API

Stressor: 137

Title

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Flutamide

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
Flutamide DTXSID7032004 Flutamide 13311-84-7 MKXKFYHWDHIYRV-UHFFFAOYSA-N MKXKFYHWDHIYRV-UHFFFAOYSA-N

AOP Evidence

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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

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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).




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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