Search PubMed⌕ Search

Biomedical subjects

C W Jameson

Publications and source records attributed to C W Jameson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Application of molecular encapsulation for toxicology studies: toxicokinetics of p-chloro-alpha,alpha,alpha-trifluorotoluene in alpha-cyclodextrin or corn oil vehicles in male F344 rats.

Toxicokinetics of p-chloro-alpha,alpha,alpha-trifluorotoluene (CTFT) after administration as an aqueous alpha-cyclodextrin (alpha-CD) molecular encapsulation suspension (alpha-CD vehicle) or as a corn oil solution (corn oil vehicle) were compared. Male F344 rats were administered intragastrically CTFT in alpha-CD vehicle or corn oil vehicle at dose levels of 10, 50, or 400 mg/kg. Other male F344 rats were administered CTFT intravenously in a 10% Tween 80 aqueous solution. Serial blood samples were taken from a cannulated jugular vein for up to 52 hr after dosing and the CTFT concentrations in whole blood were determined by gas chromatography. The biological elimination half-life of CTFT from the center compartment was not affected by the vehicle used; however, absorption of CTFT from the alpha-CD vehicle was much faster than from the corn oil vehicle. The average absorption half-lives from the alpha-CD vehicle and corn oil vehicle were 17 and 98 min, respectively. Despite the differences in absorption, no statistical difference was observed in the calculated areas under the blood concentration versus time curves (AUC) obtained from rats dosed with either vehicle. Dose proportionality for CTFT was established up to 400 mg/kg and bioavailability was shown to be complete for both vehicles.

Administration, Oral↗
PubMed1991

Isolation of the mutagenic and DNA adduct-inducing components from a commercial preparation of HC blue 1 using Salmonella (TA98) bioassay-directed HPLC fractionation.

In the present study we report the separation of the mutagenic impurities from the nitrophenylenediamine hair dye HC Blue 1. This was accomplished by bioassay-directed HPLC fractionation, using Salmonella strain TA98 and reverse phase HPLC analysis. The mutagenic fraction eluted between 80 and 90% methanol, whereas the HPLC fraction containing the parent compound HC Blue 1 eluted with 30% methanol and was non-mutagenic. 100% of the mutagenic activity applied to the column was recovered in fractions that did not possess the blue color of HC Blue 1. Also, HPLC-purified HC Blue 1 did not form DNA adducts (32P-postlabeling) in Salmonella strain TA98. On the other hand, commercial HC Blue 1 and the mutagenic fraction derived from commercial HC Blue 1 (HPLC-isolated) gave similar DNA-adduct profiles that consisted of 7 adducts. DNA adduction was examined concomitantly with mutagenicity and toxicity studies on the HC Blue 1 samples in TA98. The data indicated that, in Salmonella, both the mutagenicity and DNA adduction of commercial HC Blue 1 are due to impurities and not the parent compound.

Autoradiography↗
PubMed1991

Application of microencapsulation technology to improve the stability of citral in rodent diets.

Citral is a widely used flavoring and scenting agent which is employed in numerous food, industrial, and household products. Although the current regulatory status of citral lists it as a GRAS chemical on the FDA list, the chemical is a reactive beta-substituted vinyl aldehyde that has been shown to induce irritations of skin and mucous membranes, and to exhibit a dose-dependent teratogenic effect on embryos of white leghorn chickens. Because of these factors, citral was nominated by the National Toxicology Program for carcinogenesis study. Stability studies of dose formulations of citral (0.02%) in NIH-07 rodent diet indicated a loss of 41% of the citral after 1 day in a rat cage, due mainly to volatility and reactivity with diet components. The chemical was subsequently microencapsulated using a shell medium of food-grade modified cornstarch and sucrose, and then formulated into NIH-07 diet (0.02%) for various stability studies. Results after 7 days in a rat cage showed 95% retention of chemical; diet that had been stored 21 days retained 95% at 5 degrees C storage and 89% at room temperature. An assessment of the purity of the citral in the microcapsules indicated that total impurities increased from 0.7% in the neat chemical to 1.1% in the encapsulated chemical.

Acyclic Monoterpenes↗
PubMed1991

Comparative toxicity and tissue distribution of antimony potassium tartrate in rats and mice dosed by drinking water or intraperitoneal injection.

