Biomedical subjects

R Poon

Publications and source records attributed to R Poon.

99 records · Page 6Linked to original sources

PubMedDate not supplied

Effects of an ethanol-gasoline mixture: results of a 4-week inhalation study in rats.

The inhalation toxicity of an ethanol-gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA/charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin-O-deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol-gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible biochemical hematological and histological effects, with some indications of interactions when they were co-administered.

Administration, Inhalation↗

PubMedDate not supplied

Subchronic toxicity of a medium-chain chlorinated paraffin in the rat.

Groups of ten male and female weanling Sprague-Dawley rats were fed diet containing 0, 5, 50, 500 or 5000 ppm of a medium-chain chlorinated paraffin (C14-17, 52% chlorination) for a period of 13 weeks. Increased relative liver weight was observed at 500 and 5000 ppm in females and at 5000 ppm in males. Relative kidney weight was increased at 5000 ppm in both sexes. Serum cholesterol was increased in the females in a dose-related manner starting at 50 ppm. At 5000 ppm, animals of both sexes had elevated hepatic UDP-glucuronosyltransferase activity while only females showed increased aminopyrine N-demethylase activity. Increased urinary N-acetylglucosaminidase activity occurred at 5000 ppm in females. Increased urinary ascorbic acid excretion monitored at week 12 and a decreased hepatic vitamin A level were detected in females receiving the 500 ppm diet and male and female rats at 5000 ppm. Mild, adaptive histopathological changes were detected in the liver of rats of both sexes at 500 and 5000 ppm, and in the thyroid of males and females starting at 500 and 50 ppm respectively. Minimal changes were observed in the kidney proximal tubules of male rats fed the 5000 ppm diet and in the inner medulla tubules of female rats fed the 500 and 5000 ppm diets. These data indicate that the medium-chain chlorinated paraffin produces biochemical and histological changes at dietary levels of greater than or = 50 ppm in females and greater than or = 500 ppm in males.

Animals↗

PubMedDate not supplied

Short-term oral toxicity of gasohol in female rats.

The systemic toxicity of gasohol (10% ethanol in gasoline by volume) in female rats following 4-week oral administration was studied. Female Sprague-Dawley rats (198+/-14 g) were divided into four groups of ten animals each. The low- and medium-dose groups received by gavage corn oil containing gasoline/ethanol at 16/1.8 and 160/18 (mg kg(-1) body weight), respectively, for 28 consecutive days. The high-dose animals were administered gasoline/ethanol at 1600/180 mg kg(-1) on the first day and the dose was reduced to 800/90 mg kg(-1) for the rest of the study period. Control animals received corn oil only. Urine was obtained from all rats after weeks 1, 2 and 4 for biochemical analysis. At termination of the study, kidneys of four rats from each group were examined by electron microscopy. Body weight gains, organ weights, tissue and organ histopathology, serum biochemistry, hematology, liver enzymes and biochemistry were determined in the remaining six animals of each group. No treatment-related changes were observed in the following endpoints: body weight gain or relative weights of the brain, lungs, liver, kidneys, spleen and thymus. A significant increase in pentoxyresorufin O-deethylase (PROD) and benzoylresorufin O-dealkylase (BROD) activities was detected in the high-dose animals, whereas ethoxyresorufin O-deethylase (EROD) activity was unchanged. Treatment with gasohol did not produce any significant changes in hematology and serum clinical chemistry parameters. Biomarkers of oxidative stress such as serum and liver thiobarbituric acid reactive substances (TBARS) and liver glutathione also were unaffected by treatments. Urinary ascorbic acid was elevated markedly in the medium- and high-dose groups following the first, second and fourth weeks of treatment. Urine hippuric acid was increased significantly in the high-dose groups. A dose-related increase in urinary aldehydes also was observed in animals after the first, second and fourth week of treatment. Interestingly, a separate 1-week dosing study revealed that the increase in urinary aldehydes was associated with gasoline and not with ethanol treatment. In the high-dose animals slight increases in urinary protein and N-acetylglucosaminidase activity were observed after week 1 but not after week 2 or week 4. No histopathological changes were detected in the liver, kidneys, stomach, brain, lungs or other tissues examined. Electron microscopic examination of the kidneys also did not reveal any abnormalities. It was concluded that short-term oral administration of gasoline/ethanol at 800/90 mg kg(-1) produced a biochemical response in the liver but no adverse effects in the kidneys and lungs. The biological significance of elevated urinary aldehydes at gasoline/ethanol concentrations of 160/18 mg kg(-1) and higher remains to be studied.

