Dan:
Thought your chat group might be interested in this 2009 study with dibenzo[def,p]chrysene (dibenzo[a,l]pyrene), a polycyclic aromatic hydrocarbon (PAH) in 40,000 rainbow trout [see attached 2nd pdf]. We were able to statistically calculate the dose resulting in 1 cancer in 5000 animals, a 50-fold increase in power compared to the 2-acetylaminofluorene ED01 mouse study.
The dose response became sub-linear with dose, and the intercept on the x-axis for 1/106 tumors was more than 1000-fold higher than if the linear extrapolated dose (LED10) had been used. Surprisingly, the liver DNA adducts remained linear with dose (would not have made for a good biomarker).
I was surprised that this paper did not generate more interest. Maybe because it (“was only a fish”). George Bailey spent years documenting the validity (and superiority of fish to mice), with regard to aflatoxin B1 (AFB1)-induced hepatocellular carcinoma (HCC) as a model for human liver cancer. I repeated the same design –– later with AFB1 –– and that also generated a dose-response that became sub-linear, compared to the LED, but the data were not as dramatically as that for the PAH.
For what its worth,