Antimony potassium tartrate (APT) is a complex salt that until recently was used worldwide as an antischistosomal drug. Treatment was efficacious only if APT was administered intravenously to humans at a near lethal total dose of 36 mg/kg. Because unconfirmed epidemiologic studies suggested there might be an association between APT treatment and bladder cancer, we initiated prechronic toxicity studies with the drug to select a route of administration and doses in the event that chronic studies of APT were needed. The toxicity and concentration of tissue antimony levels were compared in 14-d studies with F344 rats and B6C3F1 mice administered APT in the drinking water or by ip injection to determine the most appropriate route for longer term studies. Drinking water doses estimated by water consumption were 0, 16, 28, 59, 94 and 168 mg/kg in rats and 0, 59, 98, 174, 273, and 407 mg/kg in mice. APT was poorly absorbed and relatively nontoxic orally, whereas ip administration of the drug caused mortality, body weight decrements, and lesions in the liver and kidney at doses about one order of magnitude below those in drinking water. Because of these data and the dose-related accumulation of antimony in the target organs, an ip dose regimen was selected for subsequent studies. Both sexes of F344 rats and B6C3F1 mice were given 0, 1.5, 3, 6, 12, and 24 mg/kg doses of APT every other day for 90 d by ip injection. There were no clinical signs of toxicity nor gross or microscopic lesions in mice that could be attributed to toxicity of APT, although elevated concentrations of antimony were detected in the liver and spleen of mice. Rats were more sensitive than mice to the toxic effects of APT, exhibiting dose-related mortality, body weight decrements, and hepatotoxicity. The concentrations of antimony measured in liver, blood, kidney, spleen, and heart of rats were proportional to dose, but there were no biochemical changes indicative of toxicity except in the liver. Hepatocellular degeneration and necrosis occurred in association with dose-related elevations in activities of the liver-specific serum enzymes sorbitol dehydrogenase and alanine aminotransferase. By alternating the site of abdominal injection and the days of treatment, mesenteric inflammation at the site of administration was minimized in the rats and mice, indicating that the ip route would be suitable for chronic studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1990

The chemotherapeutic potential of glycol alkyl ethers: structure-activity studies of nine compounds in a Fischer-rat leukemia transplant model.

Structure-activity studies with nine glycol alkyl ethers were conducted with a cellular leukemia transplant model in male Fischer rats. This in vivo assay measures the effects of chemical treatment on neoplastic progression in transplant recipients. Chemicals were given ad libitum in the drinking water simultaneously with the transplants and continued throughout the study. In all, 20 million leukemic cells were injected s.c. into syngeneic rats, which after 60 days resulted in a 10-fold increase in relative spleen weights, a 100-fold increase in white blood cell counts, and a 50% reduction in red blood cell (RBC) indices and platelet counts. At this interval, ethylene glycol monomethyl ether (2-ME) given at a dose of 2.5 mg/ml in the drinking water completely eliminated all clinical, morphological, and histopathological evidence of leukemia, whereas the same dose of ethylene glycol monoethyl ether (2-EE) reduced these responses by about 50%. Seven of the glycol ethers were ineffective as anti-leukemic agents, including ethylene glycol, the monopropyl, monobutyl, and monophenyl ethylene glycol ethers, diethylene glycol, and the monomethyl and monoethyl diethylene glycol ethers. 2-ME more than doubled the latency period of leukemia expression and extended survival for at least 210 days. A minimal effective dose for a 50% reduction in the leukemic responses was 0.25 mg/ml 2-ME in the drinking water (15 mg/kg body weight), whereas a 10-fold higher dose of 2-EE was required for equivalent antileukemic activity. In addition, the in vitro exposure of a leukemic spleen mononuclear cell culture to 2-ME caused a dose- and time-dependent reduction in the number of leukemia cells after a single exposure to 1-100 microM concentrations, whereas the 2-ME metabolite, 2-methoxyacetic acid, was only half as effective. The two glycol alkyl ethers with demonstrable anti-leukemic activity, 2-ME and 2-EE, also exhibited a favorable efficacy-to-toxicity ratio and should be considered for further development as chemotherapeutic agents.

Administration, Oral↗
PubMed1990

Arsine: absence of developmental toxicity in rats and mice.

Arsine gas is a potent hemolytic agent but the effects of exposure to tolerated concentrations on pregnancy and prenatal development have not been reported. In the present evaluation, groups of bred mice and rats were exposed to arsine at concentrations of 0.025, 0.5, or 2.5 ppm on Gestation Days (gd) 6 through 15. Animals were killed on gd 17 (mice) or on gd 20 (rats) and endpoints of maternal and developmental toxicity were evaluated. In rats, maternal spleens were enlarged in the 2.5 ppm group and there was a decrease in packed red cell volume in pregnant rats. Fetuses weighed more than in the control group but other endpoints of developmental toxicity were not affected by arsine exposure. In another experiment involving separate groups of rats, the arsenic content of maternal blood and fetal livers increased with increasing atmospheric arsine concentrations, as assessed on gd 20. In mice, maternal spleen size was significantly increased in the 2.5 ppm group. The number of live fetuses, mean fetal body weight, and percentages of resorptions or malformations per litter were not affected by arsine exposure. In conclusion, arsine at atmospheric concentrations that caused increases in maternal spleen size and measurable levels of arsenic in maternal blood and fetal livers did not adversely affect endpoints of developmental toxicity.

