API

Stressor: 282

Title

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Ketoconazole

Stressor Overview

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AOPs Including This Stressor

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Events Including This Stressor

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Chemical Table

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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

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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

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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).




Stressor Info

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Chemical/Category Description

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Characterization of Exposure

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References

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