ECOLOGICAL THRESHOLD FOR TOXICOLOGIC CONCERN

Transcription

1 ECOLOGICAL THRESHOLD FOR TOXICOLOGIC CONCERN Scott E. Belanger, PhD Co-Chair, Animal Alternatives in Environmental Risk Assessment Committee Procter & Gamble, Global Product Stewardship

2 IT S ALL ABOUT THE TEAM! Who Mace Barron Amy Beasley Scott Belanger Mark Bonnell Jessica Brill Dan Chang Dick De Zwart Michelle Embry Brianna Farr Marlies Halder Aude Kienzler Teresa Norberg-King Ryan Otter Hans Sanderson Peter Wilson Affiliation USEPA Gulf Breeze Dow P&G ECCC P&G USEPA OCSPP Mermayde ILSI-HESI ILSI-HESI EC JRC EC JRC USEPA Duluth Middle Tennessee State Univ Aarhus University Sanofi Theory Database development R programming Web implementation Stress testing Initial application Publications/presentations Outreach The Web ACCESS db R tools

3 Environmental risk science is filled with extrapolation The scope of the need What and how we protect the environment (protection goals) Tools we use A new (cool) tool that has promise Ways to bend the information and what comes next

4 Freshwater ecosystems Marine ecosystems Estuarine systems Wastewater treatment plant ecosystems Sediment/benthic ecosystems Terrestrial and agricultural ecosystems

5 Considerations that differentiate human and environmental risk assessment Protection target: all possible species in all types of ecosystems o 8.7 million described species (31,000 fish species alone) in all ecosystem types o True goal - protection of ecosystem services Energy flow Nutrient flow Biodiversity Amount of available data Often means product level exposure versus summed exposures from all uses of a chemical. Total industry volumes are necessary for assessments and as well as understanding effluents which aggregate many sources Exceptional reliance on biostatistics and extrapolation

6 You must understand all types and habits of life in the water to protect them from chemical harm Algae Fungi Protozoans Macroinvertebrates Fish Dr. Ruth Patrick, Academy of Natural Sciences of Philadelphia Studies on the Conestoga River and Potomac River (ca. 1947)

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8 Challenges for ERA are many A large number of compounds are in commerce that lack data Many low to medium volume compounds, lack QSARs, not well studied To fill the data gaps will require tremendous levels of animal testing, financial resources and time We need to assist prioritization and take advantage of what we do know (and that is quite a lot!) o Prioritization for regulatory actions of various kinds o Prioritization for product development guidance

9 A confluence of possibilities Data availability is greater than ever before (REACH, HPV, Canadian CMP, etc.) this qualifies as BIG DATA Computational power is available to do more, faster than ever before Sufficient understanding exists on chemical structure, mode of action, and chemical grouping on a wide array of compounds and organisms to construct empirical models of aquatic toxicity patterns

10 Eco-TTC Develop the ecotoxicological Threshold of Toxicologic Concern (eco-ttc) as a new tool to provide early hazard guidance for the aquatic environment Similar to human safety TTC - establishes an exposure level for chemicals below which no appreciable risk to human health or the environment is expected, based on a de minimis value for toxicity identified for many chemicals Eco-TTCs require a somewhat different endpoint approach versus than used in human safety (many TTCs focus on distributions for a particular hazard endpoint)

11 It is All About the (Eco)System! Environmental safe concentration is predicted by PNEC (Predicted No Effect Concentration for ecosystems) Distribution of most PNEC is a function of: sensitive taxa to chemicals o Numbers and types of species tested o Acute versus chronic toxicity test data availability o Regulatory environment o Recognize that a singular most sensitive species is mythology PNECs should protect system biodiversity and essential ecological functions Algae Daphnia Fish A=D A=D=F

