OECD GUIDELINE FOR THE TESTING OF CHEMICALS

Transkript

1 TG 442C OECD GUIDELINE FOR THE TESTING OF CHEMICALS In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA) INTRODUCTION in chemico in chemicoin vitro in silico in chemico in vitro OECD, (2015) 23

2 TG 442C INITIAL CONSIDERATIONS, APPLICABILITY AND LIMITATIONS in vitro in vivo OECD, (2015) 24

3 TG 442C in chemico PRINCIPLE OF THE TEST in chemico PROCEDURE OECD, (2015) 25

4 TG 442C Preparation of the cysteine or lysine-containing peptides 17. Stock solutions of C K Preparation of the test chemical OECD, (2015) 26

5 TG 442C Preparation of the positive control, reference controls and coelution controls Incubation of the test chemical with the cysteine and lysine peptide solutions Preparation of the HPLC standard calibration curve HPLC preparation and analysis OECD, (2015) 27

6 TG 442C DATA AND REPORTING Data evaluation C OECD, (2015) 28

7 TG 442C Acceptance criteria Prediction model Table1: Cysteine 1:10/lysine 1:50 prediction model 1 Mean of cysteine and lysine % depletion Reactivity Class DPRA Prediction 2 OECD, (2015) 29

8 TG 442C OECD, (2015) 30

9 TG 442C Table2: Cysteine 1:10 prediction model 1 Cysteine (Cys) % depletion Reactivity class DPRA prediction There might be other cases where Test report Test chemical o o o o o o o OECD, (2015) 31

10 TG 442C o o o o o Controls o o o o o o o o o o o o o o Preparation of peptides, positive control and test chemical OECD, (2015) 32

11 TG 442C HPLC instrument setting and analysis System suitability Analysis sequence o o o o o o o o o o o o o OECD, (2015) 33

12 TG 442C o o o Proficiency testing Discussion of the results Conclusion OECD, (2015) 34

13 TG 442C LITERATURE (1) (2) (3) (4) (5) (6) (7) et al. (8) et al. (9) et al. (10) (11) et al. (12) et al (13) et al. OECD, (2015) 35

14 TG 442C (14) et al (15) (16) (17) et al. (18) (19) et al. (20) (21) (22) (23) OECD, (2015) 36

15 TG 442C ANNEX 1 DEFINITIONS Accuracy: AOP (Adverse Outcome Pathway): in vivo Calibration curve: standard curve Coefficient of variation: Hazard: IATA (Integrated Approach to Testing and Assessment): Molecular Initiating Event: Mixture: Mono-constituent substance: Multi-constituent substance: Positive control: OECD, (2015) 37

16 TG 442C Reference control: Relevance: Reliability: Reproducibility: Sensitivity: Specificity: Substance: System suitability Test chemical: United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS): OECD, (2015) 38

17 TG 442C UVCB: Valid test method: OECD, (2015) 39

18 TG 442C ANNEX 2 PROFICIENCY SUBSTANCES In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay in vivo in vitro Proficiency substances CASRN Physical state In vivo prediction 1 DPRA Range 3 of % prediction 2 cysteine peptide depletion Range 3 of % lysine peptide depletion in vivo in vivo OECD, (2015) 40

19 TG 442C ANNEX 3 EXAMPLES OF ANALYSIS SEQUENCE Calibration standards and reference controls Co-elution controls Reference controls First set of replicates Second set of replicates Third set of replicates Reference controls OECD, (2015) 41

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