Influence of total dose and dose rate in carcinogenicity studies.
One element of the ED01 Study contained a group of animals that were dosed with 2-acetylaminofluorene for 9, 12, 15, 18, or 24 mo and then sacrificed at 18 or 24 mo. This provided data to compare the relative effects on carcinogenicity of dose rate versus total dose. The prevalence of liver and bladder tumors were used as the comparison. Animals receiving similar total doses but over a different length of time (different dose rates) were compared at the 18- and 24-mo sacrifices. When the total doses were similar, the higher dose rates for shorter time periods induced a higher prevalence of tumors. Results were more consistent for bladder tumors than for liver tumors, although the same trends were noted for both endpoints. Those groups dosed at higher rates but for fewer months had a generally higher prevalence than those receiving similar total doses but at lower rates for more months. This data from the ED01 Study illustrates the importance of experimental design, dosing regime, length of study time, and age of the animals at time of dosing in respect of calculation of risk.
D015073:2-Acetylaminofluorene / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008113:Liver Neoplasms / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D051379:Mice; D008807:Mice, Inbred BALB C; D009152:Mutagenicity Tests / Q000379:methods*; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D015073:2-Acetylaminofluorene