Rat oral toxicity studies can produce inconsistent results
The reproducibility of studies that evaluate rodent oral toxicity resulting from short-term chemical exposure is lower than expected, according to researchers from the NIEHS Division of the National Toxicology Program.
Regulatory agencies currently rely on oral toxicity data in rodents to determine hazard categorization, assign appropriate labeling to alert consumers, and perform risk assessments. However, the field of toxicology is developing approaches that do not require the use of laboratory animals. To set expectations regarding the performance of these new methods, it is necessary to develop a reliable reference dataset to characterize the limitations and variability of animal toxicity studies.
To meet this need, the researchers compiled and analyzed rat toxicity data for 2,441 chemicals. For hazard classification, they examined the dose level expected to result in 50% lethality after a single oral administration of each substance. On average, replicate studies produced the same hazard categorization for a given chemical only 60% of the time. Additional analyses suggested that the low reproducibility of the results was likely due to inherent biological or protocol variability. According to the authors, this margin of uncertainty can be leveraged to provide important context for animal-free approaches.
Citation: Karmaus AL, Mansouri K, To KT, Blake B, Fitzpatrick J, Strickland J, Patlewicz G, Allen D, Casey W, Kleinstreuer N. 2022. Evaluation of variability across rat acute oral systemic toxicity studies. Toxicol Sci 188(1):34–47.