Toward a molecular equivalent dose: use of the medaka model in comparative risk assessment

Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP
Kristen R HobbieJ McHugh Law

Abstract

Recent changes in the risk assessment landscape underscore the need to be able to compare the results of toxicity and dose-response testing between a growing list of animal models and, quite possibly, an array of in vitro screening assays. How do we compare test results for a given compound between vastly different species? For example, what dose level in the ambient water of a small fish model would be equivalent to 10 ppm of a given compound in the rat's drinking water? Where do we begin? To initially address these questions, and in order to compare dose-response tests in a standard rodent model with a fish model, we used the concept of molecular dose. Assays that quantify types of DNA damage that are directly relevant to carcinogenesis integrate the factors such as chemical exposure, uptake, distribution, metabolism, etc. that tend to vary so widely between different phyletic levels. We performed parallel exposures in F344 rats and Japanese medaka (Oryzias latipes) to the alkylating hepatocarcinogen, dimethylnitrosamine (DMN). In both models, we measured the DNA adducts 8-hydroxyguanine, N(7)-methylguanine and O(6)-methylguanine in the liver; mutation frequency using lambda cII transgenic medaka and lambda cII transgenic (Bi...Continue Reading

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Citations

May 2, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Alaa El-Din Hamid SayedHiroshi Mitani
Jan 20, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·David E HintonJeffrey A Yoder
Feb 2, 2010·Environmental and Molecular Mutagenesis·Tonya L WardKathleen A Hill
May 21, 2016·Journal of Photochemistry and Photobiology. B, Biology·Alla El-Din Hamid SayedHiroshi Mitani
Jul 3, 2010·Medicine, Health Care, and Philosophy·Shawn H E Harmon
Feb 9, 2017·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Takehiko NohmiNaomi Toyoda-Hokaiwado
Nov 27, 2020·Journal of Toxicologic Pathology·Yumiko HoshikawaAkihiko Sugiyama

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