Stressor: 655

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

Ozone

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
User term DTXID Preferred name Casrn jchem_inchi_key indigo_inchi_key
Ozone DTXSID0021098 Ozone 10028-15-6 CBENFWSGALASAD-UHFFFAOYSA-N CBENFWSGALASAD-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
Oxidative stress [MIE] Leading to Decreased Lung Function [AO]

Tracheas of Wistar rats exposed to 1.5 ppm ozone for 1 h/day for 3 days exhibited reduced CFTR protein expression. Similarly, at 4 hours following a 30-min exposure to ozone, CFTR mRNA and protein were down-regulated in 16HBE14o- cells. At 24 hours post-exposure, a reduction in forskolin-stimulated CFTR Cl− conductance was observed (Qu et al., 2009).

Continuous, exposure of human nasal epithelial cells to different concentrations of ozone at 37°C for up to 4 weeks slightly (but not significantly) reduced CBF in healthy mucosa (7.1% at 500 µg/m3 and 10.3% at 1000 µg/m3), and significantly in chronically inflamed mucosa (20.5/16.4%) at 2 weeks. During the third and fourth week of exposure at these higher concentrations CBF was significantly reduced in both healthy (after 3 weeks: 18.7/37.5%; after 4 weeks: 11.1/33.3%) and chronically inflamed mucosa (after 3 weeks: 33.8/26.8%; after 4 weeks: 21.4/38.6%). Low ozone concentrations (100 µg/m3) appeared to not have an effect on CBF (Gosepath et al., 2000).

Acute exposure (2 h) of adult ewes to 1.0 ppm ozone significantly reduced tracheal mucus transport velocity (TMV) at 40 min and 2 h post-exposure. Repeated exposure to 1.0 ppm ozone for 5 hper day, for 4 consecutive days showed a progressively significant decrease in TMV on the first and second days, and stabilized over the third and fourth days, around values ranging from -42% to -55% of the initial baseline. TMV remained depressed even after the end of exposure, persisting up to 5 days post-exposure (Allegra et al., 1991).

Acute exposure of healthy young adult subjects (aged 19 to 35 years, non-smokers) to 0.06 ppm ozone for 6.6 h resulted in a 1.71 + 0.50% (mean + SEM) decrease in FEV1 and a 2.32 + 0.41% decrease in FVC compared with air exposure (Kim et al., 2011).

A US-based study found inverse associations between increasing lifetime exposure to ozone (estimated median: 36 ppm; interquartile range 29–45 ppm; range 19–64 ppm) and FEF75 and FEF25–75 in adolescents (aged 18–20 years) (Tager et al., 2005).  

Oxidative stress [MIE] Leading to Decreased Lung Function [AO] via CFTR dysfunction

Tracheas of Wistar rats exposed to 1.5 ppm ozone for 1 h/day for 3 days exhibited reduced CFTR protein expression. Similarly, at 4 hours following a 30-min exposure to ozone, CFTR mRNA and protein were down-regulated in 16HBE14o- cells. At 24 hours postexposure, a reduction in forskolin-stimulated CFTR Cl− conductance was observed (Qu et al., 2009).

Continuous, exposure of human nasal epithelial cells to different concentrations of ozone at 37°C for up to 4 weeks slightly (but not significantly) reduced CBF in healthy mucosa (7.1% at 500 μg/m3 and 10.3% at 1000 μg/m3), and significantly in chronically inflamed mucosa (20.5/16.4%) at 2 weeks. During the third and fourth week of exposure at these higher concentrations CBF was significantly reduced in both healthy (after 3 weeks: 18.7/37.5%; after 4 weeks: 11.1/33.3%) and chronically inflamed mucosa (after 3 weeks: 33.8/26.8%; after 4 weeks: 21.4/38.6%). Low ozone concentrations (100 μg/m3) appeared to not have an effect on CBF (Gosepath et al., 2000).

Acute exposure (2 h) of adult ewes to 1.0 ppm ozone significantly reduced tracheal mucus transport velocity (TMV) at 40 min and 2 h post-exposure. Repeated exposure to 1.0 ppm ozone for 5 hper day, for 4 consecutive days showed a progressively significant decrease in TMV on the first and second days, and stabilized over the third and fourth days, around values ranging from -42% to -55% of the initial baseline. TMV remained depressed even after the end of exposure, persisting up to 5 days post-exposure (Allegra et al., 1991).

Acute exposure of healthy young adult subjects (aged 19 to 35 years, non-smokers) to 0.06 ppm ozone for 6.6 h resulted in a 1.71 + 0.50% (mean + SEM) decrease in FEV1 and a 2.32 + 0.41% decrease in FVC compared with air exposure (Kim et al., 2011).

