Search PubMed⌕ Search

Biomedical subjects

R D Kimbrough

Publications and source records attributed to R D Kimbrough.

At least 37 records · Page 2Linked to original sources
PubMed1985

Trichloroethylene: an update.

The toxicity of tricholoroethylene (TCE) has been summarized in a number of reviews. In this particular update, only the more recent studies that deal with metabolism and carcinogenicity have been examined. In reviewing the more recent publications on metabolism of TCE, we determined that differences exist in its metabolism if low doses are compared with high doses in animals. There may also be a difference in the metabolism of TCE between different species--namely mice, rats, and humans. TCE has not been shown to be a potent carcinogen in rats and it only seems to be a potent carcinogen in one specific strain of mice, namely the B6C3F1 mouse. Epidemiology studies have been rather limited. The number of persons examined so far for chronic toxic effects is small, compared with the enormous size of the work force that is exposed to TCE over prolonged periods. On an empirical basis, the occupational experience with TCE does not suggest that this compound is a potent carcinogen. The risk associated with exposure to trace amount (ppb) concentrations of TCE in water appear to be minimal or perhaps negligible. Because there are differences in metabolism of TCE, it is important that theoretical risks attributed to TCE in the past be reexamined. It is highly possible that in humans, the metabolic pathway leading to the formation of the proximate carcinogen is not activated at low doses, where TCE is excreted by first-order kinetics.

Animals↗
PubMed1985

Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice. I. Systemic toxicity.

The effects of subchronic inhalation exposure to isobutyl nitrite (IBN) on body weight, selected organ weights, hematology, and gross pathology and histopathology of BALB/c mice were evaluated. Mice of both sexes were exposed at 0, 20, 50, or 300 ppm IBN for 6.5 h/d, 5 d/wk for up to 18 wk. Most changes in measured indices occurred in mice exposed at 300 ppm IBN and included decreased thymus weight (females); decreased liver weight (males); decreased white blood cell counts (males); mild focal hyperplasia and vacuolization of the epithelium lining bronchi and bronchioles of the lungs (males and females). Organ weight and hematologic changes, however, were not accompanied by any observed histologic changes. In addition, elevated methemoglobin concentrations were detected in mice of both sexes exposed at 50 and 300 ppm IBN. Body weights were not adversely affected by exposure. These data suggest that mild tissue injury, restricted to the lung, and methemoglobinemia are the major toxic effects observed following exposures of mice to IBN at concentrations up to 300 ppm for 18 wk. No treatment-related effects were noted in mice exposed at 20 or 50 ppm IBN, except for slight elevations in methemoglobin concentrations in mice exposed at 50 ppm.

Animals↗
PubMed1985

Laboratory and human studies on polychlorinated biphenyls (PCBs) and related compounds.

Similar qualitative toxic effects have been observed in animals for a class of halogenated aromatic compounds, which include the halogenated biphenyls, naphthalenes, dibenzodioxins, and dibenzofurans. All of these compounds are lipid soluble and persist in the environment and in mammals. The polybrominated biphenyls (PBBs) are the most persistent. They are predominantly stored in fatty tissue; they pass the placenta and are excreted in milk. Some isomers of the halogenated biphenyls are more toxic than others. With some exceptions, the more toxic isomers are retained longer in tissues and are also the carcinogenic components of the mixture. Most of these chemicals seem to be promoters of carcinogenesis in animals rather than initiators. An array of toxic effects in laboratory animals has been ascribed to these compounds and numerous reviews summarizing this information are available. Less information is available on the human health effects of environmental and occupational exposure. Results of recent studies in animals to further elucidate the effects of these chemicals are presented, and results from some human studies conducted in the United States are reviewed.

Accidents↗
PubMed1984

Health implications of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) contamination of residential soil.

Extrapolations from animal toxicity experiments (including carcinogenicity and reproductive effects) to possible human heath effects can be used to estimate a reasonable level of risk for 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD). Extrapolations are derived from: (1) review of published studies, (2) a complex set of assumptions related to human exposure to contaminated soil, and (3) estimates of (a) a dose response curve, (b) appropriate margins of safety, and/or (c) applicable mechanisms of action. One ppb of 2,3,7,8-TCDD in soil is a reasonable level at which to begin consideration of action to limit human exposure for contaminated soil.

Animals↗
PubMed1984

Stunted growth, increased mortality, and liver tumors in offspring of polybrominated biphenyl (PBB) dosed sherman rats.