Administration, Oral↗

PubMedDate not supplied

Subchronic toxicity of chloral hydrate on rats: a drinking water study.

The subchronic toxicity of chloral hydrate, a disinfection byproduct, was studied in rats following 13 weeks of drinking water exposure. Male (262 +/- 10 g) and female (190 +/- 8 g) Sprague-Dawley rats, ten animals per group, were administered chloral hydrate via drinking water at 0.2, 2, 20 and 200 ppm. Control animals received distilled water only. Gross and microscopic examinations, serum chemistry, hematology, biochemical analysis, neurogenic amine analysis and serum trichloroacetic acid (TCA) analysis were performed at the end of the treatment period. Bronchoalveolar fluids were collected at necropsy and urine specimens were collected at weeks 2, 6 and 12 for biochemical analysis. No treatment-related changes in food and water intakes or body weight gains were observed. There were no significant changes in the weights of major organs. Except for a mild degree of vacuolation within the myelin sheath of the optic nerves in the highest dose males, there were no notable histological changes in the tissues examined. Statistically significant treatment-related effects were biochemical in nature, with the most pronounced being increased liver catalase activity in male rats starting at 2 ppm. Liver aldehyde dehydrogenase (ALDH) was significantly depressed, whereas liver aniline hydroxylase activity was significantly elevated in both males and females receiving the highest dose. A dose-related increase in serum TCA was detected in both males and females starting at 2 ppm. An in vitro study of liver ALDH confirmed that chloral hydrate was a potent inhibitor, with an IC(50) of 8 micro M, whereas TCA was weakly inhibitory and trichloroethanol was without effect. Analysis of brain biogenic amines was conducted on a limited number (n = 5) of male rats in the control and high dose groups, and no significant treatment-related changes were detected. Taking into account the effect on the myelin sheath of male rats and the effects on liver ALDH and aniline hydroxylase of both males and females at the highest dose level, the no-observed-effect level (NOEL) was determined to be 20 ppm or 1.89 mg kg(-1) day(-1) in males and 2.53 mg kg(-1) day(-1) in females. This NOEL is ca. 1000-fold higher than the highest concentration of chloral hydrate reported in the municipal water supply.

Administration, Oral↗

PubMedDate not supplied

HPLC determination of D-glucaric acid in human urine.

An isocratic HPLC method has been developed for the direct measurement of D-glucaric acid in human urine. Pretreatment of urine with a boronic acid gel removed many interfering substances, including L-ascorbic acid and D-glucuronic acid. This method has a detection limit of 10 microM D-glucaric acid (approximately 7 mumoles/g creatinine). The run-to-run precisions were 9.1% and 7.7% at urinary D-glucaric acid concentrations of 41 and 219 mumoles/g creatinine, respectively. Urinary D-glucaric acid concentrations in normal adults were found to cover a range of 15 to 89 mumoles/g creatinine (mean = 47 mumoles/g creatinine). The sensitivity of this method in detecting abnormal elevations in D-glucaric acid was demonstrated through its ability to measure changes in urinary concentrations with time after ingestion of D-glucuronolactone.

Adult↗

PubMedDate not supplied

Inhalation toxicity study of methanol, toluene, and methanol/toluene mixtures in rats: effects of 28-day exposure.

The inhalation toxicity of methanol and toluene was investigated in rats. Young Sprague Dawley rats of both sexes were exposed to vapors of methanol (300 ppm, 3000 ppm), toluene (30 ppm, 300 ppm) or methanol/toluene (300/30 ppm, 300/300 ppm, 3000/30 ppm, and 3000/300 ppm) six hrs per day, five days/week for four weeks. Control animals inhaled air only. Increased serum alkaline phosphatase activity was observed in males exposed to high-dose toluene, and decreased creatinine was noted in the group exposed to high-dose methanol/toluene. The thyroid gland in females appeared to be a target organ for inhaled methanol, toluene, and methanol/toluene, although the changes were confined to a mild, and occasionally moderate, reduction in follicle size. Histopathological changes of the nasal passages, consisting of subepithelial nonsuppurative inflammation, occurred in higher incidences in rats exposed to methanol/toluene than in those exposed to the individual vapors. Inhalation of methanol, toluene, or methanol/toluene produced no changes in liver weights, hepatic mixed-function oxidases, or serum aspartate transaminase activities, and onlly minimal changes in liver histopathology. The only liver changes were decreased liver weight and increased cytoplasmic density of the periportal areas in females exposed to high-dose methanol/toluene. These data indicated that exposure to methanol, toluene, or a mixture of both produced mild biochemical effects and histological changes in the thyroid and nasal passage. No apparent interactive effects were observed.

