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Biomedical subjects

C E Healy

Publications and source records attributed to C E Healy.

17 recordsLinked to original sources
PubMed1995

Acute and subchronic neurotoxicity studies with tri-N-butyl phosphate in adult Sprague-Dawley rats.

Male and female adult Sprague-Dawley rats received tributyl phosphate (TBP) in corn oil by gavage in acute (single-dose) and subchronic (three-month) studies. Dosage levels in the acute study were 100, 325, and 1000 mg/kg; they were 32.5, 100, and 325 mg/kg/day in the subchronic study. Behavioral evaluations were performed in both studies, and neuropathological evaluations were performed in the three-month study only. The methods used in the studies are as described in the U.S. Environmental Protection Agency neurotoxicity guidelines. Mean body weight decreases were statistically significant compared to controls for male rats at the high-dosage level only in the acute study. Transient changes only, attributable to the general toxicity of the material, were noted in forelimb grip strength and mean activity level during the first 24 hours after dosing for 1000 mg/kg rats. In the subchronic study high-dose males and females had statistically significant body weight decreases; some mortality also was observed at this dosage level. The motor activity levels and qualitative and quantitative functional observational battery measurements were comparable between treatment and control groups, and there were no gross or neurohistopathological findings in the rats indicative of treatment-related effects. Based on these study results, TBP was not neurotoxic to rats following either acute or subchronic exposures.

Animals↗
PubMed1992

Biochemical toxicology and disposition of Therminol 66 heat transfer fluid after inhalation or after dietary administration to male Sprague-Dawley rats.

The objectives of this study were to determine the disposition of Therminol 66 in rats and to determine the effects of this heat-transfer fluid on liver and kidney microsomal drug-metabolizing enzymes. Therminol 66 was administered to male Sprague-Dawley rats at various doses as either a single oral administration at 0, 100, or 300 mg/kg, or as a single 6-h inhalation exposure at 0 or 350 mg/m3. Animals were killed 48 h after gavage or after termination of inhalation exposure. Additional groups of animals were exposed to Therminol 66 via the diet at 0, 100, 500, or 5000 ppm for 14 d, or via repeated inhalation exposure at 0, 25, 250, or 1200 mg/m3 for 6 h/d for 14 d. These exposure scenarios represent approximately equivalent doses of Therminol 66 by the different routes of administration. No change in body weight was observed after acute oral or inhalation exposure, and little change in body weight was observed in animals administered Therminol 66 via the diet except at the highest dose. There was no change in kidney weight, and liver weights were increased only at the higher doses of Therminol 66. The body weight gain of animals exposed to Therminol 66 via inhalation decreased in a dose-dependent manner over the 2-wk exposure period. Results from the disposition study indicated that Therminol 66 did not appear to accumulate in the tissues examined and did not appear to be extensively absorbed after a single oral dose of 300 mg/kg. The whole-body elimination half-life was approximately 14 h and occurred primarily via the feces. There was no significant induction of hepatic aryl hydrocarbon hydroxylase (AHH) activity after single oral or inhalation exposures to Therminol 66. Ethoxycoumarin O-deethylase (ECOD) was significantly induced only in animals exposed to 350 mg/m3 via inhalation. Repeated dietary and inhalation exposures resulted in AHH and ECOD induction only at the highest doses, and the kidney appeared to be less sensitive than the liver. Animals exposed via inhalation demonstrated a greater hepatic inductive effect than did animals exposed via the diet, which may be due to absorption differences.(ABSTRACT TRUNCATED AT 400 WORDS)

7-Alkoxycoumarin O-Dealkylase↗
PubMed1992

Subchronic rat inhalation study with Skydrol 500B-4 fire resistant hydraulic fluid.

Skydrol 500B-4 fire resistant hydraulic fluid, a proprietary phosphate ester mixture composed principally of dibutyl phenyl phosphate (DBPP) and tributyl phosphate (TBP) and used as a commercial airline hydraulic fluid, was evaluated in an inhalation toxicity study of Sprague-Dawley rats. Target exposure levels used in the study were 0, 5, 100, and 300 mg/m3, and exposures were maintained for 6 hr/day, 5 days/week. Mass median aerodynamic diameters determined for particles in the mid- and high-exposure inhalation chambers were 2.85 microns and 3.31 microns, with geometric standard deviations of 1.99 microns and 1.92 microns, respectively. The percentage of particles less than 10 microns in diameter were 96.4% in the mid-exposure chamber and 95.5% in the high-exposure chamber. After 6 weeks of Skydrol exposure, 10 rats/sex/group were euthanized and then assessed for indications of possible chemical toxicity. Another 15 rats/sex/group were studied for a total of 13 weeks of exposure. The only clinical sign of chemical toxicity was the observation of a reddish nasal discharge with accompanying oral salivation in mid- and high-exposure animals of both sexes, indicative of an irritant response. Statistically significant reduced body weights; increased absolute and relative liver weights; and decreased erythrocyte counts, hemoglobin levels, and hematocrit values were observed in high-exposure female rats euthanized after 13 weeks of Skydrol exposure. High-exposure male rats also had increased absolute and relative liver weights and decreased hematocrit values after 13 weeks. Plasma cholinesterase levels were decreased in high-exposure female rats both 6 and 13 weeks after the study was initiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Subchronic and reproduction studies with dibutyl phenyl phosphate in Sprague-Dawley rats.

