Stressor: 137

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

Flutamide

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
Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring	High
Androgen receptor (AR) antagonism leading to decreased fertility in females	Moderate

Events Including This Stressor

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

Event Name
Decreased, Androgen receptor activity
Impaired, Spermatogenesis
Antagonism, Androgen receptor
decrease, male anogenital distance
Altered, Transcription of genes by AR

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
Flutamide	DTXSID7032004	Flutamide	13311-84-7	MKXKFYHWDHIYRV-UHFFFAOYSA-N	MKXKFYHWDHIYRV-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

Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring

Finasteride is a selective androgen receptor (AR) antagonist (Simard et al 1986) that has been shown to induce shorter male AGD in rats after in utero exposure (Foster & Harris 2005; Hass et al 2007; Kita et al 2016; McIntyre et al 2001; Mylchreest et al 1999; Scott et al 2007; Welsh et al 2007).

References:

Foster & Harris (2005), Toxicol Sci 85:1024-1032; doi: 10.1093/toxsci/kfi159

Hass et al (2007), Environ Health Perspect 115(suppl 1):122-128; doi: 10.1289/ehp.0360

Kita et al (2016), Toxicology 368-369:152-161; doi: 10.1016/j.tox.2016.08.021

McIntyre et al (2001), Toxicol Sci 62:236-249; doi: 10.1093/toxsci/62.2.236

Mylchreest et al (1999), Toxicol Appl Pharmacol 156:81-95; doi: 10.1006/taap.1999.8643

Scott et al (2007), Endocrinology 148:2027-2036; doi: 10.1210/en.2006-1622

Simard et al (1986), Mol Cell Endocrinol 44:261-270; doi: 10.1016/0303-7207(86)90132-2

Androgen receptor (AR) antagonism leading to decreased fertility in females

There is no evidence text for this AOP

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

Decreased, Androgen receptor activity

There is no evidence text for this event.

Impaired, Spermatogenesis

Flutamide impairs spermatogenesis in adult male zebrafish (Yin et al., 2017)

Male fathead minnows exposed to flutamide show spermatocyte degredation and necrosis in their testis (Jensen et al., 2004)

Antagonism, Androgen receptor

Using the AR-CALUX reporter assay in antagonism mode, flutamide showed an IC50 of 1.3 uM (Sonneveld et al, 2005).

decrease, male anogenital distance

Flutamide has been shown to cause decreased male AGD in rats following intrauterine exposure to doses between 16-100 mg/kg bw/day (Foster & Harris, 2005; Hass et al, 2007; Kita et al, 2016; McIntyre et al, 2001; Mylchreest et al, 1999; Scott et al, 2007; Welsh et al, 2007).

Altered, Transcription of genes by AR

Analysis of androgen-regulated gene expression in the LNCaP prostate cancer cell line (Ngan et al. 2009) and using the AR-CALUX reporter assay in antagonism mode, flutamide showed an IC50 of 1.3 uM (Sonneveld et al. 2005).

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