Derrick J. Bates

Toxicokinetics of Isoeugenol in F344 rats and B6C3F1 mice

Abstract 1. Isoeugenol (IEG) has been tested for toxicity and carcinogenicity due to high potential for human exposure and the structural resemblance to known carcinogenic allylbenzenes. In order to support the interpretation of toxicity and carcinogenecity study outcomes, a toxicokinetic study was performed in which both sexes of F344 rats and B6C3F1 mice were given IEG as a single intravenous (IV) or gavage administration. 2. Following IV administration, IEG was rapidly eliminated from systemic circulation in both species and sexes. Gavage administration revealed a rapid absorption of IEG with tmax values ≤20 min for both species and sexes. In rats, AUC increased in a greater than dose-proportional manner and Clapp values decreased with increasing dose in both sexes suggesting saturation of IEG metabolism. On the other hand, Clapp values in male mice increased with increasing dose suggesting induction of IEG metabolism although this was not evident in the females. 3. Absolute bioavailability was greater in female rats (19%) than male rats (10%) (p < 0.0001), but was not different between the sexes for mice (28% males; 31% females) (p = 0.2437). The collective toxicokinetic data supported that low bioavailability following administration of IEG was the result of extensive first-pass metabolism.

Toxicokinetics of methyleugenol in F344 rats and B6C3F1 mice

1. Methyleugenol (MEG) has been used as a flavouring agent in food, as a fragrance in cosmetic products, and as an insect attractant. MEG was carcinogenic in both rats and mice following gavage administration. In this study we investigated plasma toxicokinetics of MEG in F344 rats and B6C3F1 mice of both sexes following single gavage (37, 75, or 150 mg/kg) and intravenous (IV) (37 mg/kg) administration. 2. Following IV administration, MEG was rapidly distributed and cleared from the systemic circulation in both species and sexes. Absorption of MEG was rapid following gavage administration with secondary peaks in the plasma MEG concentration-versus-time profiles. Cmax and AUCT increased and the clearance decreased greater than proportional to the dose in rats and mice of both sexes. In general, rats had higher internal exposure to MEG than mice. 3. The results for AUCT and clearance suggest that perhaps the metabolism of MEG is saturated at higher doses tested in this study. Absolute bioavailability following gavage administration of 37 mg/kg was low in both rats (~4%) and mice (7–9%) of both sexes indicating extensive first-pass metabolism. There was no sex difference in plasma toxicokinetics of MEG following gavage administration both in rats and mice.

Updated Analysis of Energy and cost Savings for Utility service Program at Federal Sites

Report detailing PNNLs re-analysis of data based original analysis done in 2004. The data came from the updated Department of Energy Federal Energy Management utility energy services contract database and the analysis was also expanded to uncover information on additional areas.

Version 2.0 Visual Sample Plan (VSP): Models and Code Verification

Visual Sample Plan (VSP) is an easy-to-use visual and graphic software tool being developed by the Pacific Northwest National Laboratory (PNNL) to select the right number and location of environmental samples so that the results of statistical tests performed to provide input to environmental decisions have the required confidence and performance. It is a significant help in implementing the Data Quality Objectives (DQO) planning process that was developed by the U. S. Environmental Protection Agency. Gilbert et al. (2001) documented the quality assurance (QA) procedures that were conducted to assure that Version 0.91 of VSP was operating correctly. Subsequently, Version 0.91 was renamed Version 1.0 and placed on the internet at http://dqo.pnl.gov/vsp . Since that time VSP has been enlarged and improved and is now available as Version 2.0. The current document is an expansion of Gilbert et al (2001) to include the QA procedures and testing that were conducted to assure the validity and accuracy of the new features added to Version 1.0 to obtain Version 2.0.

Statistical Methods and Tools for Uxo Characterization (SERDP Final Technical Report)

The Strategic Environmental Research and Development Program (SERDP) issued a statement of need for FY01 titled Statistical Sampling for Unexploded Ordnance (UXO) Site Characterization that solicited proposals to develop statistically valid sampling protocols for cost-effective, practical, and reliable investigation of sites contaminated with UXO; protocols that could be validated through subsequent field demonstrations. The SERDP goal was the development of a sampling strategy for which a fraction of the site is initially surveyed by geophysical detectors to confidently identify clean areas and subsections (target areas, TAs) that had elevated densities of anomalous geophysical detector readings that could indicate the presence of UXO. More detailed surveys could then be conducted to search the identified TAs for UXO. SERDP funded three projects: those proposed by the Pacific Northwest National Laboratory (PNNL) (SERDP Project No. UXO 1199), Sandia National Laboratory (SNL), and Oak Ridge National Laboratory (ORNL). The projects were closely coordinated to minimize duplication of effort and facilitate use of shared algorithms where feasible. This final report for PNNL Project 1199 describes the methods developed by PNNL to address SERDPs statement-of-need for the development of statistically-based geophysical survey methods for sites where 100% surveys are unattainable or cost prohibitive.