Stressor: 280
Title
Stressor Overview
AOPs Including This Stressor
| AOP Name | Evidence |
|---|---|
| Inhibitor binding to topoisomerase II leading to infant leukaemia | Low |
Events Including This Stressor
Chemical Table
| User term | DTXID | Preferred name | Casrn | jchem_inchi_key | indigo_inchi_key |
|---|---|---|---|---|---|
| Chlorpyrifos | DTXSID4020458 | Chlorpyrifos | 2921-88-2 | SBPBAQFWLVIOKP-UHFFFAOYSA-N | SBPBAQFWLVIOKP-UHFFFAOYSA-N |
AOP Evidence
Inhibitor binding to topoisomerase II 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.
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Environmental chemicals |
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Aromatic compounds |
benzene, PAHs |
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Nitrosamines |
Diethylnitrosamine |
Thys et al 2015 |
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Organophosphates |
Chlorpyrifos |
Lu et al 2015 |