Differential developmental toxicity of naphthoic acid isomers in medaka (Oryzias latipes) embryos.

Journal Article (Journal Article)

Polycyclic aromatic hydrocarbons (PAHs) are widespread persistent pollutants that readily undergo biotic and abiotic conversion to numerous transformation products in rivers, lakes and estuarine sediments. Here we characterize the developmental toxicity of four PAH transformation products each structural isomers of hydroxynaphthoic acid: 1H2NA, 2H1NA, 2H3NA, and 6H2NA. Medaka fish (Oryzias latipes) embryos and eleutheroembryos were used to determine toxicity. A 96-well micro-plate format was used to establish a robust, statistically significant platform for assessment of early life stages. Individual naphthoic acid isomers demonstrated a rank order of toxicity with 1H2NA>2H1NA>2H3NA>6H2NA being more toxic. Abnormalities of circulatory system were most pronounced including pericardial edema and tube heart. To determine if HNA isomers were AhR ligands, spatial-temporal expression and activity of CYP1A was measured via in vivo EROD assessments. qPCR measurement of CYP1A induction proved different between isomers dosed at respective concentrations affecting 50% of exposed individuals (EC50s). In vitro, all ANH isomers transactivated mouse AhR using a medaka CYP1A promoter specific reporter assay. Circulatory abnormalities followed P450 induction and response was consistent with PAH toxicity. A 96-well micro-plates proved suitable as exposure chambers and provided statistically sound evaluations as well as efficient toxicity screens. Our results demonstrate the use of medaka embryos for toxicity analysis thereby achieving REACH objectives for the reduction of adult animal testing in toxicity evaluations.

Full Text

Duke Authors

Cited Authors

  • Carney, MW; Erwin, K; Hardman, R; Yuen, B; Volz, DC; Hinton, DE; Kullman, SW

Published Date

  • January 2008

Published In

Volume / Issue

  • 57 / 6-12

Start / End Page

  • 255 - 266

PubMed ID

  • 18433798

Pubmed Central ID

  • PMC4299470

Electronic International Standard Serial Number (EISSN)

  • 1879-3363

International Standard Serial Number (ISSN)

  • 0025-326X

Digital Object Identifier (DOI)

  • 10.1016/j.marpolbul.2008.02.036


  • eng