Chemical safety and big data: the industry s demands

Transcription

1 Chemical safety and big data: the industry s demands Richard CURRIE Senior Technical Expert; Group Leader & Global Predictive and Computational Toxicology Lead

2 Valid results Useful results Credit Money/Grants Science 1107/2009 REACH TSCA FQPA Etc How to change a trusted approach? Legal Chemical Safety Society All chemicals must be safe Precautionary principle No risks Minimal animal testing Willingness to change 2

3 Chemical Safety what is it? Pharmaceuticals Agrochemicals Industrial chemicals Personal Care Cosmetics Fragrance 3 Cometics etc Cannot generate data in Highly Regulated vivo, only in vitro and modelling industries Need to assure safety at known human exposures No active post-marketing surveillance only epidemiology Less a and lot toxicity of data Regulated data for a in few model Generates Exposure and species Toxicity industries data animal Society wants assurance that considered Chemical exposures are safe Industrial Agrochemicals chemicals Pharmaceuticals No Generates data for exposure most chemicals, data Some data requirements Hazards Hazards models (cut-off (cut-off and humans criteria) criteria) considered AND Risks considered Cost-benefit analysis Societal No cost-benefit analysis Development benefit focused is on Development known causes focused of failures on known causes of failures No Active active post-marketing surveillance No active post-marketing only epidemiology surveillance only epidemiology with limited exposure data

4 Chemical Safety data. In vivo toxicology Data Information collected from studies in experimental animals or human Chemical observations Data s Scientific of chemical reports in commerce Government labs and Corporate their associated Labs information which are used to build In vitro predictive Data models Information chemical descriptors, from relatively inexpensive chemical and in vitro physical assays properties Enzyme, receptor and molecular structures Cellular TGx assays Information on mechanism 4

5 Chemical Safety Data what is it? Regulatory Agency interpretations Study Interpretation(s) NOELs/LOELs IC50s Pathways/processes Group Mean Values Individual Animal Well Data Gene 5

6 Chemical Safety data what do you want to do with it? Acute toxicity for all pesticides with a given pesticidal MoA? Show me all the times we ve seen a specific tumour type in rats? For a chemical, have we identified any known key events across a set of studies? Are there common key events identified across a group of substances? Are there common key events for an AI identified across a group of studies? 26 Tumours & No histopathology What toxicity data is available for chemicals with a specific sub-structure? Adrenal tumours Show me toxicity data for chemicals which are structurally similar to this? Show me registered pesticides or drugs that are structurally similar to this? 36 No Adrenal tumours Show me registered pesticides or drugs with a given substructure present in this molecule? 2 With histopathology With histopathology & no tumours Show me two or & more tumours study endpoints, e.g. dermal and oral toxicity, across multiple compounds for which we have all the study endpoints? What is the hazard classification (ECHA/GHS/EPA) for a given compound? This compound has an R63 (hazard Classification example). Show me tox data for a study (on this compound) that might have resulted in the R63 (ie devtox, reprotox)? 6

7 Moving to mechanistic understanding Chemical databases In vitro assays TGx data In vivo toxicology Human diseases How are we going to infer and evaluate our understanding of the toxicological mechanisms for potentially dozens of mechanisms with limited number of exemplars? How are we going to transition between qualitative descriptions to quantitative ones in a scalable way? Ecotox population effects 7

8 Is chemical Safety data big data? Maybe doesn t matter we have a problem with organising, linking and making sense of multiple disparate data sources 8

9 How to organise and integrate these data to permit use in safety assessment? Structural similarity ADME/PK Models of pathways Exposure Formulated Chemical Safety problem In vitro assays In vivo data TGX data 9

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13 But where can we get the parameter values from? 13

14 Chemical Safety Now limited but growing Future bigger data Frameworks for use More toxicity data, more varied types Systems models Biomonitoring Personalised exposomes Etc. 14