODIFY THE PRELIMINARY POTENCY EVALUATION 12

4.1 Dose-response relationship 12

4.2 Site/species/strain/gender activity 12

4.3 Mechanisms including genotoxicity 13

4.4 Mechanistic relevance to humans 13

4.5 Toxicokinetics 14

4.6 Other elements relevant to potency evaluation 14

4.7 Finalizing potency evaluation 14

5. ASSIGNING SPECIFIC CONCENTRATION LIMITS 15

5.1 Specific concentration limits for Category 1 carcinogens 15

5.2 Specific concentration limits for Category 2 carcinogens 15

5.3 Specific concentration limits for Category 3 carcinogens 15

6. REFERENCES 16

ANNEX Illustration of the use of information which affect the potency classification