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Biomedical subjects

T H Connor

Publications and source records attributed to T H Connor.

46 records · Page 3Linked to original sources
PubMed1980

The mutagenic evaluation of tetrakis (hydroxymethyl) phosphonium sulfate using a combined testing protocol approach.

This study was undertaken to evaluate the mutagenicity of the flame retardant, Tetrakis (Hydroxymethyl) Phosphonium Sulfate -75% or its possible metabolic products using a battery of in vitro and in vivo assays. The starting material in the fabric treatment process, THPS was tested with five strains of Salmonella typhimurium with and without the addition of a rat liver activating system. In addition, the THPS and the treated fabric were assayed in a combined testing protocol. The mutagenicity tests which were employed in this protocol included (a) the analysis of the urine of treated mice, (b) the micronucleus test, and (c) metaphase analysis. The animals were administered the THPS both orally and dermally and the treated fabric was incorporated into the animals' feed. The THPS produced no mutagenic response in any of the strains of S. typhimurium either when tested directly or with the addition of Acroclor--or phenobarbital-- induced rat liver. The results of the combined testing protocol, with the three routes of administration, were also negative for the urine analysis, micronucleus test and metaphase analysis.

Administration, Oral↗
PubMed1979

Bile as a source of mutagenic metabolites produced in vivo and detected by Salmonella typhimurium.

The in vivo metabolic activation of several mutagenic compounds was assayed in the bile of rats, with Salmonella typhimurium as the indicator organism. It was determined that for some compounds, particularly the aromatic amines, a substantial percentage of the compound was excreted into the bile as either a nonmutagenic glucuronide conjugate or a mutagenic metabolite of the compound. Relatively low doses of the chemical were detected, and it was possible to follow the excretion pattern of the compounds over the collection period.

Acetaminophen↗
PubMed1979

A combined testing protocol approach for mutagenicity testing.

The antischistosomal agent, hycanthone methanesulfonate (HMS), was employed to illustrate the utility of carrying out several mutagenicity tests in a single concurrent animal experiment. Several commonly used procedures that were successfully integrated into a multiple testing protocol included (1) metaphase analysis in bone marrow, (2) micronucleus test in bone marrow, (3) analysis of the urine for mutagenic constituents, and (4) the host-mediated assay using Salmonella typhimurium. In addition to these animal studies, in vitro mutagenicity testing with and without activation was carried out using S. typhimurium. HMS produced positive, dose--response effects in in vitro tests, metaphase analysis, micronucleus test, and urine analysis, but not in the host-mediated assay. The results of these integrated techniques suggest that such a protocol may be a benefit to those concerned with mutagenicity testing of chemicals.

Animals↗
PubMed1977

The contribution of metronidazole and two metabolites to the mutagenic activity detected in urine of treated humans and mice.

The urine of two patients receiving therapeutic doses of the trichomonacide, metronidazole, was analyzed for mutagenic activity using the histidine auxotroph TA1535 of Salmonella typhimurium. The activity detected in the urine was significantly higher than could be accounted for by the presence of the administered drug. Chromatographic analysis of the urine indicated the presence of the metabolite 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole, which when tested in vitro with TA1535 was found to be ten times more active than metronidazole. An additional urinary metabolite, 1-acetic acid-2-methyl-5-nitroimadazole, was found to be inactive when similarly tested. The in vitro mutagenic activity of metronidazole and the two metabolites was unchanged by the addition of phenobarbital- or Aroclor-induced rat liver homogenate to the test system. In addition, metronidazole and the hydroxymethyl metabolite reverted S. typhimurium TA100 but not TA1537, TA1538, or TA98, and the acetic acid metabolite failed to revert any of the tester strains. In studies with mice, metronidazole was required in excess of the human dose in order for significant amounts of the hydroxymethyl metabolite to be detected in the urine. Urine from mice pretreated with the hepatotoxin, carbon tetrachloride, prior to the administration of metronidazole demonstrated approximately a 50% reduction in mutagenic activity, and the formation of the urinary metabolites was inhibited. These findings indicate the production of metabolites from the parent compound by the liver of the intact animal which could not be determined by use of the standard in vitro liver homogenate system.

Animals↗
PubMed1975

Detection of mutagenic activity of metronidazole and niridazole in body fluids of humans and mice.