Air Pollutants, Occupational↗
PubMed1990

The carcinogenic activity of commercial grade toluene diisocyanate in rats and mice in relation to the metabolism of the 2,4- and 2,6-TDI isomers.

Groups of 50 F344/N rats of each sex and 50 B6C3F1 mice of each sex were gavaged with corn oil or a mixture of toluene diisocyanate (TDI) in corn oil for 5 days per week for 105 or 106 weeks. Female rats and mice were given doses of 60 or 120 mg/kg body weight, while male rats received 30 or 60 mg/kg, and male mice received 120 or 240 mg/kg. The TDI reacted with the moisture in the corn oil vehicle resulting in doses that were 10% to 23% below the target dose concentrations. The chemical product used was commercial grade TDI, which was an 80%-20% mixture of the 2,4- and 2,6-isomers. Chemical disposition and metabolism studies were conducted with each of the radiolabelled TDI isomers in male rats. Absorption of both of the TDI isomers occurred, with the highest concentrations found in the stomach, cecum, large intestine, and bladder. Excretion occurred via the feces and urine. The major metabolic products from the metabolism of 2,4-TDI were shown to be identical with those from the metabolism of the carcinogen, 2,4-diaminotoluene, whereas the metabolism of the 2,6-TDI isomer yielded one major product, identified as 2,6-bis(acetylamino)toluene. Greater than 10% depression in body weight gain occurred in all dosed groups of rats throughout most of the study. The major non-neoplastic lesions that were observed in both sexes of the TDI-exposed rats were dose-related increases in acute broncho-pneumonia, characterized as chemical pneumonitis, with incidences as high as 50%. In mice mean body weight gain was depressed in dosed male and in high dose females. The principle non-neoplastic lesion in mice that was attributed to chemical treatment was cytomegaly of the kidney tubular epithelium in males. Survival in all groups of dosed rats was significantly lower than in controls. A dose-dependent pattern of mortality did not commence until 70 weeks of exposure, demonstrating that toluene diisocyanate elicited a cumulative toxic response. There was also significantly lower survival in high dose male, but not female mice, by comparison to controls. Despite the reduction of power and sensitivity in the rat studies caused by early mortality, statistically significant increases in tumor incidences were observed in many different target organs. TDI was carcinogenic in F344/N rats, causing subcutaneous fibromas and fibrosarcomas in males and females, pancreatic acinar cell adenomas in males, and pancreatic islet cell adenomas, neoplastic nodules of the liver, and mammary gland tumors in females.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Thirteen-week toxicity studies of 3,3'-dimethoxybenzidene and C.I. Direct Blue 15 in the Fischer 344 rat.

The benzidine congener 3,3'-dimethoxybenzidine (DMOB), and C.I. Direct Blue 15 (Blue 15), a prototypical compound of the DMOB-derived class of dyes, were evaluated in 13-week studies to characterize the toxicity and establish dose levels for subsequent chronic studies. Groups of 10 Fischer 344 rats of each sex were administered either DMOB, or Blue 15, at 1 of 5 concentrations in drinking water for 13 weeks. DMBO concentrations were 0, 0.017, 0.033, 0.063, 0.125, and 0.25% for males and females. For Blue 15, the concentrations were 0.063, 0.125, 0.25, 0.50, and 1.0% for females and 0, 0.125, 0.25, 0.50, 1.0, and 3.0% for male rats. Rats showed dose-related decreases in water consumption and weight gains. All DMOB-treated rats and their controls survived the 13-week treatment. There were 7 deaths in the 3% level of male rats treated with Blue 15. Liver and kidney weights were increased in rats treated with both compounds. Target organs for DMOB-treated rats were the kidney and thyroid. These lesions were characterized by chronic nephropathy, and increased pigment in the follicular cells of the thyroid. The kidney and liver were identified as target organs for Blue 15-treated rats. In the high-dose rats that died before termination of the study, renal effects were characterized by degeneration and focal necrosis of proximal tubular epithelial cells. Liver lesions in this group consisted of degeneration and necrosis of hepatocytes, fatty metamorphosis, and minimal megalocytosis. Mild chronic nephropathy was the principal histological effect in Blue 15-treated rats surviving to study termination.

