API

Stressor: 280

Title

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Stressor Overview

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AOPs Including This Stressor

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Events Including This Stressor

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This table is automatically generated and lists KE’s including this stressor.

Chemical Table

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AOP Evidence

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In-utero DNA topoisomerase II poisons leading to infant leukaemia

Chlorpyrifos

Chlorpyrifos is a widely used organophosphate insecticide, which has been suspected as a risk factor for infant and childhood leukaemia after the house-hold exposure of pregnant women. According to Lu et al (2015), chlorpyrifos and its metabolite chlorpyrifos oxon exhibit an inhibitory effect on in vitro TopoII activity. Chlorpyrifos causes DNA double strand breaks as measured by the neutral Comet assay and induces MLL gene rearrangements in human fetal liver-derived CD34+ hematopoietic stem cells via TopoII ’poisoning’ as detected by the FISH assay and in vitro isolated TopoII inhibition assay, respectively (Lu et al 2015). Chlorpyrifos also stabilizes the TopoII-DNA cleavage complex. Etoposide was used a positive reference compound in these studies and it performed as expected. The lowest concentration of chlorpyrifos used was 1 µM and it gave a statistically significant effect in many in vitro assays. The point of departure of etoposide, which was calculated to be 0.01 to 0.1 µM (Li et al 2014), is at least 10-fold lower than that of chlorpyrifos.

Environmental chemicals
Aromatic compounds	benzene, PAHs
Nitrosamines	Diethylnitrosamine	Thys et al 2015
Organophosphates	Chlorpyrifos	Lu et al 2015

Event Evidence

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This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor.

Stressor Info

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Chemical/Category Description

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Instructions

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Characterization of Exposure

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Instructions

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References

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List the bibliographic references to original papers, books or other documents used to support the Stressor.

Instructions

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