Lecture 6

Question 1

What is the AOP concept?

Answer 1

a simplified construct that can be used to link events that occur at different levels of biological organization

Question 2

Facts about AOPs

Answer 2

1. they are not chemical specific
2. they are modular
3. they are a pragmatic functional unit of development and evaluation
4. they are living documents

Question 3

What is the weight of evidence?

Answer 3

involves an evaluation of the relative values/weight of scientific evidence

Question 4

how is WoE useful

Answer 4

facilitates regulatory application through consistent consideration and communication of:
1. confidence consideration
2. the bridge between testing and regulatory application
3. increasing knowledge

Question 5

Criteria to assess the WoE supporting AOPs

Answer 5

1. draws on experience in mode of action analysis
2. based on modified Bradford/Hill considerations

Question 6

Why apply WoE consideration in AOP development?

Answer 6

to increase consistency and transparency through:
1. focus
2. consistency/simplicity
3. clarification

Question 7

WoE in AOPs

Answer 7

1. biological plausibility - KERs
2. Essentiality - KEs within AOP
3. Emperical support (KERs)

Question 8

What is biological plausibility?

Answer 8

How well do we understand the structural/functional relationships of the pathways?
Do we know enough to be able to predict what happens if we disturb the pathway

Question 9

What is essentiality?

Answer 9

What happens if we block or reverse a key event?

Question 10

What is emperical support?

Answer 10

The nature of the expected quantitative impact on downstream KEs if we disturb earlier KERs
Tested by considering dose-response relationships for stressors which impact the pathway