Biomedical subjects

K A Poirier

Publications and source records attributed to K A Poirier.

5 recordsLinked to original sources

PubMed2001

Determination of an acute no-observed-adverse-effect level (NOAEL) for copper in water.

A prospective, double-blind controlled study was designed to determine the acute no-observed-adverse-effect level (NOAEL) of nausea in an apparently healthy population of 179 individuals who drank copper-containing water as the sulfate salt. Subjects were recruited at three different international sites and given a blind, randomly selected dose (0, 2, 4, 6, or 8 mg Cu/L) in a bolus of 200 ml (final total copper dose was equivalent to 0, 0.4, 0.8, 1.2, and 1.6 mg) once weekly over a consecutive 5-week period. Gastrointestinal (GI) symptoms of nausea, abdominal pain, vomiting, or diarrhea were screened for a period of up to 24 h. Nausea was the most frequently reported effect and was reported within the first 15 min of ingestion. For the combined trisite population (n=179), 8, 9, 14, 25, and 44 subjects responded positively to one or more GI symptoms at 0, 2, 4, 6, and 8 mg Cu/L, respectively. Analysis of the data demonstrated a clear dose response to the combined positive GI effects and to nausea alone. Statistically significant greater reporting of effects occurred at 6 and 8 mg Cu/L. Therefore, an acute NOAEL and lowest-observed-adverse-effect level of 4 and 6 mg Cu/L (0.8 and 1.2 mg Cu), respectively, were determined in drinking water for a combined international human population.

Adult↗

PubMed2001

Uncertainties in the reference dose for methylmercury.

This paper critically examines the National Academy of Sciences and the National Research Council report on the toxicological effects of methyl mercury and the recently published US Environmental Protection Agency Reference Dose (RfD) for Methylmercury. Particular scrutiny is placed on the choice of the critical study and the underlining assumptions utilized in the selection of specific uncertainty factors (UFs) and the rationale for using a less-than-default factor of 10. The UFs that were utilized or considered by other agencies and organizations are also critically examined, explained and compared to one another. Based on these analyses, the authors suggest research that could be performed that would ameliorate the uncertainty of choosing a more precise partial UFor that may even provide completeness of database to allow for selecting of a UF for unity, thus improving the precision of the current published RfD.

Animals↗

PubMed1986

Differential effects of selenium on normal and neoplastic canine mammary cells.

Four different canine mammary tumor (CMT) cell lines and a nonneoplastic primary culture of mammary cells were examined for their in vitro responsiveness to selenium supplementation. These cell lines were found to vary in their metabolic response to increasing concentrations of selenium. Sensitivity to selenium, as sodium selenite, increased with increasing concentrations of this trace element in all of the neoplastic lines. These data also suggest that increasing the plating density of tumor cells further increases the sensitivity to selenium. A relatively selenium-sensitive cell line (CMT-13) and relatively insensitive cell line (CMT-11) were characterized on the basis of reduced growth resulting from selenium supplementation. Increasing the concentration of selenium to 0.75 microgram/ml depressed the growth of CMT-13 and CMT-11 cells by 75% and 11%, respectively, while no inhibition was observed in nonneoplastic cells. These cell lines also varied in their sensitivity to different forms of selenium. Selenodiglutathione was the most effective form of selenium examined that inhibited tumor cell growth. The sensitivity of the neoplastic lines was selenodiglutathione much greater than sodium selenite much greater than selenocystine greater than selenomethionine. None of the forms of selenium examined inhibited the growth of the nonneoplastic mammary cells in culture. Supplementation with sodium selenite (1 microgram Se per ml) for 60 min resulted in a dramatic depression in RNA biosynthesis in CMT-13, but not CMT-11 or nonneoplastic cells.

Animals↗

PubMed1984

Inhibition of human breast cancer cells by selenium.

The viability of human breast cancer cells (cell lines MCF-7 and MDA-MB 231) was inhibited in vitro in a dose-dependent manner by selenium supplementation. However, a normal diploid human cell line (MRC-5) was relatively resistant to selenium supplementation. The presence of selenium as Na2SeO3 at 1.1 X 10(-6) M reduced cancer cell viability by approximately 50%, whereas non-cancerous cells were not affected. Parenteral administration of sodium selenite also significantly inhibited the growth of the cancerous cell lines transplanted into nude mice. Selenium administration at 0.8 micrograms/g body wt resulted in an 80-93% reduction in the rate of tumor growth without apparent ill effects on the host.

Animals↗

PubMed1983

Factors influencing the antitumorigenic properties of selenium in mice.

Sodium selenite (Na2SeO3) was administered at 2.0 micrograms selenium (Se) to Swiss ICR mice six times over a 9-day period by intraperitoneal (i.p.) injection or by gastric gavage. Survival time was significantly increased in Ehrlich ascites tumor (EAT)-bearing mice by 170 and 20%, respectively, compared to controls. In two separate studies, 5.0 micrograms Se as Na2SeO3 or selenodiglutathione (GSSeSG) administered i.p. was more effective in inhibiting EAT propagation in mice than either untreated (control) mice or mice receiving sodium selenide, dimethyl selenide [(CH3)2Se] or seleno-DL-cystine. In another study, EAT cells were preincubated with either 1 or 3 ppm Se as GSSeSG, Na2SeO3, or (CH3)2Se, washed, and reinoculated into mice. Only in mice inoculated with cells pretreated with GSSeSG was a significant increase in survival observed. The observed tumor inhibition was not limited to ascitic tumors since growth of solid Ehrlich tumors was also significantly inhibited by i.p. treatment of Na2SeO3. Following i.p. administration of Na2(75)SeO3, the solid tumors retained more selenium-75 than did blood, lung, kidney, or liver. Supplementation of a torula yeast diet with 2.5 or 5.0 ppm Se as Na2SeO3 also significantly increased the survival time of EAT-bearing mice. These data show that the form and mode of administration of selenium influence the antitumorigenic properties of this trace element. In addition, the data suggest that some intermediate in the normal pathway for selenium detoxification is probably responsible for this trace element's antitumorigenic properties.

Animals↗