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Table 4 Main effects and mixture-related LOAECs specific for each time interval and DNT endpoint

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

3 days

‘3-Sim’

Similar MoA

‘3-Diss’

Dissimilar MoA

‘All’

Synaptogenesis

(SYP, PSD95)

⇑ SYPt

⇑ synapses

(LOAEC/4-syn)

BPA, CPF

⇑ SYPt

⇑ synapses

(LOAEC/4-syn)

Methyl-Hg, PCB138

⇑ SYPt

(LOAEC/4-syn)

BPA, CPF, Methyl-Hg, PCB138

Neurite outgrowth and % of neurons

⇓ n. branch points

⇓ neurite length

(LOAEC/4-neu)

⇑ β-III-tubulin+ neurons (LOAEC/2-neu)

CPF

⇓ n. neurites/neuron

(LOAEC/4-neu)

PCB138 (counteract)

⇓ n. neurites/neuron

(LOAEC/4-neu)

⇑ β-III-tubulin+ neurons (LOAEC-neu)

CPF

PCB138 (counteract)

BDNF levels

⇑ total BDNF

(LOAEC-bdnf)

⇑ total BDNF

(LOAEC-bdnf)

⇑ total BDNF

(LOAEC/2-bdnf)

14 days

‘3-Sim’

Similar MoA

‘3-Diss’

Dissimilar MoA

‘All’

Synaptogenesis

(SYP, PSD95)

⇑ SYPt

(LOAEC/2-syn)

BPA

⇔

⇑ SYPt

(LOAEC-syn)

BPA

Neurite outgrowth and % of neurons

⇓ neurite length

(LOAEC/4-neu)

⇑ β-III-tubulin+ neurons (LOAEC/2-neu)

CPF, Lead

⇓ n. branch points

⇓ neurite length

⇑ β-III-tubulin+ neurons

(LOAEC/2-neu)

Methyl-Hg, PCB138,

VA (counteract)

⇓ n. branch points

⇓ neurite length

⇑ β-III-tubulin+ neurons

(LOAEC/2-neu)

CPF, Lead, Methyl-Hg, PCB138

VA (counteract)

BDNF levels

⇑ total BDNF

(LOAEC/2-bdnf)

CPF, Lead

⇔ ⇑ total BDNF

(LOAEC/2-bdnf)

Methyl-Hg

⇑ total BDNF

(LOAEC/2-bdnf)

CPF, Lead, Methyl-Hg