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Biomedical subjects

G Linder

Publications and source records attributed to G Linder.

12 recordsLinked to original sources
PubMed1998

Phase III interlaboratory study of FETAX, Part 2: interlaboratory validation of an exogenous metabolic activation system for frog embryo teratogenesis assay--Xenopus (FETAX).

Interlaboratory validation of an exogenous metabolic activation system (MAS) developed for the alternative, short-term developmental toxicity bioassay, Frog Embryo Teratogenesis Assay-Xenopus (FETAX) was performed with cyclophosphamide and caffeine. Seven study groups within six separate laboratories participated in the study in which three definitive concentration-response experiments were performed with and without the MAS in a side-by-side format for each chemical. Since both chemicals had been previously tested in FETAX, the test concentrations were provided to each laboratory prior to testing. Interlaboratory coefficient of variation (CV) values for unactivated cyclophosphamide (no MAS) were 15%, 15%, 29%, and 25% for the 96-hr LC50, 96-hr EC50 (malformation), Minimum Concentration to Inhibit Growth (MCIG), and Teratogenic Index (TI) values, respectively. Addition of the MAS increased the CV values of each endpoint at least 3.9-fold. Interlaboratory CV values for unactivated caffeine were 31%, 18%, 31%, and 46% for the 96-hr LC50, 96-hr EC50 (malformation), MCIG, and TI values, respectively. Addition of the MAS decreased the CV values of each respective endpoint by at least 1.6-fold. Results indicated that bioactivated toxicants may be prone to greater variability in response amongst laboratories than compounds, which are detoxified. Even though more variability was noted with activated cyclophosphamide, results were within interlaboratory variation expected for other aquatic-based bioassays. Thus, results from these studies warrant the continued use and further refinement of FETAX for alternative developmental toxicity assessment.

Abnormalities, Drug-Induced↗
PubMed1997

The Stanford Health Information Network for Education: integrated information for decision making and learning.

Although multiple decision support systems have been built for physicians, efficient delivery of valid and complete medical knowledge remains an elusive goal. In this paper we describe a new project, the Stanford Health Information Network for Education (SHINE). SHINE unifies core medical resources in an intuitive interface to support clinical decision making. Included in the description is a novel paradigm for continuing medical education (CME).

California↗
PubMed1996

Food chain analysis of exposures and risks to wildlife at a metals-contaminated wetland.

A food chain analysis of risks to wetland receptors was performed in support of a baseline ecological risk assessment at the Milltown Reservoir Sediments Superfund site in Montana. The study area consisted of over 450 acres of primarily palustrine wetland contaminated with metals from mining wastes transported from upstream sources (average of 465 mg/kg for Cu in sediments, and 585 mg/kg in soils). The food chain analysis focused on several species of terrestrial and semiaquatic animals indigenous to montane wetlands of the northern Rocky Mountains. Receptors consisted of mice, voles, muskrats, beaver, various waterfowl species, osprey, bald eagles, and deer. Samples of aquatic and terrestrial invertebrates, small mammal tissues, fish tissue, aquatic and terrestrial vegetation, soils, sediment, and surface water were collected and analyzed for As, Cd, Cu, and Zn. A linear multimedia food-chain model was constructed to estimate daily intakes of the metals for each receptor, with assumed values for ingestion of aquatic and terrestrial food items, ingestion of local surface water, and incidental ingestion of soils and/or sediments. Evaluation of health risks to the receptors was performed by comparison of exposures expressed as daily intakes to a suite of toxicity values. The range of values consisted of the lower end of chronic toxicity data found in toxicology databases or the literature for the same or similar species, modified to account for extrapolation uncertainties. Daily intakes of chemicals of concern were below or within the range of toxicity values for all receptors. The weight of evidence from the food chain analysis and earlier bioassessment and ecological studies suggest that the health of the wetland receptors is at minimal risk due to the presence of elevated metals in sediments, upland soils, water, or food items at the site.

Animals↗
PubMed1994

Bioavailability of metals and arsenic to small mammals at a mining waste-contaminated wetland.

In support of a baseline ecological risk assessment evaluating the impacts of mining wastes at the Milltown Reservoir Sediments Superfund site in Montana, a food chain transfer analysis was performed for resident small mammals. Deer mice (Peromyscus maniculatus) and meadow voles (Microtus pennsylvanicus) were trapped from a 200 A portion of a mixed upland and palustrine wetland, and concentrations of As, Cd, Cu, Pb, and Zn in carcass, liver, kidney, and testes were quantified. Concurrent to small mammal trapping, samples of grasses, forbs, and soils were collected and analyzed for metal and As residues. Using a linear multimedia food-chain model, assuming a forage base of wetland vegetation from the site, ingestion of local surface water, and incidental ingestion of soils with vegetation, body burdens of the metals and As in the herbivores were estimated. As a means of estimating potential element bioavailability at the site, the modeled body burdens were compared with measured element concentrations in herbivore tissues. The analysis indicates that the bioavailabilities of As, Cd, Cu, Pb, and Zn were equal to or less than 0.2% for internal organs and 0.1% for carcasses, on a microgram/g tissue wet weight basis. Available site data on soil pH, cation exchange capacity, and extractable elements fraction supported the limited release of soil elements. These results suggest that the bioavailable fraction of mining waste metals in riparian wetland soils may be quite small, and, for the Milltown Reservoir site, lower than originally anticipated.

