AOP

Question 1

Issues when using animals to test chems?

Answer 1

Not feasible–expensive, have to use lots of animals–who pays?
Species extrapolation
Ethical concerns

Question 2

Classic toxicology vs omics-driven TOX

Answer 2

Classic: hypothesis driven,need to understand or anticipate the way by which a contaminant acts–based on animal tests
Omics-driven: allows for observing across all biological functions/processes at a time–> can identify new TOX pathways; more comp,eye understanding of a toxicants interaction with an organism; generates a hypothesis; development of models to predict toxicity based on their TOX pathways

Question 3

what is an AOP?

Answer 3

adverse outcome pathway–conceptual framework that protrays existing knowledge concering teh linkage between a direct MOLECULAR INITIATING EVENT and an ADVERSE OUTCOME at a level of biological organization relevant to risk assessment

Question 4

what roles does AhR having in physiological processes/

Answer 4

angiogenesis
regulation of immune system
neuronal and sensory systems
skeletogenesis
development of heart and other organs
metabolism and response to xenos

Question 5

what are some of the adverse effects that can arise from perturbation of the AhR

Answer 5

• skeletal deformities
• CV deformities
• edema
• hepatotox
• fin necrosis and impaired healing
• wasting syndrome
• immune suppression
• repro failure
• mortality

Question 6

how do Aryl hydrocarbons trigger the expression of dioxin-responsive genes?

Answer 6

AH binds to AhR, which heterodimerizes with ARNT (aryl hydrocarb receptor nuclear translocator)–>binds to dioxin response elements and transcribes/translates genes/mRNA

Question 7

what issues are associated with activation of dioxin-responsive genes?

Answer 7

• -altered CV evelopment and function;
• -hemorrhage, pericardial edema
• heart deformity
• reduced pumping efficiency
• reduced blood flow
• cardiac collapse

Question 8

which dysregulated genes cause mortality in early life stages of fish and possibly other taxa?

Answer 8

SOXb9 and COX-1

Question 9

what role does SOX9b play in AhR/ARNT activation?

Answer 9

downregulated by AhR/ARNT; may cause craniofacial deformity; roles in CV development; does not cause severe enough cardiotoxicity

Question 10

role of COX-2?

Answer 10

–contains DREs in promoter in zebrafish;
–upregulated by AhR/ARNT
has confirmed roles in CV development and homeostasis in egg laying animals