Stressor: 137
Title
Stressor Overview
AOPs Including This Stressor
Events Including This Stressor
| Event Name |
|---|
| Decreased, Androgen receptor activity |
| Impaired, Spermatogenesis |
| Antagonism, Androgen receptor |
| decrease, male anogenital distance |
| Decreased, Transcription of genes by AR |
Chemical Table
| User term | DTXID | Preferred name | Casrn | jchem_inchi_key | indigo_inchi_key |
|---|---|---|---|---|---|
| Flutamide | DTXSID7032004 | Flutamide | 13311-84-7 | MKXKFYHWDHIYRV-UHFFFAOYSA-N | MKXKFYHWDHIYRV-UHFFFAOYSA-N |
AOP Evidence
Androgen receptor (AR) antagonism leading to short anogenital distance (AGD) in male (mammalian) offspring
Finasteride is a selective androgen receptor (AR) antagonist (Simard et al 1986) that has been shown to induce shorter male AGD in rats after in utero exposure (Foster & Harris 2005; Hass et al 2007; Kita et al 2016; McIntyre et al 2001; Mylchreest et al 1999; Scott et al 2007; Welsh et al 2007).
References:
Foster & Harris (2005), Toxicol Sci 85:1024-1032; doi: 10.1093/toxsci/kfi159
Hass et al (2007), Environ Health Perspect 115(suppl 1):122-128; doi: 10.1289/ehp.0360
Kita et al (2016), Toxicology 368-369:152-161; doi: 10.1016/j.tox.2016.08.021
McIntyre et al (2001), Toxicol Sci 62:236-249; doi: 10.1093/toxsci/62.2.236
Mylchreest et al (1999), Toxicol Appl Pharmacol 156:81-95; doi: 10.1006/taap.1999.8643
Scott et al (2007), Endocrinology 148:2027-2036; doi: 10.1210/en.2006-1622
Simard et al (1986), Mol Cell Endocrinol 44:261-270; doi: 10.1016/0303-7207(86)90132-2
Androgen receptor (AR) antagonism leading to decreased fertility in females
There is no evidence text for this AOP
Event Evidence
Decreased, Androgen receptor activity
There is no evidence text for this event.
Impaired, Spermatogenesis
Flutamide impairs spermatogenesis in adult male zebrafish (Yin et al., 2017)
Male fathead minnows exposed to flutamide show spermatocyte degredation and necrosis in their testis (Jensen et al., 2004)
Antagonism, Androgen receptor
Using the AR-CALUX reporter assay in antagonism mode, flutamide showed an IC50 of 1.3 uM (Sonneveld et al, 2005).
decrease, male anogenital distance
Flutamide has been shown to cause decreased male AGD in rats following intrauterine exposure to doses between 16-100 mg/kg bw/day (Foster & Harris, 2005; Hass et al, 2007; Kita et al, 2016; McIntyre et al, 2001; Mylchreest et al, 1999; Scott et al, 2007; Welsh et al, 2007).
Decreased, Transcription of genes by AR
Analysis of androgen-regulated gene expression in the LNCaP prostate cancer cell line (Ngan et al. 2009) and using the AR-CALUX reporter assay in antagonism mode, flutamide showed an IC50 of 1.3 uM (Sonneveld et al. 2005).