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Biomedical subjects

D J Svendsgaard

Publications and source records attributed to D J Svendsgaard.

8 recordsLinked to original sources
PubMed1994

Toxicology studies of a chemical mixture of 25 groundwater contaminants: hepatic and renal assessment, response to carbon tetrachloride challenge, and influence of treatment-induced water restriction.

Because groundwater contamination is an important environmental concern, we examined the hepatic and renal effects of repeated exposure to a mixture of 25 chemicals frequently found in groundwater near hazardous-waste disposal sites and the effect of such exposure on carbon tetrachloride (CCI4) toxicity. Adult male F-344 rats received ad libitum deionized water and feed (Ad Lib Water) or ad libitum 10% MIX (referring to 10% of a technically achievable stock mixture) and feed for 14 d. Because exposure to the 25-chemical mixture via the drinking water resulted in decreased water and feed consumption, restricted deionized water and feed controls (Restricted Water) were included. On d 14, rats were gavaged with 0, 0.0375, 0.05, 0.075 or 0.15 ml CCl4/kg, and hepatic and renal toxicity assessed 24 h later. Little or no hepatic and renal toxicity was observed in rats exposed to 10% MIX alone. No hepatic or renal lesions occurred that could be attributed to 10% MIX alone. Slight but statistically significant alterations, of uncertain biological significance, resulted from the water treatments: 10% MIX increased alanine aminotransferase, urea nitrogen (BUN), and BUN/creatinine ratio; Restricted Water increased 5'-nucleotidase and decreased alkaline phosphatase. Relative kidney weight was increased by both 10% MIX and Restricted Water. CCI4 resulted in significant dosage-dependent hepatotoxicity in all three water treatment groups but had little or no effect on renal indicators of toxicity. Relative to Ad Lib Water, significantly greater hepatotoxicity occurred in both 10% MIX and Restricted Water rats. The response to CCI4 in the Restricted Water rats was similar to that of 10% MIX rats, indicating that a substantial portion of the effect of 10% MIX on CCI4 hepatotoxicity is due to decreased water and feed intake.

Analysis of Variance↗
PubMed1991

Quantitative methods for cross-species mapping (CSM).

Cross-species extrapolation will be defined as prediction from one species to another without empirical vetification. Cross-species mapping (CSM) is the same except empirical vetification is performed. CSM may be viewed as validation of methods for extrapolation. Algorithms for CSM may originate from theory, from empirical observations or a combination of the two. Regardless of their origins, CSM algorithms must be explicated and confidence intervals given around their predictions. This paper offers a quantitative method for constructing CSM equations which is useful in evaluation of the CSM and as an aid in the design of new experiments in CSM and extrapolation. The method requires fitting mathematical models for the physiological or behavioral phenomena to be mapped across species. A CSM equation can then be derived from the models in each species and approximate confidence limits may be obtained for predictions from the equation. The method is useful even when the models in the two species differ in form, implying differences in physiology or behavioral principles between species. The method proposed has a number of remaining uncertainties and possible problems.

Animals↗
PubMed1990

U-shaped dose-response curves: their occurrence and implications for risk assessment.

A class of curvilinear dose-response relationships in toxicological and epidemiological studies may be roughly described by "U-shaped" curves. Such curves reflect an apparent reversal or inversion in the effect of an otherwise toxic agent at a low or intermediate region of the dose continuum. Several examples of U-shaped dose-response functions are presented to illustrate the variety of agents and end points that can follow this form. Such findings are not thought to represent a unitary phenomenon, but may be explained through numerous possible principles or mechanisms, some of which are illustrated and discussed in general terms. U-shaped dose-response curves raise important issues for toxicological and environmental health risk assessments, particularly in the identification of no-observed-effect levels and in the evaluation of multiple outcomes and the tradeoffs between potential risks and benefits of a given agent. It is especially important to avoid focusing exclusively on an apparent improvement in one end point and failing to consider other, possibly deleterious effects of the same agent.

Animals↗
PubMed1983

Long-term accumulation of hexachlorobenzene in adipose tissue of parent and filial rats.

The concentrations of hexachlorobenzene (HCB) in adipose tissue were similar for F0 and F1b generations in rats fed 20 ppm HCB until 45 weeks of age. Nulliparous females receiving treatment equivalent to the HCB-treated F0 generation rapidly accumulated HCB in their fat and, by 13 weeks of age, the residue values coalesced with values in 13-week-old F1a females which had received additional HCB via the placenta and milk. Between 13 and 30 weeks of age, steady-state storage was approached and no significant increase in HCB concentrations occurred through 65 weeks of age. Postlactation dams, that nursed average size second litters, had considerably lower concentrations of HCB in their fat than dams weaning no pups, suggesting substantial redistribution and/or elimination of maternal stores during lactation.

Adipose Tissue↗
PubMedDate not supplied

Lead and child development.

A group of independent epidemiological studies shows that fetal exposure to levels of lead previously considered safe is linked to impairment of infant mental development.

Abnormalities, Drug-Induced↗