The Omics Flashcards
what are some classic measures of toxicity?
- Histopathology
- Clinical Chemistry
- Metabolism
- Physiology
- Enzymology
- Electron Microscopy
what is NAMs?
New approach methodologies
what are some NAMs?
- information from the exposure of chemicals in the context of hazard assessment
- in silico approaches
- in chemico approaches
- in vitro assays
- high-throughput screening
- high-content imaging
- genomics
- transcriptomics
- epigenomics
- proteomics
- lipidomics
- metabolomic
what is the tiered protocol for toxicity testing?
Tier1 :computational based assessment
Tier 2: high throughput in vitro and in vivo screening
Tier 3: in vitro whole cell activity assessment
Tier 4: fish and amphibian whole animal assessment
Tier 5: mammalian whole animal assessment
likely safe
what is the future path to reduce in vivo methods and test more compounds?
- use NAMs and develop predictive methods for biological responses
what are in silico approaches for testing?
- Data management
- Bioinformatics
- Quantitative structure activity relationship
- Read across
- Modeling
- Reverse dosimetry
what are in chemico approaches for testing?
- identify reactive compounds
- use of analytical technique
what is interpolation vs extrapolation?
interpolation: unknown is between known data so can get an approximate in between data
extrapolation: unknown is beyond the known data, so you use the general trend to predict result
how can we used high content imaging to assess phenotype? (what are the steps)
- expose cell cultures to variable amounts of compound
- fluorescent staining
- high-content imaging system
- benchmark analyses
- ToxPi analyses
what are different things you can stain and measure with fluorescent screening?
- Nucleus
- Cell viability
- Lysosomes
- Lipid droplets
- Mitochondria
- Oxidative stress
what is BMD and BMC?
dose or concentration that produces a predetermined change in response rate of an adverse effect
what is BMR?
the predetermined change in response rate used to determine the BMD/BMC
how does benchmark concentration modelling work?
- Concentration-response data (high-content imaging)
- Predefined a level of change (benchmark response =10%)
- Fitting a curve (best-fit model)
- Estimate BMC values
what are limitations of NOAEL?
- Highly dependent on dose selection
- Highly dependent on sample size
- Dose–response information (e.g., shape of dose–response curve) not taken into account
- Does not correspond to consistent response levels for comparisons across studies
what is the advantages of BMD?
- Not limited to experimental doses
- Less dependent on dose spacing
- Takes into account the shape of the dose–response curve and other related information
- Corresponds to consistent response level and can be used to compare results across chemicals and studies