After humans were treated at therapeutic doses with the trichomonacide metronidazole (Flagyl) and the antischistosomal agent niridazole mutagenic activity was demonstrable in their urines when tested with the histidine auxotroph of Salmonella typhimurium. Both compounds were active in the host-mediated assay in mice, and evidence of activity was found in the blood and urine of mice treated with niridazole but not with metronidazole.

Animals↗
PubMedDate not supplied

A comparison of methods for determining lead content in drinking water: a portable anodic stripping voltammetry instrument method versus the standard EPA 239.2 method.

Lead levels in drinking water were measured by the standard U.S. Environmental Protection Agency (EPA)-approved atomic absorption spectroscopy-graphite furnace Method 239.2 and compared with determinations made with a newly available portable anodic stripping voltammetry (PASV) instrument. A standard curve was prepared at 2, 5, 10, 15, 20, 25, and 30 microg/L of lead. PASV instrument readings were lower than standard EPA method values, with a mean difference and standard error (SE) of the mean between the two of 1.538+/-0.588 microg/L (n = 7, p = 0.040, significant at the 95% confidence interval [CI]). First-flush drinking water samples collected from 144 water fountains/coolers were preserved with nitric acid. Total lead content was tested twice for 29 EPA method samples and 54 PASV instrument samples to determine the variation within each method; results were not significant at the 95% CI. Total lead content was determined for 144 samples by both methods. PASV instrument readings were lower than standard EPA method values (mean difference and SE of the mean 0.630+/-0.206 microg/L; n = 144, p = 0.0027, significant at the 95% CI). Mean and standard deviation of the 144 samples for the EPA method and the PASV instrument were 6.5+/-11.8 microg/L and 5.9+/-11.6 microg/L, respectively. Means were below the action level for lead of 15 ppb (microg/L), but some values were above the action level (18 [13%] using the EPA method; 20 [14%] using the PASV instrument). Retesting by EPA method showed two false positive PASV values. Results indicate that in some field situations the PASV instrument may prove useful due to its relatively low price, small size, ease of use, and quick readings.

Electrochemistry↗
PubMedDate not supplied

Permeability testing of glove materials for use with cancer chemotherapy drugs.

The present study evaluated the effectiveness of several types of hospital gloves that are recommended by the manufacturers for handling chemotherapy drugs. Gloves were examined for permeability against five cancer chemotherapy drugs (doxorubicin, cyclophosphamide, 5-fluorouracil, carmustine, and cisplatin) at several time points up to 2 h using a bacterial mutation assay as the measure of permeation. Of the 5 types of gloves tested at a single thickness, 4 were completely impermeable to all drugs and the remaining 1 demonstrated only limited permeability. A latex examination glove used for comparison was permeable to carmustine. One glove material that was tested as a double thickness was impermeable to the 5 drugs. Results indicate that various types of gloves may offer protection against exposure to chemotherapy drugs for healthcare workers.

Antineoplastic Agents↗
PubMedDate not supplied

The influence of contaminants on the mutagenic activity of dibromochloropropane (DBCP).

This study investigates the possible role of impurities in dibromochloropropane in inducing mutations, and discusses the importance of contaminants in mutagenicity and carcinogenicity testing. A technical grade sample and a pure sample of DBCP (no epichlorohydrin added) were assayed in Salmonella typhimurium TA1535, with and without S-9 activation, using agar overlay procedures and dessicator procedures. Assays performed with both technical and pure DBCP without metabolic activation resulted respectively in an increase in revertants with increasing dose (0-1600 microgram/plate) when the technical grade was tested, and no substantial increase in revertants over the same dose range when the pure DBCP was tested. Distillation of technical grade DBCP yielded an initial fraction containing high amounts of epichlorohydrin (verified by GC-MS) which was highly mutagenic. The amount of epichlorohydrin in the technical DBCP sample was calculated for each dose level tested, and the number of revertants obtained in tests of the technical DBCP sample could be attributed solely to the calculated amount of epichlorohydrin in each test dose. Tests of pure and technical DBCP using a dessicator technique produced a similar differential between the technical and pure compounds in mutagenicity. Activation of both technical and pure DBCP with S-9 from Aroclor pre-treated rats resulted in high mutagenic responses, of equal magnitude, from both preparations.

Chromatography, Gas↗