Overzicht voortgang discussiepunten. Eric Verbruggen

Transcription

1 Overzicht voortgang discussiepunten Eric Verbruggen Discussion points

2 Contents 1. Introduction 2. Compartment 3. Persistence 4. Bioaccumulation Discussion Points

3 Timeline of EU PBT guidance Timeline: TGD 1996, PBT included in 2003 REACH implementation programs REACH guidance May 2008, update 2012 Annex XIII revised in 2011 New revision REACH guidance started Based on input from NL, discussed in previous workshop Input from scientific discussions, e.g. Pellston workshops Several issues identified partly policy related some purely scientific 3

4 Identified topics Topic Compartment of concern Temperature Non-extractable residue Hydrolysis Photolysis Field studies Multimedia modelling, overall persistence Dietary accumulation test Growth correction Half-life, metabolism Invertebrates Field data, trophic magnification P, B, and T Persistence Persistence Persistence Persistence Persistence Persistence Bioaccumulation Bioaccumulation Bioaccumulation Bioaccumulation Bioaccumulation 4

5 Compartment Which one? Testing in water, sediment, or soil? Persistence Bioaccumulation Toxicity P criteria are defined for water, soil and sediment B and ecot criteria are for aquatic species only! T for humans (plus secondary poisoning) is not compartment specific 5

6 Compartment - Persistence Compartment of concern? Exposure assessment Substantial mass holdup Use of multimedia modelling Included in REACH guidance document R11 Applied in several decisions of EChA Or providing most unequivocal results Aqueous test (OECD309) to circumvent nonextractable residue NER More guidance needed 6

7 Compartment- Bioaccumulation and toxicity No criteria for terrestrial and benthic organisms! Aquatic toxicity test difficult to perform Aqueous exposure hard to maintain Circumvented by feeding (OECD 305) Terrestrial/benthic tests difficult to interpret No obvious increase/decrease in regular endpoints Concentrations in mg/kg Sorption vs. Bioaccumulation/Toxicity Pore water as metric Biological half-life More guidance needed! 7

8 Persistence Temperature To what temperature do the criteria apply? Policy question!/? Retrospective analysis of formulation of criteria REACH Annex XIII: The information used for the purposes of assessment of the PBT/vPvB properties shall be based on data obtained under relevant conditions. REACH Guidance Document R7.b : Simulation tests: and a typical temperature that represents the particular environment. and Where possible simulation studies should be conducted at environmentally relevant temperatures Hydrolysis: For the PBT assessment purposes, the 10 C testing temperature is a good choice for tier 2 testing purposes. 8

9 Persistence - Temperature Update Reach Guidance Document R7.b (2014): Please note that 12 C is at present considered by authorities as the mean temperature of European surface waters and is required by the ECHA Member State Committee to be used as the testing temperature for new simulation degradation tests. 9 C for seawater? 20 C is used within PPP framework Harmonisation Policy Temperature correction Arrhenius equation? 9

10 Persistence Non-Extractable Residue (NER) Aspects of NER discussion Definition and nomenclature What is NER? What is Bound Residue (BR) Analysis Extraction procedures Theory Mechanisms of formation Implications Interpretation of results RA and PBT 10

11 Persistence Non-Extractable and Bound Residue ECETOC workshop defined Extractable: Extractable with aqueous and cold solvent extraction methods Non-extractable: Non-extractable with mild methods, but extractable with harsher extraction methods, e.g. refluxing Bound residue: Associated with solid matrix, covalent binding or similar Contradiction in definition of non-extractable Proposal for definition NER: Non-extractable even with harsher extraction methods, e.g. refluxing Total Residue Extractable Non Extractable Bound 11

12 Persistence - Formation of NER and BR Parent compound Metabolite Bound residue Chemical reaction with soil Non-extractable residue Entrapped, reduced bioavailability 12

13 Persistence - Problem Definition NER Everything extractable (mild and harsh) can be identified Parent compound Metabolites Mineralisation Bound residue can not be identified Only possible to quantify by LSC or similar after destruction Experimental: How to draw the line between not easily extractable and bound residue? Bioavailability vs. persistence Parent compound indicates persistence Metabolites/mineralisation indicate degradation Conceptual: Is bound residue formation useful information to conclude on persistence? 13

14 Persistence - Formation of NER and BR Parent compound Metabolite Bound residue Chemical reaction with soil Non-extractable residue Entrapped, reduced bioavailability 14

