Stressor: 280

Title

To create a new stressor, from the Listing Stressors page at https://aopwiki.org/stressors click ‘New stressor.’ This will bring you to a page entitled “New Stressor” where a stressor title can be entered. Click ‘Create stressor’ to create a new Stressor page listing the stressor title at the top. More help

Chlorpyrifos

Stressor Overview

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. More help

AOPs Including This Stressor

This table is automatically generated and lists the AOPs associated with this Stressor. More help

AOP Name	Evidence
Inhibitor binding to topoisomerase II leading to infant leukaemia	Low

Events Including This Stressor

This table is automatically generated and lists the Key Events associated with this Stressor. More help

Chemical Table

The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as Preferred name, “CAS- preferred name,” “JChem InChIKey – preferred name,” or “Indigo InChIKey- preferred name,” depending on by which field you perform the search. It may take several moments for the drop down list to display. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.To remove a chemical associated with a particular stressor, in the Chemical Table next to the chemical you wish to delete, click ‘Remove’ and then click 'OK.' The chemical should no longer be visible in the Chemical table. More help

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

This table is automatically generated and includes the AOPs with this associated stressor as well as the evidence term and evidence text from this AOP Stressor. More help

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.

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

Event Evidence

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

Stressor Info

Text sections under this subheading include the Chemical/Category Description and Characterization of Exposure. More help

Chemical/Category Description

To edit the Chemical/Category Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “Chemical/Category Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “Chemical/Category Description” section on the page. More help

Characterization of Exposure

To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “Characterization of Exposure” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “Characterization of Exposure” section on the page. More help

References

List of the literature that was cited for this Stressor description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “References” section on the page. More help