Table 1.
Extrapolation of MIEs predicts adverse outcomes in other species: Comparison of human in vitro screening of nine chemicals for potential MIEs related reproductive toxicity (ToxCastTM MIE) to in vivo effects of the same chemicals on reproductive end points in female fathead minnows.
| ToxCast | In vivo, female fathead minnows | |||
|---|---|---|---|---|
| MIE linked to reproductive toxicity in fisha | Plasma E2 | Plasma Vtg | Cumulative fecundity | |
| Abbreviations: E2, estradiol; MIE, molecular initiating event; sig ↓, significantly decreased; Vtg, vitellogenin.aIndicates whether activity was observed in one or more ToxCast assays (Knudsen et al. 2011) corresponding to molecular initiating events previously associated with reproductive toxicity in fish (Ankley et al. 2010). Specific MIEs of interest included androgen receptor (AR) agonism, estrogen receptor (ER) antagonism, and inhibition of steroidogenic enzyme activities, particularly aromatase (CYP19A1). bAll effects are after 21 days of continuous exposure. See Ankley et al. (2005). cFrom a 96-hr range finding study, all other data are from a 21-day exposure (Skolness et al. 2013). dMeasured after 96 hr continuous exposure (Villeneuve et al. 2012). eMartinović et al. 2008. fBencic et al. 2013. gVilleneuve et al. 2006. hAnkley et al. 2001. iTillitt et al. 2010. jBringolf et al. 2004. | ||||
| Prochlorazb | Inhibition of CYP19A1 and AR binding | Sig ↓, 0.3 mg/L | Sig ↓, 0.1 mg/L | Sig ↓, 0.1 mg/L |
| Propiconazolec | Inhibition of CYP19A1 | Sig ↓, 0.5 mg/L | Sig ↓, 0.5 mg/L | Sig ↓, 0.5 mg/L |
| Bisphenol Ad | Interacted with ER and also with the AR at higher concentrations | Sig ↓, 10 μg/L | Sig ↓, 10 μg/L | |
| Fenarimolb | None | Sig ↓, 1.0 mg/L | Sig ↓, 1.0 mg/L | Sig ↓, 1.0 mg/L |
| Vinclozoline | None | No effect | Sig ↓, 0.4 mg/L | Sig ↓, 0.1 mg/L |
| Fipronilf | None | No effect (≤ 1 mg/L) | No effect (≤ 1 mg/L) | No effect (≤ 1 mg/L) |
| Prometong | None | No effect (≤ 5 μg/L) | No effect (≤ 5 μg/L) | No effect (≤ 5 μg/L) |
| Methoxychlorh | None | No effect (≤ 5 μg/L) | No effect (≤ 5 μg/L) | Sig ↓, 5 μg/L |
| Atrazinei,j | None | No effect (≤ 50 μg/L)j | No effect (≤ 50 μg/L)j | Sig ↓, 0.5 μg/Li |
| No effect (≤ 50 μg/L) | ||||