15 Persistence - DT50: Pragmatic approach Use ratio of extracted parent compound/total radioactivity What you see is what you get But what you don t see is what you won t get Strongly dependent on extraction procedure (parent)/(total) (parent)/(total radioactivity) Fraction remaining CP ZK Fraction remaining Standard soil 2.3 Arable soil Anaerobic standard soil Time [d] Time [d] 15

16 Persistence - DT50: Precautionary approach Sum of extracted parent compound and non-extractable residue divided by total radioactivity Assumes all non-extractable residue to be parent compound Strongly dependent on extraction procedure too (parent+bound residue)/(total) (parent+bound residue)/(total) Fraction remaining CP ZK Fraction remaining Standard soil 2.3 Arable soil Anaerobic standard soil Time [d] Time [d] 16

17 Persistence - DT50: Possible alternative approach Use ratio of extracted parent compound/total extracted amount Ignores all non-extractable residue Less dependent on extraction procedure less non extractable residue, less ambiguous interpretation (parent)/(total-bound residue) (parent)/(total-bound residue) Fraction remaining CP ZK Fraction remaining Standard soil 2.3 Arable soil Anaerobic standard soil Time [d] Time [d] 17

18 Persistence - NER: Possibilities Reduce NER: Improve extraction methods Range of solvents Heating, soxhlet, SFE Circumvent bound residue Persistence test in surface water (OECD 309) No bound residue Calculation of DT50s Break-out session 18

19 Persistence - Role of Hydrolysis and Photolysis Significant contribution to the overall half-life? Hydrolysis test in dissolved phase Strong adsorption may prevent hydrolysis Examples of some substances Rapid hydrolysis No mineralisation (degradation) Photolysis study has been commisioned by RIVM Role of direct photolysis is usually limited Surface layers only Dissolved only At daytime and under sunny conditions only 19

20 Persistence Other aspects How are field studies (monitoring data) taken into account? Use of field studies is mainlyfocussed on bioaccumulation What is the role of multimedia modelling? Overall persistence (Pov) Multimedia transfer Modeling Experimental (monitoring, simulation studies) 20

21 Bioaccumulation Dietary accumulation test Added in the revision of the OECD 305 test guideline Developed for poorly soluble compounds Artifical test design Food is contaminated Water is clean Flow-through system to eliminate aqueous exposure Endpoints No BCF, not directly comparable with B/vB criteria Elimination half-life BMF 21

22 Bioaccumulation - Dietary accumulation test BMF from OECD 305 not comparable with field BMF Field: simultaneous aqueous and dietary exposure OECD 305: aqueous exposure only BCF>5000, BMF <1 (Inoue et al, 2013) Depuration rate constant (k2) Equal to k2 from aqueous exposure Uptake rate constant (k1) estimated BCF=k1/k2 Debate about accuracy Environment Agency UK: 13 methods, s.d. 0.2 log unit Break-out session 22

23 Bioaccumulation Growth correction Juvenile fish in OECD 305 (rainbow trout, carp, bluegill) 30 Consume up to 3% of their body weight per day Grow fast, body weight increase of 3% per day High caloric content of diet Grow fat, doubling of lipid content in 28 days 1 to 3% of body weight per day keeps the lipid content at a relatively constant level during the test C fish [µg/kg ww ] Steady-state is not reached Kinetic fitting leads to higher BCF Growth correction results in even higher BCF Time [d] OECD still mentions kinetic and steady-state BCF 23

24 Bioaccumulation Half-lives Biological half-life is universal for all bioaccumulation processes BCF BMF BAF Suitable metric for B? Half-life is not independent of species Dependent on size (allometry) Dependent on metabolism capacity In vitro metabolism test (OECD guideline is in development) Hepatocytes or S9 Extrapolation to in vivo Variability in metabolism 24

25 Bioaccumulation Field data Trophic magnification studies Trophic magnification factor: Average increase in normalized concentration per trophic level 1000 TMF is reflection of biomagnification potential TMF is variable TMF is dependent on test set-up Environmental characteristics of ecosystem: benthic vs pelagic, lake vs river, marine vs fresh Choice of species: poikilotherms vs homeotherms, one taxon vs several taxa, inclusion of single species Concentration Trophic level Is biomagnification only concern for B? 25

26 Bioaccumulation Field data and monitoring Non-aquatic bioaccumulation Terrestrial magnification studies Screening terrestrial and marine mammals, human food chain log K ow > 2 log K oa > 5 6 Kelly et al. (2007) Half-lives in humans Weight-of-evidence (included in Annex XIII) 26