Firemaster FF-1, a polybrominated biphenyl (PBB) mixture, was dissolved in corn oil and given as a dose of 200 mg/kg body weight to Sherman rats on d 7 and 14 of pregnancy. Control rats received equivalent doses of corn oil alone. Selected pups and all dams were killed 1 mo after pups were weaned. A total of 50 male and 50 female offspring per group were followed until they were 2 yr old. The livers of offspring killed at the ages of 2 mo and 2 yr had PBB levels of 2,4 (SD 1.2) and 0.8 (SD 0.65) mg/kg for females and 3.0 (SD 1.6) and 0.6 (SD 0.37) mg/kg for males, respectively. The incidence of hepatocellular carcinomas was 3/51 (5.9%) and 4/41 (9.6%) after 2 yr in females and males, respectively. Hepatocellular carcinomas were not observed among the controls. Neoplastic (hyperplastic) nodules of the liver were present in 9/51 (17.6%) and 2/41 (4.9%) of exposed females and males, respectively, whereas only 2/48 (4.2%) of control females and no control males had neoplastic (hyperplastic) nodules. Body weights were lower in PBB-exposed rats at ages 1, 6, 12, and 24 mo. Survival rates from birth to weaning were lower in PBB-exposed pups (89%) than in controls (98%). Mortality was two times higher in PBB-exposed males (64%) than in control males (32%) after 2 yr. Transplacental PBB exposure and exposure through milk resulted in PBB body burdens in the offspring still measurable at the end of their lifespan. These offspring had increased mortality rates and lower body weights than controls, and they developed hepatocellular carcinomas.

Animals↗
PubMed1984

Relationship between dose and health effects.

The health effects produced by chemicals depend on the inherent toxicity of the chemical and the dose received by the exposed individual. Health effects are modified by genetic make-up, life style, nutrition, and interaction with other chemicals. In some situations it may be difficult to impossible to determine through epidemiologic studies whether exposure to chemicals (naturally occurring or synthetic) has caused harm. For all practical purposes, the risk associated with minuscule doses of most chemicals is negligible.

Adipose Tissue↗
PubMed1983

Long-term effects of a single oral dose of polybrominated biphenyls on serum and liver lipids in rats.

Adult (5 months) male Sherman strain rats received a single dose of either 0 or 500 mg polybrominated biphenyls (PBB) in corn oil/kg body weight by stomach tube. After an 18-month recovery period, serum and liver samples were examined. The primary serum lipid response was an increase in cholesterol (both free and esterified) and in total phospholipids. The percentage of esterified cholesterol was not significantly different from that of the controls, and no significant differences in the cholesterol ester fatty acid composition were observed. Serum triglycerides were also unaffected. In the PBB-dosed animals, the total hepatic fatty acids contained significantly less palmitic acid and more stearic acid, consistent with an increase in palmitic acid chain elongation activity. No significant differences could be detected in the n-3 or n-6 acids except for a slight decline in the content of 22:6 (n-3). Hepatic microsomal phospholipids were slightly higher (per milligram protein) in the PBB-dosed animals, and the cholesterol content was lower. Consequently, the cholesterol-phospholipid ratio was reduced, and microsomes from the latter group appeared to have an altered lipid domain on the basis of steady-state fluorescence anisotrophy measurements. In addition, total hepatic thiobarbituric acid-reactive substances (assayed as malondialdehyde) were significantly increased in the PBB-dosed animals. This observation appeared to reflect an increased susceptibility to peroxidative stress in the latter group, probably resulting from reduced membrane antioxidant concentrations. The PBB-dosed rats had significantly lower serum retinol levels and a reduced content of this vitamin in liver microsomes. Microsomes were also deficient in alpha-tocopherol in the PBB-dosed animals, although serum levels were normal.

Animals↗
PubMed1982

Acute and subacute toxicity in Sherman strain rats exposed to 4,4'- and 2,2'-dipyridyl.

Acute and subacute toxicity was studied in adult Sherman strain rats exposed to 4,4'-and 2,2'-dipyridyl. The single oral LD50 for 4,4'-dipyridyl was 175 mg/kg in male and 172 mg/kg in female rats; for 2,2'-dipyridyl it was 100 and 107 mg/kg, respectively. Symptoms of toxicity for 4,4'-dipyridyl included subdued behavior, red stains around mouth and eyes, lacrimation, swelling around the eyes, and occasional convulsions. Rats receiving 2,2'-dipyridyl had subdued behavior, loss of muscle coordination, red urine, tremors, and convulsions. Onset of symptoms was rapid, and most rats died from internal hemorrhage within 2 d after dosing. Rats given lower single oral doses of 90 mg/kg 2,2'-dipyridyl and 155 mg/kg 4,4'-dipyridyl had no symptoms and no organic pathology 2 wk after dosing. Rats given doses of 5.1 and 25.5 mg/kg 4,4'-dipyridyl and 7.13 and 35.6 mg/kg 2,2'-dipyridyl in their drinking water for 3 mo showed no significant effects that could be related to the consumption of dipyridyl.

