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Table 2 Summary of the main effects induced by single chemicals administered at IC20, IC5 and IC20/100. In bracket, the lowest concentration eliciting a statistically significant modification of at least one of the measured DNT features is indicated (Phase 2)

From: Assessment of developmental neurotoxicity induced by chemical mixtures using an adverse outcome pathway concept

3 days

BPA

CPF

Lead

Methyl-Hg

PCB138

VA

Synaptogenesis (SYP, PSD95)

⇓ PSD95t (IC20)

⇑ SYPt (IC20)

⇓ PSD95n (IC20/100)

⇔

⇑ PSD95n (IC20)

⇔

Neurite outgrowth

⇔⇑ n. neurites

(IC5)

⇓ ⇔

⇔

⇔

⇑ (IC20/100)

⇑ n. neurites (not shown)

(IC5)

BDNF levels

⇔

⇑ BDNFt (IC20)

⇔

⇔

⇔

⇑ ratio (IC20/100)

⇔

14 days

BPA

CPF

Lead

Methyl-Hg

PCB138

VA

Synaptogenesis (SYP, PSD95)

⇓ PSD95n (IC5)

⇓ SYPn

⇑ PSD95t (IC5)

⇑ SYPt

⇓ PSD95n (IC20/100)

⇓ SYPn

(IC5)

⇔

⇔

Neurite outgrowth

⇓ n. branch points

(IC5)

⇓ ⇔

⇔

⇓ n. branch points

(IC20)

⇔

⇔

BDNF levels

⇔

⇓ ratio (IC5)

⇑ BDNFt (IC20)

⇓ ratio (IC20)

⇔

⇓ ratio (IC20)

⇑ (IC5)

⇑ BDNFn and ratio (IC20)

  1. Tested concentrations: BPA (0.29 μM, IC20/100; 12.74 μM, IC5; 28.96 μM, IC20); CPF (0.37 μM, IC20/100; 21.01 μM, IC5; 37.10 μM, IC20); Lead (0.0073 μM, IC20/100; 0.17 μM, IC5; 0.73 μM, IC20); Methyl-Hg (0.0013 μM, IC20/100; 0.05 μM, IC5; 0.13 μM, IC20); PCB138 (0.0593 μM, IC20/100; 3.53 μM, IC5; 5.93 μM, IC20); VA (2.1 μM, IC20/100; 70 μM, IC5; 210 μM, IC20)