Dibutyl phenyl phosphate (DBPP) was administered to male and female Sprague-Dawley rats in their diets in separate subchronic (91-day) and two-generation reproduction studies. Dose levels of DBPP were 5, 50, and 250 mg/kg/day in both studies. In the reproduction study, cross-fostering was performed between some high-exposure and control litter offspring and dams following a second mating of F0 animals. Compared to control animals, body weights were consistently lower in high-exposure adult animals in both studies; this observation was less consistent in mid-exposure adult rats. High-exposure rats in the subchronic study had decreased erythrocyte counts and hematocrit and hemoglobin levels. They also had increased absolute and/or relative liver weights with concomitant decreased hepatocytic vacuolation and increased fatty accumulation. In the reproduction study, mating and fertility indices were comparable among the parental animals in both generations, but survivability among high-exposure pups reared by control dams appeared to be decreased. Urinary bladder histopathologic changes, consisting of mononuclear cell infiltration and transitional epithelial hyperplasia, were noted in mid- and high-exposure rats from both studies. The no observable adverse effect level in both of these studies was 5 mg/kg/day.

Animals↗
PubMed1990

Short term toxicity of nitrous oxide on the immune, hemopoietic, and endocrine systems in CD-1 mice.

Occupational exposures to subanesthetic levels of N2O have been documented to result in suppressed proliferative cell activities. Male CD-1 mice were exposed to 0, 50, 500, and 5000 ppm of N2O for 6 hr/day, 5 days/week for 2 or 13 weeks. Tritiated-thymidine ([3H]-TdR) uptake was measured in CD-1 splenic lymphocytes cultured with and without mitogens and in a mixed lymphocyte culture (MLC). Antibody-mediated immunocompetency was determined for sheep red blood cell (SRBC)-sensitized animals by plaque forming cell (PFC) assay and serum anti-SRBC antibody (Ab) titer. Deoxyuridine suppression tests (dUrdST) were performed on bone marrow cells. There was significantly decreased splenic lymphocyte uptake of [3H]-TdR by cells cultured with mitogenic substances and in MLC following 2-week exposures to 5000 ppm. After 13-week exposures the animals' splenic lymphocytes showed increased [3H]-TdR uptake following high N2O dosing in both the mitogen-induced blastogenesis and MLC assays. Compared to control animals, the 5000 ppm exposure group had significantly depressed PFC activity and circulating anti-SRBC Ab levels following the 13-week N2O exposures, and all 13-week exposure groups demonstrated decreased liver weights and leukopenia. Bone marrow activity at these dosing levels was depressed in a dose-dependent fashion following 13-week gas exposures.

Animals↗
PubMedDate not supplied

Effect of sulfosulfuron on the urine and urothelium of male rats.

Sulfosulfuron, developed as a herbicide, caused increased microcrystalluria and the formation of urinary tract calculi when fed to male and female rats in a chronic 2-year study at doses of 5,000 ppm and 20,000 ppm. Hyperplasia was also seen in urinary bladders at 5,000 ppm and 20,000 ppm, almost exclusively in the presence of observable calculi/microcalculi. Urinary bladder tumors were found in 2 females in the 5000 ppm group, both in the presence of calculi. No increased microcrystalluria, calculi, or tumors were found at doses of 500 ppm and lower. In the current study, 5 groups of male Sprague-Dawley rats were fed sulfosulfuron at doses of 50, 500, 5,000, and 20,000 ppm for 10 weeks. Ten animals were co-administered 5,000 ppm sulfosulfuron with 12,300 ppm NH4Cl to determine if inhibition of the formation of calculi would prevent any urothelial effects of treatment with sulfosulfuron. Ten animals in the control group and in the high-dose sulfosulfuron group were fed only basal diet for an additional 10 weeks to determine if the effects of sulfosulfuron on the bladder epithelium were reversible. There was an increased incidence of microcrystalluria observed at 5,000 and 20,000 ppm. There was no increase in microcrystalluria observed in the urine of rats co-administered sulfosulfuron and NH4Cl. Urinary bladder calculi were found in the bladder of 1 animal fed 20,000 ppm. Examination by light microscopy showed diffuse papillary/nodular hyperplasia of the bladder epithelium in this animal. No increased microcrystalluria was observed after withdrawal of the chemical from the diet and the bladder epithelium was normal by light microscopy. The hyperplastic effects associated with the feeding of high doses of sulfosulfuron occur only with the appearance of urinary tract calculi. Based on these results and anatomical differences between rats and humans, it may be concluded that the hyperplastic and carcinogenic effects of sulfosulfuron in rats are high-dose, threshold phenomena that are not likely to occur in humans under environmentally relevant exposures.

Ammonium Chloride↗