2,2'-Dipyridyl↗
PubMed1981

Hyperkeratosis induced by sunlight degradation products of the major polybrominated biphenyl in Firemaster.

Sunlight photodegradation of 2,2', 4,4', 5,5' -hexabromobiphenyl, the major component of Firemaster, gave a mixture that produces severe hyperkeratosis of the rabbit ear. This component in its pure state does not cause hyperkeratosis. One or more of the four major photolysis products must be responsible for this activity. A similar photodegradation pattern was observed for 2,2', 3,4,4', 5,5' -heptabromobiphenyl, the second largest component of Firemaster.

Animals↗
PubMed1981

Association of blood pressure and polychlorinated biphenyl levels.

The geometric mean serum level of polychlorinated biphenyls (PCBs) of 458 persons in a communitywide study was 17.2 microgram/L, with 80% to 90% having levels within the range found in other community groups. As a dependent variable, PCB levels were found to be positively related to age, even when controlled for all other variables associated with PCB level: sex, local fish consumption, obesity, serum cholesterol level, and alcohol consumption. No major point source of PCB contamination was found, and fish taken in the drainage of a major population center had mean PCB levels below the current enforceable Food and Drug Administration tolerance of 5 mg/kg. As an independent variable, serum PCB levels were positively associated with gamma-glutamyl transpeptidase level, serum cholesterol level, and measured blood pressure. The PCB-blood pressure association, which was independent of age, sex, body mass index, and social class, must be confirmed in other exposed populations.

Alabama↗
PubMed1981

Cross-sectional study of a community with exceptional exposure to DDT.

The geometric mean level of total DDT in serum samples (76.2 ng/mL) from 499 persons living downstream from a defunct DDT-manufacturing plant was several times the national geometric mean (15.0 ng/mL). DDE isomers, metabolites of DDT, accounted for an average of 86.7% of total DDT. Total DDT levels increased with age, even when controlled for other independent variables also significantly associated with DDT: race, sex, fish consumption, years of residence, socioeconomic status, alcohol consumption, and serum triglyceride levels. Fish consumption, the second strongest determinant of DDT level, had one third the predictive power of age. Total DDT levels were not associated with specific illness or ill health. However, total DDT levels were positively associated with levels of serum cholesterol, triglyceride, and gamma-glutamyl transpeptidase. The finding that serum DDE levels increase with age suggests that no equilibrium in body burden has been reached or that pharmacokinetics or serum/adipose partition may vary with age.

Adolescent↗
PubMed1981

Fatal chemical pneumonia from 1,1,2,3,3-pentafluoro-3-chloropropene in an unmarked gas tank.

Fatal chemical pneumonia occurred in a worker following exposure to an unidentified gas in a salvaged cylinder. Inspection of the tank revealed a scrawled chemical formula for 1,1,2,3,3-pentafluoro-3-chloropropene, a suspected pulmonary irritant. The report underscores the potential hazards which salvaged cylinders pose to individuals who use or refill them. The population at risk includes scuba divers, emergency rescue personnel, and workers in the compressed gas industry.

Adult↗
PubMed1981

Induction of liver tumors in female Sherman strain rats by polybrominated biphenyls.

Noninbred Sherman strain rats were given the polybrominated biphenyl mixture Firemaster FF-1 (PBB). Rats given a single dose of 1,000 mg PBB/kg or 12 doses of 100 mg PBB/kg body weight in corn oil by gavage had final (when less than or equal to 26 mo old) liver PBB concentrations of 17.1 and 34.8 mg/kg (wet wt), respectively. The respective incidence of hepatocellular carcinomas was 41.4 and 67.8%. No difference in PBB concentrations was found between hepatocellular carcinomas and surrounding liver tissue. In addition, most livers of PBB-dosed rats had adenofibrosis of the liver. Livers of controls were essentially normal. Rats given a single dose of 200 mg PBB/kg as above had a 31.2% incidence of neoplastic nodules, whereas none were seen in the controls. The mean PBB concentrations (when 26 mo old) were 2.68 mg/kg in liver, 244 mg/kg in adipose tissue, and 0.22 mg/kg in blood.

Adipose Tissue↗