Sub‐acute versus sub‐chronic oral toxicity study in rats: Comparative study of 82 compounds

Toxicity data of 82 compounds, tested in both a sub‐acute and a sub‐chronic study, were evaluated to find out whether it is possible to substitute a sub‐acute for a sub‐chronic study without losing quantitative information. The no‐effect level (NEL) and the minimal‐effect level (MEL) were used as the basis for comparison. For each of the compounds, the sub‐acute and sub‐chronic studies were performed under similar conditions, with the same strain of rats and with a comparable range of dietary levels. It appeared that the NEL in the sub‐acute study was equal to the NEL in the sub‐chronic study for 56% of the compounds. For 44% of the compounds reviewed, the NEL in the sub‐chronic test was lower than the NEL in the sub‐acute test, indicating that a sub‐chronic study cannot simply be replaced by a sub‐acute study. However, it may be acceptable to use the NEL obtained in a sub‐acute study as a basis for establishing acceptable daily intakes or permissible exposure levels for humans if an additional safety factor of 10 is applied. Furthermore, it was concluded that the conventional sub‐acute study, including some selected haematological and biochemical parameters, seems extremely useful to obtain quick and reliable information on the toxicity of the numerous non‐regulated chemicals which have to be investigated in the years to come.