For fish, daphnids, and algae, acute to chronic ratios (ACRs) have been determined from experimental data regarding new and existing chemicals. Only test results in accord with the European Union Technical Guidance Document (TGD) and validated by authorities were considered. Whereas the median ACRs of 10.5 (fish), 7.0 (daphnids), and 5.4 (algae) are well below the ACR safety factor of 100 as implied by the TGD, individual ACRs vary considerably and go up to 4400. The results suggest that a safety factor of 100 is not protective for all chemicals and trophic levels. Neither a correlation between ACR and baseline toxicity as modeled through the logarithmic octanol-water partition coefficient nor an ACR correlation across trophic levels exists. Narcosis is associated with a preference for a low ACR; nevertheless, low ACRs are frequently obtained for nonnarcotics. Analysis of chemical structures led to the derivation of structural alerts to identify compounds with a significantly increased potential for a high ACR, which may prove to be useful in setting test priorities. At present, however, life-cycle tests are the only way to conservatively predict long-term toxicity.