Acute-to-chronic ratios

For the effect level, application of the invertebrate acute-to-chronic ratio to the most acutely sensitive invertebrate species, Dero, generates a chronic toxicity value of 0.6 mg/L. This value compares favorably with the measured NOECs of 1.2 and 1.4 mg/L, respectively, for the invertebrates Daphnia magna and Ceriodaphnia dubia. The fish species most sensitive to C12LAS chronic toxicity is the fathead minnow, Pimephales promelas. Most recently, Fairchild et al. (64) reported a chronic C12LAS NOEC of 0.7 mg/L for the fathead minnow. This NOEC compares favorably with the NOEC of 1.1 mg/L reported by Holman and Macek (66) for the same species. 

The extrapolation from acute responses to no-observed-effect concentrations or chronic responses is particularly important as chronic tests are more costly and time-consuming than acute tests. Traditionally, relationships between acute and chronic effects were estimated using a simple ratio, the acute-to-chronic ratio (ACR). Where acute and chronic effect measures are available for the same species, this ratio is used to estimate chronic responses in related organisms for which only acute data are available (Stephan and Rogers 1985). This approach is based on the assumption that there is a relationship between the responses in acute and chronic tests, an... 

Lange R, Hutchinson T, Scholz N, Solbe J. 1998. Analysis of the ECETOC Aquatic Toxicity (EAT) database, II comparison of acute to chronic ratios for various aquatic organisms and chemical substances. Chemosphere 36 115-127. 

As discussed in Section 4.8, and providing that some chronic data are available, use of acute-to-chronic ratios (ACRs) can be helpful if chronic data are limited to allow use of the large acute toxicity database for PNEC or EQS derivation. 

A9.3.3.2.3 Testing with algae/Lemna cannot be used for de-classifying chemicals because (1) the algae and Lemna tests are not long-term studies, (2) the acute to chronic ratio is generally narrow and (3) the endpoints are more consistent with the end points for other organisms. 

The definition of the acute to chronic ratio (ACR) has been one of the methods used to predict the threshold concentration at which a toxicant does not produce noticeable effects during a chronic exposure. This ratio is based on the same concept as the application factors, but its numerical value is the inverse (Stephan, 1982). The ACR is the ratio between chemical concentrations exerting a lethal versus sublethal toxic effect and describes the ratio of a lethal to sublethal end-point ... 

The advantage of addressing hiunan metabohtes is that there is a vast body of information on the pharmacokinetics available. Therefore, information on metabolic pathways and fractions of metabohtes formed can be taken directly from the hterature. The disadvantage is that, unhke for pesticides, there are almost no experimental ecotoxicity data available for the metabohtes. In addition, the environmental risk assessment of pharmaceuticals should rely exclusively on chronic toxicity data [53] because it is suspected that some pharmaceuticals have imusually high acute-to-chronic ratios, which was confirmed by a recent review [54]. Although the model presented here can in theory easily be used for chronic toxicity data, its practical implementation is limited by the unavailabihty of QSARs for chronic endpoints. For illustration... 

Raimondo S., Montague B.J. Barron M.G. (2007) Determinants of variability in acute to chronic toxicity ratios for aquatic invertebrates and fish. Environmental Toxicology and Chemistry 26 2019-2023. 

On the balance of the available evidence from human and animal studies presented in this chapter, it appears that CCM is well absorbed across a wide range of compositions and circumstances. For example, studies using isotopic and pharmacokinetic methods have shown that CCM is highly absorbable by both children and adults, in both tablet and beverage form, when consumed at levels ranging from an acute dose to chronic consumption (i.e., 200 mg Ca to 700 mg Ca/day, respectively), and for compositions covering a broad range of Ca citrate malate molar ratios that bracket the 6 2 3 neutral salt (i.e., molar ratios from 5 1 1 to 1.0 1.8 1.5 or the equivalent 6 10.8 9). 

Patients with severe hver failure may be at increased risk for essential fatty acid deficiency the ratio of nonessential to essential fatty acids was found to be increased in patients with acute and chronic hver failure. Poor oral intake of fat and dietary fat malabsorption in patients with cirrhosis both contribute to essential fatty acid deficiency. These changes were due to decreased hnoleic acid and increased serum... 

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