7 alternatives to in vivo testing Flashcards
there is an animal testing ban on _______ in Canada?
cosmetics
-prohibition on the conduct of cosmetic animal testing to establish cosmetic safety
-took effect on december 22, 2023
-allows the use of data resulting from animal testing on “mixed-use ingredients” (e.g. pharmaceuticals)
-cosmetic products already on the market before december 22, 2023, are allowed to continue to rely on any animal testing data to demonstrate their safety
what are the replacements of animals in toxicology experiments?
-in vitro methods
-in silico methods (computation methods like software)
what are the advantages of in vitro tests?
-controlled testing conditions
-high level of standardization
-reduction of variability between experiments
-testing is fast and in most instances inexpensive
-small amount of test material is required
-limited amount of toxic waste is produced
-human cells and tissues can be used
-reduction of testing in animals (ultimate goal)
what are the limitations of most in vitro tests?
-interactions between tissues and organs cannot be tested
-with most in vitro test systems, in vivo dose-responses cannot be obtained for human risk assessment
-systemic effects cannot be evaluated
-pharmacokinetics cannot be evaluated
what are in vitro skin irritation tests?
alternative for cosmetics on dermal tests
-the assessment of skin irritation has typically involved the use of laboratory animals
-in vitro test system that is based on the reconstructed human epidermis (RhE), which closely mimics the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis
-cells: human derived non-transformed keratinocytes
-allows to see permeation of the drug and the extent of the damage
what are in vitro eye irritation tests?
cytotoxicity based assay
-short-time exposure (STE) test determines eye irritation using a rabbit cornea cells (SIRC cells) (whether or not cells are damaged or killed)
-endpoint: cytotoxicity
reconstructed human cornea-like epithelium (RhCE)
-more objective, so can see extent of damage to layers
what are some recent advancements and application of in vitro models?
what is the graph of a microfluidic device (recent advancements)?
MPS
-represents entire organ
-each chip is a different organ
-can put in order of blood pathway
-is the drug accumulating in any organ?
-is it causing toxicity to any organ?
what is the liver microphysiological systems for applications in drug toxicity?
-a unique advantage of the ability to integrate drug metabolism and drug toxic processes in a single device
-different types of hepatic cells (hepatocytes, Kupffer cells, stellate cells, endothelial cells, cholangiocytes, and others) in 3D model
-medium is pumped to flow through the microtissue formed by these cells
-prolonged liver-specific cellular functions: enzymatic activities, transport functions, and inflammatory response
-FDA has characterized liver microphysiological systems to test their usefulness for the study of drugs with hepatotoxic effects and for studying drug metabolism, transport, and intracellular accumulation
-future: testing of chronic drug effects, drug-drug interaction effects, and drug-activated mechanisms-> replace animal studies?
what are in silico toxicity prediction?
-many in silico methods have been developed to predict the toxicity of chemicals
-it uses computational resources (i.e. methods, algorithms, software, data, etc.) to organize, analyze, model, stimulate, visualize or predict toxicity of chemicals
what are the in silico modeling methods?
-have data from different studies on toxicity of functional groups (will flag if thinks its a bad group)
quantitative structure-activity relationship (QSAR)
-utilizing mainly data generated from molecular modeling and computational chemistry
structural alert (SA)
-the adverse outcome or toxicological endpoint is linked to the molecular structure of the molecule (e.g. mutagenicity)