12 Eco-TTC Definition of ecological Threshold of Toxicologic Concern o Lower 5 th percentile of PNECs for a group of similar chemicals, defined by a mode of action, a chemical grouping attribute, or a functional use o HESI Animal Alternatives in Environment Risk Assessment Committee recognized this as a golden opportunity in the animal alternative realm and it is still mainstream ERA To achieve this we need: o Sufficient chemical coverage o Diverse toxicity test data o A means to bin chemicals o PNEC derivation processes all available these are specific to a region

13 Eco-TTC Development Database construction Vetting and curation of base information, primary and secondary sources of information Chemistry organized by CASNO o SMILES o Phys-chem properties o Mode of Action Taxonomy of test species o Taxonomic hierarchy o Naming resolution o Trophic position/categorization Ecotoxicology Link together in MYSQL through a web-enabled platform ~5600 CASNO ~2400 species ~120,000 studies

14 What group is being assessed? Eukaryotic photosynthetic organisms (algae)? Eco-TTC Development Duration of the study Is the taxon known to be slow growing? Yes <24 hrs Do not consider further (exclude) Example for algae Prokaryotic photosynthetic organisms (Cyanobacteria, bluegreen algae)? for identifying toxicity data as acute or chronic culture, depending on Defined processes toxicity o Endpoints of interest are those with regulatory relevance Eurkaryotic, nonphotosynthetic stage hrs for most species; up to d, testing system microbes or strictly non further here; go to o These differ by type of organism microbe, plant, amphibian, fish, invertebrate pohotosynthetic multicellular organisms (e.g., Tetrahymena) Prokaryotic nonphotosynthetic microbes (e.g., Pseudomonas, Vibrio, Microtox) Do not consider microinvertebrate process Do not consider further (excluded) Do not consider further (exclude) No <24 hrs hrs for most species Physiological or biochemical only Include for further consideration Do not consider further (exclude) Include for further consideration What endpoint was measured? Acute Toxicity: NOECs for acute toxicity are not to be used Acute Toxicity: Endpoint expressed as duration and EC50 (boundary of EC30 to EC70) Terminal cell density or biomass sensu USEPA Photosynthesis, biomass (pigments, cell density, biomass) Chronic Toxicity: Use lowest ECx that is biologically meaningful (priority); use lowest NOEC if ECx cannot be used Chronic Toxicity: Endpoint expressed as (in order of most to least preferred) duration and EC10 (boundary of EC5 to EC20), NOEC, Chronic Value Photosynthesis rate at test end Cell density and biomass surrogates) converted into growth rate sensu OECD 201 (Er, Eb)

15 AF of 1000 on most sensitive PNEC5 AF of 100 on most sensitive PNEC6 2 trophic levels present 3 trophic levels present 3 trophic levels present acutely, 1 chronic available PNEC8 2 chronic trophic levels are available, including most sensitive taxon AF of 10 PNEC9 3 chronic trophic levels are available, including most sensitive taxon AF of 10 PNEC10 Single species acute and chronic toxicity data Eco-TTC Development Dark boxes indicated US Europe different combinations of 3 trophic levels present acutely, 1 chronic available (fish or Daphnia only) acute, chronic and species 1 trophic 1 trophic level present level present level data that drive 1 chronic trophic level Defined processes for deriving PNECs distinctive regional applications (piloted using is available on most AF of 1000 sensitive acute taxon AF of 100 AF of 10,000 Europe PNEC4 and US) AF of 10 PNEC17 Not in EU TGD (2008), P&G guidance PNEC13 AF of 5000 on most sensitive PNEC14 AF of 1000 on most sensitive PNEC15 2 trophic levels present 3 trophic levels present 2 chronic trophic levels are available, including most sensitive acute taxon AF of 50 PNEC18 AF of 10 PNEC19 3 chronic trophic levels are available, including most sensitive acute taxon different application factors and thus PNECS Implemented as a logic algorithm, written in R, for the web-enabled platform 1 chronic trophic level is available on less sensitive acute taxon 10 or more species are availableperform SSD Mesocosm or microcosm available 3 trophic levels present acutely, 1 chronic available, but not on most sensitive acute (fish or Daphnia only) 10 or more species are availableperform SSD Mesocosm or microcosm available AF of 100 AF of 1 to 5 AF of 1 to 5 AF of 1000 AF of 1 to 5 AF of 1 to 5 PNEC7 PNEC11 PNEC12 PNEC16 PNEC20 PNEC21