Animals↗
PubMed1989

Identification of components in iodinated glycerol.

Iodinated glycerol (CAS no. 5634-39-9), therapeutically used as an expectorant and source of organically bound iodine, was analyzed to determine the purity and composition of the chemical samples used in carcinogenicity and toxicity studies. The manufactured product is described by the patent and chemical literature as a mixture of two isomeric iodopropylideneglycerols (structures 1 and 2). The results of our studies, however, indicate that the two principal components of the product were 3-iodo-1,2-propanediol (IPD) and glycerol (GLY). Analyses from GC-MS (full scan electron impact) and carbon-13 nuclear magnetic resonance spectrometry provided conclusive identification of these components. The quantification of IPD and GLY in one of two samples of commercial product using GC-flame ionization detection indicated concentrations of 33 and 17%, respectively (Sample A). Similar concentrations were determined for a second sample from the same source (Sample B), which was a gratis sample procured approximately nine years after Sample A. Numerous minor components were also observed in these two samples. These components were tentatively identified as condensation products of glycerol and iodine-containing analogues. The iodopropylideneglycerol compounds, described in the patent, were not observed in either of the two samples.

Carbon Isotopes↗
PubMed1989

Development and validation of a cellular transplant model for leukemia in Fischer rats: a short-term assay for potential anti-leukemic chemicals.

The efficacy of a leukemia cell transplant model to measure potential chemotherapeutic activity was tested with five different chemicals that had previously been evaluated in 2-year studies. Leukemic spleen cells from Fischer rats were injected subcutaneously into syngeneic recipients and the effects of chemical treatment on tumor progression were evaluated at 70 days post-transplant. The data from the short-term assay were in all cases correlated with the trends reported for mononuclear cell leukemia in 2-year studies, where two chemicals were reported to decrease the incidence and three chemicals were reported to increase the incidence of leukemia. Short-term treatment with the two chemicals which caused negative trends for leukemia (2-ethoxyethanol or ethylene glycol monoethyl ether; 4-hexylresorcinol) delayed and/or reduced tumor growth in the transplant model in a dose-related fashion, as exhibited by reduction or elimination of splenomegaly and leukoblastosis, and a reversal in the depression of red blood cell indices or platelet counts. By contrast, the rate of tumor progression was increased in the short-term assay of the three chemicals which previously caused increased trends for leukemia in 2-year studies (pyridine; 2,4,6-trichlorophenol, dichlorvos). The severity of the mononuclear cell leukemia in the transplant recipients, as measured by histopathological examination of spleen and liver, was correlated with the changes in tumor growth rates. The in vivo leukemia transplant model is a short-term assay that could be used to screen a variety of potential chemotherapeutic agents, or to study structure-activity relationships within one class of chemicals.

Animals↗
PubMed1989

14-day and 90-day toxicity studies of C.I. Pigment Red 3 in Fischer 344 rats and B6C3F1 mice.

Treatment of F344 rats and B6C3F1 mice with C.I. Pigment Red 3 in the diet (10, 5.0, 2.5, 1.25, 0.6 or 0.3%) for 14 and 90 days resulted in haematological alterations consistent with haemolytic anaemia. Rats appeared to be more sensitive than mice to the haematological effects. Histological lesions were observed in rats and mice after exposure for 90 days. Target organs in the rat were the spleen, bone marrow, liver and kidney. Lesions in the spleen consisted of a haematopoietic cell proliferation, iron-positive pigment and congestion of the red pulp, and inflammation of the splenic capsule. Changes in the livers of rats consisted of haematopoietic cell proliferation and iron-positive pigment in Kupffer cells. Haematopoietic cell proliferation also occurred in the bone marrow of treated rats. The presence of iron-positive pigment and a slightly increased incidence of protein casts were seen in the kidney. Target organs in mice were the spleen, liver and kidney. Histological lesions in mice after exposure for 90 days included increased haematopoietic cell proliferation in the liver and spleen, and iron-positive pigment in the spleen. Mild cytomegaly of the renal tubular epithelia was also observed in exposed mice.

Anemia↗
PubMed1988

Residual hematopoietic effect in mice exposed to ochratoxin A prior to irradiation.

