Stressor: 249
Title
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
Stressor Overview
AOPs Including This Stressor
Events Including This Stressor
Chemical Table
AOP Evidence
Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
- The AhR is activated by numerous planar aromatic hydrocarbons. Specifically, chemicals with molecular dimensions of 12 Å x 14 Å x 5 Å are potential ligands of the AhR (Waller & McKinney 1992; 1995).
- However, the AhR is best known as the molecular target of dioxin-like compounds (DLCs). DLCs include polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and planar polychlorinated biphenyls (PCBs). A total of seven PCDDs, ten PCDFs, and 12 PCBs are considered 'dioxin-like' because they bind to the AhR with relatively great affinity (Denison & Heath-Pagliuso 1998; Van den Berg et al 1998).
- The prototypical and among the most potent of the DLCs is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Event Evidence
Altered, Cardiovascular development/function
There is no evidence text for this event.
dimerization, AHR/ARNT
There is no evidence text for this event.
Increase, COX-2 expression
There is no evidence text for this event.
Increase, Early Life Stage Mortality
Exposure of embryos to 2,3,7,8-TCDD causes early life stage mortality in all studied species of fishes (Doering et al 2013).
Increase, cell proliferation (hepatocytes)
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
- TCDD is a potent AhR activator, and its ability to stimulate cell proliferation has been reviewed in Becker et al. (2015).
Activation, EGFR
Phosphorylation of EGFR was significantly increased in normal human bronchial epithelial cells differentiated at the air-liquid interface following treatment with 10 nM TCDD for 0.5, 3, 4, and 6 h (Lee et al., 2011).
Increase, Mucin production
Treatment of primary normal human bronchial epithelial cells and immortalized human bronchial epithelial HBE1 cells with 10 nM TCDD for up to 48 h increased MUC5AC gene expression in a time-dependent manner. TCDD treatment (10 nM) of primary normal human bronchial epithelial cells also significantly increased MUC5AC protein levels (Lee et al., 2011).