Stressor: 282
Title
Stressor Overview
AOPs Including This Stressor
Events Including This Stressor
| Event Name |
|---|
| CYP7B activity, inhibition |
| 7α-hydroxypregnenolone synthesis in the brain, decreased |
| decrease, male anogenital distance |
Chemical Table
| User term | DTXID | Preferred name | Casrn | jchem_inchi_key | indigo_inchi_key |
|---|---|---|---|---|---|
| Ketoconazole | DTXSID7029879 | Ketoconazole | 65277-42-1 | XMAYWYJOQHXEEK-OZXSUGGESA-N | XMAYWYJOQHXEEK-OZXSUGGESA-N |
AOP Evidence
Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity
Conazole is a class of fungicide that inhibits CYP51 14α-lanosterol demethylase activity in yeats and moults, thereby preventing ergosterol synthesis (Hof et al., 2006). In animals, conazoles are known to be less specific than in fungi since they can interfere with various cytochromes P450 activity. For instance, it is clearly demonstrated that ketoconazole directly inhibits CYP7B activity which induces a decrease in 7α-hydroxypregnenolone (Matsunaga et al., 2004, Tsutsui et al., 2008; Toyoda et al., 2012; Ogura et al., 2016).
Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior
There is no evidence text for this AOP
Inhibition of 11β-hydroxylase leading to male infertility in fish
Steroidogenesis enzyme inhibitors in Cushing’s syndrome European Journal of Endocrinology 172, 6; 10.1530/EJE-14-1014
Event Evidence
CYP7B activity, inhibition
It is clearly demonstrated that ketoconazole directly inhibits CYP7B (Matsunaga et al., 2004). It is expected for the other members of the conazole family to have the same effect.
Some other azoles such as clotrimazole can also inhibit CYP7B activity (Liu et al., 2011; Rose et al., 1997).
7α-hydroxypregnenolone synthesis in the brain, decreased
There is no evidence text for this event.
decrease, male anogenital distance
Ketoconazole has been shown to cause decreased male AGD in rats following intrauterine exposure to 50 mg/kg bw/day in one study (Taxvig et al, 2008), but no effect in another study using same dose (Wolf et al, 1999).