Internal Effect Concentrations

Sijm, D. T. H. M., and J. L. M. Hermens, Internal effect concentration Link between bioaccumulation and ecotoxicity for organic chemicals . In The Handbook of Environmental Chemistry, Vol. 2, Part J, B. Beek, Ed., Springer, Berlin, 2000, pp. 167-199. 

Internal Effect Concentration Link Between Bloaccumulatlon and Ecotoxicity for Organic Chemicals 169... 

For a broad applicability applied to either lethal or sublethal effects, the internal effect concentration (expressed as mol kg or mol kgupy ) approach should meet a couple of conditions. The following examples refer to lethality. The first condition may be that an organism dies when a distinct internal effect concentration, the lethal body burden, of a specific chemical has been reached. The second condition is that any individual dies when it has attained this lethal body burden. The third condition is that the lethal body burden is independent of time of death or exposure concentration. In the latter case it may take longer to die at a lower exposure concentration and shorter to die at a higher concentration, but in either case, when the lethal body burden has been reached, it should be the same for both conditions. The fourth condition is that all chemicals which have the same mechanism of action have the same lethal body burden. The latter thus enables one to deal with additivity, since the individual chemicals of a mixture, all of which have the same mechanism of action, will contribute equally to the body burden on a molar basis. 

Ecotoxicological effects of organic chemicals can be related to external and internal effect concentrations. Earlier studies already showed that a lot of information is available on external effect concentrations for different classes of compounds and different organisms. The main focus of this section therefore is on internal effect concentrations. 

Fig. 1. The concept of attaining an internal effect concentration in time as the result of bioaccumulation. An organism is exposed to a contaminant from the ambient environment, which can be water (top) or soil (middle), or from food (bottom). The more it has taken up the higher its internal concentration will be until a critical internal concentration is reached, e.g. the lethal body burden, and the associated effect, e.g. death, is elicited...

In the following sections lethal body burden associated with some mechanisms of actions will be discussed first, which will then be followed by a critical discussion of the assumptions behind the internal effect concentration. 

Fig. 2. A simplified example of the general relationships between on the one hand the oc-tanol/water partition coefficient (Ko ) and on the other hand internal effect concentrations (body residues), bioconcentration and acute toxicity for narcotic organic chemicals and small freshwater fish [16], reproduced with permission...

Table 2 and Fig. 3 show that each mechanism of action has one, but in some cases a rather broad range of, internal effect concentrations for aquatic organisms. Therefore there is not one distinct value of the lethal body burden associated with one mechanism of action, but rather a range of internal concentrations that is related to an ecotoxicological effect. Some other questions which can be asked to validate the use of the internal effect are how large is the interspecies variation in internal effect concentration (for two types of mechanisms of action), how large is the intraspecies variation in internal effect concentration (for one type of mechanism of action), and what is the time and concentration dependent influence on the internal effect concentration (for one type of mechanism of action). 

An additional explanation for the observation that lipid only explains approximately 50% of the variation in internal effect concentration may be that the different lipids of an organism do not evenly contribute to storage in target tissues [128], and that lipid normalisation may thus not be appropriate. The assumption, however, that the internal concentration is a distinct value is not valid. Intraspecies differences do exist and cannot be explained by intraspecies differences in lipid content alone, although the variation in LBB within a population is less than an order of magnitude. 

Fig. 4. Time and exposure concentration dependent concentrations in fish in addition to the lethal body burden (horizontal solid line) for 1,2,3-trichlorobenzene. The dotted lines are theoretical curves calculated with a bioaccumulation model. Exposure concentrations are 55.9 pmol 1 (I), 3.78 pmol (II), and 1.92 pmol (III). The symbols represent the mean of the internal effect concentrations of ten fish [9], reproduced with permission...

Ecotoxicological effects, such as acute or sublethal responses, can be related to both external and internal concentrations. The former is still used in risk assessment procedures, while the latter has recently been investigated for its potential use in risk assessment. External concentrations may vary by many orders of magnitude for different chemicals, even when they exert the same mechanism of action. The variability in internal concentrations is much smaller. The assumptions which form the basis for a broad applicability of the internal concentration, namely that for a given mechanism of action, i) there would be no intraspecies variation, ii) there would be no interspecies variation, and iii) there would be no time or concentration dependency, have been studied. It was found that no assumption was completely valid. However, given the magnitude of variability found, these variations are much less than those which are found for external concentrations, while some of the reasons for the variations in the internal effect concentrations may be similar for the variation in external effect concentrations. 

Prediction of ecotoxicological effects for other types of chemical classes as well as for foodchain transfer is less founded, and should be studied further to extend our knowledge and the applicability in using the internal effect concentrations. 

The use of the internal effect concentration may be of great help in classifying chemicals and their effects. However, for that purpose, more data on internal effect concentrations associated with different mechanisms of action in different organisms are a prerequisite. 

A well-known subacute effect is the growth reduction in algae. Hitherto, only external effect concentrations have been reported for this type of subacute effect, since experimental problems make it difficult to determine those internal effect concentrations, and existing bioaccumulation models for, e. g., fish, do not apply to algae, e.g. [78]. It must be noted that algae and other small organisms are prone to diffusive uptake for contaminants from the ambient environment for which the link between bioconcentration and the internal effect concentration concept would be very promising. 

Many structure-activity relationships can be used to deal with mixture toxicity. Bio accumulation models in combination with internal effect concentration may provide a good means to better predict when organisms are at risk. It must be noted, however, that in many cases there is significant variation in these internal effect concentrations, although even larger variation is found for external effect concentrations. The variation in the external effect concentrations is partly related to the variation in bioaccumulation and partly to interspecies and intraspecies variation. 

When more knowledge is available on internal effect concentrations, bio-mimetic monitoring may be a useful tool to estimate the environmental risk of organisms in the field, and at present can already be used for narcotic effects. Already mixed-function oxygenase system components and antioxidant enzymes are related to contaminant body burdens in marine bivalves in the field [151], which indicates the potential of the use of internal concentrations as parameters for ecotoxicological effects. 

Most of the internal effect concentrations that are described in this chapter are related to the in vivo situation. However, this approach may also be of value for in vitro studies. Recently, examples of relatively constant internal concentrations have been given for the inhibition of yeast H+-ATPase, Chinese hamster ovary cell... 

Na+/K -ATPase and for human skin fibroblast Na+/K+-ATPase ll52]. External effect concentrations were combined with tissue/water partition coefficients to estimate the internal effect concentrations. For these latter studies, external effect concentrations showed a much greater variation than the internal effect concentrations, as is found for in vivo external and internal effect concentrations. 

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