16 A central need is to understand MOA classifications Several systems are available varying in specificity, inclusivity, and accessibility The eco-ttc Team developed a comparative analysis of MoA classifications for >5000 compounds using several assignment approaches (Kienzler et al., in review) Different MoA frameworks have different degrees of coverage within the data set that was assessed; a large number of chemicals are not classified; Harmonization is needed regarding the certain classification/groups in order to implement reliable classification rules accordingly; Still, classification outcomes are foundational and very useful for grouping.

17 Putting it all together Detailed search functionality Sensitive to fragments Controlled access; Will be public Ability to download searches for subsequent analysis Acknowledgement of partners, developers

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22 Eco-TTC derivation based on PNECs

23 Eco-TTC derivation based on PNECs

24 Eco-TTC derivation based on PNECs

25 Eco-TTC derivation based on PNECs

26 Eco-TTC derivation based on PNECs

27 Eco-TTC derivation based on PNECs

28 Eco-TTC derivation based on PNECs

29 Eco-TTC derivation based on PNECs

30 Eco-TTC derivation based on PNECs

31 A real life example At a recent Fish Embryo Test Experts Workshop in Helsinki with ECHA, attending ecotoxicologists were faced with this scenario: Fish Embryo Tests under predict acute juvenile fish toxicity to a slight degree for one group of compounds: neurotoxicants Data base for direct comparison is relatively small (for FET) In a companion investigation, OECD is evaluating a testing strategy called The Threshold Approach The key to the TA is knowing fish are most sensitive only 15-20% of the time Algae and Daphnia otherwise drive the majority of risk assessments Do neurotoxicants fit into the group of toxicants where fish are most sensitive use our eco-ttc db and program

32 Neurotoxicity eco-ttc observations (59 compounds) Group 5 th percentile of all neuroecotox values (μg/l) Algae: Pseudokirchneriella subcapitata or Desmodemsus subspicatus Invertebrate: Daphnia magna 6.99 x 10-5 Fish: fathead minnow, rainbow trout, bluegill, zebrafish, Medaka 2.6 x 10-4 Fish is not the most sensitive by a factor of 3.7 FET is different from fish by a factor of 1.8 The lack of 100% quantitative predictivity for the FET for fish is not consequential to the ERA of neurotoxicants

33 So, what is the point Scott? What can we do with this? Early reads are very promising: the tool meets the primary goal of generating robust eco-ttcs by MoA, chemical groupings, etc. The tool can be used to: o generate trophic level (or taxon) specific hazard distributions o evaluate relative sensitivity for a particular MoA that could have direct regulatory implications c.f., the FET discussion on neurotoxicants o establish screening water quality criteria o develop comparative risk assessment scenarios across geographies o provide a process for assess other environmental compartments The data base can be a stable archive of curated and traceable ecotoxicological information Actively developing case studies, guidance documentation, etc.

34 Next steps A global HESI workshop is planned for mid-september in Ottawa, Canada (co-sponsored by Environment and Climate Change Canada) o Case studies o Regulator and other users feedback on web program and utility Publications (several!) in development o Kienzler et al. (in review) MoA evaluations o Belanger et al. (readied for internal HESI review) PNEC derivation across the globe o Beasley et al. (in preparation) Database development o Otter et al. (in preparation) Development of a web-based eco-ttc application Launching of the publicly available eco-ttc web tool

35 On behalf of the Animal Alternatives in Environmental Risk Assessment Committee, thank you for listening Sunset, Lake Superior, Duluth, Minnesota 7 September 2012 FET training Workshop