Case study in 21st century ecotoxicology: using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish

This research was designed to evaluate whether a biologically-based computational model aligned with an adverse outcome pathway (AOP) could effectively predict animal (in vivo) responses to chemicals shown to inhibit the enzyme aromatase in a non-animal (in vitro) screening assays. Aromatase is an enzyme that plays a critical role in the synthesis of estrogens, an important class of hormones, and chemicals that inhibit aromatase are viewed as probable endocrine disrupting compounds. Although the model was not able to accurately predict the average in vivo responses observed for all chemicals tested, there was strong qualitative to semi-quantitative agreement with the proposed AOP and predictions did fall within the distribution of measured values. Consequently, this “new approach methodology” likely has utility for screening-level assessments. This work helps to establish the confidence and limitations of this approach. The data set includes: 1) High throughput screening results for chemicals identified as aromatase inhibitors. 2) Novel in vitro aromatase inhibition data for six chemicals. 3) Modeled predictions of impacts on 17b-estradiol and vitellogenin concentrations over a range of concentrations. 4) Measured biological effects of 3 aromatase inhibitors in fathead minnows exposed for 24 h. 5) Measured plasma and water concentrations of the test chemicals. This dataset is associated with the following publication: Villeneuve, D., B. Blackwell, J. Cavallin, W. Cheng, R. Conolly, D. Feifarek, K. Jensen, M. Kahl, R. Milsk, S. Poole, E. Randolph, T. Saari, and G. Ankley. Case study in 21st century ecotoxicology: Using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 40(4): 1155-1170, (2021).

[
  "020:00"
]

[
  "020:095"
]

[
  "https://doi.org/10.1002/etc.4968"
]