To determine CBRs for acute mortality and chronic sublethal endpoints in midges for one or more surfactants;
Measure accumulation dynamics for each surfactant including uptake, elimination and metabolism;
Relate variability in CBRs to compound-specific differences in accumulation kinetics and/or metabolism;
Incorporate CBR information into a toxicokinetic model which defines effects of changing contaminant concentration on toxicity.

The hypothsis of the critical body residue (CBR) argues that the amount of contaminant at the target site needed to cause intoxication should not vary significantly among contaminants that share a mode of action or by species. CBRs explicitly incorporate all possible exposure routes and, toxicokinetic information thus eliminating these factors as sources of variability. Research performed on various vertebrates species suggests that CBRs for nonpolar narcotics such as PCBs vary from 2-8 mMol/kg for acute lethal endpoints. In contrast, when LC50s are estimated from environmental media concentrations, the results may span 6 or 7 orders of magnitude. CBRS, thus, offer the possibility of reducing error and uncertainty associated with hazard assessment. Thus research seeks to expand the utility of CBRs by studying key factors impacting their implementation.

We propose to determine CBRs for a range of biological endpoints (acute mortality to sublethal impairments of growth and reproduction) for 3 invertebrate species exposed to surfactants. In addition, toxicokinetic measurements of accumulation dynamics and metabolism will be made. These data will allow us to interpret variability in CBRs. Ultimately, the CBR data will be used in a hazard assessment model so that ecological risk of surfactant exposure can be defined for the entire ecosystem. The proposed resaerch will make an explicit connection between tissue concentrations of surfactants and the resulting biological effects. If the hypothesis of the CBR is true, and the effective concentration at the target site does not vary with contaminant or organism, then there would be compelling evidence to support the use of tissue concentrations of contaminants as the regulatory benchmark rather than highly variable environmental concentrations. This would simultaneously relieve the regulatory burden on industry while augmenting protection of aquatic resources.

Conventional risk assessment models are derived using environmental concentrations of contaminants in environmental media, e.g. sediment or water, as the estimate of contaminant hazard. However, because models which describe the transfer of contaminants from contaminated media into organisms are imprecise, error terms spanning multiple orders of magnitude may result from such estimations. CBRs, in contrast, tie tissue residues in aquatic organisms to toxicity outcomes. CBRs vary less than one order of magnitude for contaminants with a common mode of action even across species ranging from microbes to mammals. If the CBR hypothesis is true, it may dramatically improve hazard assessment and, at the same time, improve the cost effectiveness of measuring hazard. We seek to validate the CBR hypothesis in a species of vertebrates, the midge Chironomus riparious for a variety of endpoints ranging from acute mortality to sublethal impairments of growth and reproduction. Additionally, we will evaluate the utility of using CBRs to estimate the hazard of polar narcotics such as surfactants.

The hypothesis of the critical body residue (CBR) argues that the amount of a contaminant at a given target site needed to produce a biological effect should not vary significantly between contaminants with a common mode of action or between organisms. CBRs have the potential to significantly improve our ability to interpet residue data generated by biomonitoring studies. In addition, for companies such as P&G which have their effluents regulated on the basis of environmental concentrations, CBRs offer the prospect of regulating effluents on tissue concentrations in organisms which are much less variable.

Radioisotopes are used in combination with unlabelled surfactants to determine the body residue needed to cause mortality in acute and chronic studies and sublethal impairments of growth and reproduction in whole lifecyle studies. Each toxicity estimation is supported with a toxicokinetic study which describes the dynamics of surfactant uptake, elimination and metabolism. The latter variables are incorporated into a model which permits assessment of changing surfactant concentration on each toxic endpoint.

We are now in the third year of a three year project. In previous years, we established that CBRs can be used to evaluate the hazard of polar narcotics. Specifically, we found that the CBR for acute narcosis in surfactants is approximately 1 mMol/kg which is statistically identical to the range identified for nonpolar narcotics. Secondly, we have rigorously evaluated the toxicokinetics of surfactants in invertebrates and we have developed a multidimensional toxicokinetic model to describe the uptake, elimination and metabolism of surfactants over time. Prior to this work, most investigators avoided working with metabolizable substances since the subsequent modeling was rendered much more difficult. We now have a model which incorporates the generation of metabolites. We can, thus, analyse the impact of metabolites on CBRs which is a critical step in using them for risk assessment. A third accomplishment is the development of an assay which permits us to evaluate effect along a response spectrum. Previously, CBRs were used to evaluate only acute lethality. Later, it became possible to asssess chronic mortality. Our work has made it possible to include sublethal impairments of growth and reproduction in addition to lethality. Thus, it will become possible to employ remedial statefies long before organisms are impacted to the point where recovery is no longer possible. The validation of CBRs will also make it possible to interpret the extensive existing tissue residue data bases that exist.