Animals↗
PubMed1991

A model of additive effects of mixtures of narcotic chemicals.

Biological effects data with single chemicals are far more abundant than with mixtures. Yet, environmental exposures to chemical mixtures, for example near hazardous waste sites or non point sources, are very common and using test data from single chemicals to approximate effects of mixtures can be useful in environmental risk assessment. To facilitate the linkage, the Weibull function was used as a common model to link responses of single chemicals with the response of their mixtures. The present paper addresses the response of fish to mixtures of narcotic chemicals and a second paper addresses the developmental malformation of frog embryos when exposed to defined mixtures of teratogenic chemicals. Biological effects data with singly tested chemicals cannot be used directly to predict effects of mixtures. However, narcotic chemicals are known to produce an additive concentration effects in fish and the Weibull function with an additive concentration variable was used to model the effects of mixtures of these chemicals. The model produced good agreement with data over a wide range of chemicals and mixture ratios and provides a useful initial assessment of environmental effects of mixtures of narcotic chemicals.

Animals↗
PubMed1985

Kinetics of renal aspartate reabsorption and its inhibition by metals in the intact rat kidney.

A modified clearance technique originally developed for the intact rabbit was adapted for use in the intact rat; it permits measurement of maximum tubular capacity (Tm) and half-saturation constant (KM) without the need for high systemic plasma levels and long equilibrating infusions of the solute under study. In this manner, Tm and KM for aspartate reabsorption were determined. Subsequently, we compared these kinetics constants to renal aspartate Tm and KM values in the literature derived from single tubule studies, and analyzed the nephrotoxicity of nickel and cadmium. Aspartate KM and Tm in the intact rat were 6.1 mM and 5.8 mumole/g cortex/min respectively; in contrast, work with single tubules led to KM aspartate of 0.1 mM and Tm aspartate of 20.0 mumole/g cortex/min. The discrepancy between the two sets of results reemphasizes the difficulty in extrapolating from single tubules to intact kidney; presumably tubular heterogeneity accounts for these differences. Aspartate reabsorption was also measured in rats injected intraperitoneally with 20 mumole nickel or cadmium/kg body weight 36 to 40 hr previously. At renal nickel or cadmium concentrations of approximately 10 micrograms/g kidney glomerular filtration rate and aspartate Tm were significantly decreased while aspartate KM was not affected. The effects of the metals resemble a noncompetitive type of inhibition of aspartate reabsorption.

Absorption↗
PubMedDate not supplied

FETAX interlaboratory validation study: phase III--Part 1 testing.

The Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a 96-h whole embryo developmental toxicity screening assay that can be used in ecotoxicology and in detecting mammalian developmental toxicants when an in vitro metabolic activation system is employed. A standardized American Society for Testing and Materials (ASTM) guide for the conduct of FETAX has been published, along with a companion atlas that aids in embryo staging and identifying malformations. As part of the ASTM process, a three-phase interlaboratory validation study was undertaken to evaluate the repeatability and reliability of FETAX. Seven different participants collaborated in the study. In Phase I, FETAX proved to be more repeatable and reliable than many bioassays. However, some excessive variation was observed in a few laboratories. An initial lack of assay experience by some technicians caused variation. Phase II showed far less intra- and interlaboratory variability than Phase I. Non-teratogens showed the most consistent results, while more variability was observed for the two teratogens tested. Interlaboratory coefficient of variation values for all endpoints ranged from 7.3 to 54.7. Phase III--Part 1, using coded samples and test concentration ranges selected by each laboratory, showed results similar to Phase I. Analysis of the causes of variation suggested that some technicians judged some embryos to be malformed while others consistently judged similar embryos as normal. Concentration ranges tested by some of the laboratories varied greatly and a new protocol for selecting concentrations for initial testing was written to reduce variation from this source. Testing to date suggests that FETAX is as repeatable and reliable as other standard bioassays.

Aminopropionitrile↗
PubMedDate not supplied

Initial interlaboratory validation study of FETAX: phase I testing.

An interlaboratory validation study was undertaken to evaluate the repeatability and reliability of the Frog Embryo Teratogenesis Assay-Xenopus (FETAX), which is a whole embryo developmental toxicity screening assay. A three-phase experimental program with seven participants was carried out. Phase I was a training and protocol evaluation phase where the identity of the three test materials was known. Hydroxyurea, isoniazid and 6-aminonicotinamide were tested in Phase I. Because the chemicals has been tested previously in FETAX, the same concentrations needed to establish the 96-h median lethal concentration (LC50) and the concentration inducing malformations in 50% of the surviving embryos (EC50) were used by all laboratories. The results of Phase I are presented in this report, and FETAX has proved to be as repeatable and reliable as many other bioassays. Some excess variation was observed in individual laboratories. Some of this variation may have been due to training difficulties. One change in protocol design necessitated by this study was the use of 6-aminonicotinamide as a reference toxicant. While 6-aminonicotinamide provided excellent concentration-response data in most laboratories, the protocol was written too strictly based on historical FETAX data. Phases II and III are currently in progress.

6-Aminonicotinamide↗