Chronicity ratio

They concluded that it did not seem appropriate to rely on one particular metastudy because the selection criteria used for different distributions all have advantages and disadvantages. In addition, they also concluded that the most relevant NOAEL ratios were those based on the same species, and that the most relevant distributions of NOAEL ratios were those that included a sufficient number of matched pairs of NOAELs from various species. Whether the distributions also apply to inhalation and dermal subchronic to chronic ratios was considered to be questionable as it might be possible that the influence of the exposure period on the toxicological effect depends on the route of exposure. 

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... 

Acute-chronic ratios (acute L[E]C50 and/or chronic NOEC) from the ECETOC aquatic toxicity (EAT) database for all aquatic species... 

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. 

Same species as for acute, or 3 species and an acute-chronic ratio The same numbers of organisms are required for marine assessments, but water-type appropriate species should be used. 

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 subchronic-to-chronic UF is based on the assumption that an effect seen at shorter durations will also be seen after a lifetime of exposure, but at lower doses. This factor also assumes that effects may only be seen after an experimental group is exposed chronically. In fact, several investigators have examined subchronic-to-chronic ratios of NOAELs and LOAELs, and the average differences between subchronic and chronic values are only 2-3, while some small percentage of chemicals has ratios that exceed 10-fold. Data suggest that the routine use of a 10-fold default factor for this area of uncertainty should be examined closely. For example, short-term (2 weeks) and subchronic (90 days) NOAELs are often available for comparison, which can give an indication of the possible differences in the subchronic NOAEL and the expected chronic NOAEL. When such data are not available, a 10-fold UF may not be unreasonable, but it should be considered as a loose upper-bound estimate to the overall uncertainty. 

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 ... 

Aquatic toxicologists frequently report fish toxicity data for 24 and 96-hr durations. The chronicity ratio, R, may be defined as,... 

Figure 7. Relationship between excess toxicity (Tg) and chronicity ratio (R) for the toxicity of 37 nonelectrolyte organic compounds to the fathead minnow as follows (by increasing Tg) 2,A,5-Trimethyloxazole...

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... 

Acute/chronic ratio The ratio of the concentration or level of a toxic substance or stress that produces toxic effects after a short period of exposure to the concentration or level of the same substance or stress that produces toxic effects after a long period of exposure. 

If data on a sufficient number and diversity of organisms are available, a final chronic value for a particular toxicant may be calculated in the same way that final acute values are determined. In practice, however, there are seldom sufficient data to allow a direct graphical estimation of the toxicant concentration that would exert a chronic stress on no more than 5% of the species in the system. In such cases an acute toxicity standard is established on the basis of an adequate amount of short-term toxicity tests, and an average acute/chronic toxicity ratio is then calculated on the basis of a smaller amount of information. The rationale for this procedure is that for a given pollutant the acute/chronic ratio is likely to be more constant between species than is the chronic or sublethal stress level itself Hence less information is required to estimate the acute/chronic ratio. The chronic toxicity standard is established by dividing the acute toxicity standard by the so-called final acute/chronic ratio. The EPA considers this procedure acceptable if acute/chronic ratios are available for at least three species and (a) at least one of the species is a fish, (b) at least one is an invertebrate, and (c) at least one is an acutely sensitive fi eshwater species or saltwater species when the ratio is being used to establish freshwater or marine criteria, respectively. 

The final acute/chronic ratio is considered to be a measure of the ratio of the concentration of the toxic substance associated with acutely toxic effects to the concentration associated with chronic toxicity effects. According to the methodology recommended by the EPA (1985a), the final acute/chronic ratio may be calculated in one of four ways. First, if there is no major trend apparent among the acute/chronic ratios for the different species and the species mean acute/chronic ratios lie within a factor of 10 for a number of species, the final acute/chronic ratio is the geometric mean of all the species acute/chronic ratios available for both fi eshwater and saltwater species. Second, if the species mean acute/chronic ratios seem to be correlated with the species mean acute values, the final... 

An example of the calculation of a final acute/chronic ratio is shown in Table V for the pesticide dieldrin. Chronic values for this pesticide were available for only four species in 1980 when the guidelines for dieldrin were established (EPA, 1980a), and therefore it was necessary to use acute/chronic ratios to estabhsh the final chronic value. Acute toxicity values were available in only three of the four cases where chronic effects were studied, but the three species satisfied the criteria for calculating acute/chronic ratios in both freshwater and salt water. Since the acute/chronic ratios for the three species differed by less than a factor of 2, it was appropriate to calculate the final acute/chronic ratio for dieldrin by taking the geometric mean of the three ratios, which is [(11)(9.1)(6.2)] / = 8.5. Final acute values for dieldrin in freshwater (EPA, 1996b) and salt water are 0.48 and 0.71 ppb, respectively. Hence the final chronic values for dieldrininfreshwaterand saltwater areO.48/8.5 = 0.056 ppb and 0.71/8.5 = 0.084 ppb, respectively. 

TABLE V Acute/Chronic Ratios for Dieldrin Toxicity to Three Species of Aquatic Animals ... 

An analogous equation for the final chronic value may be calculated by simply dividing the equation for the final acute value by the final acute/chronic ratio. However, if there is evidence that there is a difference in the functional dependence of chronic toxicity and acute toxicity on water quality characteristics such as temperature and hardness, then the final chronic equation may be determined independently of the final acute equation. In the case of cadmium, for example, chronic toxicity appears to be less sensitive to water hardness than acute toxicity appears to be, thus a final fi eshwater chronic equation was developed solely from chronic toxicity studies performed with 16 fi eshwater species. The final chronic equation for dissolved cadmium in fi eshwater is... 

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