Ochratoxin A (OCT A) has the potential to cause myelotoxicity in addition to the well-known toxic effects on the liver and kidney. Whereas in previous studies the bone marrow parameters were examined shortly after injection, experiments reported here were designed to determine whether mice would recover from the myelotoxic effects induced to OCT A injection and secondly whether mice previously injected to OCT A would be more sensitive to radiation-induced myelotoxicity than vehicle controls. Six-week old female B6C3F1 mice were injected intraperitoneally on alternate days over a week with a total dose of 20 or 40 mg/kg of OCT A and bone marrow parameters monitored for up to 16 weeks. Controls received vehicle alone. There was a suppression of marrow granulocyte macrophage progenitors (CFU-C) in OCT A-treated animals which returned to normal values by 2 weeks (20 mg/kg group) or by 5 weeks (40 mg/kg group) following the last treatment. Some of the OCT A-treated mice were additionally irradiated with 200 rads of whole body irradiation (WBI) at 10 and 52 days following OCT A injections. Irradiation caused a significant reduction in CFU-Cs in all mice but the effects were more pronounced in the mice that had received OCT A previously. The bone marrow parameters of 40 mg/kg OCT A-treated mice returned to normal by 6 weeks after first WBI. A second WBI produced similar depression in CFU-Cs with again a delayed 8 weeks recovery as compared to controls in both dose groups of OCT A-treated mice. The delayed recovery in bone marrow progenitors was also reflected in lower peripheral white blood counts after the second irradiation in 40 mg/kg OCT A-treated mice as compared to the untreated irradiated controls. This indicated that residual bone marrow effect of OCT A makes the mice more sensitive to subsequent irradiation induced injury.

Animals↗
PubMed1988

Evaluation of tissue disposition, myelopoietic, and immunologic responses in mice after long-term exposure to nickel sulfate in the drinking water.

Female B6C3F1 mice were exposed to graded doses of nickel sulfate to determine a threshold response for myelotoxicity and immunotoxicity, and to identify which of the populations of lymphoreticular cells were most sensitive to the toxic effects of nickel. Animals were given free access to the chemical in the drinking water at 0, 1, 5, or 10 g/l for 180 d. Water consumption, blood and tissue nickel concentrations, body and organ weights, histopathology, immune responses, bone marrow cellularity and proliferation, and cellular enzyme activities were evaluated. There was no mortality. Mice in the 5-g/l and 10-g/l dose groups drank less water than controls; the responses measured in the 10-g/l group may have been due to a combination of dehydration and chemical toxicity. Decreases in body and organ weights were confined to mice in the 10-g/l dose group, except for the dose-related reductions in thymus weights. Blood nickel was measured at 4, 8, 16, and 23 wk of exposure. The mean blood nickel values showed increases between 4 and 8 wk that were proportional to time and dose; thereafter there was no substantial increase in blood nickel in any of the dose groups, except for an increase in the mean blood concentration in the 10-g/l group at 23 wk. The kidney was the major organ of nickel accumulation. The primary toxic effects of nickel sulfate were expressed in the myeloid system. There were dose-related decreases in bone marrow cellularity, and in granulocyte-macrophage and pluripotent stem-cell proliferative responses. In unfractionated bone marrow cells glucose-6-phosphate dehydrogenase enzyme activity from the hexose monophosphate shunt was more sensitive to nickel sulfate than were representative glycolytic or Krebs cycle enzymes, with 25-35% maximum inhibition at 5 g/l and 10 g/l. Aliquots of bone marrow cells were separated into enriched bands of lymphocytes, granulocyte-macrophages, and erythrocytes; enzyme inhibition that occurred in unfractionated bone marrow cell aliquots was only expressed after cell separation in the enriched granulocyte-macrophage cell population, suggesting that these committed stem cells were a primary target of nickel sulfate toxicity. There was one example of systemic immunotoxicity, reduction in the lymphoproliferative response to lipopolysaccharide, and it was regarded as secondary to the primary effect of nickel sulfate on the myeloid system, since this was the only significant change among a panel of seven immune parameters that were evaluated.

Animals↗
PubMed1988

Analyses of two azo dyes by high-performance liquid chromatography.

Two structurally similar azo dyes, Direct Blue No. 6 and Direct Blue No. 15, are analyzed by separate reversed-phase high-performance liquid chromatographic (HPLC) systems utilizing a dual-wavelength UV/visible detector at 254 and 546 nm. Each dye contains more than 35 impurity peaks. Different lots of each dye are compared by means of their respective chromatographic profiles. The system used to obtain a chromatographic profile for each dye is adapted to make comparisons of the major component in different lots by an internal standard method. These methods are reproducible, giving relative standard deviations ranging from approximately 1 to 5%. These HPLC systems are adaptable for the analysis of other structurally similar dyes.

Azo Compounds↗