Table 1 Directed network analysis for the derived AOP network built in Cytoscape and analyzed using the NetworkAnalyzer plugin

Increased, recruitment of pro-inflammatory cells

KE

3

0.088235

9

5

4

1.25

Loss of alveolar membrane integrity

KE

3

0.127451

8

4

4

1

Increased secretion, pro-inflammatory mediators

KE

3

0.0918

8

4

4

1

Increased ROS synthesis

KE

3

0.054367

7

3

4

0.75

Activation, T-helper type 2 cells

KE

2

0.057041

5

2

3

0.666666667

Surfactant function inhibition

KE

2

0.032531

5

3

2

1.5

ECM deposition

KE

2

0.018717

5

3

2

1.5

Fibroblast / myofibroblast proliferation

KE

2

0.016934

5

3

2

1.5

Increased, TFF2 release

KE

1

0.005348

4

1

3

0.333333333

Cellular toxicity

KE

1

0.027184

3

1

2

0.5

Activation, epithelial cells

KE

1

0.016934

3

2

1

2

Destruction of ECM, proteinases and elastases

KE

1

0.010695

3

2

1

2

Chronic inflammation

KE

1

0.004902

3

1

2

0.5

Increased, serum amyloid A expression

KE

1

0.032086

2

1

1

1

Formation, serum amyloid A-high density lipoprotein complex

KE

1

0.026738

2

1

1

1

Reduced lung volume

KE

1

0.026738

2

1

1

1

Increased, systemic cholesterol

KE

1

0.019608

2

1

1

1

Increased, DNA damage and mutation

KE

1

0.016043

2

1

1

1

Impaired oxygenation

KE

1

0.01426

2

1

1

1

Foam cell formation

KE

1

0.010695

2

1

1

1

Increased, cell proliferation

KE

1

0.008913

2

1

1

1

Loss of proteinase / antiproteinase enzymatic balance

KE

1

0.006684

2

1

1

1

Increased secretion, pro-inflammatory and pro-fibrotic mediators

KE

1

0.006239

2

1

1

1

Blood components leak into the lungs

KE

1

0.005348

2

1

1

1

Increased, IL-33 expression

KE

1

0.001783

2

1

1

1

Lung fibrosis

AO

2

0

2

2

0

Undefined

Interaction with the lung resident cell membrane components

MIE

2

0

2

0

2

0

Lung cancer

AO

1

0

1

1

0

Undefined

Plaque progression

AO

1

0

1

1

0

Undefined

Acute inhalation toxicity

AO

1

0

1

1

0

Undefined

Lung emphysema

AO

1

0

1

1

0

Undefined

Frustrated phagocytosis

MIE

1

0

1

0

1

0

Interaction with resident cell membrane components TLR2/4 binding

MIE

1

0

1

0

1

0

Interaction with epithelial cell membrane

MIE

1

0

1

0

1

0

Interaction with lung surfactant

MIE

1

0

1

0

1

0