Safety evaluation of chemicals: Relationship between Short-and Long-Term Feeding Studies in Designing an Effective Toxicity Test

Abstract

A compilation and comparison of ratios between results of short- and long-term feeding studies are presented. These data, on 33 materials fed for 90 days and 2 years, indicate that at least 50% of the time ratios of toxicity in rats for these periods were 2.0 or less. Therefore, one could transfer short-term test results with measured confidence into a prediction of the “no ill-effect” levels in 2-year studies. Only a few criteria of stress were effective in delineating the lowest dosage level of effect in such feeding tests. These are body weight gain, liver and kidney weight as percentages of body weight, and liver and kidney pathological study. With these criteria, except in special cases such as cholinesterase-inhibiting chemicals, one can perform a more reasonable, less expensive test. Furthermore, long-term dog studies were not, in 21 rat to dog long-term comparisons, more sensitive of effect than rats. Therefore, it is recommended that a short-term dog study is sufficient. If, in such a 3-month test, special effects on dogs should be discovered, additional long-term tests would be required. It is taken for granted that the experimental design will be subject to the judgment of an experienced toxicologist who will recognize the need for additional criteria in specific cases. © 1963, American Chemical Society. All rights reserved.