Stressor: 80

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

N-methyl Carbamates

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
Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function

Carbamates also initiate AChE inhibition by electrostatic interactions at the anionic site of enzyme and binding with the serine hydroxyl radicals at the esteratic site (Wilson 2010; Fukuto 1990), which is permanently attach to AChE like common organophosphate pesticides. The process by which ACh and carbamates both form covalent bonds with the enzyme with is called carbamylation.  Metabolite of some carbamates is more potent in term of AChE inhibition.  For certain procarbamates metabolism is require to form an active AChE inhibitor (e.g., carbofuran as metabolized product of carbosulfan) (Sogob and Vilanova 2002; Stenersen 2004).

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
Acetylcholinesterase (AchE) Inhibition

Carbamates trigger AChE inhibition through electrostatic interactions at the enzyme’s anionic site and binding with the serine hydroxyl group at the esteratic site (Wilson 2010; Fukuto 1990). Carbamates, which were originally based on the plant alkaloid physostigmine, attach to the AChE via a ‘reversible’ carbamylation. Note that the use of the term ‘reversible’ relates to the relative rate at which the carbamylation occurs since acetylcholine and carbamates both form covalent bonds with the enzyme. Certain steric and electronic requirements, as well as the leaving group on the pesticide, are critical to the likelihood that the methyl-carbamate will inhibit AChE (See Figure).  

Metabolism also plays a role in the potency of some carbamates.  Select procarbamates require metabolism to form an active AChE inhibitor (e.g., carbosulfan must be metabolized to carbofuran), or are made more potent via metabolism (e.g., aldicarb oxidation to the more toxic sulfoxide form) (Sogob and Vilanova 2002; Stenersen 2004). 

 

Base Structure (Carbamate)

Configuration

R1: Methyl group

R2:  Hydrogen group;

XR3:  Leaving group that is an aryloxy or oxime;

pKa:  For oxime and substituted phenols, a pKa in the range of 10 ensures carbamylation;

Carbamates must ‘fit’ in the enzyme active site to be effective inhibitors

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