A US-based study found inverse associations between increasing lifetime exposure to ozone (estimated median: 36 ppm; interquartile range 29–45 ppm; range 19–64 ppm) and FEF75 and FEF25–75 in adolescents (aged 18–20 years) (Tager et al., 2005).

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
Cystic Fibrosis Transmembrane Regulator Function, Decreased

Tracheas of Wistar rats exposed to 1.5 ppm ozone for 1 h/day for 3 days exhibited reduced CFTR protein expression. Similarly, at 4 hours following a 30-min exposure to ozone, CFTR mRNA and protein were down-regulated in 16HBE14o- cells. At 24 hours post-exposure, a reduction in forskolin-stimulated CFTR Cl− conductance was observed (Qu et al., 2009).

Decrease, Lung function

Acute exposure of healthy young adult subjects (aged 19 to 35 years, non-smokers) to 0.06 ppm ozone for 6.6 h resulted in a 1.71 + 0.50% (mean + SEM) decrease in FEV1 and a 2.32 + 0.41% decrease in FVC compared with air exposure (Kim et al., 2011).

A US-based study found inverse associations between increasing lifetime exposure to ozone (estimated median: 36; interquartile range 29–45; range 19–64) and FEF75 and FEF25–75 in adolescents (aged 18–20 years) (Tager et al., 2005).

Activation, EGFR

Exposure to O3 (0.25–1.0 ppm) concentration- and time-dependently increased EGFR Y1068 and Y845 phosphorylation in human immortalized bronchial epithelial BEAS-2B cells (Wu et al., 2015).

Exposure of Balb/c mice to 0.25, 0.5, or 1.0 ppm ozone for 3 h a day, for 7 days increased EGFR Y1068 phosphorylation in the bronchial epithelium in a concentration-dependent manner (Feng et al., 2016).

Occurrence, Metaplasia of goblet cells

Intranasal instillation with 2 or 20 µg endotoxin (150 µL/ nasal passage), followed by exposure to 1 ppm ozone for 8h (6 h after instillation) on 2 consecutive days caused goblet cell metaplasia in the axial pulmonary airways of F344 rats in a dose-dependent manner (Wagner et al., 2003).

Exposure of ovalbumin-sensitized Balb/c mice to 100 or 250 ppb ozone for 3 h caused goblet cell metaplasia in bronchi and bronchioles and significantly increased the number of PAS-positive cells (Larsen et al., 2010).

Increase, Proliferation of goblet cells

Exposure of ovalbumin-sensitized Balb/c mice to 100 or 250 ppb ozone for 3 h caused goblet cell metaplasia in bronchi and bronchioles and significantly increased the number of PAS-positive cells at 24 h post-exposure (Larsen et al., 2010).  

Occurrence, Hyperplasia of goblet cells

Goblet cell numbers increased in a time-dependent manner in ovalbumin-sensitized mice (sensitized on days 1 and 14 by intraperitoneal injection of 10 μg ovalbumin and 1 mg of aluminum potassium sulfate in 500 μL of saline solution, and challenged on days 21 to 23 by daily 30-min exposure to aerosolized 1% (wt/vol) ovalbumin) that were whole-body exposed to 2 ppm ozone for 4, 8, and 12 weeks (Jang et al., 2006).

Cilia Beat Frequency, Decreased

Continuous, exposure of human nasal epithelial cells to different concentrations of ozone at 37°C for up to 4 weeks slightly (but not significantly) reduced CBF in healthy mucosa (7.1% at 500 µg/m3 and 10.3% at 1000 µg/m3), and significantly in chronically inflamed mucosa (20.5/16.4%) at 2 weeks. During the third and fourth week of exposure at these higher concentrations CBF was significantly reduced in both healthy (after 3 weeks: 18.7/37.5%; after 4 weeks: 11.1/33.3%) and chronically inflamed mucosa (after 3 weeks: 33.8/26.8%; after 4 weeks: 21.4/38.6%). Low ozone concentrations (100 µg/m3) appeared to not have an effect on CBF (Gosepath et al., 2000).

Mucociliary Clearance, Decreased

Acute exposure (2 h) of adult ewes to 1.0 ppm ozone significantly reduced tracheal mucus transport velocity (TMV) at 40 min and 2 h post-exposure. Repeated exposure to 1.0 ppm ozone for 5 hper day, for 4 consecutive days showed a progressively significant decrease in TMV on the first and second days, and stabilized over the third and fourth days, around values ranging from -42% to -55% of the initial baseline. TMV remained depressed even after the end of exposure, persisting up to 5 days post-exposure (Allegra et al., 1991).  

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