Practical methods for meeting remediation goals at hazardous waste sites.

Risk-based cleanup goals or preliminary remediation goals (PRGs) are established at hazardous waste sites when contaminant concentrations in air, soil, surface water, or groundwater exceed specified acceptable risk levels. When derived in accordance with the Environmental Protection Agency's risk assessment guidance, the PRG is intended to represent the average contaminant concentration within an exposure unit area that is left on the site following remediation. The PRG, however, frequently has been used inconsistently at Superfund sites with a number of remediation decisions using the PRG as a not-to-exceed concentration (NTEC). Such misapplications could result in overly conservative and unnecessarily costly remedial actions. The PRG should be applied in remedial actions in the same manner in which it was generated. Statistical methods, such as Bower's Confidence Response Goal, and mathematical methods such as "iterative removal of hot spots," are available to assist in the development of NTECs that ensure the average postremediation contaminant concentration is at or below the PRG. These NTECs can provide the risk manager with a more practical cleanup goal. In addition, an acute PRG can be developed to ensure that contaminant concentrations left on-site following remediation are not so high as to pose an acute or short-term health risk if excessive exposure to small areas of the site should occur. A case study demonstrates cost savings of five to ten times associated with the more scientifically sound use of the PRG as a postremediation site average, and development of a separate NTEC and acute PRG based on the methods referenced in this article.

Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor.

We studied the role of PDZ proteins GRIP, ABP, and PICK1 in GluR2 AMPA receptor trafficking. An epitope-tagged MycGluR2 subunit, when expressed in hippocampal cultured neurons, was specifically targeted to the synaptic surface. With the mutant MycGluR2delta1-10, which lacks the PDZ binding site, the overall dendritic intracellular transport and the synaptic surface targeting were not affected. However, over time, Myc-GluR2delta1-10 accumulated at synapses significantly less than MycGluR2. Notably, a single residue substitution, S880A, which blocks binding to ABP/GRIP but not to PICK1, reduced synaptic accumulation to the same extent as the PDZ site truncation. We conclude that the association of GluR2 with ABP and/or GRIP but not PICK1 is essential for maintaining the synaptic surface accumulation of the receptor, possibly by limiting its endocytotic rate.

C-Terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors.

NMDA receptors interact via the extended intracellular C-terminal domain of the NR2 subunits with constituents of the postsynaptic density for purposes of retention, clustering, and functional regulation at central excitatory synapses. To examine the role of the C-terminal domain of NR2A in the synaptic localization and function of NR2A-containing NMDA receptors in hippocampal Schaffer collateral-CA1 pyramidal cell synapses, we analyzed mice which express NR2A only in its C-terminally truncated form. In CA1 cell somata, the levels, activation, and deactivation kinetics of extrasynaptic NMDA receptor channels were comparable in wild-type and mutant NR2A(Delta)(C/)(Delta)(C) mice. At CA1 cell synapses, however, the truncated receptors were less concentrated than their full-length counterparts, as indicated by immunodetection in cultured neurons, synaptosomes, and postsynaptic densities. In the mutant, the NMDA component of evoked EPSCs was reduced in a developmentally progressing manner and was even more reduced in miniature EPSCs (mEPSCs) elicited by spontaneous glutamate release. Moreover, pharmacologically isolated NMDA currents evoked by synaptic stimulation had longer latencies and displayed slower rise and decay times, even in the presence of an NR2B-specific antagonist. These data strongly suggest that the C-terminal domain of NR2A subunits is important for the precise synaptic arrangement of NMDA receptors.

Estimating risk assessment exposure point concentrations when the data are not normal or lognormal.

The U.S. Environmental Protection Agency (EPA) recommends the use of the one-sided 95% upper confidence limit of the arithmetic mean based on either a normal or lognormal distribution for the contaminant (or exposure point) concentration term in the Superfund risk assessment process. When the data are not normal or lognormal this recommended approach may overestimate the exposure point concentration (EPC) and may lead to unecessary cleanup at a hazardous waste site. The EPA concentration term only seems to perform like alternative EPC methods when the data are well fit by a lognormal distribution. Several alternative methods for calculating the EPC are investigated and compared using soil data collected from three hazardous waste sites in Montana, Utah, and Colorado. For data sets that are well fit by a lognormal distribution, values for the Chebychev inequality or the EPA concentration term may be appropriate EPCs. For data sets where the soil concentration data are well fit by gamma distributions, Wong's method may be used for calculating EPCs. The studentized bootstrap-t and Hall's bootstrap-t transformation are recommended for EPC calculation when all distribution fits are poor. If a data set is well fit by a distribution, parametric bootstrap may provide a suitable EPC.