Stressor: 171

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

Pyrethrins and Pyrethroids

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

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

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
Enhanced hepatic clearance of thyroid hormones leading to thyroid follicular cell adenomas and carcinomas in the rat and mouse

There is no evidence text for this AOP

Inhibition of voltage gate sodium channels leading to impairment in learning and memory during development

Natural toxins, produced by animal, plant and microorganisms, target VGSCs through diverse strategies developed over millions of years of evolution. The sodium transients can be antagonised by TTX (tetrodotoxin) (Káradóttir et al., 2008; Berrett et al., 2017) which is the classic stressor. Classic and well studied stressors for VGSCs are pyrethroid insecticides. Indeed, it is well known and accepted that pyrethroids bind to the α subunit of the neuronal VGSC (Trainer et al., 1997; Smith and Soderlund, 1998, 2001; Catterall et al., 2007; Cao et al., 2011). Mutations in the α subunit of both insects (Lee and Soderlund, 2001; Smith et al., 1997) and mammals (Vais et al., 2000, 2001; Wang et al., 2001) alter the sensitivity of VGSCs to pyrethroids, supporting the conclusion that pyrethroid interact with the α subunit (Shafer et al., 2005). The β subunit has been observed to modulate the affinity of pyrethroid interaction with the channel (Smith and Soderlund, 1998). However, the pyrethroid sensitivity of VGSCs subunits and splice variants expressed during development has yet to be examined (Shafer et al., 2005). The actions of pyrethroid insecticides on sodium channels in invertebrate and vertebrate nerve preparation have been widely documented over the past decades and has been extensively and critically summarised in numerous reviews (Soderlund et al., 2002; Chahine, 2018). Based on their chemical structure and clinical symptoms of toxicity, pyrethroids are classified in type I and type II. Following the binding to a VGSC specific isoform/s, pyrethroid slow the activation or opening, of VGSC. In addition, they slow the rate of VGSC inactivation (or closing) and shift to a more hyperpolarised potentials the membrane potentials at which VGSC activate (or open) (Narahashi, 1996). The result is that sodium channels open at more hyperpolarised potential and are held open longer, allowing more sodium ions to cross and depolarise the neuronal membrane. Type II pyrethroids delay the inactivation of VGSCs longer than do type I pyrethroids, leading to a depolarisation-dependent block. These differences in prolongation of channel open times are considered to contribute to the different toxicological profile (Ray 2001).

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
Inhibit, voltage-gated sodium channel

Natural toxins, produced by animal, plant and microorganisms, target VGSCs through diverse strategies developed over millions of years of evolution. The sodium transients can be antagonised by TTX (tetrodotoxin) (Káradóttir et al., 2008; Berrett et al., 2017) which is the classic stressor. Classic and well studied stressors for VGSCs are pyrethroid insecticides. Indeed, it is well known and accepted that pyrethroids bind to the α subunit of the neuronal VGSC (Trainer et al., 1997; Smith and Soderlund, 1998, 2001; Catterall et al., 2007; Cao et al., 2011). Mutations in the α subunit of both insects (Lee and Soderlund, 2001; Smith et al., 1997) and mammals (Vais et al., 2000, 2001; Wang et al., 2001) alter the sensitivity of VGSCs to pyrethroids, supporting the conclusion that pyrethroid interact with the α subunit (Shafer et al., 2005). The β subunit has been observed to modulate the affinity of pyrethroid interaction with the channel (Smith and Soderlund, 1998). However, the pyrethroid sensitivity of VGSCs subunits and splice variants expressed during development has yet to be examined (Shafer et al., 2005). The actions of pyrethroid insecticides on sodium channels in invertebrate and vertebrate nerve preparation have been widely documented over the past decades and has been extensively and critically summarised in numerous reviews (Soderlund et al., 2002; Chahine, 2018). Based on their chemical structure and clinical symptoms of toxicity, pyrethroids are classified in type I and type II. Following the binding to a VGSC specific isoform/s, pyrethroid slow the activation or opening, of VGSC. In addition, they slow the rate of VGSC inactivation (or closing) and shift to a more hyperpolarised potentials the membrane potentials at which VGSC activate (or open) (Narahashi, 1996). The result is that sodium channels open at more hyperpolarised potential and are held open longer, allowing more sodium ions to cross and depolarise the neuronal membrane. Type II pyrethroids delay the inactivation of VGSCs longer than do type I pyrethroids, leading to a depolarisation-dependent block. These differences in prolongation of channel open times are considered to contribute to the different toxicological profile (Ray 2001). See Figure 4 below from Shafer et al. (2005).

Figure 4: Pyrethroid effects on neuronal excitability

The figure summarises the pyrethroid effects on individual channels, whole-cell sodium currents and action potentials. Pyrethroid inhibit the function of two different ‘gates’ that control sodium flux through VGSC, delaying inactivation (indicated by the double arrow between states) of the channel and allowing continued sodium flux. Pyrethroid-mediated VGSC remain open when depolarisation ends, resulting in a ‘tail’ current. Type I pyrethroids action results in a series of action potentials, while type II pyrethroids cause greater membrane depolarisation, leading to a depolarisation-dependent block. Source: Shafer 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