Administration, Inhalation↗

PubMedDate not supplied

Short-term inhalation toxicity of methanol, gasoline, and methanol/gasoline in the rat.

Four- to five-week-old male and female Sprague Dawley rats were exposed to vapors of methanol (2500 ppm), gasoline (3200 ppm), and methanol/gasoline (2500/3200 ppm, 570/3200 ppm) six hours per day, five days per week for four weeks. Control animals were exposed to filtered room air only. Depression in body weight gain and reduced food consumption were observed in male rats, and increased relative liver weight was detected in rats of both sexes exposed to gasoline or methanol/gasoline mixtures. Rats of both sexes exposed to methanol/gasoline mixtures had increased relative kidney weight and females exposed to gasoline and methanol/gasoline mixtures had increased kidney weight. Decreased serum glucose and cholesterol were detected in male rats exposed to gasoline and methanol/gasoline mixtures. Decreased hemoglobin was observed in females inhaling vapors of gasoline and methanol/gasoline at 570/3200 ppm. Urine from rats inhaling gasoline or methanol/gasoline mixtures had up to a fourfold increase in hippuric acid, a biomarker of exposure to the toluene constituent of gasoline, and up to a sixfold elevation in ascorbic acid, a noninvasive biomarker of hepatic response. Hepatic mixed-function oxidase (aniline hydroxylase, aminopyrine N-demethylase and ethoxyresorufin O-deethylase) activities and UDP-glucuronosyltransferase activity were elevated in rats exposed to gasoline and methanol/gasoline mixtures. Histopathological changes were confined to very mild changes in the nasal passages and in the uterus, where decreased incidence or absence of mucosal and myometrial eosinophilia was observed in females inhaling gasoline and methanol/gasoline at 570/3200 ppm. It was concluded that gasoline was largely responsible for the adverse effects, the most significant of which included depression in weight gain in the males, increased liver weight and hepatic microsomal enzyme activities in both sexes, and suppression of uterine eosinophilia. No apparent interactive effects between methanol and gasoline were observed.

Animals↗

PubMedDate not supplied

Reproductive and thyroid hormone levels in rats following 90-day dietary exposure to PCB 28 (2,4,4'-trichlorobiphenyl) or PCB 77 (3,3'4,4'-tetrachlorobiphenyl).

Subchronic exposure to the PCB congener 77 (PCB 77) and 28 (PCB 28) was previously shown to induce histological changes in the thyroid and in the brain biogenic amines levels, suggesting possible effects on thyroid and reproductive hormone levels. Thus, the effects of a 90-day dietary exposure to PCB 28 or 77 on luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations were studied in male rats, as well as the levels of thyroid-stimulating hormone, thyroxine (T4) and uridine diphosphate-glucuronyl transferase (UDP-GT) activity in both genders. Weanling Sprague Dawley rats were randomly distributed into groups of 10 rats and were fed, for the next 13 weeks, purina lab chow containing 50, 500, 5,000 or 50 000 ppb of PCB 28 or 10, 100, 1000, or 10 000 ppb of PCB 77. The serum concentrations of T4 were decreased in rats of both sexes receiving 1000 ppb or more of PCB 77, and was associated with an increased activity of UDP-GT which reached significance only in the females. There was a tendency for the highest dose of PCB 28 also to decrease serum T4 concentrations in the female rats. None of the PCB treatments significantly altered gonadotropin, TSH, or testosterone concentrations. These results suggest that thyroid functions may be more susceptible or adapt less readily than the pituitary gland and the testes to endocrine disruption caused by PCB congeners.

Animals↗

PubMedDate not supplied

Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate glands in the high dose males. No other significant microscopic changes were observed in the tissues of treated animals. Based on the marked increase in urinary ascorbic acid and albumin in the high dose males and the decreased forelimb grip strength in the high dose females, we concluded that the no-observed adverse effect level (NOAEL) of methanol/gasoline vapour is 500/30 ppm.

Albuminuria↗